Severe Late Toxicities (Grade 3-5) With 13 Years of Follow-up after Hypofractionated Postprostatectomy Radiotherapy

Int J Radiat Oncol Biol Phys. 2025 Oct 1;123(2):374-380. doi: 10.1016/j.ijrobp.2025.04.002. Epub 2025 Apr 12.

Abstract

Background: We previously reported outcomes after hypofractionated postprostatectomy radiotherapy (HYPORT) with a median follow-up of 32 months. This was a primary citation supporting the fractionation selection for NRG-GU003, which showed noninferiority of HYPORT versus conventional radiotherapy.

Methods: One hundred sixty-one consecutive patients with biochemically recurrent prostate cancer after prostatectomy underwent HYPORT from 2003 to 2013 at a single academic institution using image guided intensity modulated radiation therapy, with the majority (154 of 161) receiving 65 Gy in 26 fractions.

Results: Median follow-up was 13.5 years. Forty-four patients (27.3%) experienced 58 late grade 3 to 5 toxicities (LTOX3) a median of 106 months after HYPORT. Fifty-five of 58 LTOX3 were genitourinary related. Higher-grade toxicities included 6 cystectomies and 3 deaths. At 2 years, only 2 patients had experienced an LTOX3. At 15 years, overall survival was 70%, freedom from biochemical recurrence was 52%, and the risk of LTOX3 was 34%.

Conclusions: Long follow-up is needed to fully capture severe toxicities after dose-escalated HYPORT. This should be considered prior to the broad adoption of similar regimens for this patient population with long survival potential.

MeSH terms

  • Aged
  • Cystectomy / statistics & numerical data
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local* / blood
  • Neoplasm Recurrence, Local* / mortality
  • Neoplasm Recurrence, Local* / radiotherapy
  • Prostate-Specific Antigen / blood
  • Prostatectomy
  • Prostatic Neoplasms* / blood
  • Prostatic Neoplasms* / mortality
  • Prostatic Neoplasms* / pathology
  • Prostatic Neoplasms* / radiotherapy
  • Prostatic Neoplasms* / surgery
  • Radiation Dose Hypofractionation*
  • Radiation Injuries* / mortality
  • Radiation Injuries* / pathology
  • Radiotherapy, Image-Guided / adverse effects
  • Radiotherapy, Image-Guided / methods
  • Radiotherapy, Intensity-Modulated* / adverse effects
  • Radiotherapy, Intensity-Modulated* / methods
  • Time Factors

Substances

  • Prostate-Specific Antigen