Proton Radiation Therapy for Prostate Cancer

Overseen By Pretesh Patel, MD

Age: 18+

Sex: Male

Trial Phase: Academic

Sponsor: Emory University

Disqualifiers: Bone metastasis, Distant lymph node metastasis, Previous prostate surgery, Prior radiotherapy, Uncontrolled illness, others

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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 6-8 weeks

30 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial investigates whether proton radiation therapy directed to the prostate tumor, pelvic, and para-aortic lymph nodes, is an effective way to treat patients with high-risk or lymph node positive prostate cancer who are receiving radiation therapy, and if it will result in fewer gastrointestinal and genitourinary side effects. Proton beam therapy is a new type of radiotherapy that directs multiple beams of protons (positively charged subatomic particles) at the tumor target, where they deposit the bulk of their energy with essentially no residual radiation beyond the tumor. By reducing the exposure of the healthy tissues and organs to radiation in the treatment of prostate cancer, proton therapy has the potential to better spare healthy tissue and reduce the side effects of radiation therapy.

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 Beam Radiation Therapy for prostate cancer?

Research shows that proton beam therapy for prostate cancer can effectively control the disease with minimal complications, even when higher doses are used. Studies also indicate that patients experience good long-term outcomes and quality of life after receiving this treatment. ^{1 2 3 4 5}

Is proton radiation therapy safe for treating prostate cancer?

Proton radiation therapy for prostate cancer has been studied for safety, showing low rates of serious side effects. Some patients experienced mild to moderate side effects, such as gastrointestinal and urinary issues, but these were generally manageable. ^{4 6 7 8 9}

How is proton beam therapy different from other treatments for prostate cancer?

Proton beam therapy (PBT) is unique because it allows for precise targeting of the prostate cancer with minimal damage to surrounding healthy tissues, like the rectum, due to its specific dose distribution characteristics. This can potentially reduce side effects compared to traditional radiation therapies. ^{2 9 10 11 12}

Research Team

Pretesh R. Patel

Principal Investigator

Emory University Hospital/Winship Cancer Institute

Eligibility Criteria

This trial is for men with high-risk prostate cancer, confirmed by pathology, who haven't had radical surgery or prior radiotherapy. They should have a Gleason grade of 8 or higher and may have lymph node involvement but no distant metastasis or bone metastasis. Participants need to be in good enough health to consent and follow the trial procedures.

Inclusion Criteria

Absolute neutrophil count (ANC) >= 1,500 cells/mm^3 (obtained within 60 days prior to registration on study)

Platelets >= 100,000 cells/mm^3 (obtained within 60 days prior to registration on study)

Patient must be able to provide study specific informed consent

Exclusion Criteria

I've had radiation treatment in the same area as my current cancer.

I do not have any major health issues that could interfere with the study.

My scans show no cancer spread to distant lymph nodes.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo conventionally fractionated or hypofractionated proton beam therapy daily on Monday-Friday directed to the prostate, pelvic lymph nodes, and para-aortic lymph nodes. Patients may receive an optional high-dose rate brachytherapy boost.

6-8 weeks

Daily visits (Monday-Friday)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up visits at 1, 3, 6, 9, and 12 months, and 1.5, 2, 2.5, and 3 years.

3 years

Multiple visits over 3 years

Treatment Details

Interventions

• Proton Beam Radiation Therapy

Trial Overview The study is testing proton radiation therapy aimed at the prostate tumor and certain lymph nodes. It's compared with standard treatments to see if it can more effectively target tumors while causing fewer side effects like gastrointestinal and genitourinary issues.

Participant Groups

Group I: Treatment (proton beam therapy) Experimental Treatment 4 Interventions

Patients undergo conventionally fractionated or hypofractionated proton beam therapy daily on Monday-Friday directed to the prostate, pelvic lymph nodes, and para-aortic lymph nodes. Patients may receive an optional high-dose rate brachytherapy boost. Androgen deprivation therapy is required but left to the discretion of the treating physician.

Proton Beam Radiation Therapy is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Proton Therapy for:

• Esophageal adenocarcinoma
• Esophageal squamous cell carcinoma
• Gastroesophageal junction tumors

Approved in United States as Proton Therapy for:

• Esophageal adenocarcinoma
• Esophageal squamous cell carcinoma
• Gastroesophageal junction tumors

Approved in Canada as Proton Therapy for:

• Esophageal adenocarcinoma
• Esophageal squamous cell carcinoma
• Gastroesophageal junction tumors

Approved in Japan as Proton Therapy for:

• Esophageal adenocarcinoma
• Esophageal squamous cell carcinoma
• Gastroesophageal junction tumors

Approved in China as Proton Therapy for:

• Esophageal adenocarcinoma
• Esophageal squamous cell carcinoma
• Gastroesophageal junction tumors

Approved in Switzerland as Proton Therapy for:

• Esophageal adenocarcinoma
• Esophageal squamous cell carcinoma
• Gastroesophageal junction tumors

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 211 prostate cancer patients treated with image-guided proton therapy, early outcomes showed high efficacy with only 1.9% experiencing Grade 3 genitourinary (GU) symptoms and less than 0.5% experiencing Grade 3 gastrointestinal (GI) toxicities after a minimum follow-up of 2 years.

The need for pretreatment GU symptom management was linked to higher rates of posttreatment GU symptoms, indicating that managing symptoms before therapy may help reduce complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early outcomes from three prospective trials of image-guided proton therapy for prostate cancer. Mendenhall, NP., Li, Z., Hoppe, BS., et al.[2022]

In a study of 180 prostate cancer patients treated between 1972 and 1979, those receiving a proton beam boost along with conventional x-ray therapy were able to receive a higher dose to the tumor without increasing side effects, demonstrating the safety of this approach.

Despite the increased dose delivered to the tumor using the proton beam, there were no significant differences in patient survival, disease-free survival, or local recurrence-free survival compared to those treated with conventional x-ray therapy, suggesting similar efficacy between the two methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protons or megavoltage X-rays as boost therapy for patients irradiated for localized prostatic carcinoma. An early phase I/II comparison. Duttenhaver, JR., Shipley, WU., Perrone, T., et al.[2019]

In a study of 166 patients with favorable risk prostate cancer treated with proton beam therapy (PBT) over an average follow-up of 8.3 years, the biochemical failure-free survival (BFFS) rates were high, with 97% at 5 years and 92% at 8 years, indicating effective long-term disease control.

The study found very low rates of failure, with only 7.8% experiencing biochemical failure and no cases of distant failure, suggesting that PBT is a safe and effective primary treatment option for localized prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Clinical Outcomes in Favorable Risk Prostate Cancer Patients Receiving Proton Beam Therapy. Bao, A., Barsky, AR., Maxwell, R., et al.[2022]

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 1327 men treated with image-guided proton therapy for localized prostate cancer, the 5-year freedom from biochemical progression rates were very high, at 99% for low-risk, 94% for intermediate-risk, and 74% for high-risk patients, indicating strong efficacy of this treatment.

The treatment resulted in low rates of high-grade toxicities, with only 0.6% experiencing severe gastrointestinal issues and 2.9% facing severe genitourinary toxicity, suggesting that proton therapy is a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Five-Year Biochemical Results, Toxicity, and Patient-Reported Quality of Life After Delivery of Dose-Escalated Image Guided Proton Therapy for Prostate Cancer. Bryant, C., Smith, TL., Henderson, RH., et al.[2020]

In a study of 192 prostate cancer patients treated with proton beam therapy (PBT) over a median follow-up of 1.7 years, only 5 patients experienced grade 3 toxicity, with no occurrences of grade 4 or 5 toxicity, indicating a high safety profile for this treatment.

Patient-reported outcomes showed stable urinary function post-treatment, while sexual health scores declined slightly at 1 year but did not worsen thereafter; bowel function scores also decreased but stabilized, suggesting manageable side effects associated with PBT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early toxicity and patient reported quality-of-life in patients receiving proton therapy for localized prostate cancer: a single institutional review of prospectively recorded outcomes. Lee, HJ., Macomber, MW., Spraker, MB., et al.[2019]

Proton beam therapy (PBT) as a standalone treatment for localized prostate cancer showed a high 5-year progression-free survival rate of 97% for intermediate-risk patients and 83% for high-risk patients, indicating its efficacy.

The treatment was associated with low rates of severe side effects, with only 3.9% of patients experiencing significant gastrointestinal toxicity and 23.5% experiencing acute genitourinary toxicity, suggesting that PBT can effectively preserve patients' quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton Beam Therapy Alone for Intermediate- or High-Risk Prostate Cancer: An Institutional Prospective Cohort Study. Arimura, T., Yoshiura, T., Matsukawa, K., et al.[2020]

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 of 151 patients with organ-confined prostate cancer, proton beam therapy (PBT) demonstrated a low incidence of late Grade 2 or greater rectal toxicities, reported at only 2.0% after 2 years of follow-up.

The study indicates that PBT is a safe treatment option for localized prostate cancer, with minimal acute and late toxicities, suggesting it can effectively control side effects while delivering targeted radiation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-institutional Phase II study of proton beam therapy for organ-confined prostate cancer focusing on the incidence of late rectal toxicities. Nihei, K., Ogino, T., Onozawa, M., et al.[2022]

In a study involving 9 patients with localized prostate cancer, a method to retract the rectum during proton therapy significantly reduced the volume of the rectal wall receiving high radiation doses, which is crucial for minimizing side effects.

The use of a cylindrical rod to retract the rectum allowed for a proton boost treatment of 20 Gy, combined with conventional photon therapy, indicating a promising approach to enhance treatment efficacy while protecting surrounding organs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A method to separate the rectum from the prostate during proton beam radiotherapy of prostate cancer patients. Isacsson, U., Nilsson, K., Asplund, S., et al.[2018]

Proton beam therapy (PBT) allows for higher doses of radiation to be delivered to prostate cancer tissues while minimizing damage to surrounding healthy tissues, making it a promising treatment option.

The review highlights the growing interest and advancements in PBT technology for localized prostate cancer, emphasizing the need for a deeper understanding of its application and treatment planning in radiation medicine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Proton beam therapy for the treatment of prostate cancer. Pugh, TJ., Choi, S., Nguyen, QN., et al.[2016]

In a study of 295 men who underwent postoperative radiation therapy for prostate cancer, proton beam therapy (PBT) showed similar long-term disease control outcomes compared to intensity-modulated radiation therapy (IMRT) after a median follow-up of 59 months.

Both treatment modalities had comparable rates of biochemical failure, local failure, regional failure, distant failure, and all-cause mortality, indicating that PBT is as effective as IMRT in this setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Analysis of 5-Year Clinical Outcomes and Patterns of Failure of Proton Beam Therapy Versus Intensity Modulated Radiation therapy for Prostate Cancer in the Postoperative Setting. Barsky, AR., Carmona, R., Verma, V., et al.[2021]

References

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

Early outcomes from three prospective trials of image-guided proton therapy for prostate cancer. [2022]

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

Protons or megavoltage X-rays as boost therapy for patients irradiated for localized prostatic carcinoma. An early phase I/II comparison. [2019]

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

Long-term Clinical Outcomes in Favorable Risk Prostate Cancer Patients Receiving Proton Beam Therapy. [2022]

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

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

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

Five-Year Biochemical Results, Toxicity, and Patient-Reported Quality of Life After Delivery of Dose-Escalated Image Guided Proton Therapy for Prostate Cancer. [2020]

6. England pubmed.ncbi.nlm.nih.gov

Early toxicity and patient reported quality-of-life in patients receiving proton therapy for localized prostate cancer: a single institutional review of prospectively recorded outcomes. [2019]

7. Switzerland pubmed.ncbi.nlm.nih.gov

Proton Beam Therapy Alone for Intermediate- or High-Risk Prostate Cancer: An Institutional Prospective Cohort Study. [2020]

8. 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]

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

Multi-institutional Phase II study of proton beam therapy for organ-confined prostate cancer focusing on the incidence of late rectal toxicities. [2022]

10. England pubmed.ncbi.nlm.nih.gov

A method to separate the rectum from the prostate during proton beam radiotherapy of prostate cancer patients. [2018]

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

Proton beam therapy for the treatment of prostate cancer. [2016]

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

Comparative Analysis of 5-Year Clinical Outcomes and Patterns of Failure of Proton Beam Therapy Versus Intensity Modulated Radiation therapy for Prostate Cancer in the Postoperative Setting. [2021]