External Beam Radiation Therapy (EBRT) and High-Dose-Rate (HDR) Brachytherapy for Intermediate and High-Risk Prostate Cancer: The Impact of EBRT Volume

Int J Radiat Oncol Biol Phys. 2020 Mar 1;106(3):525-533. doi: 10.1016/j.ijrobp.2019.09.044. Epub 2019 Oct 11.

Abstract

Purpose: Whole pelvis radiation therapy (WPRT) may improve clinical outcomes over prostate-only radiation therapy (PORT) in high-risk prostate cancer patients by sterilization of micrometastatic nodal disease, provided there is optimal control of the primary site.

Methods and materials: A prospective multicenter cohort study of eligible patients (stage ≥T2c, Gleason score ≥7 or presenting prostate-specific antigen ≥10) treated between 2009 and 2013 were enrolled in a United Kingdom national protocol delivering combined external beam radiation therapy and high-dose-rate brachytherapy. Centers elected to deliver WPRT, 46 Gy in 23 fractions or PORT 37.5 Gy in 15 fractions with 15 Gy single dose high-dose-rate brachytherapy. The primary endpoint was biochemical progression-free survival (bPFS). Secondary endpoints were overall survival, genitourinary, and gastrointestinal toxicity. This was not a randomized comparison and was subject to bias; the findings are therefore hypothesis generating, but not conclusive.

Results: Eight hundred and twelve patients were entered; 401 received WPRT and 411 received PORT. With a median follow-up of 4.7 years, 5-year bPFS rates for WPRT versus PORT arms were 89% versus 81% (P = .007) for all patients and 84% versus 77% (P = .001) for high-risk patients. Differences in bPFS remained significant after accounting for Gleason score, presenting prostate-specific antigen, T stage, and androgen deprivation therapy duration as covariates. There was no difference in overall survival. The overall post treatment toxicities across both cohorts were low with no greater than 1.5% of ≥grade 3 toxicities at any follow-up time point. WPRT increased both prevalence and cumulative incidence of acute genitourinary toxicity (P = .004) and acute gastrointestinal toxicity (P = .003). No difference in late radiation toxicity was observed.

Conclusions: A significant improvement in 5-year bPFS was seen in intermediate and high-risk prostate cancer treated with WPRT compared with PORT in a combined external beam radiation therapy and brachytherapy schedule with no increase in late radiation toxicity.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Androgen Antagonists / therapeutic use
  • Brachytherapy / adverse effects
  • Brachytherapy / methods*
  • Brachytherapy / statistics & numerical data
  • Cohort Studies
  • Databases, Factual
  • Dose Fractionation, Radiation
  • Follow-Up Studies
  • Humans
  • Kallikreins / blood
  • Lymphatic Metastasis
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Micrometastasis / radiotherapy*
  • Progression-Free Survival
  • Prospective Studies
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / mortality
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / radiotherapy*
  • Radiotherapy, Conformal* / statistics & numerical data
  • Radiotherapy, Intensity-Modulated / statistics & numerical data
  • United Kingdom

Substances

  • Androgen Antagonists
  • KLK3 protein, human
  • Kallikreins
  • Prostate-Specific Antigen