A Japanese Multi-Institutional Phase II Study of Moderate Hypofractionated Intensity-Modulated Radiotherapy With Image-Guided Technique for Prostate Cancer.

PURPOSE/OBJECTIVE(S) While the non-inferiority of hypofractionation (HF) to conventional fractionation for prostate cancer had been investigated in some randomized clinical trials, we started a multi-institutional phase II study to confirm the safety with the efficacy of HF intensity-modulated radiotherapy (IMRT) with image-guided technique for Japanese patients. MATERIALS/METHODS Eligibility criteria of the study included: pathologically proven adenocarcinoma; low or intermediate risk (cT1-T2c, PSA ≤ 20 and Gleason score (GS) ≤ 7) or high risk having one of the following factors, cT3a, PSA > 20/ ≤ 30, or GS = 8/9; cN0M0; age 50-80; performance status (PS) 0-1; written informed consent. HF IMRT with 70 Gy/28 fr (2.5 Gy/fr) was performed. The position of the prostate gland or inserted fiducial markers was verified with a full bladder before each treatment. Neoadjuvant hormonal therapy (HT) for 4-8 months was allowed for patients with intermediate or high risk. The GTV was defined as the prostate (+ extracapsular invasion for cT3a). The CTV was defined as the GTV for low risk, and the GTV plus proximal seminal vesicles for intermediate and high risk. The PTV was defined as the CTV plus 4-8 mm margins for organ motions and set-up errors. The bladder, rectum, small and large intestines, and femoral heads were defined as the organs at risk (OAR) as the solid organ. The dose prescription was D50% for the PTV, with Dmax ≤ 105% and Dmin ≥ 95%. The dose constraints for OARs were defined as follows: bladder V70/V65/V60/V55, 15%/25%/35%/50%; rectum V65/V55/V50/V45, 15%/25%/35%/50%; small intestine V55 < 0.5 cc; large intestine V60 < 0.5 cc; femoral heads Vmax ≤ 50 Gy. The primary endpoint was the incidence of late toxicities at 5 years. The secondary endpoints were the incidence of acute toxicities, biochemical failure-free, clinical failure-free, and overall survivals at 5 years. The sample size was calculated to 130 patients using alpha/beta errors of 0.05/0.2, with the threshold/expectation values of ≥ grade 2 late toxicities as 15%/7%. RESULTS From Jul/2012 to Oct/2014, 134 patients from 20 institutions were registered. Patients and tumor characteristics were as follows: median age 71 (54 - 79); cT1c/T2a/T2b/T2c/T3a, 53/50/7/19/5; GS 6/7/8/9, 32/80/16/6; median pretreatment PSA 9.0 ng/ml (3.15 - 28.6); low/intermediate/high risk, 20 (15%)/80 (60%)/34 (25%); PS 0/1, 67/67. HT was used for 121 patients (90%). The median follow-up time was 5.16 years. The incidences of grade 2/ ≥ 3 gastrointestinal and genitourinary late toxicities at 5 years (primary endpoint) were 5.3%/0% and 5.3%/0%, respectively. The corresponding figures of acute toxicities were 3.8%/0% and 14.5%/0%, respectively. The biochemical failure-free, clinical failure-free, and overall survivals at 5 years were 90.4%, 93.8%, and 94.5%, respectively. CONCLUSION The primary endpoint was met, and the safety and efficacy of HF IMRT was confirmed in this trial, and accepted as one of the standard of care for Japanese patients with prostate cancer.