A Multi-institutional, Propensity Score-Weighted Comparison of Moderately Hypofractionated Photon and Proton Therapy for 1850 Patients with Low or Intermediate Risk Prostate Cancer

Abstract

Moderately hypofractionated radiation therapy (MHRT) is an accepted standard of care for patients with intact low and intermediate risk prostate cancer. Proton beam therapy for prostate cancer offers certain dosimetric advantages, but data directly comparing MHRT modalities are lacking. We aim to compare late toxicity profiles of localized prostate cancer patients treated with proton and photon MHRT. Prospectively-collected institutional databases from 7 tertiary referral centers were queried for patients with intact low or intermediate risk prostate cancer treated from 1998 to 2018 with MHRT, defined as 2.4 – 4.0 Gy per daily fraction given over 4-6 weeks. Patients were stratified based on receipt of proton or photon MHRT. Primary outcomes were late Grade 3+ GU and late Grade 2+ GI toxicity, per CTCAE v4.0, scored by treating institution. Late toxicity was defined as occurring >3 months after treatment completion. Adjusted toxicity rates were calculated using inverse probability of treatment weighting, accounting for race, NCCN risk group, age, pretreatment IPSS (GU only) and anti-coagulant use (GI only). Odds ratios and significance were assessed using generalized linear mixed effects models, with random effects by site. A total of 1850 patients (1282 photon and 568 proton) were included with 1 year minimum follow up. The cohorts were similar in risk group and T stage. However, the photon group had significantly higher baseline IPSS (median 10 vs 7), anti-coagulant use (32.6% vs 15.3%), performance status (28% vs 6% ECOG 1+), PSA (7.6 vs 6.1), and percentage of patients with Gleason 6 disease (66% vs 57%). Late toxicity rates and odds ratios are described in the table below. The most common late toxicities were urinary frequency and rectal bleeding in the proton group and cystitis and rectal bleeding in the photon group. On adjusted analysis for late toxicity, no factors were significantly predictive of GU toxicity and only anti-coagulant use was significantly predictive of GI toxicity (OR 1.88, 95% CI 1.19-2.99). In this large, multi-institutional dataset analysis, rates of late GU and GI toxicity were low with both proton and photon MHRT. No statistically significant difference was seen in late GU toxicity rates. Higher rates of late GI toxicity were found with proton MHRT, but this difference lost statistical significance when adjusted for covariates. Overall, both proton and photon MHRT appear to be safe treatment approaches for low and intermediate risk prostate cancer patients.Abstracts 4058; TableLate Toxicity TypeProton MHRT Toxicity RatePhoton MHRT Toxicity RateOdds Ratio (Confidence Interval)G3+ GUUnadjusted1.6%3.7%0.45 (0.16-1.28)Adjusted2.0%3.9%0.47 (0.17-1.28)G2+ GIUnadjusted11.1%4.8%2.71 (1.17-6.26)Adjusted14.6%4.7%2.69 (0.80-9.05) Open table in a new tab