Five-year Outcomes for Moderately Accelerated Hypofractionated Proton Therapy for Prostate Cancer

Abstract

To report 5-year outcomes of a prospective trial of image-guided moderately accelerated hypofractionated proton therapy (AHPT) for prostate cancer. This is a retrospective review of the outcomes of the first 586 consecutive prostate cancer patients who were enrolled on an IRB-approved outcome tracking trial between 2008 and 2015, and treated with double-scattered moderately AHPT. There were 275 low-risk (LR) and 311 intermediate-risk (IR) patients, including 161 favorable intermediate-risk (FIR) and 150 unfavorable-risk (UIR) patients. LR patients were treated with 2.5 GyRBE per fraction to a median of 70.0 GyRBE (range, 64.4 to 72.5 GyRBE) and IR patients to a median of 72.5 GyRBE (range 67.5 to 72.5 GyRBE). Nineteen patients (13 with UIR disease) received androgen deprivation therapy (ADT) for a median of 6 months (range, 2 to 15 months). No patient had SpaceOAR placement. Toxicities were graded prospectively according to Common Terminology Criteria for Adverse Events (CTCAE), version 3.0, and prospectively or retrospectively for versions 4.0 and 5.0. Patient-reported quality of life data were reviewed. Median follow-up was 6.6 years (range, 0.6 to 11.4). The 5-year rates of freedom from biochemical and clinical disease progression (FFBCP) were 96.9%, 98.4%, and 95.6% in the overall group, and LR and IR subsets, respectively. The five-year rates of FFBCP were 98.7% and 92.0% for the FIR and UIR subsets. ADT was not associated with improvement in FFBCP for patients with UIR disease on univariate analysis (p = 0.2827). Actuarial 5-year rates of late radiation-related CTCAE versions 3.0, 4.0, and 5.0 grade 2 gastrointestinal (GI) toxicities, with medical intervention defined as inclusive of any prescription medication, were 9.4%, 10.1% and 10.1%. The corresponding grade 3 GI toxicities were 1.0%, 1.0%, and 1.0%, and grade 3 genitourinary (GU) toxicities were 1.4%, 0.9% and 0.9% respectively. Grade 3 GI toxicity was significantly related to Absolute Rectal Volume receiving 70 GyRBE (Rec V70) (p = 0.0218). The optimal cut point for Rec V70 was 6.9 cc with a 5-year risk of grade 3 GI toxicity with <6.9cc of 0% (95% CI: n/a) and with >6.9 of 3.1% (95% CI: 1.4%-6.7%). There were no grade 4 or higher GI or GU toxicities. The mean and standard deviation of the International Prostate Symptom Score, and Expanded Prostate Cancer Index Composite bowel function and bother were 6 (SD = 5), 97 (SD = 7), and 94 (SD = 6), respectively at baseline, and 6 (SD = 6), 92 (SD = 13) and 92 (SD = 9) at the 5-year follow-up. Image-guided moderately AHPT 5-year outcomes show high efficacy, minimal physician-assessed toxicity, and excellent patient-reported outcomes in this cohort of patients. These results are comparable to the 5-year results of our prospective trials of conventionally fractionated proton therapy for patients with LR and IR prostate cancer.