Cancer treatment and survivorship statistics, 2016

Kimberly D. Miller; Rebecca L. Siegel; Chun Chieh Lin; Angela B. Mariotto; Joan L. Kramer; Julia H. Rowland; Kevin D. Stein; Rick Alteri; Ahmedin Jemal

doi:10.3322/caac.21349

Cancer treatment and survivorship statistics, 2016

Miller, Kimberly D.; Siegel, Rebecca L.; Lin, Chun Chieh; Mariotto, Angela B.; Kramer, Joan L.; Rowland, Julia H.; Stein, Kevin D.; Alteri, Rick; Jemal, Ahmedin 2016-07-01 00:00:00 CA CANCER J CLIN 2016;66:271–289 1 2 3 4 Kimberly D. Miller, MPH ; Rebecca L. Siegel, MPH ; Chun Chieh Lin, PhD, MBA ; Angela B. Mariotto, PhD ; 5 6 7 8 9 Joan L. Kramer, MD ; Julia H. Rowland, PhD ; Kevin D. Stein, PhD ; Rick Alteri, MD ; Ahmedin Jemal, DVM, PhD Epidemiologist, Surveillance and Health Services Research, American Cancer ABSTRACT: The number of cancer survivors continues to increase because of both Society, Atlanta, GA; Strategic Director, advances in early detection and treatment and the aging and growth of the popula- Surveillance Information, Surveillance and tion. For the public health community to better serve these survivors, the American Health Services Research, American Cancer Society and the National Cancer Institute collaborate to estimate the number Cancer Society, Atlanta, GA; Director, Health Services Research, Intramural of current and future cancer survivors using data from the Surveillance, Epidemiol- Research Department, American Cancer ogy, and End Results cancer registries. In addition, current treatment patterns for Society, Atlanta, GA; Branch Chief, the most prevalent cancer types are presented based on information in the National Surveillance Research Program, National Cancer Institute, Bethesda, MD; Assistant Cancer Data Base and treatment-related side effects are briefly described. More Professor, Department of Hematology and than 15.5 million Americans with a history of cancer were alive on January 1, 2016, Medical Oncology, Emory University 6 and this number is projected to reach more than 20 million by January 1, 2026. The School of Medicine, Atlanta, GA; Director, 3 most prevalent cancers are prostate (3,306,760), colon and rectum (724,690), Office of Cancer Survivorship, National Cancer Institute, Bethesda, MD; Vice and melanoma (614,460) among males and breast (3,560,570), uterine corpus President, Behavioral Research Center, (757,190), and colon and rectum (727,350) among females. More than one-half American Cancer Society, Atlanta, GA; (56%) of survivors were diagnosed within the past 10 years, and almost one-half Medical Editor, American Cancer Society, (47%) are aged 70 years or older. People with a history of cancer have unique medi- Atlanta, GA; Vice President, Surveillance and Health Services Research, American cal and psychosocial needs that require proactive assessment and management by Cancer Society, Atlanta, GA primary care providers. Although there are a growing number of tools that can assist Corresponding author: Kimberly D. Miller, patients, caregivers, and clinicians in navigating the various phases of cancer survi- MPH, Surveillance and Health Services vorship, further evidence-based resources are needed to optimize care. CA Cancer J Research, American Cancer Society, 250 Clin 2016;66:271-289. 2016 American Cancer Society. Williams Street NW, Atlanta, GA 30303- 1002; [email protected]. Keywords: prevalence, statistics, survivorship, treatment patterns DISCLOSURES: The authors report no conflicts of interest. The findings and conclusions in this report are those of the authors and do not Introduction necessarily represent the official position of the National Cancer Institute. The number of cancer survivors continues to grow in the United States despite doi: 10.3322/caac.21349. Available online overall declining incidence rates in men and stable rates in women. This reﬂects at cacancerjournal.com an increasing number of new cancer diagnoses resulting from a growing and aging population, as well as increases in cancer survival because of advances in early detection and treatment. The American Cancer Society collaborates with the National Cancer Institute biennially to estimate the numbers of current and future cancer survivors to help the public health community better serve this unique population, some of whom must cope with long-term physical effects of treatment, as well as psychological and socioeconomic sequelae. In this article, we use the term “cancer survivor” to describe any person who has been diagnosed with cancer, from the time of diagno- sis through the remainder of his or her life. This includes patients currently under- going treatment and those who may have become cancer-free. Throughout this article, the terms “cancer patient” and “survivor” are used interchangeably, although not all people with a history of cancer identify with the term “cancer survivor.” We provide estimates for the most prevalent cancers, as well as statistics on treatment patterns and survival and issues related to survivorship. Materials and Methods Prevalence Estimates Cancer prevalence as of January 1, 2016 was estimated using the Prevalence Inci- dence Approach Model, which calculates prevalence from cancer incidence and survival and all-cause mortality. Incidence and survival were modeled by cancer _ _ VOLUME 66 NUMBER 4 JULY/AUGUST 2016 271 Cancer Treatment and Survivorship Statistics, 2016 type, sex, and age group using invasive malignant cases survival, which adjusts for normal life expectancy by compar- (except urinary bladder, which included in situ cases) diag- ing survival among cancer patients with that of the general nosed from 1975 through 2012 from the 9 oldest registries population, controlling for age, race, and sex. The SEER 18 in the population-based Surveillance, Epidemiology, and registries were the source for 5-year survival (diagnosis years End Results (SEER) program (2014 submission data). 2005-2011). Data from the 9 oldest SEER registries are For speciﬁc cancer site estimates, incident cases included used to describe changes in survival over time. Many of these the ﬁrst primary for the speciﬁc cancer site between 1975 statistics were originally published in the SEER Cancer and 2012. This differs from previous prevalence projec- Statistics Review, 1975-2012. In addition, 1-year, 10-year, 4,5 tions, which only included ﬁrst ever malignant primaries and 15-year relative survival rates were generated for selected and did not take into account subsequent primaries at sites using the National Cancer Institute’s SEER*Stat soft- 11,12 different sites. Total cancer prevalence was calculated as in ware (version 8.2.1). One-year survival rates are based on the previous methodology using only ﬁrst ever primary cancer patients diagnosed from 2008 to 2011, 10-year sur- cases. vival rates are based on diagnoses from 1999 and 2011, and Mortality data for 1975 through 2012 were obtained 15-year survival rates are based on diagnoses from 1994 and from the National Center for Health Statistics. Population 2011; all patients were followed through 2012. projections from 2014 through 2026 were obtained from the US Census Bureau. Projected US incidence and mor- Treatment tality for 2013 to 2026 were calculated by applying 5-year Cancer treatment data were analyzed from 2 sources: the average rates for 2008 through 2012 to the respective US National Cancer Data Base (NCDB) and the SEER program. population projections by age, sex, race, and year. Survival, incidence, and all-cause mortality rates were assumed to be NCDB constant from 2013 through 2026. For more information, The NCDB is a hospital-based cancer registry jointly spon- 6,7 see publications by Mariotto et al. sored by the American Cancer Society and the American College of Surgeons. It includes approximately 70% of all 2016 Case Estimates invasive cancers in the United States from more than 1500 The method for estimating the number of new US cancer facilities accredited by the American College of Surgeons’ 13,14 cases in 2016 is described elsewhere. Brieﬂy, the total Commission on Cancer (CoC). Studies have shown number of cases is estimated using a spatiotemporal model that disease severity and treatment patterns in the NCDB based on incidence data from 49 states and the District of stratiﬁed by clinical and sociodemographic factors for com- Columbia for the years 1998 through 2012 that met the mon cancer types are remarkably similar to those found in 15,16 North American Association of Central Cancer Registries’ population-based registries. high-quality data standard for incidence. Then, the number Treatment data are for cases diagnosed in the ﬁrst 6 of new cases is temporally projected 4 years ahead using months of 2013 for all sites except testis, for which aggre- vector autoregression. This method considers geographic gated data from 2009 through 2013 were used because of variations in sociodemographic and lifestyle factors, medi- the relatively small number of cases. In the 2013 NCDB cal settings, and cancer screening behaviors as predictors of data release, many common targeted therapy drugs are clas- incidence and also accounts for expected delays in case siﬁed as chemotherapy. For this report, we also include reporting. drugs classiﬁed as immunotherapy in the chemotherapy cat- egory (chemotherapy does not include hormone therapy). Stage at Diagnosis For more information regarding drug classiﬁcation catego- Several different staging systems are used to classify can- ries, see the SEER-Rx Web site (seer.cancer.gov/tools/ cers. In this report, the American Joint Committee on seerrx). Our analysis of treatment patterns does not include 8,9 Cancer staging system, which is commonly used in clini- diagnostic procedures. Methods of drug delivery are not cal settings, is used for the description of treatment pat- available in the NCDB, so topical or intravesical chemo- terns; whereas SEER Summary Stage, a staging system therapy cannot be distinguished from systemic chemother- frequently used by population-based cancer registries, is apy. More information can be found on the NCDB Web used to describe population-based patterns of stage at site (facs.org/cancer/ncdb). diagnosis and survival. SEER Survival The SEER 18 registries were the source for prostate cancer There are 2 common measures of cancer survival: relative treatment patterns because data are substantially less com- survival and observed survival. In this article, we use relative plete in the NCDB. However, use of androgen- 272 CA: A Cancer Journal for Clinicians CA CANCER J CLIN 2016;66:271–289 FIGURE 1. The Estimated Number of US Cancer Survivors. Note: Estimates for specific cancer types take into account the potential for a history of more than one cancer type. Source: Surveillance Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, MD. deprivation therapy is not collected, so could not be cancer, and an additional 246,660 women will be diagnosed in 2016. Seventy-ﬁve percent of breast cancer survivors included. (more than 2.6 million women) are ages 60 years or older, while 7% are younger than 50 years (Fig. 2). Selected Findings: Cancer Prevalence Breast cancer tends to be diagnosed at a younger age More than 15.5 million Americans with a history of cancer than other common cancers, with a median age at diagnosis were alive on January 1, 2016. By January 1, 2026, this of 61 years compared with 70 years for lung cancer and 68 number is projected to reach 20.3 million (Fig. 1). These years for colorectal cancer (Fig. 3). About 19% of breast estimates do not include carcinoma in situ for any cancer cancers are diagnosed in women ages 30 to 49 years, and except urinary bladder and do not include basal cell or squa- 44% occur among women who are age 65 years or older. mous cell skin cancers. The 3 most prevalent cancers in Treatment and survival 2016 are prostate (3,306,760), colon and rectum (724,690), Surgical treatment for breast cancer involves breast- and melanoma (614,460) among males and breast conserving surgery (BCS, also known as partial mastectomy (3,560,570), uterine corpus (757,190), and colon and rec- or lumpectomy) or mastectomy. When BCS followed by tum (727,350) among females (Fig. 1). The distribution of radiation to the breast is appropriately used for localized or cancer prevalence by type differs from that for new cases, regional cancers, long-term survival is the same as with reﬂecting differences in survival as well as age at diagnosis. 17,18 mastectomy. However, some patients require mastec- More than one-half (56%) of survivors were diagnosed tomy because of tumor characteristics (eg, locally advanced within the past 10 years (Table 1). Twenty-one percent of stage, large or multiple tumors), because postsurgery radia- female survivors were diagnosed more than 20 years ago tion is contraindicated (eg, preexisting medical condition, compared to only 13% of males. Nearly one-half (47%) are such as active connective tissue disease), or other obstacles. age 70 years or older, although age distribution varies by Younger women (<40 years) and patients with larger and/or cancer type (Table 2). For example, the majority of prostate more aggressive tumors are more likely to be treated with cancer survivors (64%) are age 70 years or older, compared 19,20 mastectomy. BCS-eligible women are increasingly elect- with only one-third of melanoma survivors (Fig. 2). ing mastectomy for a variety of reasons, including reluctance to undergo radiation therapy and fear of recurrence. The Selected Cancers proportion of women with nonmetastatic disease who Breast (female) undergo contralateral prophylactic mastectomy has also It is estimated that there are more than 3.5 million women increased rapidly, from 5% of total mastectomies in 1998 to living in the United States with a history of invasive breast 30% in 2011. _ _ VOLUME 66 NUMBER 4 JULY/AUGUST 2016 273 Cancer Treatment and Survivorship Statistics, 2016 TABLE 1. Estimated Number of US Cancer Survivors as of January 1, 2016, by Sex and Time Since Diagnosis MALE AND FEMALE MALE FEMALE YEARS SINCE CUMULATIVE CUMULATIVE CUMULATIVE DIAGNOSIS NO. PERCENT PERCENT NO. PERCENT PERCENT NO. PERCENT PERCENT 0to <5 y 5,189,400 33 33 2,713,350 37 37 2,476,050 30 30 5to <10 y 3,530,890 23 56 1,798,090 24 61 1,732,800 21 52 10 to <15 y 2,493,340 16 72 1,212,930 16 78 1,280,410 16 67 15 to <20 y 1,655,400 11 83 729,830 10 87 925,570 11 79 20 to <25 y 1,082,460 7 90 443,630 6 94 638,830 8 86 25 to <30 y 660,180 4 94 228,710 3 97 431,470 5 92 30 y 921,550 6 100 250,560 3 100 670,990 8 100 Note: Percentages do not sum to 100% due to rounding. Source: Surveillance Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute. Among women diagnosed with stage I or II breast can- des, because of improvements in treatment (ie, chemother- cer, 61% undergo BCS (with the majority also receiving apy, hormone therapy, and targeted drugs) and earlier additional therapy) and 36% undergo mastectomy (Fig. 4). detection through increased awareness and widespread use A much smaller percentage of stage III patients undergo of mammography. The 5-year, 10-year, and 15-year rela- BCS (21%), whereas 72% undergo mastectomy. Women tive survival rates for breast cancer are 89%, 83%, and 78%, diagnosed with stage IV disease most often receive radia- respectively. tion and/or chemotherapy alone (48%). Among women Cancer-related factors that inﬂuence survival include with hormone-receptor positive breast cancer of any stage, stage, tumor grade and histology, hormone receptor status, 79% receive hormonal therapy. and human epidermal growth factor receptor 2 (HER2) Breast reconstruction for women who undergo mastec- status. Sixty-one percent of breast cancers are diagnosed at tomy may involve the use of a saline or silicone implant, a tis- a localized stage, for which the 5-year relative survival rate sue ﬂap, or a combination thereof. Although reported rates is 99%. However, compared with white women, black of breast reconstruction in the United States vary widely, a women are less likely to be diagnosed with local stage breast recent large study found that the 57% of women with non- cancer (53% vs 62%) and have lower survival within each metastatic disease who received mastectomies underwent stage. These differences are driven in part by socioeco- reconstructive procedures. Women who undergo bilateral nomic factors and differences in comorbidities, less access mastectomy, are unmarried, or who have higher education or to and use of high-quality medical care among black income are more likely to undergo reconstruction. women, and biological differences in cancers (eg, higher The overall 5-year relative survival rate for female incidence of triple negative cancers among black 24–26 patients with breast cancer has improved in the past 3 deca- women). TABLE 2. Estimated Number of US Cancer Survivors as of January 1, 2016, by Sex and Age at Prevalance MALE AND FEMALE MALE FEMALE CUMULATIVE CUMULATIVE CUMULATIVE NO. PERCENT PERCENT NO. PERCENT PERCENT NO. PERCENT PERCENT All Ages, y 15,533,220 7,377,100 8,156,120 0–14 65,190 <1 <1 32,060 <1 <1 33,130 <1 <1 15–19 47,180 <1 1 23,610 <1 1 23,570 <11 20–29 187,490 1 2 90,730 1 2 96,760 1 2 30–39 408,790 3 5 166,170 2 4 242,620 3 5 40–49 958,600 6 11 347,700 5 9 610,900 7 12 50–59 2,389,670 15 26 963,410 13 22 1,426,260 17 30 60–69 4,141,950 27 53 2,027,150 27 49 2,114,800 26 56 70–79 4,011,790 26 79 2,148,940 29 79 1,862,850 23 79 80 3,322,560 21 100 1,577,330 21 100 1,745,230 21 100 Note: Percentages do not sum to 100% due to rounding. Source: Surveillance Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute. 274 CA: A Cancer Journal for Clinicians CA CANCER J CLIN 2016;66:271–289 FIGURE 2. Age Distribution of Survivors for Selected Cancer Types, January 1, 2016. Percentages may not sum to 100% because of rounding. Short-term and long-term health effects ments may also cause menopausal symptoms, such as hot ﬂashes, night sweats, and atrophic vaginitis, which can lead Lymphedema of the arm occurs in 20% of women who to dyspareunia. Breast cancer survivors may also experience undergo axillary lymph node dissection and in about 6% of 30,40 cognitive impairments and chronic fatigue. women who undergo sentinel lymph node biopsy. Early diagnosis of lymphedema is important for optimizing treat- Cancers in Children and Adolescents ment and slowing progression. Some forms of cancer reha- bilitation may reduce the risk and lessen the severity of this It is estimated that there are 65,190 cancer survivors aged 29,30 condition. birth to 14 years (children) and 47,180 survivors aged 15 to Other potential effects include numbness, tingling, or 19 years (adolescents) living in the United States as of Janu- tightness in the chest wall, arms, or shoulders following ary 1, 2016. An additional 10,380 children aged birth to 14 surgery and/or radiation. Studies have shown that between years will be newly diagnosed in 2016. The 3 most com- 25% and 60% of women develop chronic pain after breast monly diagnosed cancers in children are leukemia (30%), 31–33 cancer treatment, although it is usually not severe. In brain and central nervous system (CNS) tumors (26%, addition, treatment with chemotherapy can lead to including benign and borderline tumors), and soft tissue impaired fertility and premature menopause, which increase sarcomas (7%), about one-half of which are rhabdomyosar- the risk of osteoporosis. Chemotherapy with taxanes comas. Among adolescents, the most common cancers are often leads to neuropathy, which can persist long after brain and CNS tumors (20%), followed by leukemia (14%) treatment ends. Anthracyclines and HER-2–targeted 1 and Hodgkin lymphoma (HL) (13%). drugs can lead to cardiomyopathy and congestive heart fail- Treatment and survival ure. Treatment with aromatase inhibitors, which is gener- Pediatric cancers are treated with a combination of thera- ally reserved for postmenopausal women, can also cause osteoporosis, as well as myalgia and arthralgia, whereas pies (surgery, radiation, chemotherapy, and targeted ther- tamoxifen treatment slightly increases the risk of endome- apy) chosen based on the type and stage of cancer. trial cancer and thromboembolic disease. Hormonal treat- Treatment often occurs in specialized centers and is _ _ VOLUME 66 NUMBER 4 JULY/AUGUST 2016 275 Cancer Treatment and Survivorship Statistics, 2016 FIGURE 3. Age Distribution of New Cases (%), Median Age at Diagnosis, Estimated Number of New Cases, and 5-year Relative Survival by Cancer Type. *The new case estimate includes other biliary cancers. Note that sites are ranked in order of the median age at diagnosis from oldest to youngest. Sources: Age distribution based on 2011 to 2012 data from the North American Association of Central Cancer Registries and excludes Arkansas and Nevada. The median age at diagnosis and 5-year relative survival are based on cases diagnosed during 2008 through 2012 and 2005 through 2011, respectively, from the Surveillance, Epidemiology, and End Results 18 registries and were previously published in Howlader et al, and the 2016 estimated cases are from Siegel et al. FIGURE 4. Female Breast Cancer Treatment Patterns (%) by Stage, 2013. BCS indicates breast-conserving surgery; chemo, chemotherapy (includes immunotherapy and targeted therapy); RT, radiation therapy. Source: National Cancer Data Base, 2013. 276 CA: A Cancer Journal for Clinicians CA CANCER J CLIN 2016;66:271–289 coordinated by a team of experts, including pediatric oncol- reproductive organs may cause infertility in both males and 48,49 ogists, surgeons and nurses, social workers, child life spe- females. The potential impact on fertility and plans for cialists, psychologists, and others. fertility preservation should be discussed before commenc- Adolescents (ages 15-19 years) diagnosed with cancers ing treatment. Treatment may delay maturation and normal that are more common in childhood are usually most development in survivors and lead to negative body image appropriately treated at pediatric facilities or by pediatric and psychological distress. specialists. For example, studies have shown that pediatric Given these concerns, it is important that survivors of protocols result in better outcomes than adult protocols for pediatric cancers are monitored for long-term and late adolescent patients with acute lymphocytic leukemia effects as well as emotional and psychosocial concerns. The (ALL). In addition, childhood cancer centers are more Children’s Oncology Group, a National Cancer Institute- likely than adult cancer centers to offer adolescent patients supported clinical trials group that cares for greater than the opportunity to participate in clinical trials. For teen 90% of US children and adolescents diagnosed with cancer, patients with cancers that are more common among adults, has developed long-term follow-up guidelines for the such as melanoma, testicular, and thyroid cancers, treatment screening and management of late effects in survivors of by adult-care specialists is more appropriate. childhood cancer (survivorshipguidelines.org). The overall 5-year relative survival rate for all childhood cancers (aged birth-14 years) combined has improved markedly over the past 30 years, from 58% for patients Colon and Rectum diagnosed between 1975 and 1977 to 83% for those diag- It is estimated that, as of January 1, 2016, there are more nosed during 2005 through 2011, because of new and than 1.4 million men and women living in the United improved treatments. Although there has been less dramatic States with a previous colorectal cancer diagnosis, and an improvement in survival for adolescents, the current 5-year additional 134,490 cases will be diagnosed in 2016. Eighty- 10,44 relative survival rate (84%) is similar to that for children. ﬁve percent of colorectal cancer survivors (about 1.2 million However, survival rates vary considerably by cancer type. men and women) are aged 60 years and older, while only For example, the 5-year survival rate during 2005 through 4% (60,610) are aged younger than 50 years (Fig. 2). The 2011 was 89% for children and 76% for adolescents for median age at diagnosis for colorectal cancer is 66 years for ALL, compared to 69% and 61%, respectively, for males and 70 years for females. Patients with rectal cancer osteosarcoma. tend to be younger at diagnosis than those with colon Short-term and long-term health effects cancer (median age, 63 vs 70 years, respectively). Childhood cancer survivors may experience both long-term (chronic) and late (occurring months or years after diagno- Treatment and survival sis or treatment) effects. Aggressive treatments used for The majority of patients with stage I and II colon cancer childhood cancers, especially in the 1970s and 1980s, have undergo partial or total colectomy alone (84%), while about resulted in several late effects, including increased risk of two-thirds of those with stage III disease (as well as some subsequent neoplasms and cardiomyopathies. A recent with stage II disease) receive chemotherapy in addition to study found that 50% of childhood cancer survivors had colectomy to lower their risk of recurrence (Fig. 5). For developed a severe or life-threatening chronic health condi- patients with rectal cancer, proctectomy or proctocolectomy tion by age 50 years. Among childhood cancer survivors is the most common treatment (61%) for stage I disease, who were diagnosed and treated between 1962 and 2001, and about one-half also receive radiation and/or chemo- 65% of those who were exposed to pulmonary toxic cancer therapy (Fig. 6). Stage II and III rectal cancers are often treatments experienced pulmonary dysfunction, and 57% of treated with neoadjuvant chemotherapy plus radiation. A those who were exposed to potentially cardiotoxic therapies colostomy (usually temporary) is required during surgery experienced cardiac abnormalities. more often for patients with rectal cancer (29%) than for Recent declines in late morbidity and mortality among those with colon cancer (12%). Chemotherapy is the childhood cancer survivors are due in part to reduced use of main treatment for stage IV rectal cancers. Growing num- certain treatments, such as cranial radiation for ALL and bers of targeted drugs are also available to treat metastatic abdominal radiation for Wilms tumor. However, even colorectal cancer. many newer, less toxic therapies increase the risk of serious The 5-year and 10-year relative survival rates for persons health conditions in long-term childhood cancer survivors. Cognitive impairment, which can vary in severity, affects up with colorectal cancer are 65% and 58%, respectively. to one-third of childhood cancer survivors. In addition, When colorectal cancers are detected at a localized stage surgery, radiation, and some chemotherapies affecting the (39% of cases), the 5-year relative survival rate is 90%. _ _ VOLUME 66 NUMBER 4 JULY/AUGUST 2016 277 Cancer Treatment and Survivorship Statistics, 2016 FIGURE 5. Colon Cancer Treatment Patterns (%) by Stage, 2013. Chemo indicates chemotherapy (includes immunotherapy and targeted therapy); RT, radiation therapy. *A small number of these patients received RT. Source: National Cancer Data Base, 2013. Short-term and long-term health effects most common types in adults, whereas ALL is most the common among children and teens (Fig. 3). Neuropathy is a common side effect of chemotherapy regi- There are 2 basic categories of lymphoma: Hodgkin lym- mens containing oxaliplatin. Chronic diarrhea occurs in phoma (HL) and non-Hodgkin lymphoma (NHL). NHLs about one-half of colorectal cancer survivors. Bowel dys- can be further divided into indolent and aggressive catego- function (including increased stool frequency, incontinence, ries, each of which includes many subtypes that progress radiation proctitis, and perianal irritation) is common among and respond to treatment differently. Prognosis and treat- rectal cancer survivors, especially those treated with pelvic 54,55 ment depend on the stage and type of lymphoma. It is esti- radiation. Survivors may also suffer from bladder dys- 39,56,57 mated that, as of January 1, 2016, there were 219,570 HL function, sexual dysfunction, and negative body image. survivors and 686,370 NHL survivors. About 8500 new Referral to a trained ostomy therapist may beneﬁt patients cases of HL and 72,580 new cases of NHL will be diag- with a colostomy who experience these issues. In addition, nosed in 2016. Although both HL and NHL occur in chil- cancer recurrence is not uncommon among colorectal survi- 59,60 dren and adults, the majority of HL cases (64%) are vors, who are also at increased risk of second primary diagnosed before age 50 years, whereas most NHL cases cancers of the colon and rectum and other cancer sites, (85%) occur in those aged 50 years and older (Fig. 3). particularly those within the digestive system. Treatment and survival for the most common types of Leukemias and Lymphomas leukemia and lymphoma There are an estimated 407,950 leukemia survivors in the AML United States, and an additional 60,140 people will be diagnosed in 2016. Although leukemia is the most com- Chemotherapy is the standard treatment for AML, mon type of cancer among children aged birth to 14 years, although many older adults, among whom the disease is the majority (92%) of patients with leukemia are diagnosed most common, are not able to tolerate the most aggressive at age 20 years and older. Acute myeloid leukemia and potentially curative protocols. Patients may also (AML) and chronic lymphocytic leukemia (CLL) are the undergo allogeneic stem cell transplantation, and some FIGURE 6. Rectal Cancer Treatment Patterns (%) by Stage, 2013. Chemo indicates chemotherapy (includes immunotherapy and targeted therapy); RT, radiation therapy. Source: National Cancer Data Base, 2013. 278 CA: A Cancer Journal for Clinicians CA CANCER J CLIN 2016;66:271–289 receive radiation therapy, often as part of a conditioning 2005 through 2011 (89% vs 92%). Survival declines with regimen before stem cell transplantation. increasing age at diagnosis, and the current 5-year survival Approximately 60% to 85% of adults aged 60 years and rate is 46% for patients aged 20 to 39 years, 30% for those younger with AML can expect to attain complete remission aged 40 to 64 years, and 15% for those aged 65 years and status after the ﬁrst phase of treatment, and 35% to 40% of older. 63,64 patients in this age group will be cured. In contrast, CLL 40% to 60% of patients aged older than 60 years will CLL is the most common type of leukemia in adults, and achieve complete remission, and only 5% to 15% will be 95% of cases are diagnosed in individuals aged 50 years and cured. About 4% of AML cases occur in children and ado- older (Fig. 3). Treatment is generally reserved for sympto- lescents, for whom the prognosis is substantially better. matic patients or for those who have cytopenia or other The 5-year relative survival rate for children and adoles- complications because the disease is slow-growing and cents (aged birth-19 years) is 65% but declines to 50%, treatment is unlikely to result in a cure. Available treat- 32%, and 6% for patients aged 20 to 49 years, 50 to 64 ments include chemotherapy, immunotherapy, targeted years, and 65 years and older, respectively. therapy, radiation therapy, and splenectomy, but it is often 69–71 CML not clear whether these treatments extend survival. The overall 5-year relative survival rate for CLL is 82%; Chronic myeloid leukemia (CML) is most common in however, there is large variation in survival among individ- adults, and only 2% of cases are diagnosed in children and ual patients, ranging from several months to a normal life adolescents. The cancer cells in CML contain a charac- expectancy. About 5% to 10% of patients with CLL teristic fusion gene, bcr-abl (breakpoint cluster region- develop diffuse large B-cell lymphoma (DLBCL), a process Abelson), which is caused by a translocation of genetic known as “Richter transformation.” material between chromosomes 9 and 22, resulting in the Philadelphia chromosome. Modern treatment of CML has HL been transformed by tyrosine kinase inhibitors (TKIs) There are 2 major types of HL. Classical HL (CHL) is the aimed at the BCR-ABL protein, which induce remission most common and is characterized by the presence of in most patients but must be taken indeﬁnitely. Stem cell Reed-Sternberg cells. Nodular lymphocyte-predominant transplantation may be used in younger patients and those HL (NLPHL), which is characterized by “popcorn cells,” who become resistant to TKIs, whereas chemotherapy is comprises only about 5% of cases. NLPHL is a more only used in TKI-resistant patients. Primarily because of indolent disease with a generally favorable prognosis. the discovery and widespread use of the BCR-ABL TKIs, CHL is generally treated with multiagent chemotherapy the 5-year survival rate for CML increased from 31% for (88%), sometimes in combination with radiation therapy patients diagnosed during 1990 through 1992 to 63% for (30% among chemotherapy recipients), although the use of 10,65 those diagnosed during 2005 through 2011. radiotherapy is declining. If these treatments are not effective, stem cell transplantation or the targeted drug ALL brentuximab vedotin may be options. For patients with More than one-half of ALL cases (56%) are diagnosed in NLPHL, radiation alone may be appropriate for early stage patients younger than 20 years. Chemotherapy is the stand- disease. For those with later stage disease, chemotherapy ard treatment for ALL. About 20% to 30% of adult ALL plus radiation as well as the monoclonal antibody rituximab cases and <5% of childhood cases are Philadelphia may be recommended. chromosome-positive and may beneﬁt from the addition of 66,67 The 5-year and 10-year survival rates for HL are 86% a BCR-ABL TKI to chemotherapy. More than 95% of and 80%, respectively. The 5-year survival rate is 94% for children and from 78% to 92% of adults with ALL attain NLPHL and 85% for CHL. remission. Allogeneic stem cell transplantation is recom- NHL mended for some patients who have high-risk disease char- acteristics and for those who relapse after remission or who The most common types of NHL are DLBCL, represent- fail to achieve remission after successive courses of induc- ing 37% of cases, and follicular lymphoma, representing tion chemotherapy. 20% of cases. Although DLBCLs grow quickly, most Survival rates for ALL have increased signiﬁcantly over patients with localized disease and about 50% of those with 10 74,75 the past 3 decades, particularly among children. Notably, advanced-stage disease are cured. In contrast, follicular the black-white 5-year relative survival disparity in children lymphomas tend to grow slowly and often do not require and adolescents with ALL has diminished from a 21- treatment until symptoms develop, but many are not cura- percentage-point difference during 1980 through 1984 ble. Some cases of follicular lymphoma transform into (49% vs 70%) to a 3-percentage-point difference during DLBCL. _ _ VOLUME 66 NUMBER 4 JULY/AUGUST 2016 279 Cancer Treatment and Survivorship Statistics, 2016 The ﬁrst course of treatment for all NHL subtypes com- bined is usually chemotherapy, either alone (58%) or in combination with radiation (11%) (Fig. 7). Approximately 17% of patients receive no treatment. A monoclonal anti- body like rituximab is often given along with chemotherapy for B-cell lymphomas and for some T-cell lymphomas. The 5-year survival rate is 86% for follicular lymphoma and 61% for DLBCL; 10-year survival declines to 77% and 53%, respectively. Short-term and long-term health effects People treated for leukemia and lymphoma can experience several signiﬁcant long-term and late effects. Some leuke- mia and lymphoma survivors, such as those who undergo stem cell transplantation, have problems with recurrent infections and with anemia, which may require blood trans- FIGURE 7. Non-Hodgkin Lymphoma Treatment Patterns (%), fusions. Certain chemotherapy drugs, as well as high-dose 2013. Chemo indicates chemotherapy (includes immunotherapy and targeted ther- chemotherapy used for stem cell transplantation, can lead apy); RT, radiation therapy. Source: National Cancer Data Base, 2013. to infertility. Allogeneic transplantation used to treat acute leukemias can lead to chronic graft-versus-host disease, which can cause skin changes, dry mucous membranes phoma kinase (ALK) inhibitors, are also an important part (eyes, mouth, vagina), joint pain, weight loss, shortness of of the treatment for NSCLC. Recently, immunotherapy breath, and fatigue. drugs that act by targeting the programmed cell death Chest radiation for HL increases the risk for cardiac dys- receptor on T cells have been approved to treat some types function as well as breast cancer among women who were of NSCLC. treated in childhood and adolescence. Patients with HL, The 1-year relative survival for lung cancer increased NHL, and ALL are commonly treated with anthracyclines, from 34% during 1975 through 1977 to 45% during 2008 which can also be cardiotoxic. In the past, some children through 2011, largely because of improvements in surgical with ALL who were at increased risk for CNS relapse techniques and chemoradiation. The majority of lung can- received cranial radiation therapy. This treatment can cause cers (57%) are diagnosed at a distant stage, because early long-term cognitive deﬁcits, and it is used less frequently disease is typically asymptomatic; only 16% of cases are and at lower dosages today. diagnosed at a local stage. The 5-year survival rate is 55% for cases detected when the disease is still localized, 27% Lung and Bronchus for regional disease, and 4% for distant stage disease. The It is estimated that there are 526,510 men and women liv- 5-year survival for small cell lung cancer (7%) is lower than ing in the United States with a history of lung cancer, and that for NSCLC (21%). an additional 224,390 cases will be diagnosed in 2016. The Short-term and long-term health effects median age at diagnosis for lung cancer is 70 years. Many lung cancer survivors have impaired pulmonary func- Treatment and survival tion, although some may have had preexisting respiratory Lung cancer is classiﬁed as small cell (13% of cases) or non- problems. In some cases respiratory therapy and medica- small cell (83%) for the purposes of treatment (3% of cases tions can improve ﬁtness and allow survivors to resume nor- in the SEER database lack information on histologic mal daily activities. Treatment with EGFR inhibitors can type). Most patients with small cell lung cancer receive lead to a severe acneiform rash. Immunotherapy drugs used chemotherapy. In addition, some patients are also treated in lung cancer treatment can lead to several immune mediated with thoracic radiation therapy. For stage I and II nonsmall toxicities, including pneumonitis, colitis, nephritis, and cell lung cancers (NSCLC), the majority of patients (69%) endocrinopathy. undergo surgery, and about 25% of surgical cases also Lung cancer survivors who are current or former smokers receiving chemotherapy and/or radiation therapy (Fig. 8). are at increased risk for subsequent smoking-related can- Most patients with stage III and IV NSCLC receive chem- cers, especially lung, head and neck, and esophageal, as well otherapy with or without radiation (53%). Targeted therapy as other smoking-related health problems. Survivors may drugs, such as angiogenesis inhibitors, epidermal growth feel stigmatized because of the social perception that lung factor receptor (EGFR) inhibitors, and anaplastic lym- cancer is a self-inﬂicted disease, which can be particularly 280 CA: A Cancer Journal for Clinicians CA CANCER J CLIN 2016;66:271–289 FIGURE 8. Nonsmall Cell Lung Cancer Treatment Patterns (%) by Stage, 2013. Chemo indicates chemotherapy (includes immunotherapy and targeted therapy); RT, radiation therapy. Source: National Cancer Data Base, 2013. difﬁcult for those who never smoked. Data suggest that Short-term and long-term health effects there is a beneﬁt to smoking cessation even after a lung Depending on the size and location of the melanoma, 80,81 cancer diagnosis. removal of these cancers can be disﬁguring. Male and female melanoma survivors are nearly 13 and 16 times Melanoma more likely, respectively, than the general population to develop additional melanomas because of skin type and It is estimated that there are more than 1.2 million mela- other genetic or behavioral risk factors. From 10% to 15% noma survivors living in the United States, and an addi- of patients treated with ipilimumab experience serious tional 76,380 people will be diagnosed in 2016. Sixty-three autoimmune-related side effects that sometimes can lead to percent of melanoma survivors are under the age of 70, and death. Autoimmune-related side effects occur less often 17% are under the age of 50 (Fig. 2). Melanoma incidence with pembrolizumab and nivolumab. Patients treated with rates continue to increase in men but have recently stabi- BRAF inhibitors have an increased risk of developing squa- lized in women. Women tend to be diagnosed at a mous cell skin carcinomas. younger age than men (58 vs 65 years, respectively), reﬂecting differences in occupational and recreational expo- Prostate sure to ultraviolet radiation, as well as early detection; It is estimated that there are more than 3.3 million men women are more likely to be diagnosed at a localized stage, living with prostate cancer in the United States, and an 86% versus 82% of men. additional 180,890 cases will be diagnosed in 2016. The Treatment and survival majority (64%) of prostate cancer survivors are over the age of 70 years, and less than 1% are under age 50 years (Fig. 2). Surgery is the primary treatment for most melanomas. The median age at diagnosis is 66 years (Fig. 3). Most pros- Patients with stage III disease may be offered adjuvant tate cancers in the United States are diagnosed by prostate- immunotherapy with interferon or the anticytotoxic T- speciﬁc antigen (PSA) testing, although many expert lymphocyte-associated protein (anti-CTLA) antibody ipili- groups, including the American Cancer Society, have con- mumab, although these treatments can have serious side cluded that data on the efﬁcacy of PSA screening are insufﬁ- effects. Treatment for patients with stage IV melanoma has cient to recommend routine use of this test. changed in recent years and typically includes immunother- apy (ipilimumab, pembrolizumab, and nivolumab) or tar- Treatment and survival geted therapy drugs, both of which have been shown to Treatment options vary, depending on the extent of disease 82–84 extend survival. BRAF (B-Raf proto-oncogene, serine/ and the risk of recurrence, as well as patient characteristics, threonine kinase) inhibitors have been shown to improve such as age and comorbidity, and personal preferences. Fig- survival for melanomas with the BRAF gene mutation, ure 9 shows primary treatment among men diagnosed dur- 85–87 which account for about one-half of all cases. Almost ing 2010 through 2012 based on SEER data [information one-half (46%) of patients with stage IV disease who on the use of androgen deprivation therapy (ADT) is not receive either chemotherapy or immunotherapy also receive available] for all stages combined, although most (92%) of radiation therapy. cases are diagnosed at the localized stage. Men younger The 5-year and 10-year relative survival rates for persons than 65 years are most likely to be treated with radical pros- with melanoma are 92% and 89%, respectively. About 84% tatectomy (with or without radiation), whereas about one- of melanomas are diagnosed at a localized stage, for which half of men 75 years or older do not undergo surgery or the 5-year survival rate is 98%. radiation. _ _ VOLUME 66 NUMBER 4 JULY/AUGUST 2016 281 Cancer Treatment and Survivorship Statistics, 2016 103–106 and diabetes. Although some studies indicate an increased risk of cardiovascular disease or death associated with the use of hormone therapy, the evidence is inconsis- 104,105,107 tent. Careful monitoring of cardiovascular risk factors is recommended for men who have received 108,109 ADT. Testis It is estimated that there are 266,550 testicular cancer sur- vivors in the United States, and an additional 8720 men will be diagnosed in 2016. Testicular germ cell tumors (TGCTs) account for approximately 97% of all testicular cancers. The 2 main types of TGCTs are seminomas and nonseminomas. Nonseminomas are more common, gener- ally occur in men in their late teens to early 40s, and tend to be more aggressive than seminomas. Seminomas are FIGURE 9. Prostate Cancer Treatment Patterns (%) by Age, slow-growing and are generally diagnosed in men in their United States, 2010-2012. RT indicates radiation therapy. Patients with missing treatment data were late 30s to early 50s. excluded. Source: Surveillance, Epidemiology, and End Results (SEER) Pro- gram, SEER 18 Registries, 2010 to 2012. Treatment and survival Treatment of almost all TGCTs begins with orchiectomy. Active surveillance rather than immediate treatment is a While the most common treatment for stage I and II semi- reasonable and commonly recommended approach, espe- nomas is surgery alone (46%), many surgical patients also cially for men who have less aggressive tumors, are older, receive radiation (31%) or chemotherapy (22%) (Fig. 10). 91–93 and/or have serious comorbid conditions. ADT, chem- Over the last decade, postsurgical active surveillance has otherapy, bone-directed therapy (such as zoledronic acid or become an increasingly preferred management option for denosumab), radiation, or a combination of these treat- patients with stage I seminomas, and long-term study results ments are used to treat more advanced disease. Newer 110 support this treatment strategy. Stage III and IV semino- forms of hormone therapy, such as abiraterone and enzalu- mas are generally treated with surgery and chemotherapy tamide, have been approved in recent years to treat with or without radiation therapy (70%). Among patients advanced prostate cancer that is no longer responding to with stage I and II nonseminomas, approximately 20% 94–97 traditional hormone therapy. undergo retroperitoneal lymph node dissection, which is The 5-year relative survival rate approaches 100% for recommended to reduce the likelihood of recurrence patients with localized disease, but declines to 28% for (Fig. 11). Patients with stage III and IV nonseminomas are those diagnosed at a distant stage. The 5-year relative sur- treated with surgery and adjuvant chemotherapy, and some vival for all stages combined increased from 83% in in the require additional surgery after completion of late 1980s to 99% in the most recent time period (2005- chemotherapy. 2011), primarily reﬂecting lead time and overdetection. The 5-year, 10-year, and 15-year survival rates are all The 10-year and 15-year relative survival rates are 98% and approximately 95%. Most testicular cancers (68%) are diag- 95%, respectively. nosed at a localized stage, for which the 5-year relative sur- vival rate is 99%. Short-term and long-term health effects Short-term and long-term health effects Surgery and radiotherapy for prostate cancer are associated with risk of substantial physical impairments, including uri- Although most men who have one healthy testicle produce nary incontinence, erectile dysfunction, and bowel compli- sufﬁcient male hormones and sperm to continue sexual rela- 98–101 cations. In one long-term follow-up study, greater tions and father children, sperm banking is recommended than 95% of patients with prostate cancer who underwent before treatment. Consultation about fertility risks before surgery or received radiation experienced some sexual dys- treatment and referral for sperm banking as appropriate are function, and about 50% reported urinary or bowel important in efforts to promote quality-of-life outcomes. dysfunction. Patients receiving hormonal treatment Retroperitoneal lymph node dissection can lead to retro- may experience loss of libido, hot ﬂashes, night sweats, irri- grade ejaculation, making unassisted reproduction impossi- tability, and breast development. In the long term, ble. Men treated with chemotherapy have increased risks of ADT also increases the risk of osteoporosis, obesity, coronary artery disease as they age, so these patients and 282 CA: A Cancer Journal for Clinicians CA CANCER J CLIN 2016;66:271–289 FIGURE 10. Treatment Patterns (%) for Seminomatous Testicular Germ Cell Tumors by Stage, 2009 to 2013. Chemo indicates chemotherapy (includes immunotherapy and targeted therapy); RT, radiation therapy. Source: National Cancer Data Base, 2013. their physicians should be particularly mindful of risk fac- Treatment and survival tors like hyperlipidemia, hypertension, obesity, and smok- Most thyroid cancers are either papillary or follicular car- ing. Men who have bilateral tumors have both testes cinomas, which are highly curable, but about 3% are removed and require lifelong testosterone supplementation. medullary or anaplastic carcinomas, which are more dif- ﬁcult to treat because they do not respond to radioactive iodine treatment. These cancers also grow more quickly Thyroid and often have metastasized by the time they are It is estimated that there are 805,750 people living with a diagnosed. previous thyroid cancer diagnosis in the United States, and The ﬁrst choice of treatment in nearly all patients with an additional 64,300 will be diagnosed in 2016. Thyroid thyroid cancer is surgery, with most patients undergoing total cancer is the most rapidly increasing cancer in the United (86%) or partial (12%) thyroidectomy. About one-half of States and has been increasing worldwide over the past surgically treated patients who have papillary or follicular few decades. Studies suggest that the rise is primarily thyroid cancer receive radioactive iodine (I-131) after surgery due to the increased incidental detection of indolent papil- to destroy any remaining thyroid tissue and cancer. After lary tumors through widespread use of imaging. Accu- total thyroidectomy, thyroid hormone-replacement therapy mulating awareness of this “epidemic of diagnoses” has is required and is often prescribed in a dosage sufﬁcient to resulted in more conservative clinical practice guidelines inhibit pituitary production of thyroid-stimulating hormone about when to biopsy and a subsequent stabilization of to decrease the likelihood of recurrence. overall incidence rates. However, increasing trends for Total thyroidectomy is the primary treatment for larger and follicular tumors indicate that risk factors may patients with medullary thyroid cancer. When the tumor is also be contributing to a true increase in disease occur- extensive or cannot be completely resected, radiation ther- 115,116 rence. The median age at diagnosis—54 years for apy may be given after surgery. Targeted drugs can be use- males and 49 years for females—is younger than that for ful in treating metastatic disease. Anaplastic thyroid cancers most other adult cancers (Fig. 3). are often widespread and resistant to treatment; in selected FIGURE 11. Treatment Patterns (%) for Nonseminomatous Testicular Germ Cell Tumors by Stage, 2009 to 2013. Chemo indicates chemotherapy (includes immunotherapy and targeted therapy); RPLND, retroperitoneal lymph node dissection; RT, radiation therapy. Note that a small proportion of patients (<1% of those with early stage disease and about 5% of those with late-stage disease) who underwent surgery also received RT. Source: National Cancer Data Base, 2013. _ _ VOLUME 66 NUMBER 4 JULY/AUGUST 2016 283 Cancer Treatment and Survivorship Statistics, 2016 patients, radiation therapy alone or in combination with chemotherapy may be used. The 5-year relative survival rate for patients with thyroid cancer who were diagnosed during 2005 through 2011 is 98%, although survival varies by age at diagnosis, stage, and histologic type. Notably, blacks are more likely to be diagnosed at a localized stage compared with whites (78% vs 68%, respectively) but have lower survival within each stage and overall. For patients with medullary and ana- plastic carcinomas, the 5-year relative survival rates are 88% and 9%, respectively. Short-term and long-term health effects Patients who undergo total thyroidectomy require thyroid hormone-replacement therapy, and thyroid hormone levels must be monitored to prevent hypothyroidism, which can FIGURE 12. Muscle-invasive Bladder Cancer Treatment Pat- cause cold intolerance and weight gain. Surgical removal of terns (%), 2013. the thyroid gland can damage the underlying parathyroid Chemo indicates chemotherapy (includes immunotherapy and targeted ther- apy); RT, radiation therapy; TURBT, transurethral resection of the bladder glands, leading to disorders of calcium metabolism. Surgery tumor. Source: National Cancer Data Base, 2013. can also damage nerves to the larynx and lead to voice changes. Treatment with radioactive iodine can affect fer- tility and may be linked to an increased risk of leukemia. have metastasized, but other treatments might be used as About 25% of medullary thyroid cancers occur as part of a well. genetic syndrome (such as multiple endocrine neoplasia For all stages combined, the 5-year relative survival rate [MEN] type 2), so these patients should be screened for is 77%. Survival declines to 70% at 10 years and to 65% at other cancers and referred for genetic counseling and possi- 15 years after diagnosis. The 5-year relative survival rate for ble testing. in situ urinary bladder cancer, which accounts for 51% of cases, is 96%. For the 35% of patients with invasive Urinary Bladder tumors diagnosed at a localized stage, the 5-year survival It is estimated that there are 765,950 urinary bladder cancer rate is 70% (81% for those with nonmuscle-invasive disease survivors living in the United States, and an additional and 47% for those with muscle-invasive disease). 76,960 cases will be diagnosed in 2016. Bladder cancer inci- dence is about 4 times higher in men than in women. Short-term and long-term health effects The median age at diagnosis is 73 years. More than 70% of Posttreatment surveillance is crucial given the high rate of patients who have bladder cancer are diagnosed with 124,125 recurrence (estimates range from 50% to 90%). Sur- nonmuscle-invasive disease. veillance can include screening for urine biomarkers and Treatment and survival cytology as well as cystoscopy. Patients who require repeated bladder surgeries can end up with a small or For nonmuscle-invasive cancers, most patients are diag- scarred bladder, which may lead to urinary frequency or nosed and treated with transurethral resection of the blad- der tumor (TURBT), which may be followed by incontinence. Partial cystectomy results in a smaller blad- der, sometimes causing the patient to have more frequent intravesical chemotherapy (22%) or biologic therapy with urination. Patients undergoing cystectomy in which the bacillus Calmette-Guerin (29%). (The NCDB does not entire bladder is removed require urinary diversion with distinguish between systemic and intravesical chemother- apy but, based on treatment guidelines, it is likely that vir- either construction of a neobladder with urethral anastomo- sis or a urostomy. Those with a neobladder retain most of tually all chemotherapy is intravesical administration.) their urinary continence after appropriate rehabilitation. Among patients with muscle-invasive disease, about one-half undergo TURBT, and 39% undergo cystectomy, However, creation of a neobladder remains much less com- with or without chemotherapy and/or radiation (Fig. 12). mon than urostomy (9% vs 91%), largely because of the TURBT followed by combined chemotherapy and technical complexity of the procedure; its use is substan- radiation therapy is as effective as cystectomy at preventing tially higher at larger, higher volume hospitals. Younger, 121–123 recurrence in appropriately selected cases. healthier patients and those who are male are also more Chemotherapy is usually the ﬁrst treatment for cancers that likely to undergo the procedure. 284 CA: A Cancer Journal for Clinicians CA CANCER J CLIN 2016;66:271–289 FIGURE 13. Uterine Corpus Cancer Treatment Patterns (%) by Stage, 2013. Chemo indicates chemotherapy (includes immunotherapy and targeted therapy); RT, radiation therapy. Source: National Cancer Data Base, 2013. Uterine Corpus Quality of Life and Other Concerns in Long-Term Survivorship There are an estimated 757,190 women living in the United States with a previous diagnosis of uterine corpus cancer Although quality of life may decline considerably during and an additional 60,050 cases will be diagnosed in 2016. active cancer treatment and remain low for a short period thereafter, many side effects are acute and short-lived, and the Cancer of the uterine corpus is the second most prevalent cancer among women after breast cancer. The median age majority of disease-free cancer survivors report good quality of at diagnosis is 62 years (Fig. 3). life 1 year posttreatment. The type and prevalence of long- term or late side effects vary with clinical factors (eg, cancer type, treatment) and patient characteristics (eg, age, sex, Treatment and survival comorbidity). While emotional well-being for longer term Surgery, consisting of hysterectomy (often including bilat- survivors (5 years) is generally comparable to that of individ- eral salpingo-oophorectomy) alone, is used to treat 69% of uals with no history of cancer, a signiﬁcant number report patients with stage I and II disease, whereas 28% of women 2,130 lower overall physical well-being than their peers. Many receive radiation and/or chemotherapy in addition to surgery survivors also suffer from a fear of recurrence and subsequent (Fig. 13). Two-thirds of women with stage III and IV disease primary cancers. Quality-of-life issues also encompass the undergo surgery followed by radiation and/or chemotherapy. concerns of cancer caregivers, who provide substantial emo- Clinical trials are currently assessing the most appropriate reg- tional and physical support to survivors and who frequently imen of radiation and chemotherapy for women with meta- report having unmet psychosocial and medical needs. static or recurrent cancers. There is increasing emphasis on improving cancer survi- The 5-year and 10-year relative survival rates for women vors’ overall well-being and quality of life through the with uterine corpus cancer are 82% and 79%, respectively. application of principles of disease self-management and Most cancers (67%) are diagnosed at an early stage, usually the promotion of healthy lifestyles, such as avoiding because of postmenopausal bleeding, for which the 5-year tobacco, maintaining a healthy body weight, avoiding survival rate is 95%. The overall 5-year survival for white intense ultraviolet radiation exposure, and being physically women (84%) is about 22 percentage points higher than active throughout life. Several practical interventions for that for black women (62%). survivors addressing diet, weight, and physical activity among cancer survivors have been developed and tested. Short-term and long-term health effects In addition, support for smoking cessation and increased Any hysterectomy causes infertility. Bilateral oophorectomy access to cessation aids are essential, because approximately will cause menopause in premenopausal women, which can 10% of cancer survivors continue to smoke even up to 9 lead to symptoms such as hot ﬂashes, night sweats, atrophic years after diagnosis. Younger cancer survivors in partic- vaginitis, and osteoporosis. Long-term side effects of radia- ular have been shown to have a higher prevalence of smok- tion therapy for uterine cancer can include bladder and ing after diagnosis than the general population. bowel dysfunction as well as atrophic vaginitis and stenosis. It is therefore important for providers to understand the Sexual problems are commonly reported among uterine unique medical and psychosocial needs of survivors as well cancer survivors. Pelvic lymphadenectomy can lead to as their caregivers and to be aware of resources that can lower extremity lymphedema, particularly for women who assist in navigating the various phases of cancer survivor- also receive radiation. ship. The American College of Surgeons’ CoC has issued _ _ VOLUME 66 NUMBER 4 JULY/AUGUST 2016 285 Cancer Treatment and Survivorship Statistics, 2016 standards for quality, patient-centered cancer care that survivors, many challenges remain. These include a frac- include recommendations for patient navigation, palliative tured health care system, poor integration of survivorship care, distress management, and survivorship care plan- care between oncology and primary care settings, lack of ning. The Alliance for Quality Psychosocial Cancer strong evidence-based guidelines for posttreatment care, Care, a coalition of professional and advocacy organiza- and ﬁnancial and other barriers to quality care, particularly tions, including the American Cancer Society, formed to among the medically underserved. To address these chal- advance these recommendations and issued a comprehen- lenges, ongoing efforts to identify best practices for the sive resource guide, which is available to assist CoC- delivery of quality posttreatment cancer care are needed. accredited facilities in meeting the new standards. Sev- Future research should also focus on identifying the best eral organizations, including the American Cancer Soci- methods for encouraging cancer survivors to adopt and 30,58,109,138 ety, have begun to produce guidelines to assist maintain a healthy lifestyle. Models for the integration of primary care and other survivorship physicians in the provi- comprehensive care for cancer survivors, including self- sion of care for people with a history of cancer. The ACS management, wellness and healthy lifestyle promotion, and guidelines focus on comprehensive survivorship care, cancer rehabilitation, are beginning to emerge. As the evi- including ongoing surveillance and cancer screening, sup- dence base grows, efforts at the individual, provider, sys- port for health behavior changes, and the assessment and tem, and policy levels will help cancer survivors live longer management of the long-term and late effects of cancer and and healthier lives. its treatment. Author Contributions: Kimberly D. Miller: Conceptualization, formal analy- Conclusion sis, investigation, writing–original draft, writing–review and editing, and pro- ject administration. Rebecca L. Siegel: Conceptualization, methodology, In this article, we document the continued growth of the writing–review and editing, and supervision. Chun Chieh Lin: Conceptualiza- tion, formal analysis, and writing–review and editing. Angela Mariotto: cancer survivor population in the United States and Methodology, formal analysis, and investigation. Joan L. Kramer: Conceptual- describe patterns of treatment and common side effects ization and writing–original draft. Julia Rowland: Conceptualization, writing– original draft, and writing–review and editing. Kevin Stein: Writing–review across the most prevalent cancers. Despite increasing and editing. Rick Alteri: Writing–review and editing. 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Publisher: Wiley
Copyright: © 2016 American Cancer Society
ISSN: 0007-9235
eISSN: 1542-4863
DOI: 10.3322/caac.21349
pmid: 27253694
Publisher site: See Article on Publisher Site

Abstract

CA CANCER J CLIN 2016;66:271–289 1 2 3 4 Kimberly D. Miller, MPH ; Rebecca L. Siegel, MPH ; Chun Chieh Lin, PhD, MBA ; Angela B. Mariotto, PhD ; 5 6 7 8 9 Joan L. Kramer, MD ; Julia H. Rowland, PhD ; Kevin D. Stein, PhD ; Rick Alteri, MD ; Ahmedin Jemal, DVM, PhD Epidemiologist, Surveillance and Health Services Research, American Cancer ABSTRACT: The number of cancer survivors continues to increase because of both Society, Atlanta, GA; Strategic Director, advances in early detection and treatment and the aging and growth of the popula- Surveillance Information, Surveillance and tion. For the public health community to better serve these survivors, the American Health Services Research, American Cancer Society and the National Cancer Institute collaborate to estimate the number Cancer Society, Atlanta, GA; Director, Health Services Research, Intramural of current and future cancer survivors using data from the Surveillance, Epidemiol- Research Department, American Cancer ogy, and End Results cancer registries. In addition, current treatment patterns for Society, Atlanta, GA; Branch Chief, the most prevalent cancer types are presented based on information in the National Surveillance Research Program, National Cancer Institute, Bethesda, MD; Assistant Cancer Data Base and treatment-related side effects are briefly described. More Professor, Department of Hematology and than 15.5 million Americans with a history of cancer were alive on January 1, 2016, Medical Oncology, Emory University 6 and this number is projected to reach more than 20 million by January 1, 2026. The School of Medicine, Atlanta, GA; Director, 3 most prevalent cancers are prostate (3,306,760), colon and rectum (724,690), Office of Cancer Survivorship, National Cancer Institute, Bethesda, MD; Vice and melanoma (614,460) among males and breast (3,560,570), uterine corpus President, Behavioral Research Center, (757,190), and colon and rectum (727,350) among females. More than one-half American Cancer Society, Atlanta, GA; (56%) of survivors were diagnosed within the past 10 years, and almost one-half Medical Editor, American Cancer Society, (47%) are aged 70 years or older. People with a history of cancer have unique medi- Atlanta, GA; Vice President, Surveillance and Health Services Research, American cal and psychosocial needs that require proactive assessment and management by Cancer Society, Atlanta, GA primary care providers. Although there are a growing number of tools that can assist Corresponding author: Kimberly D. Miller, patients, caregivers, and clinicians in navigating the various phases of cancer survi- MPH, Surveillance and Health Services vorship, further evidence-based resources are needed to optimize care. CA Cancer J Research, American Cancer Society, 250 Clin 2016;66:271-289. 2016 American Cancer Society. Williams Street NW, Atlanta, GA 30303- 1002; [email protected]. Keywords: prevalence, statistics, survivorship, treatment patterns DISCLOSURES: The authors report no conflicts of interest. The findings and conclusions in this report are those of the authors and do not Introduction necessarily represent the official position of the National Cancer Institute. The number of cancer survivors continues to grow in the United States despite doi: 10.3322/caac.21349. Available online overall declining incidence rates in men and stable rates in women. This reﬂects at cacancerjournal.com an increasing number of new cancer diagnoses resulting from a growing and aging population, as well as increases in cancer survival because of advances in early detection and treatment. The American Cancer Society collaborates with the National Cancer Institute biennially to estimate the numbers of current and future cancer survivors to help the public health community better serve this unique population, some of whom must cope with long-term physical effects of treatment, as well as psychological and socioeconomic sequelae. In this article, we use the term “cancer survivor” to describe any person who has been diagnosed with cancer, from the time of diagno- sis through the remainder of his or her life. This includes patients currently under- going treatment and those who may have become cancer-free. Throughout this article, the terms “cancer patient” and “survivor” are used interchangeably, although not all people with a history of cancer identify with the term “cancer survivor.” We provide estimates for the most prevalent cancers, as well as statistics on treatment patterns and survival and issues related to survivorship. Materials and Methods Prevalence Estimates Cancer prevalence as of January 1, 2016 was estimated using the Prevalence Inci- dence Approach Model, which calculates prevalence from cancer incidence and survival and all-cause mortality. Incidence and survival were modeled by cancer _ _ VOLUME 66 NUMBER 4 JULY/AUGUST 2016 271 Cancer Treatment and Survivorship Statistics, 2016 type, sex, and age group using invasive malignant cases survival, which adjusts for normal life expectancy by compar- (except urinary bladder, which included in situ cases) diag- ing survival among cancer patients with that of the general nosed from 1975 through 2012 from the 9 oldest registries population, controlling for age, race, and sex. The SEER 18 in the population-based Surveillance, Epidemiology, and registries were the source for 5-year survival (diagnosis years End Results (SEER) program (2014 submission data). 2005-2011). Data from the 9 oldest SEER registries are For speciﬁc cancer site estimates, incident cases included used to describe changes in survival over time. Many of these the ﬁrst primary for the speciﬁc cancer site between 1975 statistics were originally published in the SEER Cancer and 2012. This differs from previous prevalence projec- Statistics Review, 1975-2012. In addition, 1-year, 10-year, 4,5 tions, which only included ﬁrst ever malignant primaries and 15-year relative survival rates were generated for selected and did not take into account subsequent primaries at sites using the National Cancer Institute’s SEER*Stat soft- 11,12 different sites. Total cancer prevalence was calculated as in ware (version 8.2.1). One-year survival rates are based on the previous methodology using only ﬁrst ever primary cancer patients diagnosed from 2008 to 2011, 10-year sur- cases. vival rates are based on diagnoses from 1999 and 2011, and Mortality data for 1975 through 2012 were obtained 15-year survival rates are based on diagnoses from 1994 and from the National Center for Health Statistics. Population 2011; all patients were followed through 2012. projections from 2014 through 2026 were obtained from the US Census Bureau. Projected US incidence and mor- Treatment tality for 2013 to 2026 were calculated by applying 5-year Cancer treatment data were analyzed from 2 sources: the average rates for 2008 through 2012 to the respective US National Cancer Data Base (NCDB) and the SEER program. population projections by age, sex, race, and year. Survival, incidence, and all-cause mortality rates were assumed to be NCDB constant from 2013 through 2026. For more information, The NCDB is a hospital-based cancer registry jointly spon- 6,7 see publications by Mariotto et al. sored by the American Cancer Society and the American College of Surgeons. It includes approximately 70% of all 2016 Case Estimates invasive cancers in the United States from more than 1500 The method for estimating the number of new US cancer facilities accredited by the American College of Surgeons’ 13,14 cases in 2016 is described elsewhere. Brieﬂy, the total Commission on Cancer (CoC). Studies have shown number of cases is estimated using a spatiotemporal model that disease severity and treatment patterns in the NCDB based on incidence data from 49 states and the District of stratiﬁed by clinical and sociodemographic factors for com- Columbia for the years 1998 through 2012 that met the mon cancer types are remarkably similar to those found in 15,16 North American Association of Central Cancer Registries’ population-based registries. high-quality data standard for incidence. Then, the number Treatment data are for cases diagnosed in the ﬁrst 6 of new cases is temporally projected 4 years ahead using months of 2013 for all sites except testis, for which aggre- vector autoregression. This method considers geographic gated data from 2009 through 2013 were used because of variations in sociodemographic and lifestyle factors, medi- the relatively small number of cases. In the 2013 NCDB cal settings, and cancer screening behaviors as predictors of data release, many common targeted therapy drugs are clas- incidence and also accounts for expected delays in case siﬁed as chemotherapy. For this report, we also include reporting. drugs classiﬁed as immunotherapy in the chemotherapy cat- egory (chemotherapy does not include hormone therapy). Stage at Diagnosis For more information regarding drug classiﬁcation catego- Several different staging systems are used to classify can- ries, see the SEER-Rx Web site (seer.cancer.gov/tools/ cers. In this report, the American Joint Committee on seerrx). Our analysis of treatment patterns does not include 8,9 Cancer staging system, which is commonly used in clini- diagnostic procedures. Methods of drug delivery are not cal settings, is used for the description of treatment pat- available in the NCDB, so topical or intravesical chemo- terns; whereas SEER Summary Stage, a staging system therapy cannot be distinguished from systemic chemother- frequently used by population-based cancer registries, is apy. More information can be found on the NCDB Web used to describe population-based patterns of stage at site (facs.org/cancer/ncdb). diagnosis and survival. SEER Survival The SEER 18 registries were the source for prostate cancer There are 2 common measures of cancer survival: relative treatment patterns because data are substantially less com- survival and observed survival. In this article, we use relative plete in the NCDB. However, use of androgen- 272 CA: A Cancer Journal for Clinicians CA CANCER J CLIN 2016;66:271–289 FIGURE 1. The Estimated Number of US Cancer Survivors. Note: Estimates for specific cancer types take into account the potential for a history of more than one cancer type. Source: Surveillance Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, MD. deprivation therapy is not collected, so could not be cancer, and an additional 246,660 women will be diagnosed in 2016. Seventy-ﬁve percent of breast cancer survivors included. (more than 2.6 million women) are ages 60 years or older, while 7% are younger than 50 years (Fig. 2). Selected Findings: Cancer Prevalence Breast cancer tends to be diagnosed at a younger age More than 15.5 million Americans with a history of cancer than other common cancers, with a median age at diagnosis were alive on January 1, 2016. By January 1, 2026, this of 61 years compared with 70 years for lung cancer and 68 number is projected to reach 20.3 million (Fig. 1). These years for colorectal cancer (Fig. 3). About 19% of breast estimates do not include carcinoma in situ for any cancer cancers are diagnosed in women ages 30 to 49 years, and except urinary bladder and do not include basal cell or squa- 44% occur among women who are age 65 years or older. mous cell skin cancers. The 3 most prevalent cancers in Treatment and survival 2016 are prostate (3,306,760), colon and rectum (724,690), Surgical treatment for breast cancer involves breast- and melanoma (614,460) among males and breast conserving surgery (BCS, also known as partial mastectomy (3,560,570), uterine corpus (757,190), and colon and rec- or lumpectomy) or mastectomy. When BCS followed by tum (727,350) among females (Fig. 1). The distribution of radiation to the breast is appropriately used for localized or cancer prevalence by type differs from that for new cases, regional cancers, long-term survival is the same as with reﬂecting differences in survival as well as age at diagnosis. 17,18 mastectomy. However, some patients require mastec- More than one-half (56%) of survivors were diagnosed tomy because of tumor characteristics (eg, locally advanced within the past 10 years (Table 1). Twenty-one percent of stage, large or multiple tumors), because postsurgery radia- female survivors were diagnosed more than 20 years ago tion is contraindicated (eg, preexisting medical condition, compared to only 13% of males. Nearly one-half (47%) are such as active connective tissue disease), or other obstacles. age 70 years or older, although age distribution varies by Younger women (<40 years) and patients with larger and/or cancer type (Table 2). For example, the majority of prostate more aggressive tumors are more likely to be treated with cancer survivors (64%) are age 70 years or older, compared 19,20 mastectomy. BCS-eligible women are increasingly elect- with only one-third of melanoma survivors (Fig. 2). ing mastectomy for a variety of reasons, including reluctance to undergo radiation therapy and fear of recurrence. The Selected Cancers proportion of women with nonmetastatic disease who Breast (female) undergo contralateral prophylactic mastectomy has also It is estimated that there are more than 3.5 million women increased rapidly, from 5% of total mastectomies in 1998 to living in the United States with a history of invasive breast 30% in 2011. _ _ VOLUME 66 NUMBER 4 JULY/AUGUST 2016 273 Cancer Treatment and Survivorship Statistics, 2016 TABLE 1. Estimated Number of US Cancer Survivors as of January 1, 2016, by Sex and Time Since Diagnosis MALE AND FEMALE MALE FEMALE YEARS SINCE CUMULATIVE CUMULATIVE CUMULATIVE DIAGNOSIS NO. PERCENT PERCENT NO. PERCENT PERCENT NO. PERCENT PERCENT 0to <5 y 5,189,400 33 33 2,713,350 37 37 2,476,050 30 30 5to <10 y 3,530,890 23 56 1,798,090 24 61 1,732,800 21 52 10 to <15 y 2,493,340 16 72 1,212,930 16 78 1,280,410 16 67 15 to <20 y 1,655,400 11 83 729,830 10 87 925,570 11 79 20 to <25 y 1,082,460 7 90 443,630 6 94 638,830 8 86 25 to <30 y 660,180 4 94 228,710 3 97 431,470 5 92 30 y 921,550 6 100 250,560 3 100 670,990 8 100 Note: Percentages do not sum to 100% due to rounding. Source: Surveillance Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute. Among women diagnosed with stage I or II breast can- des, because of improvements in treatment (ie, chemother- cer, 61% undergo BCS (with the majority also receiving apy, hormone therapy, and targeted drugs) and earlier additional therapy) and 36% undergo mastectomy (Fig. 4). detection through increased awareness and widespread use A much smaller percentage of stage III patients undergo of mammography. The 5-year, 10-year, and 15-year rela- BCS (21%), whereas 72% undergo mastectomy. Women tive survival rates for breast cancer are 89%, 83%, and 78%, diagnosed with stage IV disease most often receive radia- respectively. tion and/or chemotherapy alone (48%). Among women Cancer-related factors that inﬂuence survival include with hormone-receptor positive breast cancer of any stage, stage, tumor grade and histology, hormone receptor status, 79% receive hormonal therapy. and human epidermal growth factor receptor 2 (HER2) Breast reconstruction for women who undergo mastec- status. Sixty-one percent of breast cancers are diagnosed at tomy may involve the use of a saline or silicone implant, a tis- a localized stage, for which the 5-year relative survival rate sue ﬂap, or a combination thereof. Although reported rates is 99%. However, compared with white women, black of breast reconstruction in the United States vary widely, a women are less likely to be diagnosed with local stage breast recent large study found that the 57% of women with non- cancer (53% vs 62%) and have lower survival within each metastatic disease who received mastectomies underwent stage. These differences are driven in part by socioeco- reconstructive procedures. Women who undergo bilateral nomic factors and differences in comorbidities, less access mastectomy, are unmarried, or who have higher education or to and use of high-quality medical care among black income are more likely to undergo reconstruction. women, and biological differences in cancers (eg, higher The overall 5-year relative survival rate for female incidence of triple negative cancers among black 24–26 patients with breast cancer has improved in the past 3 deca- women). TABLE 2. Estimated Number of US Cancer Survivors as of January 1, 2016, by Sex and Age at Prevalance MALE AND FEMALE MALE FEMALE CUMULATIVE CUMULATIVE CUMULATIVE NO. PERCENT PERCENT NO. PERCENT PERCENT NO. PERCENT PERCENT All Ages, y 15,533,220 7,377,100 8,156,120 0–14 65,190 <1 <1 32,060 <1 <1 33,130 <1 <1 15–19 47,180 <1 1 23,610 <1 1 23,570 <11 20–29 187,490 1 2 90,730 1 2 96,760 1 2 30–39 408,790 3 5 166,170 2 4 242,620 3 5 40–49 958,600 6 11 347,700 5 9 610,900 7 12 50–59 2,389,670 15 26 963,410 13 22 1,426,260 17 30 60–69 4,141,950 27 53 2,027,150 27 49 2,114,800 26 56 70–79 4,011,790 26 79 2,148,940 29 79 1,862,850 23 79 80 3,322,560 21 100 1,577,330 21 100 1,745,230 21 100 Note: Percentages do not sum to 100% due to rounding. Source: Surveillance Research Program, Division of Cancer Control and Population Sciences, National Cancer Institute. 274 CA: A Cancer Journal for Clinicians CA CANCER J CLIN 2016;66:271–289 FIGURE 2. Age Distribution of Survivors for Selected Cancer Types, January 1, 2016. Percentages may not sum to 100% because of rounding. Short-term and long-term health effects ments may also cause menopausal symptoms, such as hot ﬂashes, night sweats, and atrophic vaginitis, which can lead Lymphedema of the arm occurs in 20% of women who to dyspareunia. Breast cancer survivors may also experience undergo axillary lymph node dissection and in about 6% of 30,40 cognitive impairments and chronic fatigue. women who undergo sentinel lymph node biopsy. Early diagnosis of lymphedema is important for optimizing treat- Cancers in Children and Adolescents ment and slowing progression. Some forms of cancer reha- bilitation may reduce the risk and lessen the severity of this It is estimated that there are 65,190 cancer survivors aged 29,30 condition. birth to 14 years (children) and 47,180 survivors aged 15 to Other potential effects include numbness, tingling, or 19 years (adolescents) living in the United States as of Janu- tightness in the chest wall, arms, or shoulders following ary 1, 2016. An additional 10,380 children aged birth to 14 surgery and/or radiation. Studies have shown that between years will be newly diagnosed in 2016. The 3 most com- 25% and 60% of women develop chronic pain after breast monly diagnosed cancers in children are leukemia (30%), 31–33 cancer treatment, although it is usually not severe. In brain and central nervous system (CNS) tumors (26%, addition, treatment with chemotherapy can lead to including benign and borderline tumors), and soft tissue impaired fertility and premature menopause, which increase sarcomas (7%), about one-half of which are rhabdomyosar- the risk of osteoporosis. Chemotherapy with taxanes comas. Among adolescents, the most common cancers are often leads to neuropathy, which can persist long after brain and CNS tumors (20%), followed by leukemia (14%) treatment ends. Anthracyclines and HER-2–targeted 1 and Hodgkin lymphoma (HL) (13%). drugs can lead to cardiomyopathy and congestive heart fail- Treatment and survival ure. Treatment with aromatase inhibitors, which is gener- Pediatric cancers are treated with a combination of thera- ally reserved for postmenopausal women, can also cause osteoporosis, as well as myalgia and arthralgia, whereas pies (surgery, radiation, chemotherapy, and targeted ther- tamoxifen treatment slightly increases the risk of endome- apy) chosen based on the type and stage of cancer. trial cancer and thromboembolic disease. Hormonal treat- Treatment often occurs in specialized centers and is _ _ VOLUME 66 NUMBER 4 JULY/AUGUST 2016 275 Cancer Treatment and Survivorship Statistics, 2016 FIGURE 3. Age Distribution of New Cases (%), Median Age at Diagnosis, Estimated Number of New Cases, and 5-year Relative Survival by Cancer Type. *The new case estimate includes other biliary cancers. Note that sites are ranked in order of the median age at diagnosis from oldest to youngest. Sources: Age distribution based on 2011 to 2012 data from the North American Association of Central Cancer Registries and excludes Arkansas and Nevada. The median age at diagnosis and 5-year relative survival are based on cases diagnosed during 2008 through 2012 and 2005 through 2011, respectively, from the Surveillance, Epidemiology, and End Results 18 registries and were previously published in Howlader et al, and the 2016 estimated cases are from Siegel et al. FIGURE 4. Female Breast Cancer Treatment Patterns (%) by Stage, 2013. BCS indicates breast-conserving surgery; chemo, chemotherapy (includes immunotherapy and targeted therapy); RT, radiation therapy. Source: National Cancer Data Base, 2013. 276 CA: A Cancer Journal for Clinicians CA CANCER J CLIN 2016;66:271–289 coordinated by a team of experts, including pediatric oncol- reproductive organs may cause infertility in both males and 48,49 ogists, surgeons and nurses, social workers, child life spe- females. The potential impact on fertility and plans for cialists, psychologists, and others. fertility preservation should be discussed before commenc- Adolescents (ages 15-19 years) diagnosed with cancers ing treatment. Treatment may delay maturation and normal that are more common in childhood are usually most development in survivors and lead to negative body image appropriately treated at pediatric facilities or by pediatric and psychological distress. specialists. For example, studies have shown that pediatric Given these concerns, it is important that survivors of protocols result in better outcomes than adult protocols for pediatric cancers are monitored for long-term and late adolescent patients with acute lymphocytic leukemia effects as well as emotional and psychosocial concerns. The (ALL). In addition, childhood cancer centers are more Children’s Oncology Group, a National Cancer Institute- likely than adult cancer centers to offer adolescent patients supported clinical trials group that cares for greater than the opportunity to participate in clinical trials. For teen 90% of US children and adolescents diagnosed with cancer, patients with cancers that are more common among adults, has developed long-term follow-up guidelines for the such as melanoma, testicular, and thyroid cancers, treatment screening and management of late effects in survivors of by adult-care specialists is more appropriate. childhood cancer (survivorshipguidelines.org). The overall 5-year relative survival rate for all childhood cancers (aged birth-14 years) combined has improved markedly over the past 30 years, from 58% for patients Colon and Rectum diagnosed between 1975 and 1977 to 83% for those diag- It is estimated that, as of January 1, 2016, there are more nosed during 2005 through 2011, because of new and than 1.4 million men and women living in the United improved treatments. Although there has been less dramatic States with a previous colorectal cancer diagnosis, and an improvement in survival for adolescents, the current 5-year additional 134,490 cases will be diagnosed in 2016. Eighty- 10,44 relative survival rate (84%) is similar to that for children. ﬁve percent of colorectal cancer survivors (about 1.2 million However, survival rates vary considerably by cancer type. men and women) are aged 60 years and older, while only For example, the 5-year survival rate during 2005 through 4% (60,610) are aged younger than 50 years (Fig. 2). The 2011 was 89% for children and 76% for adolescents for median age at diagnosis for colorectal cancer is 66 years for ALL, compared to 69% and 61%, respectively, for males and 70 years for females. Patients with rectal cancer osteosarcoma. tend to be younger at diagnosis than those with colon Short-term and long-term health effects cancer (median age, 63 vs 70 years, respectively). Childhood cancer survivors may experience both long-term (chronic) and late (occurring months or years after diagno- Treatment and survival sis or treatment) effects. Aggressive treatments used for The majority of patients with stage I and II colon cancer childhood cancers, especially in the 1970s and 1980s, have undergo partial or total colectomy alone (84%), while about resulted in several late effects, including increased risk of two-thirds of those with stage III disease (as well as some subsequent neoplasms and cardiomyopathies. A recent with stage II disease) receive chemotherapy in addition to study found that 50% of childhood cancer survivors had colectomy to lower their risk of recurrence (Fig. 5). For developed a severe or life-threatening chronic health condi- patients with rectal cancer, proctectomy or proctocolectomy tion by age 50 years. Among childhood cancer survivors is the most common treatment (61%) for stage I disease, who were diagnosed and treated between 1962 and 2001, and about one-half also receive radiation and/or chemo- 65% of those who were exposed to pulmonary toxic cancer therapy (Fig. 6). Stage II and III rectal cancers are often treatments experienced pulmonary dysfunction, and 57% of treated with neoadjuvant chemotherapy plus radiation. A those who were exposed to potentially cardiotoxic therapies colostomy (usually temporary) is required during surgery experienced cardiac abnormalities. more often for patients with rectal cancer (29%) than for Recent declines in late morbidity and mortality among those with colon cancer (12%). Chemotherapy is the childhood cancer survivors are due in part to reduced use of main treatment for stage IV rectal cancers. Growing num- certain treatments, such as cranial radiation for ALL and bers of targeted drugs are also available to treat metastatic abdominal radiation for Wilms tumor. However, even colorectal cancer. many newer, less toxic therapies increase the risk of serious The 5-year and 10-year relative survival rates for persons health conditions in long-term childhood cancer survivors. Cognitive impairment, which can vary in severity, affects up with colorectal cancer are 65% and 58%, respectively. to one-third of childhood cancer survivors. In addition, When colorectal cancers are detected at a localized stage surgery, radiation, and some chemotherapies affecting the (39% of cases), the 5-year relative survival rate is 90%. _ _ VOLUME 66 NUMBER 4 JULY/AUGUST 2016 277 Cancer Treatment and Survivorship Statistics, 2016 FIGURE 5. Colon Cancer Treatment Patterns (%) by Stage, 2013. Chemo indicates chemotherapy (includes immunotherapy and targeted therapy); RT, radiation therapy. *A small number of these patients received RT. Source: National Cancer Data Base, 2013. Short-term and long-term health effects most common types in adults, whereas ALL is most the common among children and teens (Fig. 3). Neuropathy is a common side effect of chemotherapy regi- There are 2 basic categories of lymphoma: Hodgkin lym- mens containing oxaliplatin. Chronic diarrhea occurs in phoma (HL) and non-Hodgkin lymphoma (NHL). NHLs about one-half of colorectal cancer survivors. Bowel dys- can be further divided into indolent and aggressive catego- function (including increased stool frequency, incontinence, ries, each of which includes many subtypes that progress radiation proctitis, and perianal irritation) is common among and respond to treatment differently. Prognosis and treat- rectal cancer survivors, especially those treated with pelvic 54,55 ment depend on the stage and type of lymphoma. It is esti- radiation. Survivors may also suffer from bladder dys- 39,56,57 mated that, as of January 1, 2016, there were 219,570 HL function, sexual dysfunction, and negative body image. survivors and 686,370 NHL survivors. About 8500 new Referral to a trained ostomy therapist may beneﬁt patients cases of HL and 72,580 new cases of NHL will be diag- with a colostomy who experience these issues. In addition, nosed in 2016. Although both HL and NHL occur in chil- cancer recurrence is not uncommon among colorectal survi- 59,60 dren and adults, the majority of HL cases (64%) are vors, who are also at increased risk of second primary diagnosed before age 50 years, whereas most NHL cases cancers of the colon and rectum and other cancer sites, (85%) occur in those aged 50 years and older (Fig. 3). particularly those within the digestive system. Treatment and survival for the most common types of Leukemias and Lymphomas leukemia and lymphoma There are an estimated 407,950 leukemia survivors in the AML United States, and an additional 60,140 people will be diagnosed in 2016. Although leukemia is the most com- Chemotherapy is the standard treatment for AML, mon type of cancer among children aged birth to 14 years, although many older adults, among whom the disease is the majority (92%) of patients with leukemia are diagnosed most common, are not able to tolerate the most aggressive at age 20 years and older. Acute myeloid leukemia and potentially curative protocols. Patients may also (AML) and chronic lymphocytic leukemia (CLL) are the undergo allogeneic stem cell transplantation, and some FIGURE 6. Rectal Cancer Treatment Patterns (%) by Stage, 2013. Chemo indicates chemotherapy (includes immunotherapy and targeted therapy); RT, radiation therapy. Source: National Cancer Data Base, 2013. 278 CA: A Cancer Journal for Clinicians CA CANCER J CLIN 2016;66:271–289 receive radiation therapy, often as part of a conditioning 2005 through 2011 (89% vs 92%). Survival declines with regimen before stem cell transplantation. increasing age at diagnosis, and the current 5-year survival Approximately 60% to 85% of adults aged 60 years and rate is 46% for patients aged 20 to 39 years, 30% for those younger with AML can expect to attain complete remission aged 40 to 64 years, and 15% for those aged 65 years and status after the ﬁrst phase of treatment, and 35% to 40% of older. 63,64 patients in this age group will be cured. In contrast, CLL 40% to 60% of patients aged older than 60 years will CLL is the most common type of leukemia in adults, and achieve complete remission, and only 5% to 15% will be 95% of cases are diagnosed in individuals aged 50 years and cured. About 4% of AML cases occur in children and ado- older (Fig. 3). Treatment is generally reserved for sympto- lescents, for whom the prognosis is substantially better. matic patients or for those who have cytopenia or other The 5-year relative survival rate for children and adoles- complications because the disease is slow-growing and cents (aged birth-19 years) is 65% but declines to 50%, treatment is unlikely to result in a cure. Available treat- 32%, and 6% for patients aged 20 to 49 years, 50 to 64 ments include chemotherapy, immunotherapy, targeted years, and 65 years and older, respectively. therapy, radiation therapy, and splenectomy, but it is often 69–71 CML not clear whether these treatments extend survival. The overall 5-year relative survival rate for CLL is 82%; Chronic myeloid leukemia (CML) is most common in however, there is large variation in survival among individ- adults, and only 2% of cases are diagnosed in children and ual patients, ranging from several months to a normal life adolescents. The cancer cells in CML contain a charac- expectancy. About 5% to 10% of patients with CLL teristic fusion gene, bcr-abl (breakpoint cluster region- develop diffuse large B-cell lymphoma (DLBCL), a process Abelson), which is caused by a translocation of genetic known as “Richter transformation.” material between chromosomes 9 and 22, resulting in the Philadelphia chromosome. Modern treatment of CML has HL been transformed by tyrosine kinase inhibitors (TKIs) There are 2 major types of HL. Classical HL (CHL) is the aimed at the BCR-ABL protein, which induce remission most common and is characterized by the presence of in most patients but must be taken indeﬁnitely. Stem cell Reed-Sternberg cells. Nodular lymphocyte-predominant transplantation may be used in younger patients and those HL (NLPHL), which is characterized by “popcorn cells,” who become resistant to TKIs, whereas chemotherapy is comprises only about 5% of cases. NLPHL is a more only used in TKI-resistant patients. Primarily because of indolent disease with a generally favorable prognosis. the discovery and widespread use of the BCR-ABL TKIs, CHL is generally treated with multiagent chemotherapy the 5-year survival rate for CML increased from 31% for (88%), sometimes in combination with radiation therapy patients diagnosed during 1990 through 1992 to 63% for (30% among chemotherapy recipients), although the use of 10,65 those diagnosed during 2005 through 2011. radiotherapy is declining. If these treatments are not effective, stem cell transplantation or the targeted drug ALL brentuximab vedotin may be options. For patients with More than one-half of ALL cases (56%) are diagnosed in NLPHL, radiation alone may be appropriate for early stage patients younger than 20 years. Chemotherapy is the stand- disease. For those with later stage disease, chemotherapy ard treatment for ALL. About 20% to 30% of adult ALL plus radiation as well as the monoclonal antibody rituximab cases and <5% of childhood cases are Philadelphia may be recommended. chromosome-positive and may beneﬁt from the addition of 66,67 The 5-year and 10-year survival rates for HL are 86% a BCR-ABL TKI to chemotherapy. More than 95% of and 80%, respectively. The 5-year survival rate is 94% for children and from 78% to 92% of adults with ALL attain NLPHL and 85% for CHL. remission. Allogeneic stem cell transplantation is recom- NHL mended for some patients who have high-risk disease char- acteristics and for those who relapse after remission or who The most common types of NHL are DLBCL, represent- fail to achieve remission after successive courses of induc- ing 37% of cases, and follicular lymphoma, representing tion chemotherapy. 20% of cases. Although DLBCLs grow quickly, most Survival rates for ALL have increased signiﬁcantly over patients with localized disease and about 50% of those with 10 74,75 the past 3 decades, particularly among children. Notably, advanced-stage disease are cured. In contrast, follicular the black-white 5-year relative survival disparity in children lymphomas tend to grow slowly and often do not require and adolescents with ALL has diminished from a 21- treatment until symptoms develop, but many are not cura- percentage-point difference during 1980 through 1984 ble. Some cases of follicular lymphoma transform into (49% vs 70%) to a 3-percentage-point difference during DLBCL. _ _ VOLUME 66 NUMBER 4 JULY/AUGUST 2016 279 Cancer Treatment and Survivorship Statistics, 2016 The ﬁrst course of treatment for all NHL subtypes com- bined is usually chemotherapy, either alone (58%) or in combination with radiation (11%) (Fig. 7). Approximately 17% of patients receive no treatment. A monoclonal anti- body like rituximab is often given along with chemotherapy for B-cell lymphomas and for some T-cell lymphomas. The 5-year survival rate is 86% for follicular lymphoma and 61% for DLBCL; 10-year survival declines to 77% and 53%, respectively. Short-term and long-term health effects People treated for leukemia and lymphoma can experience several signiﬁcant long-term and late effects. Some leuke- mia and lymphoma survivors, such as those who undergo stem cell transplantation, have problems with recurrent infections and with anemia, which may require blood trans- FIGURE 7. Non-Hodgkin Lymphoma Treatment Patterns (%), fusions. Certain chemotherapy drugs, as well as high-dose 2013. Chemo indicates chemotherapy (includes immunotherapy and targeted ther- chemotherapy used for stem cell transplantation, can lead apy); RT, radiation therapy. Source: National Cancer Data Base, 2013. to infertility. Allogeneic transplantation used to treat acute leukemias can lead to chronic graft-versus-host disease, which can cause skin changes, dry mucous membranes phoma kinase (ALK) inhibitors, are also an important part (eyes, mouth, vagina), joint pain, weight loss, shortness of of the treatment for NSCLC. Recently, immunotherapy breath, and fatigue. drugs that act by targeting the programmed cell death Chest radiation for HL increases the risk for cardiac dys- receptor on T cells have been approved to treat some types function as well as breast cancer among women who were of NSCLC. treated in childhood and adolescence. Patients with HL, The 1-year relative survival for lung cancer increased NHL, and ALL are commonly treated with anthracyclines, from 34% during 1975 through 1977 to 45% during 2008 which can also be cardiotoxic. In the past, some children through 2011, largely because of improvements in surgical with ALL who were at increased risk for CNS relapse techniques and chemoradiation. The majority of lung can- received cranial radiation therapy. This treatment can cause cers (57%) are diagnosed at a distant stage, because early long-term cognitive deﬁcits, and it is used less frequently disease is typically asymptomatic; only 16% of cases are and at lower dosages today. diagnosed at a local stage. The 5-year survival rate is 55% for cases detected when the disease is still localized, 27% Lung and Bronchus for regional disease, and 4% for distant stage disease. The It is estimated that there are 526,510 men and women liv- 5-year survival for small cell lung cancer (7%) is lower than ing in the United States with a history of lung cancer, and that for NSCLC (21%). an additional 224,390 cases will be diagnosed in 2016. The Short-term and long-term health effects median age at diagnosis for lung cancer is 70 years. Many lung cancer survivors have impaired pulmonary func- Treatment and survival tion, although some may have had preexisting respiratory Lung cancer is classiﬁed as small cell (13% of cases) or non- problems. In some cases respiratory therapy and medica- small cell (83%) for the purposes of treatment (3% of cases tions can improve ﬁtness and allow survivors to resume nor- in the SEER database lack information on histologic mal daily activities. Treatment with EGFR inhibitors can type). Most patients with small cell lung cancer receive lead to a severe acneiform rash. Immunotherapy drugs used chemotherapy. In addition, some patients are also treated in lung cancer treatment can lead to several immune mediated with thoracic radiation therapy. For stage I and II nonsmall toxicities, including pneumonitis, colitis, nephritis, and cell lung cancers (NSCLC), the majority of patients (69%) endocrinopathy. undergo surgery, and about 25% of surgical cases also Lung cancer survivors who are current or former smokers receiving chemotherapy and/or radiation therapy (Fig. 8). are at increased risk for subsequent smoking-related can- Most patients with stage III and IV NSCLC receive chem- cers, especially lung, head and neck, and esophageal, as well otherapy with or without radiation (53%). Targeted therapy as other smoking-related health problems. Survivors may drugs, such as angiogenesis inhibitors, epidermal growth feel stigmatized because of the social perception that lung factor receptor (EGFR) inhibitors, and anaplastic lym- cancer is a self-inﬂicted disease, which can be particularly 280 CA: A Cancer Journal for Clinicians CA CANCER J CLIN 2016;66:271–289 FIGURE 8. Nonsmall Cell Lung Cancer Treatment Patterns (%) by Stage, 2013. Chemo indicates chemotherapy (includes immunotherapy and targeted therapy); RT, radiation therapy. Source: National Cancer Data Base, 2013. difﬁcult for those who never smoked. Data suggest that Short-term and long-term health effects there is a beneﬁt to smoking cessation even after a lung Depending on the size and location of the melanoma, 80,81 cancer diagnosis. removal of these cancers can be disﬁguring. Male and female melanoma survivors are nearly 13 and 16 times Melanoma more likely, respectively, than the general population to develop additional melanomas because of skin type and It is estimated that there are more than 1.2 million mela- other genetic or behavioral risk factors. From 10% to 15% noma survivors living in the United States, and an addi- of patients treated with ipilimumab experience serious tional 76,380 people will be diagnosed in 2016. Sixty-three autoimmune-related side effects that sometimes can lead to percent of melanoma survivors are under the age of 70, and death. Autoimmune-related side effects occur less often 17% are under the age of 50 (Fig. 2). Melanoma incidence with pembrolizumab and nivolumab. Patients treated with rates continue to increase in men but have recently stabi- BRAF inhibitors have an increased risk of developing squa- lized in women. Women tend to be diagnosed at a mous cell skin carcinomas. younger age than men (58 vs 65 years, respectively), reﬂecting differences in occupational and recreational expo- Prostate sure to ultraviolet radiation, as well as early detection; It is estimated that there are more than 3.3 million men women are more likely to be diagnosed at a localized stage, living with prostate cancer in the United States, and an 86% versus 82% of men. additional 180,890 cases will be diagnosed in 2016. The Treatment and survival majority (64%) of prostate cancer survivors are over the age of 70 years, and less than 1% are under age 50 years (Fig. 2). Surgery is the primary treatment for most melanomas. The median age at diagnosis is 66 years (Fig. 3). Most pros- Patients with stage III disease may be offered adjuvant tate cancers in the United States are diagnosed by prostate- immunotherapy with interferon or the anticytotoxic T- speciﬁc antigen (PSA) testing, although many expert lymphocyte-associated protein (anti-CTLA) antibody ipili- groups, including the American Cancer Society, have con- mumab, although these treatments can have serious side cluded that data on the efﬁcacy of PSA screening are insufﬁ- effects. Treatment for patients with stage IV melanoma has cient to recommend routine use of this test. changed in recent years and typically includes immunother- apy (ipilimumab, pembrolizumab, and nivolumab) or tar- Treatment and survival geted therapy drugs, both of which have been shown to Treatment options vary, depending on the extent of disease 82–84 extend survival. BRAF (B-Raf proto-oncogene, serine/ and the risk of recurrence, as well as patient characteristics, threonine kinase) inhibitors have been shown to improve such as age and comorbidity, and personal preferences. Fig- survival for melanomas with the BRAF gene mutation, ure 9 shows primary treatment among men diagnosed dur- 85–87 which account for about one-half of all cases. Almost ing 2010 through 2012 based on SEER data [information one-half (46%) of patients with stage IV disease who on the use of androgen deprivation therapy (ADT) is not receive either chemotherapy or immunotherapy also receive available] for all stages combined, although most (92%) of radiation therapy. cases are diagnosed at the localized stage. Men younger The 5-year and 10-year relative survival rates for persons than 65 years are most likely to be treated with radical pros- with melanoma are 92% and 89%, respectively. About 84% tatectomy (with or without radiation), whereas about one- of melanomas are diagnosed at a localized stage, for which half of men 75 years or older do not undergo surgery or the 5-year survival rate is 98%. radiation. _ _ VOLUME 66 NUMBER 4 JULY/AUGUST 2016 281 Cancer Treatment and Survivorship Statistics, 2016 103–106 and diabetes. Although some studies indicate an increased risk of cardiovascular disease or death associated with the use of hormone therapy, the evidence is inconsis- 104,105,107 tent. Careful monitoring of cardiovascular risk factors is recommended for men who have received 108,109 ADT. Testis It is estimated that there are 266,550 testicular cancer sur- vivors in the United States, and an additional 8720 men will be diagnosed in 2016. Testicular germ cell tumors (TGCTs) account for approximately 97% of all testicular cancers. The 2 main types of TGCTs are seminomas and nonseminomas. Nonseminomas are more common, gener- ally occur in men in their late teens to early 40s, and tend to be more aggressive than seminomas. Seminomas are FIGURE 9. Prostate Cancer Treatment Patterns (%) by Age, slow-growing and are generally diagnosed in men in their United States, 2010-2012. RT indicates radiation therapy. Patients with missing treatment data were late 30s to early 50s. excluded. Source: Surveillance, Epidemiology, and End Results (SEER) Pro- gram, SEER 18 Registries, 2010 to 2012. Treatment and survival Treatment of almost all TGCTs begins with orchiectomy. Active surveillance rather than immediate treatment is a While the most common treatment for stage I and II semi- reasonable and commonly recommended approach, espe- nomas is surgery alone (46%), many surgical patients also cially for men who have less aggressive tumors, are older, receive radiation (31%) or chemotherapy (22%) (Fig. 10). 91–93 and/or have serious comorbid conditions. ADT, chem- Over the last decade, postsurgical active surveillance has otherapy, bone-directed therapy (such as zoledronic acid or become an increasingly preferred management option for denosumab), radiation, or a combination of these treat- patients with stage I seminomas, and long-term study results ments are used to treat more advanced disease. Newer 110 support this treatment strategy. Stage III and IV semino- forms of hormone therapy, such as abiraterone and enzalu- mas are generally treated with surgery and chemotherapy tamide, have been approved in recent years to treat with or without radiation therapy (70%). Among patients advanced prostate cancer that is no longer responding to with stage I and II nonseminomas, approximately 20% 94–97 traditional hormone therapy. undergo retroperitoneal lymph node dissection, which is The 5-year relative survival rate approaches 100% for recommended to reduce the likelihood of recurrence patients with localized disease, but declines to 28% for (Fig. 11). Patients with stage III and IV nonseminomas are those diagnosed at a distant stage. The 5-year relative sur- treated with surgery and adjuvant chemotherapy, and some vival for all stages combined increased from 83% in in the require additional surgery after completion of late 1980s to 99% in the most recent time period (2005- chemotherapy. 2011), primarily reﬂecting lead time and overdetection. The 5-year, 10-year, and 15-year survival rates are all The 10-year and 15-year relative survival rates are 98% and approximately 95%. Most testicular cancers (68%) are diag- 95%, respectively. nosed at a localized stage, for which the 5-year relative sur- vival rate is 99%. Short-term and long-term health effects Short-term and long-term health effects Surgery and radiotherapy for prostate cancer are associated with risk of substantial physical impairments, including uri- Although most men who have one healthy testicle produce nary incontinence, erectile dysfunction, and bowel compli- sufﬁcient male hormones and sperm to continue sexual rela- 98–101 cations. In one long-term follow-up study, greater tions and father children, sperm banking is recommended than 95% of patients with prostate cancer who underwent before treatment. Consultation about fertility risks before surgery or received radiation experienced some sexual dys- treatment and referral for sperm banking as appropriate are function, and about 50% reported urinary or bowel important in efforts to promote quality-of-life outcomes. dysfunction. Patients receiving hormonal treatment Retroperitoneal lymph node dissection can lead to retro- may experience loss of libido, hot ﬂashes, night sweats, irri- grade ejaculation, making unassisted reproduction impossi- tability, and breast development. In the long term, ble. Men treated with chemotherapy have increased risks of ADT also increases the risk of osteoporosis, obesity, coronary artery disease as they age, so these patients and 282 CA: A Cancer Journal for Clinicians CA CANCER J CLIN 2016;66:271–289 FIGURE 10. Treatment Patterns (%) for Seminomatous Testicular Germ Cell Tumors by Stage, 2009 to 2013. Chemo indicates chemotherapy (includes immunotherapy and targeted therapy); RT, radiation therapy. Source: National Cancer Data Base, 2013. their physicians should be particularly mindful of risk fac- Treatment and survival tors like hyperlipidemia, hypertension, obesity, and smok- Most thyroid cancers are either papillary or follicular car- ing. Men who have bilateral tumors have both testes cinomas, which are highly curable, but about 3% are removed and require lifelong testosterone supplementation. medullary or anaplastic carcinomas, which are more dif- ﬁcult to treat because they do not respond to radioactive iodine treatment. These cancers also grow more quickly Thyroid and often have metastasized by the time they are It is estimated that there are 805,750 people living with a diagnosed. previous thyroid cancer diagnosis in the United States, and The ﬁrst choice of treatment in nearly all patients with an additional 64,300 will be diagnosed in 2016. Thyroid thyroid cancer is surgery, with most patients undergoing total cancer is the most rapidly increasing cancer in the United (86%) or partial (12%) thyroidectomy. About one-half of States and has been increasing worldwide over the past surgically treated patients who have papillary or follicular few decades. Studies suggest that the rise is primarily thyroid cancer receive radioactive iodine (I-131) after surgery due to the increased incidental detection of indolent papil- to destroy any remaining thyroid tissue and cancer. After lary tumors through widespread use of imaging. Accu- total thyroidectomy, thyroid hormone-replacement therapy mulating awareness of this “epidemic of diagnoses” has is required and is often prescribed in a dosage sufﬁcient to resulted in more conservative clinical practice guidelines inhibit pituitary production of thyroid-stimulating hormone about when to biopsy and a subsequent stabilization of to decrease the likelihood of recurrence. overall incidence rates. However, increasing trends for Total thyroidectomy is the primary treatment for larger and follicular tumors indicate that risk factors may patients with medullary thyroid cancer. When the tumor is also be contributing to a true increase in disease occur- extensive or cannot be completely resected, radiation ther- 115,116 rence. The median age at diagnosis—54 years for apy may be given after surgery. Targeted drugs can be use- males and 49 years for females—is younger than that for ful in treating metastatic disease. Anaplastic thyroid cancers most other adult cancers (Fig. 3). are often widespread and resistant to treatment; in selected FIGURE 11. Treatment Patterns (%) for Nonseminomatous Testicular Germ Cell Tumors by Stage, 2009 to 2013. Chemo indicates chemotherapy (includes immunotherapy and targeted therapy); RPLND, retroperitoneal lymph node dissection; RT, radiation therapy. Note that a small proportion of patients (<1% of those with early stage disease and about 5% of those with late-stage disease) who underwent surgery also received RT. Source: National Cancer Data Base, 2013. _ _ VOLUME 66 NUMBER 4 JULY/AUGUST 2016 283 Cancer Treatment and Survivorship Statistics, 2016 patients, radiation therapy alone or in combination with chemotherapy may be used. The 5-year relative survival rate for patients with thyroid cancer who were diagnosed during 2005 through 2011 is 98%, although survival varies by age at diagnosis, stage, and histologic type. Notably, blacks are more likely to be diagnosed at a localized stage compared with whites (78% vs 68%, respectively) but have lower survival within each stage and overall. For patients with medullary and ana- plastic carcinomas, the 5-year relative survival rates are 88% and 9%, respectively. Short-term and long-term health effects Patients who undergo total thyroidectomy require thyroid hormone-replacement therapy, and thyroid hormone levels must be monitored to prevent hypothyroidism, which can FIGURE 12. Muscle-invasive Bladder Cancer Treatment Pat- cause cold intolerance and weight gain. Surgical removal of terns (%), 2013. the thyroid gland can damage the underlying parathyroid Chemo indicates chemotherapy (includes immunotherapy and targeted ther- apy); RT, radiation therapy; TURBT, transurethral resection of the bladder glands, leading to disorders of calcium metabolism. Surgery tumor. Source: National Cancer Data Base, 2013. can also damage nerves to the larynx and lead to voice changes. Treatment with radioactive iodine can affect fer- tility and may be linked to an increased risk of leukemia. have metastasized, but other treatments might be used as About 25% of medullary thyroid cancers occur as part of a well. genetic syndrome (such as multiple endocrine neoplasia For all stages combined, the 5-year relative survival rate [MEN] type 2), so these patients should be screened for is 77%. Survival declines to 70% at 10 years and to 65% at other cancers and referred for genetic counseling and possi- 15 years after diagnosis. The 5-year relative survival rate for ble testing. in situ urinary bladder cancer, which accounts for 51% of cases, is 96%. For the 35% of patients with invasive Urinary Bladder tumors diagnosed at a localized stage, the 5-year survival It is estimated that there are 765,950 urinary bladder cancer rate is 70% (81% for those with nonmuscle-invasive disease survivors living in the United States, and an additional and 47% for those with muscle-invasive disease). 76,960 cases will be diagnosed in 2016. Bladder cancer inci- dence is about 4 times higher in men than in women. Short-term and long-term health effects The median age at diagnosis is 73 years. More than 70% of Posttreatment surveillance is crucial given the high rate of patients who have bladder cancer are diagnosed with 124,125 recurrence (estimates range from 50% to 90%). Sur- nonmuscle-invasive disease. veillance can include screening for urine biomarkers and Treatment and survival cytology as well as cystoscopy. Patients who require repeated bladder surgeries can end up with a small or For nonmuscle-invasive cancers, most patients are diag- scarred bladder, which may lead to urinary frequency or nosed and treated with transurethral resection of the blad- der tumor (TURBT), which may be followed by incontinence. Partial cystectomy results in a smaller blad- der, sometimes causing the patient to have more frequent intravesical chemotherapy (22%) or biologic therapy with urination. Patients undergoing cystectomy in which the bacillus Calmette-Guerin (29%). (The NCDB does not entire bladder is removed require urinary diversion with distinguish between systemic and intravesical chemother- apy but, based on treatment guidelines, it is likely that vir- either construction of a neobladder with urethral anastomo- sis or a urostomy. Those with a neobladder retain most of tually all chemotherapy is intravesical administration.) their urinary continence after appropriate rehabilitation. Among patients with muscle-invasive disease, about one-half undergo TURBT, and 39% undergo cystectomy, However, creation of a neobladder remains much less com- with or without chemotherapy and/or radiation (Fig. 12). mon than urostomy (9% vs 91%), largely because of the TURBT followed by combined chemotherapy and technical complexity of the procedure; its use is substan- radiation therapy is as effective as cystectomy at preventing tially higher at larger, higher volume hospitals. Younger, 121–123 recurrence in appropriately selected cases. healthier patients and those who are male are also more Chemotherapy is usually the ﬁrst treatment for cancers that likely to undergo the procedure. 284 CA: A Cancer Journal for Clinicians CA CANCER J CLIN 2016;66:271–289 FIGURE 13. Uterine Corpus Cancer Treatment Patterns (%) by Stage, 2013. Chemo indicates chemotherapy (includes immunotherapy and targeted therapy); RT, radiation therapy. Source: National Cancer Data Base, 2013. Uterine Corpus Quality of Life and Other Concerns in Long-Term Survivorship There are an estimated 757,190 women living in the United States with a previous diagnosis of uterine corpus cancer Although quality of life may decline considerably during and an additional 60,050 cases will be diagnosed in 2016. active cancer treatment and remain low for a short period thereafter, many side effects are acute and short-lived, and the Cancer of the uterine corpus is the second most prevalent cancer among women after breast cancer. The median age majority of disease-free cancer survivors report good quality of at diagnosis is 62 years (Fig. 3). life 1 year posttreatment. The type and prevalence of long- term or late side effects vary with clinical factors (eg, cancer type, treatment) and patient characteristics (eg, age, sex, Treatment and survival comorbidity). While emotional well-being for longer term Surgery, consisting of hysterectomy (often including bilat- survivors (5 years) is generally comparable to that of individ- eral salpingo-oophorectomy) alone, is used to treat 69% of uals with no history of cancer, a signiﬁcant number report patients with stage I and II disease, whereas 28% of women 2,130 lower overall physical well-being than their peers. Many receive radiation and/or chemotherapy in addition to surgery survivors also suffer from a fear of recurrence and subsequent (Fig. 13). Two-thirds of women with stage III and IV disease primary cancers. Quality-of-life issues also encompass the undergo surgery followed by radiation and/or chemotherapy. concerns of cancer caregivers, who provide substantial emo- Clinical trials are currently assessing the most appropriate reg- tional and physical support to survivors and who frequently imen of radiation and chemotherapy for women with meta- report having unmet psychosocial and medical needs. static or recurrent cancers. There is increasing emphasis on improving cancer survi- The 5-year and 10-year relative survival rates for women vors’ overall well-being and quality of life through the with uterine corpus cancer are 82% and 79%, respectively. application of principles of disease self-management and Most cancers (67%) are diagnosed at an early stage, usually the promotion of healthy lifestyles, such as avoiding because of postmenopausal bleeding, for which the 5-year tobacco, maintaining a healthy body weight, avoiding survival rate is 95%. The overall 5-year survival for white intense ultraviolet radiation exposure, and being physically women (84%) is about 22 percentage points higher than active throughout life. Several practical interventions for that for black women (62%). survivors addressing diet, weight, and physical activity among cancer survivors have been developed and tested. Short-term and long-term health effects In addition, support for smoking cessation and increased Any hysterectomy causes infertility. Bilateral oophorectomy access to cessation aids are essential, because approximately will cause menopause in premenopausal women, which can 10% of cancer survivors continue to smoke even up to 9 lead to symptoms such as hot ﬂashes, night sweats, atrophic years after diagnosis. Younger cancer survivors in partic- vaginitis, and osteoporosis. Long-term side effects of radia- ular have been shown to have a higher prevalence of smok- tion therapy for uterine cancer can include bladder and ing after diagnosis than the general population. bowel dysfunction as well as atrophic vaginitis and stenosis. It is therefore important for providers to understand the Sexual problems are commonly reported among uterine unique medical and psychosocial needs of survivors as well cancer survivors. Pelvic lymphadenectomy can lead to as their caregivers and to be aware of resources that can lower extremity lymphedema, particularly for women who assist in navigating the various phases of cancer survivor- also receive radiation. ship. The American College of Surgeons’ CoC has issued _ _ VOLUME 66 NUMBER 4 JULY/AUGUST 2016 285 Cancer Treatment and Survivorship Statistics, 2016 standards for quality, patient-centered cancer care that survivors, many challenges remain. These include a frac- include recommendations for patient navigation, palliative tured health care system, poor integration of survivorship care, distress management, and survivorship care plan- care between oncology and primary care settings, lack of ning. The Alliance for Quality Psychosocial Cancer strong evidence-based guidelines for posttreatment care, Care, a coalition of professional and advocacy organiza- and ﬁnancial and other barriers to quality care, particularly tions, including the American Cancer Society, formed to among the medically underserved. To address these chal- advance these recommendations and issued a comprehen- lenges, ongoing efforts to identify best practices for the sive resource guide, which is available to assist CoC- delivery of quality posttreatment cancer care are needed. accredited facilities in meeting the new standards. Sev- Future research should also focus on identifying the best eral organizations, including the American Cancer Soci- methods for encouraging cancer survivors to adopt and 30,58,109,138 ety, have begun to produce guidelines to assist maintain a healthy lifestyle. Models for the integration of primary care and other survivorship physicians in the provi- comprehensive care for cancer survivors, including self- sion of care for people with a history of cancer. The ACS management, wellness and healthy lifestyle promotion, and guidelines focus on comprehensive survivorship care, cancer rehabilitation, are beginning to emerge. As the evi- including ongoing surveillance and cancer screening, sup- dence base grows, efforts at the individual, provider, sys- port for health behavior changes, and the assessment and tem, and policy levels will help cancer survivors live longer management of the long-term and late effects of cancer and and healthier lives. its treatment. Author Contributions: Kimberly D. Miller: Conceptualization, formal analy- Conclusion sis, investigation, writing–original draft, writing–review and editing, and pro- ject administration. Rebecca L. Siegel: Conceptualization, methodology, In this article, we document the continued growth of the writing–review and editing, and supervision. Chun Chieh Lin: Conceptualiza- tion, formal analysis, and writing–review and editing. Angela Mariotto: cancer survivor population in the United States and Methodology, formal analysis, and investigation. Joan L. Kramer: Conceptual- describe patterns of treatment and common side effects ization and writing–original draft. Julia Rowland: Conceptualization, writing– original draft, and writing–review and editing. Kevin Stein: Writing–review across the most prevalent cancers. Despite increasing and editing. Rick Alteri: Writing–review and editing. 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