Ten- and 15-yr Prostate Cancer-specific Mortality in Patients with Nonmetastatic Locally Advanced or Aggressive Intermediate Prostate Cancer, Randomized to Lifelong Endocrine Treatment Alone or Combined with Radiotherapy: Final Results of The Scandinavian Prostate Cancer Group-7

Abstract

BackgroundIn high-risk prostate cancer (PCa), no study with observation times beyond 10 yr has demonstrated survival improvement after addition of prostatic radiotherapy (RAD) to endocrine treatment (ET) alone. ObjectiveTo compare mortality rates in patients receiving ET alone versus ET + RAD. Design, settings, and participantsFrom 1996 to 2002, 875 Scandinavian patients with high-risk (90%) or intermediate PCa were randomized to ET or ET + RAD (The Scandinavian Prostate Cancer Group-7). After 3 mo with total androgen blockade in all patients, all individuals continued lifelong antiandrogen monotherapy. Those randomized to ET + RAD started prostate radiotherapy (70Gy) at 3 mo. Outcome, measurements and statistical analysisPCa-specific 15-yr mortality represented the primary endpoint. Assessment of the combination treatment effect and prognostic factors was performed in competing risk analyses and Cox proportional-hazard models. InterventionRAD added to ET. Results and limitationsWith a median observation time of 12 yr, the 15-yr PCa-specific mortality rates were 34% (95% confidence interval, 29–39%) and 17% (95% confidence interval, 13–22%) in the ET and ET + RAD arms respectively (p<0.001). Compared with the ET arm, the median overall survival in the ET + RAD arm was prolonged by 2.4 yr. Treatment with ET alone, age ≥65 yr and increasing histology grade independently increased the risk of PCa-specific and overall mortality. Limitations include nonformal evaluation of comorbidity, the inability to calculate progression-free survival, and lack of information about salvage therapy and toxicity. ConclusionsIn patients with nonmetastatic locally advanced or aggressive PCa, ET + RAD reduces the absolute risk of PCa-specific death by 17% at 15 yr compared with ET alone; the comparable 15-yr PCa-specific mortality rates being 17% and 34%. The results warrant a phase 3 study comparing ET + RAD with radical prostatectomy in high-risk PCa. Patient summaryAdding prostatic therapy to lifelong antiandrogen therapy halves the absolute risk of death from prostate cancer from 34% to 17% 15 yr after diagnosis.