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.

BACKGROUND: In 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.

OBJECTIVE: To compare mortality rates in patients receiving ET alone versus ET + RAD.

DESIGN, SETTINGS, AND PARTICIPANTS: From 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 ANALYSIS: PCa-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.

INTERVENTION: RAD added to ET.

RESULTS AND LIMITATIONS: With 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.

CONCLUSIONS: In 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 SUMMARY: Adding prostatic therapy to lifelong antiandrogen therapy halves the absolute risk of death from prostate cancer from 34% to 17% 15 yr after diagnosis.