Proton Therapy vs. Photon Radiation for Prostate Cancer

(COMPPARE Trial)

Recruiting at 57 trial locations

Overseen By COMPPARE Study Team

Age: 18+

Sex: Male

Trial Phase: Academic

Sponsor: University of Florida

Disqualifiers: Metastatic disease, Very high-risk cancer, Prior prostate procedures, Invasive pelvic malignancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 39

3000 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares two types of radiation therapy, proton and photon, to determine which is more effective for treating prostate cancer. The researchers will examine how each treatment impacts quality of life, side effects, and cancer control. The trial includes several treatment groups: standard proton therapy, shorter-course proton therapy (hypofractionated proton therapy), and traditional photon therapy (IMRT). Men with prostate cancer who have not undergone previous treatments like surgery or other specific therapies may be suitable candidates for this study. As an unphased trial, it provides patients the chance to contribute to valuable research that could enhance future prostate cancer treatments.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that proton therapy is generally safe for treating prostate cancer. Studies have found that standard proton therapy is easy for patients to handle and usually causes only mild side effects, particularly related to digestion and urination. As a result, most patients experience little to no discomfort.

For hypofractionated proton therapy, which uses fewer but stronger doses, research indicates it is safe for those with less aggressive prostate cancer. Studies have demonstrated that patients experience similar safety outcomes compared to traditional treatments.

In both types of treatment, the side effects are considered manageable and similar to those from standard radiation therapies. This suggests a reassuring safety profile for individuals considering participation in a trial involving these therapies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for prostate cancer because they are exploring the potential benefits of proton therapy over traditional photon radiation. Proton therapy is unique in its ability to precisely target tumors, which may minimize damage to surrounding healthy tissues. Within the study, standard proton therapy is compared to a hypofractionated version, which delivers higher doses in fewer sessions, potentially making treatment shorter and more convenient for patients. This trial aims to determine if these proton techniques can offer better outcomes or reduced side effects compared to the standard photon-based IMRT, which is currently a common treatment option.

What evidence suggests that this trial's treatments could be effective for prostate cancer?

This trial will compare different radiation treatments for prostate cancer. Research has shown that proton therapy, one of the treatments under study, is highly effective for treating prostate cancer. Specifically, studies indicate that five years after receiving standard proton therapy, about 99% of patients with low- and intermediate-risk prostate cancer remain cancer-free. This suggests that proton therapy is as effective, if not more so, than traditional radiation treatments. In this trial, some participants will receive standard proton therapy, while others will receive hypofractionated proton therapy, which involves fewer treatment sessions. Data shows a 90% chance of staying cancer-free five years after hypofractionated proton therapy. Both types of proton therapy provide strong results for prostate cancer, with high rates of disease control and survival. ^{1 2 3 6 7}

Who Is on the Research Team?

Nancy P. Mendenhall, MD

Principal Investigator

University of Florida

Are You a Good Fit for This Trial?

Men aged 30-85 with localized prostate cancer and a life expectancy of at least 8 years can join. They must have no history of invasive pelvic cancers, prior prostate cancer treatments (except certain therapies for benign conditions), or metastatic disease. Participants need to be physically able to complete the study and give informed consent.

Inclusion Criteria

My prostate cancer is localized and has been confirmed with specific tests.

I have been diagnosed with prostate adenocarcinoma.

I am between 30 and 85 years old and expected to live 8 more years or longer.

Exclusion Criteria

My cancer has spread to nearby lymph nodes or other parts of my body.

I have active symptoms of inflammatory bowel disease.

I have difficulty understanding the risks and benefits of research studies.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation

Participants receive either proton or photon radiation therapy as part of the study

8-10 weeks

39 visits (in-person) for standard fractionation or 20 visits (in-person) for hypofractionation

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Proton Arm 1: Standard Proton Therapy
• Proton Arm 2: Hypofractionated Proton Therapy
• Standard of Care IMRT (Photon)
• Standard of Care Proton Therapy

Trial Overview This trial compares quality of life, toxicity, and disease control between proton therapy and conventional photon-based IMRT in treating prostate cancer. Patients are treated at different facilities but under similar standards to see which method is more effective.

How Is the Trial Designed?

Group I: Standard Proton Therapy Experimental Treatment 1 Intervention

78.0 Gy (RBE) in 39 fractions. This is Arm 1 of the embedded randomized trial.

Group II: Hypofractionated Proton therapy Experimental Treatment 1 Intervention

60.0 Gy (RBE) in 20 fractions This is Arm 2 of the embedded randomized trial.

Group III: IMRT (Photon) Active Control 1 Intervention

As this trial is pragmatic, all treatment will be standard of care.

Group IV: Proton Therapy Standard of Care Active Control 1 Intervention

As this trial is pragmatic, all treatment will be standard of care.

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

Patient-Centered Outcomes Research Institute

Collaborator

Trials

592

Recruited

27,110,000+

Published Research Related to This Trial

Intensity-modulated photon radiotherapy (IMRT) provided better dose conformity to the prostate cancer target compared to three-dimensional conformal proton therapy (3D-CPT), while both methods effectively delivered the prescribed dose to at least 98% of the target volume.

Proton therapy, particularly with optimized configurations, significantly reduced radiation exposure to the bladder and rectum at lower doses, indicating a potential advantage in sparing healthy tissues during prostate cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiotherapy treatment of early-stage prostate cancer with IMRT and protons: a treatment planning comparison. Trofimov, A., Nguyen, PL., Coen, JJ., et al.[2020]

In a study involving 10 post-prostatectomy patients, intensity-modulated proton therapy (IMPT) demonstrated similar coverage of the clinical target volume (CTV) compared to intensity-modulated radiation therapy (IMRT) while significantly reducing radiation exposure to surrounding organs at risk (OARs).

IMRT resulted in higher doses to critical areas such as the bladder, bowel, and rectum, with mean doses significantly lower in IMPT, suggesting that IMPT may offer a safer treatment option for patients undergoing postoperative radiation for prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In silico comparison of whole pelvis intensity-modulated photon versus proton therapy for the postoperative management of prostate cancer. Gogineni, E., Cruickshank, IK., Chen, H., et al.[2023]

In a study of 27,647 Medicare beneficiaries with prostate cancer, proton radiotherapy (PRT) was associated with lower genitourinary toxicity at 6 months compared to intensity-modulated radiotherapy (IMRT), but this difference disappeared by 12 months post-treatment.

PRT was significantly more expensive than IMRT, with median Medicare reimbursements of $32,428 for PRT compared to $18,575 for IMRT, yet no long-term differences in toxicity were observed between the two treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton versus intensity-modulated radiotherapy for prostate cancer: patterns of care and early toxicity. Yu, JB., Soulos, PR., Herrin, J., et al.[2022]

Proton therapy significantly reduces the integral dose to patients, with approximately 60% lower exposure compared to photon therapies, making it particularly beneficial for pediatric patients with developing tissues.

While proton therapy shows promising results and safety for various tumors, its higher cost compared to photon therapy raises questions about cost-effectiveness, especially for adult cancers like prostate cancer, necessitating further comparative studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton therapy in the clinic. DeLaney, TF.[2022]

Proton radiation therapy has better dose distribution characteristics than photon radiation therapy, which could lead to improved treatment outcomes in certain clinical applications.

However, there is still a lack of substantial clinical evidence demonstrating clear advantages of proton therapy over more affordable photon treatments, partly due to the smaller number of patients receiving proton therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton versus photon radiation therapy: A clinical review. Chen, Z., Dominello, MM., Joiner, MC., et al.[2023]

In a study of 1850 patients with early-stage prostate cancer, both moderately hypofractionated proton beam therapy (PBT) and intensity modulated radiation therapy (IMRT) resulted in low rates of late genitourinary (GU) and gastrointestinal (GI) toxicity, indicating that both treatments are safe options.

There was no significant difference in late toxicity rates between PBT and IMRT, with late grade 3+ GU toxicity at 2.0% for PBT and 3.9% for IMRT, and late grade 2+ GI toxicity at 14.6% for PBT and 4.7% for IMRT, suggesting both modalities are equally effective in minimizing side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Pooled Toxicity Analysis of Moderately Hypofractionated Proton Beam Therapy and Intensity Modulated Radiation Therapy in Early-Stage Prostate Cancer Patients. Vapiwala, N., Wong, JK., Handorf, E., et al.[2022]

In a study of 289 prostate cancer patients, hypofractionated proton beam therapy (PBT) showed no significant differences in acute adverse event rates or quality of life, as measured by the International Prostate Symptom Score (IPSS), compared to conventionally fractionated PBT.

The study evaluated patients treated with different doses (2.0, 2.5, and 3.0 Gy RBE per fraction) and found that factors like diabetes, age, and androgen deprivation therapy did not influence the IPSS outcomes, suggesting that hypofractionated PBT is a safe option without increased toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute toxicity and patient-reported symptom score after conventional versus moderately hypofractionated proton therapy for prostate cancer. Iizumi, T., Ishikawa, H., Sekino, Y., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39672515/

Five-Year Outcomes of Moderately Hypofractionated ... At 5 years, RFR and DFS were 90% and 89%, respectively. Seven patients had PCa recurrence, all detected by PSA relapse initially. Three patients ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2331518023001300

Hypofractionated Proton Therapy in Early Prostate Cancer Hypofractionated proton therapy of 60 Gy in 20 fractions was safe and effective for patients with low-risk prostate cancer.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10526468/

5-Years Analysis of Effectivity and Toxicity of Ultra- ... Ultra-hypofractionated proton radiotherapy using PBS is highly effective in the treatment of low- and intermediate-risk prostate cancer. We ...

4. thegreenjournal.com thegreenjournal.com/article/S0167-8140(24)00186-5/abstract

Photon vs proton hypofractionation in prostate cancer Five- and seven-year outcomes for image-guided moderately accelerated hypofractionated proton therapy for prostate cancer. Acta Oncologica. 2022; 61:468-477.

5. mdproton.com mdproton.com/advances-in-prostate-cancer-therapy-the-efficacy-of-hypofractionation-and-proton-therapy/

Advances in Prostate Cancer Therapy: The Efficacy of ... With hypofractionation, the treatment period is reduced by nearly 50% to four to six weeks. Advancing even further, studies are underway to ...

6. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.962697/epub

comparison of acute toxicity and early quality of life outcomes Conclusion. Moderately hypofractionated proton therapy has an acceptable early safety profile. Acute toxicity and QoL outcomes are not inferior ...

7. foxchase.org foxchase.org/news/2021-04-09-research-comparing-radiation-therapies-show-they-are-safe-for-prostate-cancer-patients

Research Comparing Radiation Therapies Show They Are ... The findings demonstrate that moderate hypofractionation is safe when used to treat patients with low- or intermediate-risk prostate cancer, ...