Proton Therapy for Localized Prostate Cancer: Long-term Results in 2,021 Patients.

Abstract: Purpose While controversial, proton therapy has been used to treat localized prostate cancer over the past two decades. The purpose of this study is to examine the long term efficacy and toxicity of proton therapy for localized prostate cancer. Methods and Materials This was a retrospective observational study of 2,021 patients from 2003-2014 at a single institution. Patients were classified using the risk groups defined by the National Comprehensive Cancer Network guidelines, version 4.2019. Ninety-eight percent of the patients received 74 Gy (relative biological effectiveness) in 37 fractions. Fifty-one and six percent of the patients received neoadjuvant and adjuvant androgen deprivation therapy, respectively. The outcomes were the time of freedom from biochemical relapse and the time to late toxicity by the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. The outcomes were estimated with the Kaplan-Meier method and were also analyzed using multivariable Cox proportional hazards models. Results The median follow-up period was 84 months (IQR, 60-110). The 5- and 10-year freedom from biochemical relapse rates were 100/100%, 99/88%, 93/86%, 90/79%, 88/68%, and 76/63% for the very low, low, favorable intermediate, unfavorable intermediate, high, and very high risk groups, respectively. Patients with higher risk experienced biochemical relapse after shorter periods. The 5-year rates of grade 2 or higher late genitourinary and gastrointestinal toxicity were 2.2% and 4.0%, respectively. Based on the results of multivariable analyses, younger patients more often experienced biochemical relapse. Conclusions This study demonstrates the favorable biochemical controls of proton therapy even in advanced localized prostate cancer patients with a low incidence of late toxicities, supporting the feasibility of conducting prospective clinical trials. The risk groups defined by the NCCN guidelines, version 4.2019, are useful to classify patients with localized prostate cancer. Our findings might suggest the necessity to develop a treatment strategy that takes into account the patient's age.