Proton Therapy vs. Photon Radiation for Prostate Cancer

(COMPPARE Trial)

Recruiting at 56 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

Trial Summary

What is the purpose of this trial?

This study is a large, prospective, pragmatic, controlled comparison of patient-centric outcomes \[quality of life (QOL), toxicity, and disease control\] between parallel cohorts of men with prostate cancer treated simultaneously at proton therapy facilities and at geographically similar conventional (photon-based) radiation facilities using intensity-modulated radiation therapy (IMRT) techniques.

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.

What data supports the effectiveness of the treatment Proton Therapy vs. Photon Radiation for Prostate Cancer?

Proton therapy is known to reduce the overall radiation dose to the patient compared to photon therapy, which can be beneficial in sparing healthy tissues. However, while proton therapy shows promise, especially in reducing side effects, its cost-effectiveness and clear clinical advantage over photon therapy for prostate cancer remain uncertain. ^{1 2 3 4 5}

Is proton therapy safe for treating prostate cancer?

Proton therapy is generally considered safe for treating prostate cancer, with studies showing it has similar or reduced side effects compared to traditional photon radiation therapy. However, more research is needed to fully understand its long-term safety and benefits. ^{3 6 7 8 9}

How does proton therapy differ from photon radiation for prostate cancer treatment?

Proton therapy is unique because it uses protons, which can be more precisely targeted to the tumor, potentially reducing damage to surrounding healthy tissue compared to standard photon radiation (IMRT). This precision may lead to fewer side effects and better quality of life for patients. ^{3 5 10 11 12}

Research Team

Nancy P. Mendenhall, MD

Principal Investigator

University of Florida

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Proton therapy in the clinic. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Proton versus photon radiation therapy: A clinical review. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Finding Value for Protons: The Case of Prostate Cancer? [2018]

4. United States pubmed.ncbi.nlm.nih.gov

A Prospective Comparison of the Effects of Interfractional Variations on Proton Therapy and Intensity Modulated Radiation Therapy for Prostate Cancer. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Radiotherapy treatment of early-stage prostate cancer with IMRT and protons: a treatment planning comparison. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Proton versus intensity-modulated radiotherapy for prostate cancer: patterns of care and early toxicity. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Is there any benefit to particles over photon radiotherapy? [2020]

8. United States 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. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Acute toxicity and patient-reported symptom score after conventional versus moderately hypofractionated proton therapy for prostate cancer. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Sociodemographic disparities in the utilization of proton therapy for prostate cancer at an urban academic center. [2020]

11. England pubmed.ncbi.nlm.nih.gov

In silico comparison of whole pelvis intensity-modulated photon versus proton therapy for the postoperative management of prostate cancer. [2023]

12. United States pubmed.ncbi.nlm.nih.gov

Comparative effectiveness study of patient-reported outcomes after proton therapy or intensity-modulated radiotherapy for prostate cancer. [2021]