Hypofractionated Proton Therapy for Low-Risk Prostate Cancer: Preliminary Results of a Phase 1/2 Study

Purpose/Objective(s): Proton therapy has been shown to be very effective for low-risk prostate cancer, with 10-year bRFS over 90%. A Phase I/II study was undertaken to use hypofractionation in an attempt to significantly reduce the cost of proton treatment for low-risk prostate cancer, while still retaining excellent control with minimal toxicity. Materials/Methods: In 2009, an IRB-approved trial was initiated, utilizing protons delivered in a hypofractionated schedule. Patients with low-risk prostate cancer (cT1-T2bN0M0 and PSA < 10 and Gleason Score ≥6) received protons to the prostate only, treating all fields per day, to a total dose of 60 Gy in 20 fractions over 4 weeks. Sixty-three patients entered the trial through November 2009; two ultimately decided not to start protocol therapy, for a total of 61 completing treatment. Toxicity was followed using NCI CTCAE for adverse events at three-month intervals. Biochemical control was evaluated using the Phoenix definition (PSA nadir + 2 ng/mL). All patients but four, one who died of MI six months after treatment and three who refused or were lost to follow-up, were eligible for the minimum 36-month follow-up. Results: At the time of analysis, median follow-up was 36 months, ranging from 3 to 42 months. GI toxicity at 24 months was seen in 6%, 2% and 0% for grade 1, 2, and 3 toxicity, respectively. At 36 months, GI toxicity by grade was 5.4%, 0%, and 0%, respectively. Grade 1 GU toxicity was 24% at both 24 and 36 months; grade 2 toxicity was 0% at 24 months and 3% at 36 months. Overall, no grade 3 or greater toxicities have been seen. No biochemical failures have been seen to date. Posttreatment PSA values continued to decrease with time. At 24 months, 68% and 32% of patients had post-treatment PSA nadirs below 1.0 and 0.5, respectively; by 36 months, the same respective PSA nadirs were 78% and 33%. Conclusions: Preliminary analysis shows that hypofractionated proton therapy for low-risk prostate cancer, as delivered in this protocol, yields minimal toxicity and severe (≥ grade 3) GI or GU toxicity has not been seen. PSA reductions are consistent with previous reports at this time, albeit longer follow-up is necessary to fully define the role of hypofractionated protons in low-risk prostate cancer.