For Patients With Cancer, Cure Is Not Enough

Advances in cancer therapy have led to increased survival; there aremore than9million 5-year survivors of cancer in the UnitedStates.1 As this number continues to grow, focuson improved health and quality of life becomes a priority. It is especially important in survivors of childhood, adolescent, and young adult cancer who have 5-year survival rates exceeding 80%1 and who are expected to live many decades after diagnosis and treatment. Because of their young ageat treatment, thispopulation is themostvulnerable to longtermdetrimental effects of cancer therapy.Many studieshave shown that childhood and adolescent cancer survivors are at increased risk for chronicmedicalproblemsandemotional late effectsas theyage.2-5These lateeffects influenceoverallhealth and quality of life. While the impact of cancer and its treatment on children is an area of increasing research, there is a paucity of lateeffectsdata foryoungadults.The riskofdeveloping treatmentrelated sequelae and the type of surveillance screening necessary for this population are often extrapolated fromstudies of children ormiddle-aged adults. However, adolescents and young adults (AYAs) have auniquepattern of cancer development with distinct biological findings6 and different psychosocial stressors associated with the transition to adulthood. This distinctive biology and psychosocial environment suggest that the late-effects burden inAYAsmaydiffer greatly from that of other survivors. Studies are needed in this age group to describe the breadth of late effects to guide screening and treatment. In this issue of JAMA Oncology, Rugbjerg and Olsen7 provide a glimpse into the late-effects burden among AYA survivors through theuseofnationalDanish registries. Theauthors compare the long-term risk of hospitalization in 33 555 5-year survivorsofAYAcancer (diagnosedatage 15-39years)with that of 228 447 ageand sex-matched population controls. They identified 53 032 hospitalizations among survivors compared with 38 423 expected, based on the control population, leading to a standardized hospitalization rate ratio (RR) of 1.38 (95%CI, 1.37-1.39)andabsoluteexcess risk (AER)of2803 (95% CI, 2712-2893) hospitalizations per 100 000 personyears. The highest AERs were found for malignant neoplasms, diseases of the digestive system, and cardiovascular disorders. Those with the highest risk of hospitalization included survivors of leukemia (RR, 2.21; 95% CI, 2.02-2.42), brain tumors (RR, 1.93; 95% CI, 1.86-2.00), and Hodgkin lymphoma (RR, 1.87; 95%CI, 1.80-1.94), which aremalignant conditions known to have increased late effects in pediatric survivors. More than 50% of the cancer-specific AER for survivors of brain cancerwas due toneurologic or endocrine disorders, while approximately 50% of the AER for survivors of Hodgkin lymphoma was attributed to malignant neoplasms and cardiovascular disease. Of interest, the AER for leukemia survivorswasattributedmostly to infectious andparasiticdiseases (20%) and respiratory conditions (28%), especially influenza and pneumonia. The large sample size and low attrition rate of this study7 allow for a comprehensive view of the inpatient treatment of AYA survivors and offer early insight into their overall diseaseburden.However, the full rangeof treatmentsequelaecannot be evaluated using these data, since many late effects of cancer therapy are treated in the outpatient setting. For example, in contrast to infectious or respiratory complications seen in the Rugbjerg and Olsen study,7 the preponderance of treatment-related sequelae inpreviously published reports of survivors of childhood leukemia are musculoskeletal, cardiac, endocrine, or neurologic in origin8,9; these are often treated inoutpatient clinics.Because leukemia treatment isoften longer than treatment for othermalignant conditions, and many patients who have relapsed are treated more than 5 years after the original diagnosis, it is difficult to determine if the infectious and respiratory complications observed in this study are owing to long-term immunocompromise in these survivors, which requires further surveillance, or acute sequelae in patients who have experienced a relapse requiring hospitalization. Importantly, the subsequent malignant neoplasms described in this study7 differ greatly from those previously observed in survivors of childhood and adolescent cancers. The most common malignant conditions leading to hospitalization in AYA survivors were nonmelanoma skin cancer, neoplasms of the digestive organs, and cancers of the respiratory system. It is surprising that breast and thyroid cancer, 2 of the most commonly reported subsequentmalignantneoplasms in survivors of childhood and adolescent cancer,10 were not as prevalent in this study.However, this variation in typesof subsequentcancersmaybeowing to thedifference inprimarycancer location and treatment. In this study,7 survivors of cervical, testicular, andprimarybreast cancermadeupnearly 50% of the study population. These cancers are often treatedwith irradiation to the pelvis or chest, which increases the risk of gastrointestinal and lung cancer. As evidenced by Rugbjerg and Olsen,7 treatment sequelae in AYA cancer survivors, including subsequent malignant neoplasms, differ from those in survivors of childhood cancer. Prevention and management of late effects necessitate early detection and intervention, which require a comprehensive view of the treatment-related sequelae that canRelated articles Opinion