Dose Escalation for Prostate Cancer Radiotherapy: Predictors of Long-Term Biochemical Tumor Control and Distant Metastases-Free Survival 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. (C) 2011 European Association of Urology. Published by Elsevier B. V. All rights reserved.