Castration remains despite decreasing definitive treatment of localized prostate cancer in the elderly: A case for de‐implementation

In their important study, Yang and colleagues used the National Cancer Data Base to examine definitive therapy (prostatectomy or radiotherapy) among 400,000 patients who were diagnosed with intermediate-risk or high-risk prostate cancer between 2004 and 2012. By using multivariable regression to adjust for patient and sociodemographic factors, the investigators observed that patients decreasingly received definitive treatment with increasing age and worsening comorbidity. Indeed, greater than 40% of patients aged >80 years did not receive definitive treatment with radiation or surgery. Moreover, one-half of patients aged 80 years with high-risk prostate cancer who did not receive definitive treatment went on to undergo receive primary androgen-deprivation therapy (ADT) instead. In this editorial, the authors conclude that significant under treatment of unfavorable-risk prostate cancer in the elderly puts them at up to 20% risk of prostate cancer-related death at 10 years. On the 1 hand, less use of definitive prostate cancer treatment among patients who are least likely to benefit (ie, elderly, comorbid patients) argues against the widely held belief that we are overtreating patients with prostate cancer. Indeed, compared with men who received definitive treatment, those who did not receive such treatment were more likely to die within 1 year of diagnosis, regardless of age or prostate cancer disease risk, suggesting that decision making was reasonably aligned with life expectancy. An increasing comorbidity score also was associated with a lower likelihood of receiving definitive treatment, such that men who had 2 or more Charlson-Deyo comorbidity points had approximately one-half the odds of receiving definitive treatment compared with men who had no comorbidities. The finding that sicker patients were less likely to receive definitive treatment for localized prostate cancer after taking into consideration other factors (eg, demographics) was encouraging. Conversely, Yang et al observed overtreatment of elderly patients through a different mechanism—a high rate of chemical castration with ADT as the primary treatment for many elderly patients with localized prostate cancer who were not treated definitively with radiation or surgery. With increasing age, patients were less likely to receive definitive treatment but more likely to be treated with primary ADT. Although receipt of primary ADT was more pronounced among patients with high-risk, localized disease who did not receive definitive prostate cancer treatment (41%), 1 in 5 men with intermediate-risk disease who did not undergo definitive treatment also received primary ADT. Because the benefits of castration are associated primarily with advanced rather than localized disease, and because safer, effective treatment approaches, such as observation (ie, watchful waiting) or radiation therapy exist, the authors point out that these findings are troubling, citing decreased overall survival with primary ADT for localized prostate cancer and its notable harms (eg, metabolic syndrome, fractures, and cognitive, cardiovascular, and sexual dysfunction). In patients who do not undergo definitive treatment for localized disease, the early versus delayed castration dilemma has been studied in randomized trials. For example, European Organization for Research and Treatment