Postoperative Radiotherapy for Prostate Cancer

Recruiting at 3 trial locations

Overseen By Matthew Morocco

Age: 18+

Sex: Male

Trial Phase: Academic

Sponsor: Proton Collaborative Group

Must not be taking: Saw palmetto, Methotrexate

Disqualifiers: Distant metastasis, Chemotherapy, Hip replacement, others

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

Compensation: Varies

Number of Visits: Unknown

70 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how different types of radiation therapy, such as proton and conventional radiation, affect prostate cancer that has returned or might return. The goal is to determine which treatments most effectively prevent cancer recurrence. Participants will receive one of several radiation treatments, such as Intensity-Modulated Radiation Therapy (IMRT) or Proton Therapy, which may also include hormonal therapy. The trial seeks men who have undergone prostate surgery and have a PSA level (a protein produced by the prostate) of up to 20 ng/ml. As an unphased trial, it offers participants the chance to contribute to innovative research that could shape future prostate cancer treatments.

Will I have to stop taking my current medications?

If you are taking Saw Palmetto or methotrexate, you will need to stop using them during the radiation treatment.

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

Research has shown that both IMRT (Intensity-Modulated Radiation Therapy) with a proton boost and proton therapy alone are generally well-tolerated treatments for prostate cancer. Studies have found that IMRT can lead to high survival rates and good cancer control. However, some side effects may occur; about 9% of patients experience moderate urinary issues, and around 5% face moderate digestive problems.

Proton therapy also delivers promising results with high cancer control rates and fewer side effects. Research found that proton therapy successfully controlled cancer with fewer side effects compared to some traditional radiation methods. After nearly four years, many patients maintained high control rates and experienced low toxicity, indicating minimal harm to their bodies.

Overall, both treatments have proven effective and generally safe, with some manageable side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for postoperative prostate cancer because they explore the potential benefits of using proton therapy and intensity-modulated radiation therapy (IMRT) to precisely target the prostate bed. Unlike traditional radiation therapy, which can affect surrounding healthy tissues, proton therapy allows for more focused radiation doses, potentially reducing side effects. The use of IMRT in combination with a proton boost could offer a more effective approach by enhancing the precision and intensity of the radiation delivered. These treatments are distinctive because they aim to improve outcomes specifically for patients with varying levels of risk after surgery, tailoring the approach to individual patient needs.

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

Research has shown that proton therapy, one of the treatments studied in this trial, can accurately target prostate cancer tumors, reducing side effects while effectively controlling the cancer. Proton therapy has demonstrated a high five-year survival rate for prostate cancer, with 97% of men surviving. It also has low rates of long-term side effects affecting the urinary and reproductive organs.

In contrast, IMRT (intensity-modulated radiation therapy), another treatment option in this trial, is a standard and effective treatment for prostate cancer that hasn't spread. It has a five-year survival rate without cancer returning of about 90%. IMRT is known for having fewer long-term digestive system side effects compared to some other treatments. Both treatments are effective, each with its own strengths in terms of precision and side effects. ^{6 7 8 9 10}

Who Is on the Research Team?

Randal H Henderson, MD

Principal Investigator

University of Florida Proton Therapy Institute

Are You a Good Fit for This Trial?

This trial is for men who've had surgery for prostate cancer with a maximum PSA of 20 ng/ml and no distant metastasis. It's not for those with hip replacements, active inflammatory bowel disease affecting the rectum, other cancers (except certain skin cancers) within the last 5 years, previous chemotherapy, or pelvic radiation that affects this treatment.

Inclusion Criteria

My prostate cancer was treated with surgery.

Maximum PSA value of 20 ng/ml

Exclusion Criteria

History of hip replacement

My cancer has spread to distant parts of my body.

I've had radiation to my pelvis that affects new treatments.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Radiation Treatment

Participants receive proton radiation and/or conventional radiation therapy, with hormonal therapy if applicable, based on risk group

6-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after radiation treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• IMRT to 45 Gy; prostate bed proton boost of 21.6 CGE
• IMRT to 45 Gy; proton boost to prostate bed to 25.2 CGE
• Proton (prostate bed) to 70.2 CGE
• Proton to 66.6 CGE

Trial Overview The study tests whether proton radiation alone or combined with conventional radiation and possibly hormonal therapy can prevent prostate cancer from returning after surgery. Different doses and combinations are compared to find out which is more effective.

How Is the Trial Designed?

Group I: Salvage Non-High Risk Experimental Treatment 1 Intervention

Proton to 70.2 CGE

Group II: Salvage High Risk Experimental Treatment 1 Intervention

IMRT to 45 Gy; proton boost to prostate bed to 25.2 CGE

Group III: Postop Non-High Risk Experimental Treatment 1 Intervention

Proton to 66.6 CGE

Group IV: Postop High Risk Experimental Treatment 1 Intervention

IMRT to 45 Gy; prostate bed proton boost of 21.6 CGE

IMRT to 45 Gy; prostate bed proton boost of 21.6 CGE is already approved in United States, European Union, Canada for the following indications:

Approved in United States as IMRT for:

• Localized prostate cancer
• Postoperative adjuvant therapy
• Salvage therapy for biochemical or local recurrence

Approved in European Union as IMRT for:

• Localized prostate cancer
• Postoperative adjuvant therapy
• Salvage therapy for biochemical or local recurrence

Approved in Canada as IMRT for:

• Localized prostate cancer
• Postoperative adjuvant therapy
• Salvage therapy for biochemical or local recurrence

Who Is Running the Clinical Trial?

Proton Collaborative Group

Lead Sponsor

Trials

10

Recruited

41,100+

University of Florida Health

Collaborator

Trials

10

Recruited

4,200+

Published Research Related to This Trial

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]

Prostate cancer treatment has advanced significantly from traditional 2D radiotherapy to more precise methods like intensity-modulated radiation therapy (IMRT) and stereotactic radiotherapy, enhancing treatment efficacy and reducing side effects.

Emerging techniques such as proton therapy and carbon therapy are being explored to further improve treatment outcomes, shorten treatment times, and minimize toxicity and costs for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[What is the level of evidence of new techniques in prostate cancer radiotherapy?]. Khadige, M., Peiffert, D., Supiot, S.[2018]

In a study of 272 patients with locally advanced prostate cancer, proton-photon radiation therapy significantly reduced the incidence of acute gastrointestinal toxicity compared to conventional photon therapy, with 54.4% experiencing toxicity versus 69.2% in the control group.

While the proton-photon therapy did not reduce genitourinary toxicity or improve overall survival rates compared to standard photon therapy, it was effective in minimizing late gastrointestinal damage, with only 10.2% of patients experiencing severe late effects compared to 34.8% in the control group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Options of hypofractionation of proton boost in locally advanced prostate cancer]. Khmelevskiĭ, EV., Pan'shin, GA., Kancheli, IN., et al.[2018]

Proton therapy has been used for decades in treating prostate cancer, and advancements like pencil-beam scanning have improved its application, but the clinical benefits compared to traditional treatments are still unclear.

A randomized trial is underway to compare proton beam therapy with intensity-modulated radiotherapy for early-stage prostate cancer, which will help clarify the effectiveness and role of proton therapy in this context.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical controversies: proton therapy for prostate cancer. Mouw, KW., Trofimov, A., Zietman, AL., et al.[2021]

Proton therapy (PT), especially intensity modulated proton therapy (IMPT), shows superior treatment planning for prostate cancer by providing better homogeneity in the planning target volume (PTV) and sparing surrounding healthy tissues, such as the rectum, compared to traditional intensity-modulated radiation therapy (IMRT).

Proton therapy significantly reduces the dose to normal tissues outside the PTV, exposing them to less than 50% of the dose delivered by IMRT, making it a promising option for prostate cancer treatment in Australian facilities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of proton therapy and IMRT treatment plans for prostate radiotherapy. Dowdell, SJ., Metcalfe, PE., Morales, JE., et al.[2019]

In a Phase III trial involving 202 patients with Stage T3-T4 prostate cancer, increasing the radiation dose to 75.6 CGE using a conformal proton boost improved local control in patients with poorly differentiated tumors, but did not significantly affect overall survival or disease-specific survival compared to the conventional dose of 67.2 Gy.

The higher dose treatment was associated with increased late radiation side effects, such as rectal bleeding and potential urethral stricture, indicating a trade-off between improved local control and safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advanced prostate cancer: the results of a randomized comparative trial of high dose irradiation boosting with conformal protons compared with conventional dose irradiation using photons alone. Shipley, WU., Verhey, LJ., Munzenrider, JE., et al.[2022]

A study involving 531 patients with localized prostate cancer showed that a hypofractionated proton boost of 20 Gy followed by photon therapy was effective, achieving 5-year PSA relapse-free survival rates of 100% for low-risk and 72% for very high-risk patients.

The treatment demonstrated a low toxicity profile, with only 2% of patients experiencing grade 3 or higher genitourinary toxicity and 0% gastrointestinal toxicity, indicating that this approach is safe even for patients with higher risk and larger prostate volumes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High efficacy of hypofractionated proton therapy with 4 fractions of 5 Gy as a boost to 50 Gy photon therapy for localized prostate cancer. Johansson, S., Isacsson, U., Sandin, F., et al.[2020]

In a study involving 8 patients, intensity modulated radiation therapy (IMRT) generally outperformed standard bilateral proton therapy in protecting normal tissues, especially when using a fixed relative biological effectiveness (RBE) of 1.1.

The research highlights the need for further validation of RBE models, as using variable RBE assumptions with anterior oblique proton therapy often resulted in excessive radiation exposure to the rectum, raising concerns about its safety for prostate cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can We Advance Proton Therapy for Prostate? Considering Alternative Beam Angles and Relative Biological Effectiveness Variations When Comparing Against Intensity Modulated Radiation Therapy. Underwood, T., Giantsoudi, D., Moteabbed, M., et al.[2022]

The combination of hypofractionated proton boost therapy (20 Gy) followed by external beam radiotherapy (50 Gy) resulted in excellent 5-year PSA progression-free survival rates of 100% for low-risk, 95% for intermediate-risk, and 74% for high-risk prostate cancer patients, indicating strong efficacy in treating localized prostate cancer.

The treatment was associated with acceptable levels of genitourinary and gastrointestinal toxicities, with a decline in these side effects over time, suggesting that while bladder toxicities may be dose-limiting, the overall safety profile is favorable, especially with a median follow-up of 57 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated proton boost combined with external beam radiotherapy for treatment of localized prostate cancer. Johansson, S., Aström, L., Sandin, F., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9399820/

Long-term outcomes of prostate intensity-modulated ... This retrospective study demonstrates the long-term outcomes of treating prostate cancer using intensity modulated (IMRT) with incorporation of MRI-directed ...

2. academic.oup.com academic.oup.com/jrr/article/66/1/39/7954234

Real-world comparative outcomes and toxicities after ... IMRT is a standard treatment for localized prostate cancer with a 5-year bRFS of approximately 90% [13, 17–19]. In this study, there was a ...

3. jamanetwork.com jamanetwork.com/journals/jamainternalmedicine/fullarticle/1689975

Comparative Effectiveness of Intensity-Modulated ... However, a study comparing IMRT with CRT for primary prostate cancer treatment found that IMRT was associated with lower rates of long-term GI ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1879850023001753

Long-Term Outcomes of a Prospective Study on Highly ... No grade ≥3 adverse events were observed, suggesting that highly hypofractionated IMRT is a safe treatment. Conventional fractionated radiation therapy at 1.8 ...

5. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/1471-2407-13-530

Intensity-modulated radiotherapy versus radical prostatectomy ... Our results showed a better OS at 5 and 7 years for the RP group than the IMRT group. However, mortality from other causes is higher in the IMRT ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6043750/

Intensity-modulated radiotherapy for prostate cancer - PMC Multiple clinical trials have demonstrated improved cancer outcomes with dose escalation, but toxicities using 3D-CRT and escalated doses have been problematic.

7. myrxtoolkit.com myrxtoolkit.com/web/public/brands/medicalpolicy/external-policies/intensity-modulated-radiotherapy-of-the-prostate/

Intensity-Modulated Radiotherapy of the Prostate Data comparing IMRT with 3D-CRT supported the theory that higher doses (up to 81 Gy) can improve biochemical survival for patients with localized prostate ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7528218/

Comparison of outcomes and toxicities among radiation ... We review radiation therapy (RT) options available for prostate cancer, including external beam (EBRT; with conventional fractionation, hypofractionation, ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S0360301622031601

Quality-of-Life Outcomes and Toxicity Profile Among ... The median (range) prostate bed dose was 32 (30-34) Gy. Acute and late grade 2 GU toxicities were both 9% while acute and late grade 2 GI toxicities were 5% and ...

10. cancer.org cancer.org/cancer/types/prostate-cancer/treating/radiation-therapy.html

Side Effects of Radiation Therapy for Prostate Cancer IMRT, an advanced form of 3D-CRT therapy, is the most common type of external radiation therapy for prostate cancer. It uses a computer-driven ...