A Phase II trial of Hypofractionated Proton Therapy in Prostate Cancer: 3-year Physician and Patient Reported Outcomes

Abstract

To investigate the role of hypofractionated proton beam therapy (HFPBT) in men with localized prostate cancer. Men with localized prostate carcinoma were treated with HFPBT on this prospective phase II trial. All patients were treated with a total dose of 55.5Gy for 15 fractions with 3.7Gy per fractions. Patients completed Expanded Prostate Cancer Index Composite (EPIC) questionnaire at baseline and every 6-12 months after HFPBT. Using modified Radiation Therapy Oncology Group scoring, acute and chronic gastrointestinal (GI) and genitourinary (GU) toxicities were determined and scored. The cumulative incidence (CI) rates were estimated using the method of Kaplan and Meier. EPIC scores were compared between baseline and a specific time point using the paired t tests. A clinically significant change from baseline for an EPIC domain score is defined as ½ the baseline standard deviation for that domain. In total 210 patients were enrolled on this Phase II trial from Oct, 2013 to Jan, 2019 out of which 181 patients were included in the analysis. 29 patients were excluded due to: patients withdrew consents (n=19), patients have not started treatment yet (n=10). Mean age was 66 years. Median follow-up was 2.6 years with max of 5 years. 50.8% patients received androgen deprivation therapy with a mean of 4 months. At 3 year follow-up, there were no grade 3 or higher acute and chronic GU or GI adverse events reported. Acute grade 2 GU and GI toxicity occurred in 15.0% and 4.8% patients respectively. The CI rates of chronic grade 2 GU toxicity at 1, 2 and 3 years were 9.0%, 12.4%, and 14.41%. The CI rates of chronic grade 2 GI toxicity at 1, 2 and 3 years were 2.7%, 3.6%, 4.6%. Acute Grade 2 GU toxicity were hesitancy (6.3%), dysuria (4.4%), frequency (1.9%), urgency (0.6 %). Chronic Grade 2 GU toxicity were frequency (6.3%), nocturia (5.7%), dysuria (1.7 %), urgency (1.7%) and hematuria (1.7%). Acute Grade 2 GI toxicity was diarrhea (4.8%) and chronic Grade 2 GI toxicity was bleeding (5.3%) and diarrhea (1.3%). At 3 year follow-up, 95% of patients reported no use of pads for incontinence. The EPIC mean score of bowel function at baseline was 93.9 and at 36 months was 90.8. The mean score of sexual function at baseline was 34.9 and at 36 months was 39.4. The mean score of urinary function at baseline was 95 and at 36 months was 91. At baseline, 73 patients (40.3%) reported erections firm enough for intercourse. Of those 73 pts, 26 reached 36 months follow-up and 15 (58%) among them reported erections firm enough for intercourse. At 3 years, HFPBT in men with localized prostate cancer treated with 55.5Gy in 15 fractions generated no Grade 3, 4 or 5 acute or chronic GI/GU toxicities. Patent reported urinary, bowel and erectile function, demonstrates no clinically significant difference. However sexual potency declined while overall patient satisfaction remained high.