Dose escalation for prostate cancer radiotherapy: predictors of long-term biochemical tumor control and distant metastases-free survival outcomes

Michael J Zelefsky, Xin Pei, Joanne F Chou, Michael Schechter, Marisa Kollmeier, Brett Cox, Yoshiya Yamada, Anthony Fidaleo, Dahlia Sperling, Laura Happersett, Zhigang Zhang
European Urology 2011, 60 (6): 1133-9

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.

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