Progression free survival (PFS) after whole-pelvic (WP) vs. mini-pelvic (MP) or prostate only (PO) radiotherapy (RT): A subset analysis of RTOG 9413, a Phase III prospective randomized trial using neoadjuvant and concurrent (N&CHT)

Abstract

Despite the report of RTOG 9413 demonstrating a better PFS with WP compared to PO RT many physicians continue to favor smaller fields for the treatment of men with intermediate to high risk prostate cancer. This secondary analysis was performed to determine whether patients treated with MP RT had a PFS comparable to patients treated with WP RT, and whether patients treated with MP RT might have less toxicity than those treated with WP RT. Eligibility included histologically confirmed clinically localized adenocarcinoma of the prostate with an elevated prostate specific antigen (PSA) <100 ng/ml. Patients were stratified by T stage, PSA and Gleason Score (GS) and required to have an estimated risk of lymph node (LN) involvement >15%, based on the equation +LN = (2/3) PSA + [(GS − 6) × 10]. N&CHT consisted of flutamide 250 mg p.o. TID and either leuprolide or goserelin acetate depot preparations administered 2 months before and during RT. The study was activated on April 1, 1995 and closed June 1, 1999 with a total of 1323 cases. To avoid the bias due to total duration of treatment (4 mo. vs. 6 mo.), only patients treated on arms 1 and 2 were selected for this subset analysis. Three hundred twenty five men (arm 1), and 324 men (arm 2) were randomized to WP RT, and PO RT, respectively. Patients randomized to WP RT, were compared to subsets of patients randomized to PO RT (arm 2), dichotomized as PO with a radiation field size less than the median (i.e., 10cm × 11cm) vs. mini pelvic (MP) with a field size greater than or equal to the median. The Chi-Square and F tests were used to assess baseline imbalances among the three groups for proportions and continuous measures, respectively. Actuarial estimates for PFS were calculated using Kaplan-Meier methods. The log-rank test was used to test differences in the PFS curves among the radiation field size groups. The median follow-up since study entry for all patients was 59.3 months. Pre-treatment characteristics were well distributed among the radiation field size groups with the exception of intercurrent disease favoring the PO group (p = 0.011). The 4-year PFS was 60% for the WP, 48% for the MP and 40% for the PO groups, respectively (see table 1 below). The log-rank test revealed a statistically significantly difference between the PFS distributions over time (p = 0.002). Pairwise comparisons showed that there were statistically significant differences in PFS between the WP and MP groups (p = 0.032) but no difference between PO and MP groups (p = 0.24). There were no significant differences in the incidence of late grade 2 and 3+ GI and GU between WP and MP RT (p > 0.05). WP RT is associated with an improvement in PFS compared to MP and PO RT in patients with a risk of LN involvement >15%. Late grade 3+ GI toxicity was similar with WP RT compared to MP RT, however both were higher than PO RT. This study supports WP RT as the standard of care for intermediate to high risk prostate cancer treated with RTsN&CHT. Longer follow-up is required to determine if this subset analysis eventually translates into a survival difference.