Survival Among Men at High Risk of Disseminated Prostate Cancer Receiving Initial Locally Directed Radical Treatment or Initial Androgen Deprivation Therapy

Abstract Background There is increasing low-quality evidence rationalizing the use of radical therapy for men at high risk of disseminated prostate cancer. Objective To investigate, using high-quality epidemiologic data, whether initial radical therapy in men at high risk of disseminated prostate cancer improves survival. Design, setting, and participants An observational population-based Swedish study from 1996 to 2010 of men at high risk of disseminated prostate cancer (prostate-specific antigen [PSA] > 50) initially treated by radical therapy (radiation therapy [ n = 630] or radical prostatectomy [ n = 120]) or androgen deprivation therapy ( n = 17 602), and followed for up to 15 yr. Outcome measurements and statistical analysis Prostate-cancer and other-cause mortality was estimated for the treatment groups. We also matched the two cohorts for grade, T stage, M stage, Charlson score, year of diagnosis, age, and PSA, and found androgen deprivation therapy patient matches for 575 of the radical therapy patients, and then repeated comparative effectiveness analyses. Results and limitation Prostate-cancer mortality was substantially greater in the androgen deprivation therapy group compared with the radically treated one, in unmatched (9062/17 602 vs 86/750) and matched (177/575 vs 71/575) cohorts. Among matched cohorts, initial androgen deprivation therapy was associated with nearly three-fold higher hazard of prostate-cancer death compared with initial radical therapy (2.87; 95% confidence interval 2.16–3.82). Multiple sensitivity analyses suggested that the findings were robust, although the general limitations of nonrandomized studies remain. Further, the study cohort may have included men with both systemic and nonsystemic disease, as a sole eligibility criterion of PSA > 50 was used. Conclusions This large and comprehensive population-based study suggests that initial radical therapy in men at high risk of disseminated prostate cancer improves survival. Patient summary This large Swedish study suggests that men with prostate cancer that has spread beyond the prostate benefit from treating the prostate itself with radiation therapy or surgery rather than treating the disease with hormones alone.