External beam radiotherapy (EBRT) and high-dose rate (HDR) brachytherapy for intermediate and high-risk prostate cancer: the impact of EBRT volume

Abstract Background Whole pelvis radiotherapy (WPRT) may improve clinical outcomes over prostate-only radiotherapy (PORT)in high-risk prostate cancer patients by sterilization of micrometastatic nodal disease provided there is optimal control of the primary site. Methods A prospective multicentre cohort study of eligible patients (stage ≥T2c, Gleason score ≥7 or presenting prostate-specific antigen (pPSA) ≥10) treated between 2009 and 2013 were enrolled in a UK national protocol deliveringcombined EBRT and HDR BT. Centres elected to deliver WPRT, 46Gy in 23 fractions or PORT 37.5Gy in 15 fractions with 15Gy single dose HDR BT. The primary endpoint was biochemical progression-free survival (bPFS). Secondary endpoints were overall survival (OS), genitourinary and gastrointestinal toxicity. This was not a randomised comparison and therefore subject to bias and the findings are therefore hypothesis generating but not conclusive. Results 812 patients were entered; 401 received WPRT and 411 received PORT. With a median follow- up of 4.7 years, five-year bPFS rates for WPRT versus PORT arms were 89% vs 81% (p = 0.007) for all patients and 84% vs 77% (p = 0.001) for high-risk patients. Differences in bPFS remained significant after accounting for Gleason score, pPSA, T stage and androgen deprivation therapy duration as co-variates. There was no difference in OS. The overall post treatment toxicities across both cohorts were low with no greater than 1.5% of ≥ grade 3 toxicities at any follow-up time point. WPRT increased both prevalence and cumulative incidence of acute genitourinary toxicity (p = 0.004) and acute gastrointestinal toxicity (p = 0.003). No difference in late radiation toxicity was observed. Conclusion A significant improvement in 5-year bPFS was seen in intermediate and high-risk prostate cancer treated with WPRT compared to PORT in a combined EBRT and BT schedule with no increase in late radiation toxicity.