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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.

Background The management of biochemical failure (BF) following external beam radiotherapy (EBRT) for prostate cancer is controversial, due to both the heterogeneous disease course following a BF and a lack of clinical trials in this setting. Objective We sought to characterize the natural history and predictors of outcome for patients experiencing BF in a large cohort of men with localized prostate cancer undergoing definitive dose-escalated EBRT. Design, setting, and participants This retrospective analysis included 2694 patients with localized prostate cancer treated with EBRT at a large academic center. Of these, 609 experienced BF, defined as prostate-specific antigen (PSA) nadir + 2 ng/ml. The median follow-up was 83 mo for all patients and 122 mo for BF patients. Intervention(s) All patients received EBRT at doses of 75.6–86.4 Gy. Outcome measurements and statistical analysis The primary objective of this study was to determine predictors of distant progression at the time of BF. Cox proportional hazards models were used in univariate and multivariate analyses of distant metastases (DM), and a competing risks method was used to analyze prostate cancer–specific mortality (PCSM). Results and limitations From the date of BF, the median times to DM and PCSM mortality were 5.4 yr and 10.5 yr, respectively. Shorter posttreatment PSA doubling time, a higher initial clinical tumor stage, a higher pretreatment Gleason score, and a shorter interval from the end of radiotherapy to BF were independent predictors for clinical progression following BF. Patients with two of these risk factors had a significantly higher incidence of DM and PCSM following BF than those with zero or one risk factor. The main limitations of this study are its retrospective nature and heterogeneous salvage interventions. Conclusions Clinical and pathologic factors can help identify patients at high risk of clinical progression following BF. Patient summary In this report, we look at predictors of outcome for patients with prostate cancer recurrence, as determined by prostate-specific antigen (PSA) levels, following radiation treatment. We found that the approximate median times to distant metastasis and death from prostate cancer for patients in this situation were 5 yr and 10 yr, respectively. Furthermore, we found that patients with a rapid increase in PSA levels following treatment, a short time to PSA recurrence, invasion of extraprostatic organs, or a high Gleason score had worse outcomes.

Background Higher radiation dose levels have been shown to be associated with improved tumor-control outcomes in localized prostate cancer (PCa) patients. Objective Identify predictors of biochemical tumor control and distant metastases–free survival (DMFS) outcomes for patients with clinically localized PCa treated with conformal external-beam radiotherapy (RT) as well as present an updated nomogram predicting long-term biochemical tumor control after RT. Design, setting, and participants This retrospective analysis comprised 2551 patients with clinical stages T1–T3 PCa. Median follow-up was 8 yr, extending >20 yr. Intervention Prescription doses ranged from 64.8 to 86.4 Gy. A total of 1249 patients (49%) were treated with neoadjuvant and concurrent androgen-deprivation therapy (ADT); median duration of ADT was 6 mo. Measurements A proportional hazards regression model predicting the probability of biochemical relapse and distant metastases after RT included pretreatment prostate-specific antigen (PSA) level, clinical stage, biopsy Gleason sum, ADT use, and radiation dose. A nomogram predicting the probability of biochemical relapse after RT was developed. Results and limitations Radiation dose was one of the important predictors of long-term biochemical tumor control. Dose levels <70.2 Gy and 70.2–79.2 Gy were associated with 2.3-and 1.3-fold increased risks of PSA relapse compared with higher doses. Improved PSA relapse– free survival (PSA-RFS) outcomes with higher doses were observed for all risk groups. Use of ADT, especially for intermediate- and high-risk patients, was associated with significantly improved biochemical tumor-control outcomes. A nomogram predicting PSA-RFS was generated and was associated with a concordance index of 0.67. T stage, Gleason score, pretreatment PSA, ADT use, and higher radiation doses were also noted to be significant predictors of improved DMFS outcomes. Conclusions Higher radiation dose levels were consistently associated with improved biochemical control outcomes and reduction in distant metastases. The use of short-course ADT in conjunction with RT improved long-term PSA-RFS and DMFS in intermediate- and high-risk patients; however, an overall survival advantage was not observed.