Major clinical trial pits proton versus photon radiotherapy in prostate cancer


The national 3000-patient COMPPARE trial, which is examining outcomes with proton versus photon radiotherapy in prostate cancer, continues its robust enrollment at more than 50 clinical sites.1

Both forms of therapy are considered standard of care in prostate cancer; however, some data suggest that proton therapy may offer a safer alternative without sacrificing efficacy.2 The safety difference may arise because while photon therapy delivers X-rays that go through the tumor, potentially damaging nearby healthy tissue, proton therapy transmits proton particles that stop directly at the tumor, sparing healthy cells.

The open-label, nonrandomized, parallel assignment COMPPARE study (NCT03561220) is enrolling patients with adenocarcinoma of the prostate who have localized disease based on a composite of biopsy, PSA, clinical stage, Gleason score, and digital rectal exam.3 Prior treatment for prostate cancer—other than androgen-deprivation therapy per NCCN guidelines—is not allowed. Patients are also not eligible if they have metastatic disease, very high-risk prostate cancer per NCCN guidelines and joint AUA/ASTRO/SUO guidelines, or any prior prostate surgical procedure.

The global aim of the COMPPARE trial is to determine whether proton therapy or radiation therapy is more effective in terms of cure rates, side effects, and quality of life for patients with localized prostate cancer. There is also an embedded randomized trial in which patients assigned to proton therapy can choose to participate. The embedded analysis is comparing standard proton therapy in hypofractionated proton therapy.

The primary study end point is bowel, urinary, and sexual dysfunction Expanded Prostate Cancer Index Composite (EPIC) domain scores. Secondary end points include grade 2 or higher toxicity for each adverse event assessed by CTCAE, grade 2 or higher toxicity for each adverse event assessed by PRO-CTCAE, and freedom from biochemical progression using PSA results. 

The targeted enrollment for the trial is 3000 patients. At the latest study update in February 2021, it was reported that 1210 patients had enrolled. Data are accrued through patients answering brief surveys for 3 years or more.4 The estimated primary completion date is March 1, 2023.

David Marshall, MD, a radiation oncologist and principal investigator at MUSC Hollings Cancer Center, one of the sites of the trial, commented in a recent press release on his center’s participation in the study.1

“The reason we like this trial at Hollings is because it doesn’t change our patients’ course of treatment. They can still choose how they get treated, and they’re able to help future patients determine the best, most cost-effective way to get treated,” said Marshall. “It’s also important for our community to participate in this clinical trial so that we can set the appropriate standard of care for our own patient population, which includes minorities who historically have not been appropriately represented in clinical trials.”

Regarding the importance of the trial in the prostate cancer paradigm overall, Marshall said, “Around 200,000 men are diagnosed with prostate cancer every year in the United States, and somewhere between 15% and 20% of those patients will eventually die of their disease. We’re going to learn a lot from this trial that can help us continue to improve outcomes for these men going forward.”


1. Trial to compare radiation therapies for treating prostate cancer. Published online Accessed April 26, 2021. Accessed April 26, 2021.

2. Is Proton Therapy Safer than Traditional Radiation? NIH: National Cancer Institute. Published online February 11, 2020. Accessed April 26, 2021.

3. NIH A Prospective Comparative Study of Outcomes With Proton and Photon Radiation in Prostate Cancer (COMPPARE). Last updated January 5, 2021. Accessed April 26, 2021.

4. COMPPARE Enrolls 1,000 Patients. Published online November 13, 2020. Accessed April 26, 2021.

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