Moderate vs Ultra-Hypofractionated Radiation for Prostate Cancer

Overseen By Cancer AnswerLine

Age: 18+

Sex: Male

Trial Phase: Phase 2

Sponsor: University of Michigan Rogel Cancer Center

Must not be taking: Androgen deprivation therapy

Disqualifiers: Pelvic radiation, Crohn's, Ulcerative colitis, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 3-6 weeks

136 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial compares the quality of life of prostate cancer patients treated with a short-term, high-dose radiation therapy to those treated with the standard, longer-term radiation therapy. The new method aims to reduce the number of treatments, making it easier for patients to complete their treatment and potentially improve their quality of life. This newer radiotherapy method for prostate cancer aims to shorten the treatment duration and improve patient convenience.

Do I need to stop my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are on androgen deprivation therapy, there are specific conditions regarding its initiation and type that may affect your eligibility.

What data supports the effectiveness of the treatment Moderate vs Ultra-Hypofractionated Radiation for Prostate Cancer?

Research shows that ultra-hypofractionated radiation therapy, including stereotactic body radiation therapy (SBRT), is increasingly studied and adopted for prostate cancer, with studies indicating it is feasible and well-tolerated. Moderate hypofractionation has been shown to be as effective as conventional fractionation, and ultra-hypofractionated therapy allows for shorter treatment courses, although it may increase short-term side effects. ^{1 2 3 4 5}

Is ultra-hypofractionated radiation therapy safe for prostate cancer treatment?

Ultra-hypofractionated radiation therapy, including stereotactic body radiation therapy (SBRT) and stereotactic ablative radiotherapy (SABR), has been studied for prostate cancer and is generally well-tolerated with careful planning. However, it may increase acute toxicity (short-term side effects) compared to conventional methods, so it is important to consider this when evaluating its safety. ^{1 4 5 6 7}

How does ultra-hypofractionated radiation therapy differ from other treatments for prostate cancer?

Ultra-hypofractionated radiation therapy for prostate cancer is unique because it delivers higher doses of radiation in fewer sessions, allowing for a shorter treatment period compared to conventional or moderately hypofractionated radiation. This approach has been shown to be non-inferior in terms of effectiveness and safety, although it may increase the risk of acute side effects. ^{1 2 5 8 9}

Research Team

William Jackson, M.D.

Principal Investigator

University of Michigan Rogel Cancer Center

Eligibility Criteria

Men aged 18+ who've had prostate cancer confirmed by tissue review after surgery, with a PSA level of at least 0.1 ng/mL. They should be able to start radiation therapy at least 6 months post-surgery and have a KPS score of 70 or above, indicating they can carry out daily activities. Participants must be capable of completing a quality-of-life survey and provide consent.

Inclusion Criteria

I can provide tissue from my prostate surgery for review.

My pelvic lymph nodes are small or unclear on scans, and any suspicious areas outside the pelvis have been biopsied and are cancer-free.

It has been 6 months or more since my prostate surgery.

Exclusion Criteria

I have a history of moderate to severe Crohn's disease or ulcerative colitis.

Any condition that in the opinion of the investigator would preclude participation in this study

I have had a narrowing of my bladder neck or urethra.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either moderately hypo-fractionated radiation therapy over 5-6 weeks or ultra-hypofractionated radiation therapy over 3-4 weeks

3-6 weeks

Follow-up

Participants are monitored for safety, effectiveness, and quality of life after treatment

60 months

Treatment Details

Interventions

• Moderately Hypo-fractionated Radiation Therapy
• Ultra-hypofractionated radiation therapy

Trial Overview This study compares two types of radiation therapy for prostate cancer patients after surgery: ultra-hypofractionated (SBRT) versus moderately hypo-fractionated radiation. The main goal is to see which treatment leads to better self-reported quality of life two years later.

Participant Groups

Group I: Ultra-Hypofractionated Radiation Therapy Experimental Treatment 1 Intervention

5 fractions of ultra-hypofractionated radiation therapy with at least one day between each treatment over the course of no more than 3-4 weeks

Group II: Moderately Hypo-fractionated Radiation Therapy Active Control 1 Intervention

20 fractions of moderately hypofractionated radiation therapy over no more than 5-6 weeks.

Moderately Hypo-fractionated Radiation Therapy is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Moderately Hypo-fractionated Radiation Therapy for:

• Prostate cancer

Approved in United States as Moderately Hypo-fractionated Radiation Therapy for:

• Prostate cancer

Approved in Canada as Moderately Hypo-fractionated Radiation Therapy for:

• Prostate cancer

Who Is Running the Clinical Trial?

University of Michigan Rogel Cancer Center

Lead Sponsor

Trials

303

Recruited

20,700+

Findings from Research

A systematic review of studies on stereotactic body radiation therapy (SBRT) for prostate cancer found that most patients experienced mild to moderate side effects, with severe toxicity occurring in less than 3% of cases, indicating that SBRT is generally well tolerated.

The review identified important dosimetric factors that influence toxicity, such as recommended dose constraints for the bladder, urethra, and rectum, which can help optimize treatment safety and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate Stereotactic Body Radiation Therapy: An Overview of Toxicity and Dose Response. Wang, K., Mavroidis, P., Royce, TJ., et al.[2022]

In a pilot study involving 24 patients with low- to intermediate-risk prostate cancer, highly hypofractionated intensity modulated radiation therapy (IMRT) delivered 54 Gy in 15 fractions over 3 weeks resulted in high survival rates: 91.7% biochemical relapse-free survival and 95.8% overall survival at 5 years.

The treatment was well-tolerated, with no severe late gastrointestinal or grade ≥3 genitourinary toxicities observed, suggesting that this approach may be a safe and effective alternative to traditional radiation therapy methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Outcomes of a Prospective Study on Highly Hypofractionated Intensity Modulated Radiation Therapy for Localized Prostate Cancer for 3 Weeks. Nakamura, K., Ikeda, I., Inokuchi, H., et al.[2023]

Moderately hypofractionated external beam radiotherapy (2.4-3.4 Gy per fraction) provides similar biochemical control for localized prostate cancer as conventional radiotherapy, without increasing late toxicity, making it a preferred treatment option for many patients.

Ultrahypofractionated radiotherapy (SBRT, at least 5 Gy per fraction) shows promising results in biochemical control and acceptable toxicity, particularly in low- and intermediate-risk prostate cancer, suggesting it could be a viable alternative to traditional treatment methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated Radiotherapy for Localized Prostate Cancer: When and for Whom? Roy, S., Morgan, SC.[2020]

Stereotactic ablative radiotherapy (SABR) has been shown to be feasible and well tolerated for low- and intermediate-risk prostate cancer patients, with promising results from large randomized studies comparing it to conventional treatments.

While SABR shows potential benefits and cost-effectiveness, there is currently insufficient data to recommend its use for high-risk prostate cancer patients outside of clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stereotactic Ablative Body Radiotherapy for Intermediate- or High-Risk Prostate Cancer. Loblaw, A.[2021]

In a study involving 874 men with localized prostate cancer, stereotactic body radiotherapy (SBRT) was found to have similar rates of acute gastrointestinal and genitourinary toxicity compared to conventionally fractionated or moderately hypofractionated radiotherapy, suggesting that shorter treatment courses do not increase immediate side effects.

The study showed that only 12% of patients receiving conventional treatment experienced severe gastrointestinal toxicity, compared to 10% in the SBRT group, and 27% versus 23% for genitourinary toxicity, indicating that SBRT is a safe alternative without compromising patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intensity-modulated fractionated radiotherapy versus stereotactic body radiotherapy for prostate cancer (PACE-B): acute toxicity findings from an international, randomised, open-label, phase 3, non-inferiority trial. Brand, DH., Tree, AC., Ostler, P., et al.[2022]

A systematic review of 25 studies involving 4821 prostate cancer patients showed that ultrahypofractionated stereotactic body radiation therapy (SBRT) can achieve high tumor control probabilities (TCP) of 90% to 95% with specific dose regimens, indicating its efficacy in treating localized prostate cancer.

Despite variations in treatment protocols, the study found that doses of 31.7 Gy to 36.1 Gy in 5 fractions for low-intermediate risk patients and 37.6 Gy to 38.7 Gy in 5 fractions for high-risk patients were effective, highlighting the potential of SBRT for dose escalation and shorter treatment times.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumor Control Probability Modeling and Systematic Review of the Literature of Stereotactic Body Radiation Therapy for Prostate Cancer. Royce, TJ., Mavroidis, P., Wang, K., et al.[2022]

In a study of 41 hormone-naïve intermediate-risk prostate cancer patients treated with hypofractionated SBRT, the treatment resulted in a significant decrease in PSA levels from an average of 7.67 ng/mL to 0.64 ng/mL at a median follow-up of 21 months, indicating effective early clinical outcomes.

No severe toxicities (Grade 3 or 4) were observed, and while there was a temporary decline in urinary and bowel quality of life scores post-treatment, they returned to baseline levels, suggesting that SBRT is a safe option for this patient group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypofractionated stereotactic body radiation therapy as monotherapy for intermediate-risk prostate cancer. Ju, AW., Wang, H., Oermann, EK., et al.[2021]

In the HYPO-RT-PC trial involving 1180 patients with localized prostate cancer, ultra-hypofractionated radiotherapy showed higher acute toxicity compared to conventional fractionation, particularly in bowel symptoms, but long-term quality of life (QOL) was similar between the two treatment methods up to 6 years post-treatment.

Despite the initial increase in bowel-related issues for patients receiving ultra-hypofractionation, there were no significant differences in urinary, bowel, or sexual functioning between the two groups after the treatment period, indicating that ultra-hypofractionation is a viable option for patients with intermediate-to-high-risk prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer (HYPO-RT-PC): patient-reported quality-of-life outcomes of a randomised, controlled, non-inferiority, phase 3 trial. Fransson, P., Nilsson, P., Gunnlaugsson, A., et al.[2021]

The Scandinavian HYPO-RT-PC trial, involving 1200 men with intermediate-to-high-risk prostate cancer, demonstrated that ultra-hypofractionated radiotherapy (42.7 Gy in seven fractions) is non-inferior to conventional fractionation (78.0 Gy in 39 fractions) in terms of failure-free survival over a median follow-up of 5 years.

While ultra-hypofractionation resulted in more acute urinary and bowel symptoms during treatment, late toxicity rates were similar to those of conventional fractionation, suggesting that ultra-hypofractionation is a safe and effective option for prostate cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer: 5-year outcomes of the HYPO-RT-PC randomised, non-inferiority, phase 3 trial. Widmark, A., Gunnlaugsson, A., Beckman, L., et al.[2019]

References

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

Prostate Stereotactic Body Radiation Therapy: An Overview of Toxicity and Dose Response. [2022]

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

Long-Term Outcomes of a Prospective Study on Highly Hypofractionated Intensity Modulated Radiation Therapy for Localized Prostate Cancer for 3 Weeks. [2023]

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

Hypofractionated Radiotherapy for Localized Prostate Cancer: When and for Whom? [2020]

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

Stereotactic Ablative Body Radiotherapy for Intermediate- or High-Risk Prostate Cancer. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Intensity-modulated fractionated radiotherapy versus stereotactic body radiotherapy for prostate cancer (PACE-B): acute toxicity findings from an international, randomised, open-label, phase 3, non-inferiority trial. [2022]

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

Tumor Control Probability Modeling and Systematic Review of the Literature of Stereotactic Body Radiation Therapy for Prostate Cancer. [2022]

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

Hypofractionated stereotactic body radiation therapy as monotherapy for intermediate-risk prostate cancer. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer (HYPO-RT-PC): patient-reported quality-of-life outcomes of a randomised, controlled, non-inferiority, phase 3 trial. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Ultra-hypofractionated versus conventionally fractionated radiotherapy for prostate cancer: 5-year outcomes of the HYPO-RT-PC randomised, non-inferiority, phase 3 trial. [2019]