Late Gastrointestinal and Genitourinary Toxicities of a Moderately Hypofractionated Regimen of Intensity-Modulated Proton Therapy Targeting the Prostate/Seminal Vesicles and Pelvic Lymph Nodes for High Risk or Unfavorable Intermediate Risk Prostate Cancer

Abstract

<h3>Purpose/Objective(s)</h3> To assess late gastrointestinal (GI) and genitourinary (GU) toxicities of intensity-modulated proton therapy (IMPT) targeting the prostate/seminal vesicles and regional pelvic lymph nodes for high risk (HR) or unfavorable intermediate risk (UIR) prostate cancer (Pca). <h3>Materials/Methods</h3> A prospective study (ClinicalTrials.gov: NCTXXX) to evaluate a moderately hypofractionated regimen of IMPT for HR-Pca or UIR-Pca accrued a target sample size of 55 patients. The prostate/seminal vesicles and pelvic lymph nodes were treated simultaneously with 67.5 Gy (2.7 Gy/fraction) and 45 Gy (1.8 Gy/fraction), respectively, in 25 fractions over 5 weeks. IMPT plan was prepared with pre-defined dose-volume histogram objectives for target volumes and organs at risk. All received androgen deprivation therapy (ADT). GI and GU toxicities were prospectively assessed, using the CTCAEv.4, at baseline (before IMPT); 3-, 6-, and 12-month post-RT and then every 6 months thereafter. Late toxicity was defined as toxicity persisting for > 3 months, or developing > 3 months post-RT. Late GI and GU toxicity rates were computed using Kaplan-Meier estimates, and log-rank tests were utilized for comparisons of time-to-event distributions. <h3>Results</h3> Median age was 75 years (range: 55-87). Median PSA was 10.5 ng/mL (range: 0.65 -97.3). Fifty-three patients had HR-Pca; 2 had UIR-Pca. Median duration of ADT was 18 months. Fifty-four patients were available for late toxicity assessment. Median follow-up was 46 months (range: 16-66). 29% and 6% experienced late grade 1 and 2 GI toxicity, respectively. One patient (2%) had late grade 3 GI toxicity (proctitis). The actuarial rate of late grade ≥ 2 GI toxicity was 7% (95% CI: 0.2-14%) at both 2 and 3 years. The actuarial rate of late grade 3 GI toxicity was 2% (95% CI: 0-5%) at both 2 and 3 years. 76% and 24% experienced late grade 1 and 2 GU toxicity, respectively. None had late grade ≥ 3 GU toxicity. The actuarial rate of late grade 2 GU toxicity was 21% (95% CI: 9-31%) at 2 years, and 29% (95% CI: 15-40%) at 3 years. None had late grade ≥ 4 GI or GU toxicity. The presence of baseline GU symptom was associated with a greater likelihood of experiencing late grade 2 GU toxicity. Of 44 patients with baseline GU symptoms, late grade 2 GU toxicity rate at 3 years was 36% (95%: 19-49%), compared to 0% among 10 patients with no baseline GU symptoms (p=0.02). <h3>Conclusion</h3> A moderately hypofractionated regimen of IMPT targeting prostate/seminal vesicles and pelvic lymph nodes for HR-Pca or UIR-Pca yielded very acceptable late GI and GU toxicity.