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


Authors: Zelefsky, M. J.; Pei, X.; Chou, J. F.; Schechter, M.; Kollmeier, M.; Cox, B.; Yamada, Y.; Fidaleo, A.; Sperling, D.; Happersett, L.; Zhang, Z.
Article Title: Dose escalation for prostate cancer radiotherapy: Predictors of long-term biochemical tumor control and distant metastases-free survival outcomes
Abstract: 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. © 2011 European Association of Urology.
Keywords: cancer survival; treatment outcome; aged; disease-free survival; middle aged; retrospective studies; major clinical study; overall survival; cancer radiotherapy; disease free survival; radiation dose; chemotherapy, adjuvant; neoadjuvant therapy; cancer staging; neoplasm staging; prostate specific antigen; proportional hazards models; radiotherapy dosage; risk factors; tumor biopsy; retrospective study; distant metastasis; high risk patient; time factors; risk assessment; cancer hormone therapy; prostate cancer; gleason score; prostate-specific antigen; prostatic neoplasms; radiotherapy, intensity-modulated; nomograms; androgen antagonists; new york city; predictor variable; cancer relapse; radiotherapy, conformal; external beam radiotherapy; antineoplastic agents, hormonal; cancer control; androgen deprivation therapy; nomogram; kaplan-meier estimate; psa relapse-free survival; dose escalation
Journal Title: European Urology
Volume: 60
Issue: 6
ISSN: 0302-2838
Publisher: Elsevier Science, Inc.  
Date Published: 2011-12-01
Start Page: 1133
End Page: 1139
Language: English
DOI: 10.1016/j.eururo.2011.08.029
PROVIDER: scopus
PUBMED: 21889832
PMCID: PMC4037155
DOI/URL:
Notes: --- - "Cited By (since 1996): 1" - "Export Date: 9 December 2011" - "CODEN: EUURA" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Joanne Fu-Lou Chou
    153 Chou
  2. Zhigang Zhang
    240 Zhang
  3. Brett Wayne Cox
    62 Cox
  4. Michael J Zelefsky
    615 Zelefsky
  5. Yoshiya Yamada
    357 Yamada
  6. Marisa A Kollmeier
    144 Kollmeier
  7. Xin Pei
    98 Pei