HDR vs LDR Brachytherapy for Prostate Cancer

(LDR/HDRmono Trial)

Overseen By Francois Bachand, MD

Age: 18+

Sex: Male

Trial Phase: Academic

Sponsor: British Columbia Cancer Agency

Must not be taking: Androgen deprivation therapy

Disqualifiers: Prior prostate surgery, Pelvic radiation, Chemotherapy, others

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

Compensation: Varies

Number of Visits: 37

Duration: 2-4 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial compares two radiation treatments for men with specific types of prostate cancer. The researchers aim to determine which approach—high dose rate or low dose rate brachytherapy—is more effective for those with favorable or intermediate-risk prostate cancer. Participants will receive either high dose rate treatment, delivered in two sessions, or low dose rate treatment, completed in one session with a follow-up imaging visit. Suitable candidates include men whose prostate cancer hasn't spread beyond certain levels, who haven't undergone prior prostate surgery or radiation, and who are not eligible for active surveillance. As an unphased trial, this study allows participants to contribute to valuable research that could enhance future treatment options.

Will I have to stop taking my current medications?

The trial does not specify whether you need to stop taking your current medications, but it does mention that participants should not be on androgen deprivation therapy (a treatment to lower male hormones).

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you cannot have had androgen deprivation therapy (a treatment to lower male hormones).

What prior data suggests that these brachytherapy techniques are safe for prostate cancer treatment?

Research has shown that high dose rate (HDR) brachytherapy is generally safe for treating prostate cancer. Studies have found that HDR brachytherapy, whether used alone or with other treatments, effectively controls the disease. Patients typically manage this treatment well, with side effects that are usually manageable.

Similarly, low dose rate (LDR) brachytherapy is also considered safe. It involves a single outpatient procedure performed under anesthesia. Patients return for follow-up imaging to ensure the treatment's safety and effectiveness.

Both HDR and LDR brachytherapy have demonstrated positive results in men with prostate cancer, and safety data support their use. These treatments have been thoroughly studied, and while side effects can occur, they are typically manageable and do not outweigh the potential benefits. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the treatments in this trial because they offer innovative approaches to prostate cancer brachytherapy. High dose rate (HDR) brachytherapy is distinct because it delivers radiation in two outpatient procedures, two weeks apart, without the need for follow-up imaging, potentially reducing the overall treatment burden. Meanwhile, low dose rate (LDR) brachytherapy is delivered in a single session but requires a follow-up for imaging to ensure proper implant positioning. Unlike traditional treatments that may involve more frequent hospital visits or longer recovery times, these methods aim to streamline the treatment process while maintaining effectiveness. By exploring these differences, researchers hope to provide more convenient and efficient options for patients.

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

This trial will compare high dose rate (HDR) brachytherapy and low dose rate (LDR) brachytherapy for prostate cancer. Research has shown that HDR brachytherapy effectively controls prostate cancer, with studies indicating high rates of disease control. Specifically, one study found that combining HDR brachytherapy with external beam radiation therapy improves survival rates and reduces the chance of cancer returning. LDR brachytherapy is also commonly used and effective for treating prostate cancer. This trial's ongoing comparisons between HDR and LDR brachytherapy aim to determine which is more effective for different risk levels. ^{1 2 3 6 7}

Who Is on the Research Team?

Ross Halperin, MD

Principal Investigator

British Columbia Cancer Agency Program Director

Are You a Good Fit for This Trial?

Men with favorable to intermediate-risk prostate cancer, who have a life expectancy of at least 10 years and are not candidates for active surveillance. They should have no prior radical prostate surgeries or treatments like TURP, cryosurgery, pelvic radiation, or chemotherapy for prostate cancer. Their PSA levels and Gleason scores must meet specific criteria.

Inclusion Criteria

My prostate cancer is at an early or intermediate stage, and I am expected to live 10 more years.

My prostate cancer is at an early stage, with specific test results.

My prostate cancer is at an early stage, with low PSA and Gleason scores, and I'm mostly active.

Exclusion Criteria

I have had radiation therapy to my pelvic area before.

I have had surgery or cryotherapy for prostate issues before.

I have had major surgery for prostate cancer.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either low dose rate or high dose rate prostate brachytherapy. LDR is delivered in a single session, while HDR is delivered in two sessions, two weeks apart.

2-4 weeks

1-2 visits (in-person)

Follow-up

Participants are monitored for safety, quality of life, and treatment efficacy. Follow-up assessments include imaging, symptom tracking, and biopsies.

36 months

Multiple visits over 36 months

Long-term Follow-up

Long-term monitoring of biochemical outcomes and toxicity, with assessments up to 10 years.

10 years

What Are the Treatments Tested in This Trial?

Interventions

• High dose rate prostate brachytherapy
• Low dose rate prostate brachytherapy

Trial Overview This trial compares two types of internal radiation therapy for treating prostate cancer: high dose rate (HDR) vs. low dose rate (LDR) brachytherapy. It's designed to see which method is more effective in patients with certain risk levels of prostate cancer.

How Is the Trial Designed?

Group I: High dose rate brachytherapy Experimental Treatment 1 Intervention

Device: Radiation. High dose rate prostate brachytherapy is delivered in 2 procedures, 2 weeks apart, also under anesthesia, but no follow-up imaging visit is required. HDR brachytherapy is also accomplished as an out-patient.

Group II: Low dose rate brachytherapy Active Control 1 Intervention

Device: Radiation. Low dose rate prostate brachytherapy is delivered under anesthesia in a single 1.5-2 hour procedure as an out-patient. The men return 4 weeks later for detailed imaging to assess implant quality.

High dose rate prostate brachytherapy is already approved in European Union, United States, Canada, United Kingdom for the following indications:

Approved in European Union as HDR Brachytherapy for:

• Localized prostate cancer
• Recurrent prostate cancer

Approved in United States as HDR Brachytherapy for:

• Localized prostate cancer
• Recurrent prostate cancer

Approved in Canada as HDR Brachytherapy for:

• Localized prostate cancer
• Recurrent prostate cancer

Approved in United Kingdom as HDR Brachytherapy for:

• Localized prostate cancer
• Recurrent prostate cancer

Who Is Running the Clinical Trial?

British Columbia Cancer Agency

Lead Sponsor

Trials

181

Recruited

95,900+

BC Cancer Foundation

Collaborator

Trials

20

Recruited

8,600+

Published Research Related to This Trial

In a study involving 10 patients with localized prostate cancer, both high-dose rate (HDR) and low-dose rate (LDR) brachytherapy techniques significantly reduced radiation exposure to critical organs like the rectum and bladder compared to volumetric modulated arc therapy (VMAT).

HDR brachytherapy was particularly effective in sparing the urethra from radiation damage compared to both VMAT and LDR, highlighting its potential as a safer treatment option for localized prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dosimetric and radiobiological comparison of volumetric modulated arc therapy, high-dose rate brachytherapy, and low-dose rate permanent seeds implant for localized prostate cancer. Yang, R., Zhao, N., Liao, A., et al.[2017]

In a study of 164 men treated with high-dose-rate (HDR) brachytherapy for prostate cancer, the procedure showed a low incidence of genitourinary (GU) and gastrointestinal (GI) complications, indicating it is a safe treatment option.

With a median follow-up of 18.6 months, HDR brachytherapy resulted in a high overall survival rate of 98.7% and a disease-free survival rate of 96.2%, demonstrating its efficacy in treating localized prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Building a High-Dose-Rate Prostate Brachytherapy Program With Real-Time Ultrasound-Based Planning: Initial Safety, Quality, and Outcome Results. Zhang, H., Kang, S., Ali, N., et al.[2022]

Low-dose-rate (LDR) brachytherapy is a one-time procedure with a long history of excellent outcomes and low side effects, making it the gold standard for low-risk prostate cancer patients.

High-dose-rate (HDR) brachytherapy, while more invasive and requiring multiple sessions, offers better control over dosimetry, allowing for safe dose escalation, but lacks extensive long-term data compared to LDR. Both techniques show equivalent effectiveness in treating localized prostate cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose-rate or high-dose-rate brachytherapy in treatment of prostate cancer - between options. Skowronek, J.[2022]

Both low-dose rate (LDR) and high-dose rate (HDR) brachytherapy provide effective tumor control for localized prostate cancer, with similar outcomes based on current clinical data and radiobiological modeling of tumor control probabilities.

HDR brachytherapy, especially with dose escalation, may offer superior tumor control compared to LDR, particularly for prostate cancers that are more sensitive to dose fractionation, suggesting potential for improved treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LDR vs. HDR brachytherapy for localized prostate cancer: the view from radiobiological models. King, CR.[2022]

High-dose rate brachytherapy (HDR-BT) shows promising results in controlling prostate cancer and preserving erectile function, making it a potentially advantageous alternative to low-dose rate brachytherapy (LDR-BT).

Despite its benefits, HDR-BT is still considered experimental and not yet recommended as a standard treatment for prostate cancer outside of clinical trials, indicating the need for further research to confirm its efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Do theoretical potential and advanced technology justify the use of high-dose rate brachytherapy as monotherapy for prostate cancer? Zaorsky, NG., Doyle, LA., Hurwitz, MD., et al.[2014]

In a study of 201 patients treated with low-dose-rate (LDR) brachytherapy for localized prostate cancer, there was a significant and persistent decline in prostate-specific antigen (PSA) levels over time, indicating effective cancer control.

After 10 years of follow-up, only 9 patients experienced tumor recurrence, and while some urinary symptoms were noted initially, they significantly decreased after 18 months, suggesting that LDR brachytherapy is both safe and effective with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose-rate brachytherapy as a minimally invasive curative treatment for localised prostate cancer has excellent oncological and functional outcomes: a retrospective analysis from a single centre. D'hulst, P., Mattelaer, P., Darras, J., et al.[2022]

In a study of 832 patients with localized prostate cancer treated with high-dose-rate brachytherapy (HDR-BT) and external beam radiotherapy (EBRT), higher biologically effective doses (BED) correlated with improved biochemical failure-free survival (BFFS) rates, particularly in the group receiving doses greater than 260Gy.

While higher BED regimens showed better control of PSA levels, the increase in urinary toxicity was minimal and considered clinically acceptable, with only a small percentage of patients experiencing severe toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose-rate brachytherapy boost for prostate cancer treatment: Different combinations of hypofractionated regimens and clinical outcomes. Vigneault, E., Mbodji, K., Magnan, S., et al.[2022]

Prostate brachytherapy, whether using permanent Low Dose Rate (LDR) or temporary High Dose Rate (HDR) techniques, is an effective treatment for non-metastatic prostate cancer, allowing for safe radiation dose escalation while minimizing damage to surrounding tissues.

Clinical evidence shows that brachytherapy improves PSA control compared to external beam radiotherapy alone, making it a valuable option in prostate cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GEC-ESTRO ACROP prostate brachytherapy guidelines. Henry, A., Pieters, BR., André Siebert, F., et al.[2022]

A study of 50,326 patients with localized prostate cancer from 2004 to 2014 found that while both high-dose-rate (HDR) and low-dose-rate (LDR) brachytherapy are effective, the use of HDR has declined over time, from 27% in 2004 to 19.2% in 2014.

Despite similar overall survival rates (127.0 months for HDR and 125.4 months for LDR), factors such as age, treatment at academic centers, and income influenced the likelihood of receiving HDR over LDR, indicating a shift in treatment patterns rather than differences in efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment patterns of high-dose-rate and low-dose-rate brachytherapy as monotherapy for prostate cancer. Barnes, J., Kennedy, WR., Fischer-Valuck, BW., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6043748/

High dose-rate brachytherapy in the treatment of prostate cancer In summary, HDR brachytherapy boost results in a high disease control rates for men with localized prostate cancer, with strong evidence that it provides ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S2452109425001484

High-dose-rate brachytherapy boost for prostate cancer: A ... Overall, this study demonstrated the efficacy of EBRT-boosted brachytherapy in the treatment of intermediate- and high-risk prostate cancer, ...

3. thegreenjournal.com thegreenjournal.com/article/S0167-8140(24)00651-0/fulltext

Prostate high dose-rate brachytherapy as monotherapy for ... We report on the efficacy of a randomized Phase II trial comparing HDR monotherapy delivered as 27 Gy in 2 fractions vs. 19 Gy in 1 fraction with a median ...

4. myhealthplanner.com myhealthplanner.com/web/public/brands/medicalpolicyhb/external-policies/high-dose-rate-temporary-prostate-brachytherapy/

High-Dose Rate Temporary Prostate Brachytherapy In another study, 4-year biochemical recurrence-free survival was significantly higher after HDR brachytherapy plus EBRT than after EBRT alone. The evidence is ...

5. urotoday.com urotoday.com/conference-highlights/astro-2024/astro-2024-prostate-cancer/155302-astro-2024-a-randomized-comparison-of-low-dose-rate-or-high-dose-rate-brachytherapy-combined-with-external-beam-radiation-for-unfavorable-intermediate-or-high-risk-prostate-cancer-efficacy-results-at-median-6-years.html

ASTRO 2024: A Randomized Comparison of Low Dose ... A randomized trial comparing low- and high-dose rate brachytherapy, combined with external beam radiotherapy, for intermediate- or high-risk prostate cancer.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12190164/

Long-Term Outcomes After High-Dose-Rate Brachytherapy ... Our findings confirm that this combined therapy yields promising outcomes at 24 years, with a biochemical control rate of 68% and a cancer- ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03424850

NCT03424850 | Safety and Efficacy of 21 Gy, 23 Gy and 25 ... The purpose of this research study is to learn more about the outcomes and early and late side effects of treating early stage prostate cancer with high dose ...