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

Eur Urol. 2011 Dec;60(6):1133-9. doi: 10.1016/j.eururo.2011.08.029. Epub 2011 Aug 22.

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.

MeSH terms

  • Aged
  • Androgen Antagonists / therapeutic use
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Chemotherapy, Adjuvant
  • Disease-Free Survival
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoadjuvant Therapy
  • Neoplasm Staging
  • New York City
  • Nomograms
  • Proportional Hazards Models
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms / immunology
  • Prostatic Neoplasms / mortality
  • Prostatic Neoplasms / radiotherapy*
  • Prostatic Neoplasms / secondary
  • Radiotherapy Dosage*
  • Radiotherapy, Conformal* / adverse effects
  • Radiotherapy, Conformal* / mortality
  • Radiotherapy, Intensity-Modulated* / adverse effects
  • Radiotherapy, Intensity-Modulated* / mortality
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome

Substances

  • Androgen Antagonists
  • Antineoplastic Agents, Hormonal
  • Prostate-Specific Antigen