Whole Pelvis Radiation Therapy Does Not Significantly Improve Prostate-Cancer Specific Survival in Patients With Gleason Score 9-10 Prostate Adenocarcinoma: An Analysis of 942 Patients Treated in the Modern Era

Abstract

Purpose/Objective(s) To assess the effect on clinical outcomes of the addition of whole pelvis radiation (WPRT) to definitive prostate external beam radiation therapy (EBRT) or external beam radiation therapy plus brachytherapy boost (EBRT-BT) for patients with Gleason Score (GS) 9-10 prostate cancer (PCa), who are at high risk of having occult nodal metastases. Materials/Methods Nine-hundred-forty-two patients with biopsy-proven GS 9-10 PCa treated between 2000 and 2013 at 10 institutions (506 with EBRT and 436 with EBRT+BT) were included. 299 EBRT patients (59%) and 320 EBRT+BT patients (73.4%) received WPRT. A cohort of surgically-treated patients from the same multi-institutional database had a pathologic node positivity rate of 17%. Biochemical recurrence-free survival (bRFS), distant metastasis-free survival (DMFS), and prostate cancer-specific mortality (PCSM) were compared between groups using Cox proportional hazards models with propensity score adjustment. Propensity scores were calculated as the conditional probability of receiving WPRT given age, tumor stage, GS, and initial PSA. Results The median follow-up was 5.6 years. The median doses were isoeffective to 81 Gy and 96 Gy in 1.8 Gy fractions in the EBRT and EBRT-BT groups, respectively. The median WPRT dose was isoeffective to 50.4 Gy in 1.8 Gy fractions. In the EBRT group 94% of patients receiving WPRT and 96% of patients not receiving WPRT received ADT (median duration 23 months), and in the EBRT-BT group, 80% of patients receiving WPRT received ADT, and 98% not receiving WPRT received ADT (median duration 12 months). WPRT did not significantly improve PCSM in the EBRT group (HR = 0.76, 95% CI 0.45-1.3, p = .3), though it trended towards improvement in the EBRT-BT group (HR 0.46, 0.19-1.11, p = .08). Similar results were seen in a competing risks regression model, treating other cause mortality as a competing risk. WPRT improved bRFS among patients treated with EBRT-BT (HR = 0.4, 95% CI 0.29-0.54, p < .001) but not in those treated with EBRT (HR 1.1, 95% CI 0.67-1.68, p = 0.8). There was borderline improvement in DMFS in the EBRT-BT group (HR 0.64, 95% CI .40-1.03, p = .065), but not the EBRT group (HR = 1.21, 95% CI 0.76-1.93, p= .4). Conclusion WPRT offered a trend towards improved DMFS and PCSM in this large cohort of patients with biopsy GS 9-10 PCa, but only in those treated with EBRT+BT. This trend did not reach statistical significance. WPRT did significantly improve bRFS, but again only in patients treated with EBRT+BT. These results are hypothesis-generating in suggesting that a long-term clinical benefit to WPRT, if present, might only be seen in the setting of extreme dose-escalation to the prostate itself.

Additional details