Dose-Escalated Intensity Modulated Radiation Therapy for Prostate Cancer: 15-Year Outcomes Data

Abstract

To report 15-year outcomes data for dose-escalated IMRT for localized prostate cancer (PC) by evaluating biochemical relapse, distant metastases (DM), overall survival, and long-term toxicity. A database search was conducted for the first cohort of patients treated at this institution with 81 or 86.4 Gy between 1996 and 1998 using IMRT. Toxicity data was scored according to the Common Terminology Criteria for Adverse Events Version 3.0. The median follow-up was 11.6 years (range 5 to 21 years). During this time, 301 patients were treated with 81 Gy (n = 269, 89%) or 86.4 Gy (n = 32, 11%). Patients were also analyzed by NCCN risk group, with 29% low risk (LR) patients, 49% intermediate risk (IR), and 22% high risk (HR). Late grade 3 gastrointestinal (GI) toxicity was seen in 3 patients (1.0%). All 3 cases were due to rectal bleeding requiring transfusion, and 1 required embolization. No grade 4 GI toxicity events occurred. Median time from RT to late grade 3 GI toxicity was 2.9 years, and 1 event occurred after 10 years. Late grade 3 and 4 genitourinary (GU) toxicity were seen in 6 (2.0%) and 1 (0.3%) patient, respectively. Grade 3 toxicities were due to stricture requiring procedural intervention or hematuria/cystitis requiring bladder irrigation/debridement. Grade 4 toxicity was due to persistent hematuria ultimately requiring cytectomy. Median time to late grade 3+ GU toxicity was 5.5 years, and 2 events occurred after 10 years. 38 (12.6%) had second primary malignancies (SPM) diagnosed after prostate RT, 8 (22%) of which were in-field malignancies including colorectal and bladder cancers and 1 case of pubic bone sarcoma. Median time from RT to all SPM and in-field SPM was 10 years. The 15-year PSA relapse-free survival was 76%, 65%, and 55% in the LR, IR, and HR groups, respectively. DM-free survival was 88%, 75%, and 63% for LR, IR, and HR patients. Prostate cancer-specific mortality was 1.9%, 7.1%, and 12.2% for LR, IR, and HR risk patients. This report represents the longest follow-up data set to our knowledge of patients treated with high-dose IMRT for PC. Our findings indicate that it is well tolerated with 1.0% and 2.3% incidence of long-term grade 3+ GI and GU toxicity, respectively. The cohort had excellent PC-specific survival.