RE: A Reappraisal of Sex-Specific Cancer Survival Trends Among Adolescents and Young Adults in the United States

We have several concerns about the survival trends report on American adolescents and young adults (AYA, age 15–39 years, inclusive) with cancer (1). The report states that the role of the HIV/AIDS epidemic in AYA cancer survival assessment had not been evaluated previously. Since 2006, multiple reports included adjustments for the incidence and survival of AYAs with cancer relative to the HIV/AIDS epidemic (2–4). Thyroid cancer should not be included in survival trend assessments of AYAs because the increasing and substantial rate of overdiagnosis of thyroid cancer artificially inflates the survival rate (5) and because thyroid cancer is five to six times more common in AYAs than in either younger or older persons (5,6). To adjust for HIV/AIDS-related cancers during the HIV/AIDS epidemic, there is no need to exclude Hodgkin lymphoma in males or females, Kaposi sarcoma or non-Hodgkin lymphoma in females and Burkitt lymphoma in males since these cancers/sex combinations did not peak in incidence during the epidemic (Supplementary Figure 1). Most importantly, we disagree with the authors’ conclusions that “AYA cancer survival is, in fact, largely superior to other age groups” and “continues to exceed that of other age groups” (1). As shown in Figure 1, with more current data and Joinpoint analysis (7), and as similarly described previously (4,8), a more accurate assessment shows no evidence since 1993 that AYAs have a superior 5-year relative (or absolute, not shown) survival. In absolute trend terms, the Joinpoint regression (7) increase in 5-year relative survival over 35 years from 1975 to 2010 was 25.0%, 15.5%, and 21.6% for younger, AYA, and older patients, respectively. In relative terms, the AYA increase was a steady 0.58% per year and superior only to those 40 years and older before 1983. Thereafter, the older age group had consecutive greater survival trends of 2.61% and 0.69% per year. Younger patients had a greater rate at 1.52% per year until 1993, after which they and AYAs have had the same trend. Joinpoint/AAPC* analysis (7) of annual 5-year overall survival, 1975–2010, invasive cancer excluding neoplasms with increased incidence during HIV/AIDS epidemic, by age. The excluded cancers depend on sex: Kaposi sarcoma and non-Burkitt non-Hodgkin lymphoma in males and thyroid cancer in females and males. These neoplasms were increased in incidence during the HIV/AIDS epidemic of the 1980s–1990s (Supplementary Figure 1, available online). *Average annual percent change as provided by the Joinpoint Regression Program (7) using weighted least squares method and logarithmic transformation. P values were also provided by the Joinpoint Program (7). Data source: SEER*Stat (6). If the authors had analyzed individual type of cancer, they would have found many cancers in AYAs (eg, colorectal carcinoma, breast carcinoma, malignant melanoma, leukemia, non-Hodgkin lymphoma, osteosarcoma, rhabdomyosarcoma, Ewing family of tumors, most sarcomas) that have lagged behind younger and/or older patient populations in survival improvement (8) and several that have had no improvement since 1975 (eg, lung, head/neck, ovary, cervix carcinomas) (8, also authors’ reference 7). A more accurate conclusion would be that, in general and as of 2010, American AYAs with cancer have had no evidence for acceleration in their 5-year survival rate improvement, in contrast to both younger and older cancer patients (Figure 1). Whereas four of six AYAs diagnosed with cancer in 1975 survived 5 years, progress over the next 35 years has enabled one more (five of six) to survive 5 years or more (Figure 1), clearly indicating less improvement than in younger or older patients. European AYAs with cancer evaluated similarly have had an inferior survival improvement compared with younger patients and no evidence for survival trend acceleration (4). There is still much left to accomplish in the diagnosis and treatment of cancer and quality and quantity of outcomes in all age groups, especially in AYAs. Affiliations of authors: Critical Mass Young Adult Alliance (SES); Department of Pediatrics, University of Nebraska Medical Center, Omaha, NE (PFC); Departments of Pediatrics, Pathology and Medicine, McMaster University and McMaster Children’s Hospital, Hamilton, Ontario, Canada (RB); Department of Medicine and Knight Cancer Institute, Oregon Health and Science University, Portland, OR (BHL); Department of Radiation Medicine and Knight Cancer Institute, Oregon Health and Science University, Portland, OR (AB); Department of Pediatrics, University of Texas Medical School, Houston, TX (AB). All authors have no disclosures.

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