A new proton therapy prostate readout from the large COMPPARE study suggests the two modern radiotherapy options produce similar early outcomes. Proton therapy and intensity-modulated radiation therapy (IMRT) tracked closely on toxicity, bowel side effects, and disease control at 2 and 3 years.

Nancy P. Mendenhall, MD, presented the data at the American Society of Clinical Oncology (ASCO) 2026 annual meeting in Chicago. Mendenhall is with the University of Florida College of Medicine in Jacksonville, Florida.

Why the proton therapy prostate study matters

Proton therapy cuts radiation dose to nontargeted tissues. That dose-sparing edge is the main pitch for using it over IMRT in localised prostate cancer.

But the field still lacks randomised evidence that proton therapy outperforms IMRT, the standard of care today. As use has crept up in US cancer centres, the field has needed real prospective comparison data.

The COMPPARE study tries to plug that gap.

How COMPPARE was set up

COMPPARE is a nonrandomized prospective study at 51 US centres. The team enrolled 2343 men with treatment-naive localised prostate cancer between 2018 and 2022.

• 1404 patients received proton therapy.
• 939 patients received IMRT.

The trial was pragmatic. Daily standard fractionation was allowed (1.8-2.1 Gy). Moderate hypofractionation was also allowed (2.4-3.1 Gy). Rectal spacers, used to cut radiation injury to nearby tissue, were left to the physician's choice. So was androgen deprivation therapy (ADT).

Outcomes tracked patient-reported bowel urgency and frequency. Grade 2 or worse gastrointestinal toxicity was logged at 2 years. Freedom from biochemical progression was tracked at 3 years. Median follow-up ran to 4 years.

Toxicity tracked closely between the two arms

After inverse probability weighting, bowel urgency scores did not differ between arms across the 2-year window. Bowel frequency scores told the same story.

Grade 2 or higher gastrointestinal toxicity rates at 2 years were almost identical in the proton therapy prostate cohorts:

• 5.2% with proton therapy.
• 5.6% with IMRT.

Those numbers sit at the low end of what radiotherapy series have shown in the past decade. The team credited the wider uptake of rectal spacers for the drop in rectum and bowel injury. They called the early outcomes "outstanding" with both modalities.

Disease control was nearly the same

The disease control signal mirrored the safety signal. In an exploratory analysis, 3-year freedom from biochemical progression was:

• 98% with proton therapy.
• 97.9% with IMRT.

That is as close to a tie as a cancer trial will produce. PSA outcomes did not favor one option.

What the authors concluded

The COMPPARE team did not crown a winner. The proton therapy prostate data support keeping both options on the table.

"Based on no significant early differences between patient-reported quality of life, toxicity, and freedom from PSA progression outcomes, both IMRT and [proton therapy] should be considered standard of care," the study authors wrote.

The team flagged a clear caveat. Long-term disease control, late toxicity, and secondary cancers will need longer follow-up. Four years is short for prostate cancer outcomes.

The proton therapy prostate trial was nonrandomized. That design can create selection bias. Other factors may shape how well the proton and IMRT cohorts can be compared.

The team used inverse probability weighting to adjust for baseline differences. That helps, but it does not fully replace random assignment. The early signal is informative, not definitive.

What radiation oncology teams should take from the proton therapy prostate data

For radiation oncology teams, the proton therapy prostate findings hit two practical notes. They back IMRT as a solid first-line option. They also leave room for proton therapy where it is clinically available.

Cost will keep mattering. Proton therapy costs more to deliver. If long-term toxicity and disease control match, payers will keep pushing back on routine proton use for localized prostate disease.

Coverage on Medigear.uk shows why urology and radiation oncology teams must track how the proton therapy prostate findings shape care.

Source: Originating coverage based on Medscape reporting on the COMPPARE study presented by Nancy P. Mendenhall, MD, of the University of Florida College of Medicine in Jacksonville, Florida, at the American Society of Clinical Oncology (ASCO) 2026 annual meeting in Chicago. Funded by the Patient-Centered Outcomes Research Institute (PCORI).