Older Men With Locally Advanced Prostate Cancer: To Treat or Not to Treat?

TO THE EDITOR: Bekelman et al have published an article on treating older men with locally advanced prostate cancer in Journal ofClinicalOncology,whichwasaccompaniedbyaneditorialbyShumway and Hamstra. The authors should be congratulated for their significant contribution to our understanding of both age-dependent bias against treatment and the benefits of radiotherapy (RT) added to androgendeprivation therapy (ADT) in elderly men with locally advanced or screen-detected high-risk prostate cancer. Bekelman et al report on their proof-of-concept populationbased observational cohort study using the Surveillance, Epidemiology, and End Results Medicare database, in which they found pronounced survival benefit in the setting of addition of RT to ADT in men with screen-detected high-risk prostate cancer and elderly men older than 75 years. In the elderly cohort, ADT plus RT was associated with reduced cause-specific mortality (propensity score–adjusted hazard ratio [HR], 0.51; 95% CI, 0.44 to 0.59) and all-cause mortality (propensity score–adjusted HR, 0.63; 95% CI, 0.59 to 0.67). In the screen-detected cohort, ADT plus RT was associated with reduced cause-specific mortality (propensity score–adjusted HR, 0.25; 95% CI, 0.19 to 0.33) and all-cause mortality (propensity score–adjusted HR, 0.50; 95% CI, 0.45 to 0.55). They come to the conclusion that men older than 75 years with locally advanced prostate cancer or men older than 65 years with screen-detected prostate cancer who receive ADT alone risk reduction in cause-specific and overall survival. Indeed, level I evidence supports the role of ADT plus RT for patients with locally advanced prostate cancer in prolonging survival compared with ADT alone in two recent landmark randomized clinical trials. However, whether the results of these two landmark trials are generalized to the real world outside-of-trial patient population is a critical issue given that elderly men, those with multiple comorbidities, and those from an ethnic minority or a socioeconomically disadvantaged population, are often underrepresented in clinical trials. In fact, in our daily clinical practice, considerable uncertainty surrounds the incremental benefit of local therapy in addition to androgen deprivation among elderly men with newly diagnosed prostate cancer, particularly given the exclusion of these men from randomized clinical trials. Even though this study confirms the survival benefits of RT plus ADT in the setting of locally advanced prostate cancer and extends the generalizability of these findings to two subgroups not well represented in the clinical trials— elderly men older than 75 years and men age 65 years and older with screen-detected highrisk prostate cancer—it remains imperfect and raises multiple questions for future studies. First, there is a paucity of randomized clinical trials in elderly patients and lack of coherence for the definition of elderly. Age stigma often excludes elderly people from clinical trials to reduce attrition, minimize confounding variables associated with comorbidities, and avoid lengthier study processes. Furthermore, health care professionals’ attitudes can be tainted with ageism, thus leading to undesirable consequences for elderly cancer patients. It is important to base treatment decisions on functional age and not chronological age. Tools like the Chemotherapy Risk Assessment Scale for High-Age Patients, the Cancer and Aging Research Group model, the Comprehensive Geriatric Assessment, or the Multidisciplinary Geriatric Assessment can be used to assess elderly cancer patients. But more studies are needed to clarify their utility and value in the context of geriatric oncology. Second, RT serves as one of the most effective treatment modalities for localized prostate cancer. However, the standard conventional fractionated RT regimen for localized prostate cancer consists of approximately 7 to 9 weeks of daily treatment in 1.8 or 2 Gy per fraction, with the disadvantage of inconvenience for the patient and a higher cost burden for the health care system. How to improve convenience and lower cost without compromising safety and efficacy, especially in elderly men with locally advanced prostate cancer, is a critical issue not yet resolved. Treatment decisions in the elderly are not one size fits all; it is all about patient-bypatient assessment. For the therapy to have clinical utility in the elderly, patients would have to possess an accurate understanding of the natural course of their disease, their life expectancy, and a realistic expectation of the toxic effects related to treatment. The findings of this study could be used to counsel patients considering options for localized or locally advanced disease. In the future, prospective studies of decision making in this age group would be useful in answering some unsolved questions.