External beam radiotherapy (EBRT) and high dose rate (HDR) brachytherapy for intermediate and high-risk prostate cancer: Whole pelvis or prostate-only EBRT?

Abstract

86 Background: In high-risk prostate cancer, the risk of occult lymph node metastases in the pelvic lymph nodes can be as high as 40%. However, the use of whole pelvis radiotherapy (WPRT) in high-risk patients remains controversial with mixed retrospective evidence and two negative prospective trials. Data from a national UK database of patients treated with external-beam radiotherapy (EBRT) and high-dose rate (HDR) brachytherapy was reviewed to evaluate the benefit of pelvic treatment. Methods: From 2009 to 2013, 755 patients with intermediate- and high-risk prostate cancer (clinical stage ≥T2c, Gleason score ≥7 or presenting prostate-specific antigen (pPSA) ≥10) were treated with EBRT and HDR brachytherapy. The pelvic nodes to the level of the common iliac chain were treated in 370 patients with a dose of 46Gy in 23 fractions. The remaining 385 patients received radiotherapy to the prostate only (PORT) at a dose of 37.5Gy in 15 fractions. A single dose of 15Gy was delivered with HDR brachytherapy in each case. Corresponding biologic effective doses to the prostate were 107Gy and 100Gy respectively (α/β = 1.5). 96.5% of patients received ADT with a median duration of 24 months. Biochemical failure was defined as a PSA rise of ≥2ng/ml above nadir. Analysis used log-rank and Cox univariate and multivariate tests. Results: Median follow-up was 4.5 years; 5-year biochemical progression-free survival rates for the WPRT versus the PORT arms were 88% vs 80% (p < 0.05) for all patients and 89% vs 76% (p < 0.05) for high-risk patients. Differences in bPFS remained significant (p < 0.05) after accounting for Gleason score, pPSA, T stage and ADT duration as co-variates. There was no difference in overall survival. Conclusions: Whole pelvis EBRT with HDR brachytherapy appears to significantly improves 5-year biochemical progression-free survival in intermediate- and high-risk prostate cancer compared to prostate-only EBRT and HDR brachytherapy which persists after allowing for covariates including presenting tumour parameters and ADT use. The PIVOTAL boost trial in the UK will assess this further in a prospective randomised study.