Standard care for localized or locally advanced prostate cancer includes radical prostatectomy, radiotherapy, and watchful waiting. In addition, adjuvant hormonal therapy is sometimes used.OBJECTIVES
The Early Prostate Cancer (EPC) program was set up to evaluate the addition of the antiandrogen bicalutamide to standard care for localized or locally advanced, nonmetastatic prostate cancer, and to determine whether patients with early prostate cancer benefit from hormonal therapy. Early results have been published previously. The objective of this analysis was to present longer-term findings.DESIGN
The EPC program consists of three ongoing randomized, double-blind, placebo-controlled trials in men with localized (stages T1-T2, N0/Nx) or locally advanced (stages T3-4, any N; or any T, N+) prostate cancer, with no evidence of distant metastases. The trials are being conducted in North America; in Australia, Europe, Israel, Mexico, and South Africa; and in Scandinavia. They were designed and powered for combined analysis, but data have also been analyzed within each trial, and according to primary therapy and disease stage. Selection criteria and primary treatment varied according to the clinical practice of each geographic region.INTERVENTION
After primary treatment with radiotherapy, radical prostatectomy, or watchful waiting, patients were randomly allocated to oral bicalutamide 150 mg once daily or placebo. Randomized treatment Adjuvant bicalutamide for early prostate cancer: an update was scheduled to last for 2 years or until disease progression, depending on the trial protocol.OUTCOME MEASURES
The primary outcome measures were objective progression-free survival (PFS), and overall survival. Tolerability was also assessed.RESULTS
Of 8,113 patients (mean age 67 years), 4,052 received adjuvant bicalutamide, and 4,061 received standard care alone. The median follow-up for this analysis was 7.4 years. Overall, bicalutamide improved objective PFS compared with standard care alone (hazard ratio [HR] 0.79, 95% CI 0.73-0.85, P <0.001), but had no significant effect on overall survival (HR 0.99, 95% CI 0.91-1.09, P=0.89). In patients with localized disease, bicalutamide provided no benefit in terms of PFS or overall survival, regardless of primary treatment. In patients with locally advanced disease, bicalutamide improved objective PFS compared with standard care alone, both overall (HR 0.69, 95% CI 0.58-0.82; P<0.001), and in all primary treatment subgroups, but had no effect on overall survival (HR 0.95; 95% CI 0.77-1.16, P=0.59). In the subgroup of patients receiving radiotherapy for locally advanced disease, however, bicalutamide improved overall survival (HR 0.65, 95% 0.44-0.95; P=0.03). For these patients, the risk of prostate-cancer-related death was reduced following treatment with bicalutamide compared with standard care alone (16.1% versus 24.3%). Among patients receiving bicalutamide, breast pain (73.6%) and gynecomastia (68.8%) were the most frequently reported adverse events, but were mild to moderate in >90% of cases.CONCLUSION
Adjuvant bicalutamide provided no benefit to patients with localized prostate cancer, but improved PFS in patients with locally advanced disease, and appeared to increase overall survival in select patients.