Adverse effect of docetaxel versus surveillance after radical prostatectomy for high risk prostate cancer: Post-hoc analysis of the prospective randomized, open-label phase III SPCG 12 trial.

Abstract

30 Background: Adjuvant chemotherapy is standard treatment for other solid tumours, but so far has not proven effective in prostate cancer. Methods: Open-label, randomised multinational phase III trial. Enrolment 459 patients after prostatectomy. Inclusion criteria high risk (pT2 margin positive or pT3a Gleason score (GS) ≥4+3, pT3b or lymph node positive disease ≥GS 3+4). Patients assigned (1:1) to either six cycles of adjuvant docetaxel 75mg/m2 every three weeks without daily prednisone (ArmA) or surveillance (Arm B) until endpoint was reached. Primary endpoint was PSA progression ≥0.5ng/ml. Results: Median time to progression, death or last follow up was 56.8 months. Primary endpoint was reached in 190/459 patients (41.4%), 103 of 230 (44.8%) patients in Arm A and 87 (38.0%) of 229 in Arm B. In Kaplan-Myer analysis, there was evidence of non-proportional hazards over time. When 76 patients with PSA > 0.2 after surgery were excluded from the analysis, the outcome showed proportional hazards and favoured surveillance in the KM-analysis (p = 0.02). The significant favour of surveillance remained in a Cox multivariate analysis including Gleason score, pT-stage, surgical margins and lymph node status (p = 0.03). Limitations were that not all patients received docetaxel by protocol, some patients received radiation treatment before end-point and lack of stratification for PSA after surgery. Conclusions: Adjuvant docetaxel without hormonal therapy or continuous corticosteroids may have an adverse effect on biochemical progression in patients with low or undetectable levels of PSA after surgery. Clinical trial information: NCT00376792.