High vs Low Dose Rate Brachytherapy for Prostate Cancer

Not currently recruiting at 9 trial locations

Overseen By Wendy Parulekar

Age: 18+

Sex: Male

Trial Phase: Academic

Sponsor: Canadian Cancer Trials Group

Must not be taking: Androgen deprivation, Alpha-reductase inhibitors

Disqualifiers: Bleeding diathesis, Metastatic disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Varies by treatment type

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two types of brachytherapy, a form of internal radiation treatment, to evaluate their effectiveness against prostate cancer. Researchers compare a low dose rate (seeds placed near the tumor) with a high dose rate (higher radiation given in two parts) to assess cancer management and side effects. Men diagnosed with localized prostate cancer in the last nine months, who have not received certain prior treatments, might be suitable candidates. The goal is to determine which treatment better controls cancer and what side effects may occur. As an unphased trial, this study allows patients to contribute to important research that could enhance future prostate cancer treatments.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have used alpha-reductase inhibitors (a type of medication for prostate issues) within 90 days before joining the study.

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

Past studies have shown that high dose rate (HDR) brachytherapy is a safe and effective treatment for intermediate-risk prostate cancer. Research indicates it controls the disease well and is generally safe. However, some studies have noted that long-term survival rates might be lower compared to other treatments.

For low dose rate (LDR) brachytherapy, studies have found it effective for treating both low- and intermediate-risk prostate cancer. It delivers a high dose directly to the prostate, helping to protect nearby organs from damage. However, patients have reported more urinary symptoms in the first six months after treatment. Overall, it is considered safe.

Both treatments have been used for years in prostate cancer care and have a good safety record. While each has its own potential side effects, they are generally well-tolerated by patients. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the differences between high dose rate (HDR) and low dose rate (LDR) brachytherapy for prostate cancer. HDR brachytherapy delivers a higher dose of radiation in a shorter timeframe, potentially leading to fewer side effects and shorter treatment durations compared to traditional methods. On the other hand, LDR brachytherapy involves implanting radioactive seeds that provide a continuous, targeted dose over a longer period, which might enhance precision in treating cancerous tissues. Both methods aim to improve the effectiveness of prostate cancer treatment while minimizing damage to surrounding healthy tissue, offering hope for better patient outcomes.

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

This trial will compare high dose rate (HDR) brachytherapy with low dose rate (LDR) brachytherapy for prostate cancer. Research has shown that HDR brachytherapy effectively controls prostate cancer. One study found that using HDR brachytherapy alone provided good disease control for men with localized prostate cancer. Another study reported that combining HDR brachytherapy with external beam radiation therapy (EBRT) led to better cancer control than using EBRT alone.

For LDR brachytherapy, research also supports its effectiveness. One study showed that LDR brachytherapy maintained a high rate of patients whose cancer did not worsen over seven years. Another study found that most patients did not experience a return of cancer over eight years after receiving LDR brachytherapy.

Both HDR and LDR brachytherapy, which this trial compares, have shown promising results in managing prostate cancer. ^{1 2 3 4 6}

Who Is on the Research Team?

Gerard Morton

Principal Investigator

Sunnybrook Health Sciences, Toronto ON

Eric Vigneault

Principal Investigator

Hotel Dieu de Quebec, Montreal, QC

Are You a Good Fit for This Trial?

Men over 18 with recently diagnosed low or intermediate risk prostate cancer, who haven't had hormone therapy, surgery, radiation, or chemotherapy for it. They should be fit for brachytherapy, have a prostate size ≤60 cc and an AUA score ≤20. Participants must complete questionnaires in English/French and agree to prevent pregnancy during the trial.

Inclusion Criteria

I am being actively monitored for my condition, it's getting worse, and I had a prostate biopsy in the last 9 months.

My prostate cancer was confirmed by a biopsy within the last 9 months.

Exclusion Criteria

I have not taken alpha-reductase inhibitors in the last 90 days.

I do not have any serious health issues that would stop me from following the study's requirements.

I have a history of unusual bleeding or clotting.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either High Dose Rate (HDR) brachytherapy or Low Dose Rate (LDR) brachytherapy as monotherapy for localized prostate cancer

Varies by treatment type

Multiple visits for treatment administration

Follow-up

Participants are monitored for prostate cancer control and treatment-related side effects

48 months

Regular follow-up visits

Long-term Follow-up

Participants are monitored for long-term safety and economic analysis

7 years

What Are the Treatments Tested in This Trial?

Interventions

• High dose rate brachytherapy
• Low dose rate brachytherapy

Trial Overview The study compares two types of radiation treatments: High Dose Rate (HDR) brachytherapy with a new higher dose against Low Dose Rate (seed) brachytherapy. It aims to see which is better at controlling cancer and assesses short/long-term side effects.

How Is the Trial Designed?

Group I: Arm 3 HDR Active Control 1 Intervention

High Dose Rate brachytherapy: 27 Gy in 2 fractions

Group II: Arm 1 LDR Active Control 1 Intervention

Low Dose Rate (LDR) brachytherapy with I-125 to a total dose of 144 Gy

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

Approved in European Union as HDR Brachytherapy for:

• Localized prostate cancer
• Locally advanced prostate cancer
• Recurrent prostate cancer

Approved in United States as HDR Brachytherapy for:

• Localized prostate cancer
• Locally advanced prostate cancer
• Recurrent prostate cancer

Approved in Canada as HDR Brachytherapy for:

• Localized prostate cancer
• Locally advanced prostate cancer
• Recurrent prostate cancer

Approved in Japan as HDR Brachytherapy for:

• Localized prostate cancer
• Locally advanced prostate cancer
• Recurrent prostate cancer

Who Is Running the Clinical Trial?

Canadian Cancer Trials Group

Lead Sponsor

Trials

135

Recruited

70,300+

Published Research Related to This Trial

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]

High dose rate (HDR) brachytherapy combined with external beam radiation therapy has been shown to be a safe and effective treatment for intermediate and high-risk prostate cancer, leading to a significant increase in treatment options and outcomes.

The success of HDR brachytherapy has prompted its use as a standalone treatment for low to intermediate-risk prostate cancer, supported by excellent toxicity profiles and clinical results from ongoing research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of high dose rate brachytherapy in the treatment of prostate cancer. Ghilezan, M.[2012]

In a study of 195 patients treated with low-dose rate brachytherapy (LDR-BT) for low-risk prostate cancer, the five-year biochemical failure-free survival (BFFS) rate was an impressive 95.7%.

The study found that the dose delivered to the prostate (D90%) was significantly linked to BFFS, indicating that a dose range of 170-180 Gy leads to excellent treatment outcomes with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose rate brachytherapy with I-125 seeds has an excellent 5-year outcome with few side effects in patients with low-risk prostate cancer. Rasmusson, E., Gunnlaugsson, A., Kjellén, E., et al.[2022]

High-dose-rate (HDR) brachytherapy is increasingly used for treating prostate cancer, allowing for large doses to be delivered directly to the tumor while minimizing damage to surrounding healthy tissues.

This technique is particularly effective for high-risk prostate cancer patients when combined with external beam radiotherapy, leveraging the unique sensitivity of prostate tumors to higher radiation doses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HDR Brachytherapy in the Management of High-Risk Prostate Cancer. Masson, S., Persad, R., Bahl, A.[2021]

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]

In a randomized phase II trial involving 170 patients with localized prostate cancer, HDR brachytherapy delivered in two fractions of 13.5 Gy resulted in significantly better 5-year biochemical disease-free survival (95%) compared to a single fraction of 19 Gy (73.5%).

The two-fraction treatment was well tolerated, with low rates of late rectal toxicity (1%) and manageable urinary toxicity (45% grade 2), indicating it is a safe and effective option for prostate cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate high dose-rate brachytherapy as monotherapy for low and intermediate risk prostate cancer: Efficacy results from a randomized phase II clinical trial of one fraction of 19 Gy or two fractions of 13.5 Gy. Morton, G., McGuffin, M., Chung, HT., et al.[2021]

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]

Brachytherapy (BT) is a safe and effective treatment for prostate cancer across all risk groups, with 5-year freedom from biochemical failure rates exceeding 85% for low-risk patients and 63-80% for high-risk patients.

Both high-dose-rate (HDR) and low-dose-rate (LDR) brachytherapy show similar outcomes, with low rates of severe toxicities (<4%) and improved quality of life compared to surgical options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The evolution of brachytherapy for prostate cancer. Zaorsky, NG., Davis, BJ., Nguyen, PL., et al.[2023]

In a study of 119 patients with locally-recurrent prostate cancer, both high-dose-rate (HDR) and low-dose-rate (LDR) brachytherapy showed similar efficacy in terms of relapse-free survival (RFS) and cause-specific survival (CSS) after salvage therapy, with a 5-year RFS rate of 71%.

There were no significant differences in toxicity between HDR and LDR brachytherapy, with 23.5% of patients experiencing severe side effects, indicating that both techniques are comparably safe for salvage treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Salvage brachytherapy for locally-recurrent prostate cancer after radiation therapy: A comparison of efficacy and toxicity outcomes with high-dose rate and low-dose rate brachytherapy. Henríquez López, I., González-San Segundo, C., Vegas, JO., et al.[2020]

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

Long-Term Outcomes After High-Dose-Rate Brachytherapy ... These outcomes included lower biochemical recurrence-free survival at 5 and 8 years, lower OS, and lower prostate CSS compared to patients with ...

3. advancesradonc.org advancesradonc.org/article/S2452-1094(25)00148-4/fulltext

High-Dose-Rate Brachytherapy Boost for Prostate Cancer However, studies have shown that combining brachytherapy with EBRT results in a higher rate of cancer control than EBRT alone. Nevertheless, the ...

4. 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 ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0360301625003037

A Randomized Comparison of High-Dose-Rate and Low- ... This randomized trial compares HDR BT with LDR BT when used in combination with EBRT for unfavorable prostate cancer.

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0167814025046286

A randomized Phase II trial of High Dose-Rate (HDR) and ... LDR brachytherapy has high prostate cancer disease control rate at 4 years, although with worse impact on urinary symptoms in the first 6 months ...