A Prospective Comparison Addresses a Persistent Evidence Gap

Proton therapy (PT) can reduce radiation exposure to nontarget tissues, a dosimetric advantage that has made it an appealing option for localized prostate cancer. However, prospective comparative-effectiveness data have been limited, and less than 2% of patients with prostate cancer who receive radiation are treated with PT. The COMPPARE study was designed to compare PT with photon-based intensity-modulated radiation therapy (IMRT), focusing on quality of life, toxicity, and disease control.

The nonrandomized, prospective study enrolled 2524 patients at 51 PT and IMRT centers from July 2018 through October 2022. Eligible participants had nonmetastatic prostate cancer, excluding very-high-risk disease. The study accrued approximately 1500 patients to the proton cohort and 1000 to the photon cohort. The median age was 69 years; most patients had Gleason 6/7 disease, and approximately three-quarters received a rectal spacer. Analyses used inverse propensity weighting to address prespecified differences between treatment groups.

Early Outcomes Were Comparable Across Modalities

At 2 years, the prespecified comparisons did not show statistically significant differences between PT and IMRT. Patient-reported bowel urgency occurred in 5.7% of patients receiving PT and 6.0% receiving IMRT (P=.28), while bowel frequency was reported in 3.5% and 4.0%, respectively (P=.43). Grade 2 or higher gastrointestinal toxicity was similarly low, at 5.2% with PT and 5.6% with IMRT (P=.60).

Early disease-control findings were also closely aligned. Freedom from disease progression at 3 years was 98.0% with PT and 97.9% with IMRT (P=.90).

Rectal Spacers May Matter More Than Radiation Modality

A notable analysis evaluated the association between rectal spacer use and 2-year grade 2 or higher gastrointestinal toxicity. Toxicity rates were lower among patients who received a spacer, regardless of radiation modality: 4.4% with IMRT plus a spacer and 4.7% with PT plus a spacer. Without a spacer, rates were 7.2% with IMRT and 8.7% with PT. The overall comparison was statistically significant (P=.009), reinforcing the potential importance of contemporary rectal-sparing strategies in reducing treatment-related bowel injury.

Clinical Takeaway

At early follow-up, PT and photon-based IMRT produced similarly favorable bowel, gastrointestinal toxicity, and disease-control outcomes. Longer follow-up is needed for late toxicity, secondary malignancy, and durable disease control.

Sources

Mendenhall NP, Bryant CM, Katz AJ, et al. Early results of COMPPARE, a prospective comparison of outcomes with proton and photon radiation in prostate cancer. Presented at: 2026 American Society of Clinical Oncology Annual Meeting; May 31, 2026.

UroToday-GU Oncology Today. ASCO 2026: Early Results of COMPPARE, a Prospective Comparison of Outcomes with Proton and Photon Radiation in Prostate Cancer.
www.urotoday.com/conference-highlights/asco-2026/asco-2026-prostate-cancer/169534-asco-2026-lba5012-early-results-of-comppare-a-prospective-comparison-of-outcomes-with-proton-and-photon-radiation-in-prostate-cancer.html