Four-Year Outcomes From a Prospective Phase II Clinical Trial of Moderately Hypofractionated Proton Therapy for Localized Prostate Cancer

Int J Radiat Oncol Biol Phys. 2019 Nov 15;105(4):713-722. doi: 10.1016/j.ijrobp.2019.05.069. Epub 2019 Jun 11.

Abstract

Purpose: Moderately hypofractionated radiation therapy represents an effective treatment for localized prostate cancer (PC). Although large randomized trials have reported the efficacy of photon-based hypofractionated therapy, hypofractionated proton therapy (HFPT) has not been extensively studied. This study was performed to determine the clinical and patient-reported outcomes for patients with PC treated with HFPT.

Methods and materials: Between 2010 and 2017, 184 men were enrolled on a trial of 70 Gy in 28 fractions of HFPT for low- to intermediate-risk PC. Acute and late toxicity was evaluated using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Patient-reported outcomes were measured by International Prostate Symptom Score, International Index of Erectile Function Questionnaire, and Expanded Prostate Cancer Index Composite scores.

Results: Median follow-up was 49.2 months. Enrolled patients had low-risk (n = 18), favorable intermediate-risk (n = 78), and unfavorable intermediate-risk (n = 88) PC. Four-year rates of biochemical-clinical failure-free survival were 93.5% (95% confidence interval, 89%-98%), 94.4% (89%-100%), 92.5% (86%-100%), and 93.8% (88%-100%) in the overall group and the low-risk, favorable intermediate-risk, and unfavorable intermediate-risk cohorts, respectively (log-rank P > .4). The incidence of acute grade 2 or higher gastrointestinal (GI) and urologic toxicities were 3.8% and 12.5%, respectively. The 4-year incidence of late grade 2 or higher urologic and GI toxicity was 7.6% (4%-13%) and 13.6% (9%-20%), respectively. One late grade 3 GI toxicity was reported. All late toxicities were transient. Patient-reported International Prostate Symptom, International Index of Erectile Function, and Expanded Prostate Cancer Index Composite scores had no significant long-term changes after completion of HFPT (Supplementary Table 1, available at https://doi.org/10.1016/j.ijrobp.2019.05.069).

Conclusions: HFPT is associated with low rates of toxicity and does not appear to negatively affect 4-year patient reported urinary and bowel health. Further comparative analyses are warranted to better understand differences between proton and photon HFRT.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Androgen Antagonists / therapeutic use
  • Erectile Dysfunction / etiology
  • Follow-Up Studies
  • Health Surveys
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / blood
  • Patient Reported Outcome Measures
  • Prospective Studies
  • Prostate-Specific Antigen / blood
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / mortality
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / radiotherapy*
  • Proton Therapy / adverse effects
  • Proton Therapy / methods*
  • Radiation Dose Hypofractionation
  • Radiation Injuries / complications
  • Radiotherapy Planning, Computer-Assisted / methods
  • Rectal Diseases / etiology
  • Time Factors
  • Treatment Outcome
  • Urination Disorders / etiology

Substances

  • Androgen Antagonists
  • Prostate-Specific Antigen