Nearly ten years after the launch of the COMPPARE study at the UF Health Proton Therapy Institute, its insights are helping to define the future of prostate cancer treatment.
In December 2017, COMPPARE’s Principal Investigator Nancy P. Mendenhall, MD, FACR, FASTRO and her team were awarded a five-year, $11.9 million grant by the Patient-Centered Outcomes Research Institute (PCORI) to directly compare the potential benefits and harms of proton therapy to standard radiation therapy when treating prostate cancer.
Five years later, COMPPARE, or the COMparative Study of Outcomes with Proton and Photon RAdiation in Prostate CancEr, had enrolled a total of 2,524 men with localized prostate cancer from 51 institutions across the United States. Now the study’s investigators are sharing new findings and preparing benchmark publications that will impact clinical practice worldwide.
COMPPARE at ASCO
COMPPARE reached an important milestone at the 2026 ASCO Annual Meeting May 31, 2026, when Dr. Mendenhall presented the study’s first major clinical outcomes: Two- and three-year results indicated no significant early differences between the modalities in patient-reported quality of life, toxicity, and progression. In addition, the study found that the use of temporary rectal spacers significantly reduced rectal and bowel toxicity in both photon and proton radiation patients.
“More follow-up is needed to assess important long-term outcomes like disease control, late effects, and development of secondary cancers,” remarked Dr. Mendenhall at ASCO. Visit the UF Health Cancer Institute website for details about her talk.
COMPPARE at PTCOG
On the heels of the ASCO meeting, COMPPARE took center stage at the Particle Therapy Co-Operative Group’s (PTCOG) 64th Annual Conference in June and was selected to be part of the American Society for Radiation Oncology (ASTRO) Scientific Program “Trials Shaping Prostate Cancer Care”, slated to take place during its annual meeting in September.
Dr. Mendenhall presented “Proton Therapy Practice Patterns in Prostate Cancer on the COMPPARE Clinical Trial” at PTCOG 64, which examined how proton therapy was delivered across the 29 proton therapy centers participating in the study, providing a comprehensive snapshot of proton therapy practice in the United States.
Using data from 1,438 evaluable proton therapy patients treated between 2018 and 2022, researchers evaluated treatment planning and delivery approaches across participating institutions, documenting how advances in proton therapy technology have been incorporated into routine patient care.
Among the findings, pencil beam scanning (PBS) centers were found to be more likely to use moderate hypofractionation than centers using only double-scatter technology, more frequently treated multiple fields per day, and more likely to include pelvic lymph nodes in high-risk patients. Overall practice patterns closely aligned with COMPPARE protocol recommendations and National Comprehensive Cancer Network (NCCN) guidelines.
COMPPARE at ASTRO
Dr. Mendenhall continued to discuss clinical results at ASTRO on September 27, 2026, in Boston, MA. Her presentation, “Three-Year Outcomes of a Prospective Randomized Trial of Moderately Hypofractionated and Standard Fractionated Proton Therapy,” reported the results of the study’s randomized arm, which compares standard fractionation of 78 Gy(RBE) delivered in 39 treatments with moderately hypofractionated proton therapy of 60 Gy(RBE) delivered in 20 treatments.
Within COMPPARE, 600 patients were randomized equally between these treatment approaches, creating one of the largest prospective randomized studies evaluating hypofractionated proton therapy for localized prostate cancer.
The ASTRO presentation provided important three-year data evaluating disease control, treatment-related toxicity, and patient-reported quality-of-life outcomes, helping clinicians better understand whether shorter treatment courses can achieve outcomes comparable to conventional schedules, and reducing the treatment burden for patients.
COMPPARE in the Red Journal
Building on this momentum, the article “Can Engagement Aid in Design and Accrual on Clinical Trials Observations from COMPPARE” was published in press on July 29, 2026, in the prestigious International Journal of Radiation Oncology • Biology • Physics (Red Journal). It is expected to encourage the broader oncology community to embrace engagement as an indispensable, evidence-based research strategy.
The Red Journal report proposes that patients are more likely to participate in clinical research when studies are designed with their needs in mind. The article also outlines how COMPPARE researchers worked closely with patients prior to the study’s launch to learn what mattered most to them.
Participant feedback shaped all aspects of COMPPARE, and its patient-centered approach resulted in successful enrollment across the United States despite the impact of COVID on recruitment during that time. Importantly, the study exceeded its goal for enrolling Black participants. These findings suggest that engaging patients early in research planning can enhance their involvement and promote outcomes that are relevant to participants.
As long-term follow-up, presentations, and publications continue, COMPPARE will undoubtedly help physicians personalize treatment and empower prostate cancer patients to make more informed decisions about their care.
