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TOPLINE:

Proton therapy reduces radiation to nontargeted tissues, but for men with localized prostate cancer that may not translate to better outcomes, according to early results from the large prospective COMPPARE study.

METHODOLOGY:

• Proton therapy curbs radiation doses to nontargeted tissues and is considered a promising way to reduce radiotherapy toxicity. Although proton therapy is gaining traction as a treatment for prostate cancer, there is no randomized evidence that it beats the current standard of care, intensity-modulated radiation therapy (IMRT).
• The COMPPARE study is a nonrandomized prospective study at 51 US centers involving 2343 patients with treatment-naive localized prostate cancer. Patients were enrolled between 2018 and 2022, with 1404 receiving proton therapy and 939 receiving IMRT.
• Treatment was pragmatic, allowing daily standard fractionation (1.8-2.1 Gy) and moderate hypofractionation (2.4-3.1 Gy), with rectal spacers to reduce radiation injury used at physician discretion. Use of androgen deprivation therapy was also physician-directed.
• Outcomes included patient-reported bowel urgency/frequency and grade 2 or worse gastrointestinal toxicity at 2 years and freedom from biochemical progression at 3 years. Median follow-up duration was 4 years.

TAKEAWAY:

• After inverse probability weighting, there was no significant difference in bowel urgency scores or bowel frequency scores between the proton therapy and IMRT groups at any point up to the 2-year mark.
• Similarly, the 2-year cumulative incidence of grade 2 or higher gastrointestinal toxicity was virtually the same in the two groups: 5.2% with proton therapy and 5.6% with IMRT.
• Disease control also appeared nearly identical. In an exploratory analysis, 3-year freedom from biochemical progression was 98% with proton therapy and 97.9% with IMRT.
• According to the researchers, current use of rectal spacers has substantially decreased radiation-induced injury to the rectum and bowel, leading to “outstanding” early outcomes with both radiotherapy modalities.

IN PRACTICE:

“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 concluded. However, they cautioned, assessment of long-term disease control, late toxicity, and secondary malignancy will require longer follow-up.

SOURCE:

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

LIMITATIONS:

The study was nonrandomized, which may introduce selection bias and confounding factors affecting the comparability of the proton therapy and IMRT cohorts, despite the use of inverse probability weighting to adjust for baseline differences.

DISCLOSURES:

The Patient-Centered Outcomes Research Institute funded the study. Several co-authors reported financial relationships with various pharmaceutical and radiotherapy technology companies.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.