Comparative risk-adjusted mortality outcomes after primary surgery, radiotherapy, or androgen-deprivation therapy for localized prostate cancer

Background: Because no adequate randomized trials have compared active treatment modalities for localized prostate cancer, the authors analyzed risk-adjusted, cancer-specific mortality outcomes among men who underwent radical prostatectomy, men who received external-beam radiation therapy, and men who received primary androgen-deprivation therapy.

Methods: The Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry comprises men from 40 urologic practice sites who are followed prospectively under uniform protocols, regardless of treatment. In the current study, 7538 men with localized disease were analyzed. Prostate cancer risk was assessed using the Kattan preoperative nomogram and the Cancer of the Prostate Risk Assessment (CAPRA) score, both well validated instruments that are calculated from clinical data at the time of diagnosis. A parametric survival model was constructed to compare outcomes across treatments adjusting for risk and age.

Results: In total, 266 men died of prostate cancer during follow-up. Adjusting for age and risk, the hazard ratio for cancer-specific mortality relative to prostatectomy was 2.21 (95% confidence interval [CI], 1.50-3.24) for radiation therapy and 3.22 (95% CI, 2.16-4.81) for androgen deprivation. Absolute differences between prostatectomy and radiation therapy were small for men at low risk but increased substantially for men at intermediate and high risk. These results were robust to a variety of different analytic techniques, including competing risks regression analysis, adjustment by CAPRA score rather than Kattan score, and examination of overall survival as the endpoint.

Conclusions: Prostatectomy for localized prostate cancer was associated with a significant and substantial reduction in mortality relative to radiation therapy and androgen-deprivation monotherapy. Although this was not a randomized study, given the multiple adjustments and sensitivity analyses, it is unlikely that unmeasured confounding would account for the large observed differences in survival.