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Summary We report long-term outcomes on 1002 patients treated to 8640 cGy for localized prostate cancer using IMRT. High dose-escalation results in excellent tumor control with minimal toxicity when implementing strict dose constraints. Dose-escalation beyond 80 Gy is feasible and safe, and should be considered for select men with localized prostate cancer. Purpose To report the long-term survival and toxicity outcomes with the use of high dose intensity modulated radiation therapy (IMRT) to 86.4 Gy for patients with localized prostate cancer. Materials and Methods Between August 1997 and December 2008, 1002 patients were treated to a dose of 86.4 Gy using a 5–7 field IMRT technique. Patients were stratified into prognostic risk groups based on the National Comprehensive Cancer Network risk classification criteria. Five hundred eighty-seven patients (59%) were treated with neoadjuvant and concurrent androgen deprivation therapy (ADT). The median follow-up for the entire cohort was 5.5 years (range, 1–14 yrs). Results For low-, intermediate- and high-risk groups the 7-year biochemical relapse-free survival outcomes were 98.8%, 85.6%, and 67.9% (p<0.001), and distant metastasis-free survival rates of 99.4%, 94.1%, and 82.0% (p<0.001), respectively. On multivariate analysis T-stage (p<0.001), Gleason score (p<0.001), and >50% of initial biopsy cores positive (p=0.001) were predictive for DM. No prostate cancer related deaths were observed in the low-risk group. The 7-year prostate cancer–specific mortality (PCSM) using competing risk analysis for intermediate- and high-risk groups was 3.3% and 8.1%, respectively (p=0.008). On multivariate analysis Gleason score (p=0.004), percent biopsy core positivity (p=0.003), and T-stage (p=0.033) were predictive for PCSM. Actuarial 7-year grade 2 or higher late gastrointestinal and genitourinary toxicities were 4.4% and 21.1%, respectively. Late grade 3 gastrointestinal and genitourinary toxicity was experienced by 7 patients (0.7%) and 22 patients (2.2%), respectively. Of the 427 men with full potency at baseline, 317 men (74%) retained sexual function at time of last follow-up. Conclusions This represents the largest cohort of patients treated with high dose radiation to 86.4 Gy using IMRT for localized prostate cancer with the longest follow-up to date. Our findings indicate that this treatment results in excellent clinical outcomes with acceptable toxicity.

Background In vitro data and early clinical results suggest that metformin has desirable antineoplastic effects and has a theoretical benefit on castration-resistant prostate cancer (CRPC). Objective To determine whether the use of metformin would be associated with improved clinical outcomes and a reduction in the development of CRPC. Design, setting, and participants Data from 2901 consecutive patients (157 metformin, 162 diabetic non-metformin, and 2582 nondiabetic) with localized prostate cancer treated with external-beam radiation therapy from 1992 to 2008 were collected from a single institution in the United States. Intervention Use of metformin in localized prostate cancer. Outcome measurements and statistical analysis Univariate and multivariate regression models utilizing k-sample, Fine and Gray, Cox regression, log-rank, and Kaplan-Meier methods to assess prostate-specific antigen-recurrence-free survival (PSA-RFS), distant metastases-free survival (DMFS), prostate cancer–specific mortality (PCSM), overall survival (OS), and development of CRPC. Results and limitations With a median follow-up of 8.7 yr, the 10-yr actuarial rates for metformin, diabetic non-metformin, and nondiabetic patients for PCSM were 2.7%, 21.9%, and 8.2% (log-rank p ≤ 0.001), respectively. Metformin use independently predicted (correcting for PSA, T stage, Gleason score, age, diabetic status, and androgen-deprivation therapy use) improvement in all outcomes compared with the diabetic non-metformin group; PSA-RFS (hazard ratio [HR]: 1.99 [1.24–3.18]; p = 0.004), DMFS (adjusted HR: 3.68 [1.78–7.62]; p < 0.001), and PCSM (HR: 5.15 [1.53–17.35]; p = 0.008). Metformin use was also independently associated with a decrease in the development of CRPC in patients experiencing biochemical failure compared with diabetic non-metformin patients (odds ratio: 14.81 [1.83–119.89]; p = 0.01). The retrospective study design was the primary limitation of the study. Conclusions To our knowledge, our results are the first clinical data to indicate that metformin use may improve PSA-RFS, DMFS, PCSM, OS, and reduce the development of CRPC in prostate cancer patients. Further validation of metformin's potential benefits is warranted.

BACKGROUND. The authors investigated long‐term tumor control and toxicity outcomes after high‐dose, intensity‐modulated radiation therapy (IMRT) in patients who had clinically localized prostate cancer. METHODS. Between April 1996 and January 1998, 170 patients received 81 gray (Gy) using a 5‐field IMRT technique. Patients were classified according to the National Comprehensive Cancer Network‐defined risk groups. Toxicity data were scored according to the Common Terminology Criteria for Adverse Events Version 3.0. Freedom from biochemical relapse, distant metastases, and cause‐specific survival outcomes were calculated. The median follow‐up was 99 months. RESULTS. The 10‐year actuarial prostate‐specific antigen relapse‐free survival rates were 81% for the low‐risk group, 78% for the intermediate‐risk group, and 62% for the high‐risk group; the 10‐year distant metastases–free rates were 100%, 94%, and 90%, respectively; and the 10‐year cause‐specific mortality rates were 0%, 3%, and 14%, respectively. The 10‐year likelihood of developing grade 2 and 3 late genitourinary toxicity was 11% and 5%, respectively; and the 10‐year likelihood of developing grade 2 and 3 late gastrointestinal toxicity was 2% and 1%, respectively. No grade 4 toxicities were observed. CONCLUSIONS. To the authors' knowledge, this report represents the longest followed cohort of patients who received high‐dose radiation levels of 81 Gy using IMRT for localized prostate cancer. The findings indicated that high‐dose IMRT is well tolerated and is associated with excellent long‐term tumor‐control outcomes in patients with localized prostate cancer Cancer 2011. © 2010 American Cancer Society.