Long-Term Outcomes of Proton Therapy for Prostate Cancer in Japan: Retrospective Analysis of a Multi-institutional Survey

Abstract

Proton therapy (PT) is spreading worldwide as a new treatment modality. Although PT provides a more focused dose distribution on the tumor compared with X-ray therapy, there remains much controversy about its routine use in prostate cancer treatment. This is the first multi-institutional retrospective survey of the long-term outcomes of PT for prostate cancer in Japan. This retrospective analysis comprises prostate cancer patients treated with PT at 7 centers between January 2008 and December 2011 and was approved by each Institutional Review Board. The NCCN classification was used. The biochemical relapse free survival (bRFS) was based on the Phoenix definition (nadir + 2.0 ng/mL). The rates of bRFS, overall survival (OS) and incidence of late gastrointestinal (GI) and genitourinary (GU) toxicities were estimated using the Kaplan-Meier methods. Toxicities were evaluated with the Common Terminology Criteria for Adverse Events version 4.0. The inclusion criteria for this analysis were as follows: (1) histologically confirmed prostate cancer, (2) no lymph node and distant metastasis, (3) Japanese men, (4) no prior radiotherapy, (5) no castration-resistant prostate cancer, (6) minimum follow-up of 6 months for surviving patients, and (7) written informed consent. The very-high risk group based on NCCN criteria was included in the high-risk group. The total number of prostate cancer patients in all institutions during this period was 1,302 and 11 patients were excluded because of above criteria. Therefore, 1,291 patients were analyzed. The number of patients in the low-risk, intermediate-risk, and high-risk groups were 215, 520, and 556, respectively. The median follow-up period of surviving patients was 69 months (range: 7-107). In total, 98.8% of patients were treated using conventional fractionation (1.8-2.0GyE) schedule (70-82 GyE/35-41 Fr) and 1.2% of patients were treated by hypofractionation schedule (63-66 GyE/ 21-22 Fr); 58.5% and 21.5 %of patients received neoadjuvant and adjuvant androgen deprivation therapy, respectively. The 5-year rates of bRFS and OS in the low-risk, intermediate-risk, and high-risk patients were 97.0%, 91.1%, 83.1% for bRFS, and 98.4%, 96.8%, 95.2% for OS, respectively. T classification, Gleason score, and NCCN classification were significant prognostic factors for bRFS in multivariate analysis. The incidence of grade 2 late GI and GU toxicities were 3.6% and 2.6%, retrospectively, but grade 3 toxicities were observed only 6 and 4 patients, respectively. This retrospective analysis of a multi-institutional survey suggested that PT is favorable and well tolerated for prostate cancer. Based on this result, multi-institutional prospective clinical trial for patients with intermediate risk group will be started to define its role in the treatment of prostate cancer in Japan.