Docetaxel Versus Surveillance After Radical Radiotherapy for Intermediate- or High-risk Prostate Cancer-Results from the Prospective, Randomised, Open-label Phase III SPCG-13 Trial.

BACKGROUND: Docetaxel combined with androgen deprivation therapy (ADT) has improved patient survival for advanced prostate cancer (PCa). OBJECTIVE: This randomised trial aimed to evaluate whether six courses of docetaxel improved biochemical disease-free survival (BDFS) after radical radiotherapy (RT) for intermediate- or high-risk PCa patients. DESIGN, SETTING, AND PARTICIPANTS: A total of 376 patients were randomised in this multinational phase III study, and received either six cycles of adjuvant docetaxel 75 mg/m2 every 3 wk without continuous prednisone (arm A, n = 188) or surveillance (arm B, n = 188) after RT (NTC006653848). Neoadjuvant/adjuvant ADT was mandatory for all the patients. The primary endpoint was rising prostate-specific antigen (PSA) ≥2 ng/ml above the nadir PSA value. Intermediate- or high-risk PCa was defined as T2 with a Gleason score (GS) of 4 + 3, PSA > 10; T2, GS 8-10, ≤ 70 ng/ml; or any T3. The patients were followed for 5 yr by assessing PSA levels every 3 mo for 2 yr and every 6 mo thereafter. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The study power was 89% to detect a difference in BDFS between groups, and the sample size calculation accounted for the T2/T3 distribution, where a 12%/15% difference in BDFS was assumed for the T2/T3 patients. RESULTS AND LIMITATIONS: All six cycles were completed in 147 (78%) of the patients in arm A. The median age was 67 yr in both treatment groups, 75% had T3 disease, and 47% had GS 8-10. The median follow-up was 59 mo (range 1-111 mo). The primary endpoint was observed for 58 patients in arm A (docetaxel) and for 57 patients in arm B (surveillance). The Kaplan-Meier analysis showed no difference in the BDFS curves (p = 0.6) between the treatment groups. The 5-yr estimated biochemical progression rates were 31% for arm A and 28% for arm B. Febrile neutropenia occurred in 16% of the docetaxel patients. No deaths were related to the docetaxel treatment. There were 43 deaths during the trial, including 20 in arm A and 23 in arm B, of which nine and seven, respectively, were due to PCa. The hazard ratio from Cox multivariate analysis for PSA progression of arm A (docetaxel) versus arm B (surveillance) was 1.14 (95% confidence interval 0.79-1.64, p = 0.5). CONCLUSIONS: Adjuvant docetaxel without prednisone did not improve BDFS after radical RT with ADT for intermediate- or high-risk PCa. PATIENT SUMMARY: We compared six cycles of adjuvant docetaxel given after radical external radiotherapy plus androgen deprivation therapy to surveillance in intermediate- and high-risk localised prostate cancer. We found no overall benefit in this setting.