High vs Low Dose Rate Brachytherapy for Prostate Cancer

Recruiting at 8 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

334 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the dose of High Dose Rate (HDR) brachytherapy chosen for this study as well as a commonly used alternate form of brachytherapy called low dose rate (or seed) brachytherapy. Investigators would like to understand how these treatments control the prostate cancer and look at their short and long term treatment related side effects. The dose of radiation for HDR brachytherapy for this study has been changed since the study started. Other studies using the dose of radiation for HDR brachytherapy that was originally chosen for this study (Arm 2) found that this dose of radiation may be linked to a greater chance of the cancer coming back in the prostate. Therefore since March 2020, for new participants entering the study, a new HDR brachytherapy arm with a higher amount of radiation given over two doses will be tested in this study

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.

What data supports the effectiveness of high-dose-rate and low-dose-rate brachytherapy for prostate cancer treatment?

Research shows that both high-dose-rate (HDR) and low-dose-rate (LDR) brachytherapy are effective treatments for prostate cancer. LDR brachytherapy has been used successfully for over a decade with excellent long-term outcomes and few side effects, especially in low-risk patients. HDR brachytherapy, often combined with external beam radiation, has shown promising results in intermediate and high-risk patients, with good safety and effectiveness. ^{1 2 3 4 5}

Is brachytherapy safe for treating prostate cancer?

Research shows that both high-dose-rate (HDR) and low-dose-rate (LDR) brachytherapy are generally safe for treating prostate cancer, with few side effects reported. HDR brachytherapy tends to have fewer acute irritative symptoms, while LDR brachytherapy has robust safety data from clinical trials. ^{1 2 6 7 8}

How does high vs low dose rate brachytherapy for prostate cancer differ from other treatments?

High-dose-rate (HDR) brachytherapy is unique because it allows precise control over radiation delivery, enabling higher doses to be safely administered in fewer sessions, while low-dose-rate (LDR) brachytherapy is typically a one-time procedure with long-term follow-up data supporting its effectiveness. HDR is more invasive but offers flexibility in dose adjustment, whereas LDR is less invasive and has been a standard for low-risk patients. ^{1 4 5 9 10}

Research Team

Eric Vigneault

Principal Investigator

Hotel Dieu de Quebec, Montreal, QC

Gerard Morton

Principal Investigator

Sunnybrook Health Sciences, Toronto ON

Eligibility Criteria

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

Patients with localized prostate cancer meeting the following criteria: Clinical stage T1-T2 and Gleason 6 and PSA <20 ng/mL, Clinical stage T1-T2 and Gleason 7 (3+4) and PSA < 15 ng/mL and ≤ 50% of positive nontargeted cores in patients who undergo systematic biopsy, Eastern Cooperative Oncology Group status 0-1, Bone scan and pelvic CT scan/MRI within the last 6 months, Patient must be ≥ 18 years of age, Judged to be medically fit for brachytherapy, Prostate volume by Trans-rectal Ultrasound (TRUS) or Magnetic Resonance Imaging (MRI) ≤ 60 cc within the last 6 months, American Urological Association (AUA) score ≤ 20 within the last 4 weeks, Patient is able and willing to complete quality of life questionnaires in English or French, Patient consent obtained in accordance with applicable local and regulatory requirements, Patients must be accessible for treatment and follow-up, Protocol treatment to begin within 12 weeks of patient randomization, Patients must take precautions to prevent pregnancy while on study, Patients with a prior or concurrent malignancy not interfering with safety or efficacy assessment are eligible

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

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]

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 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]

References

1. Poland pubmed.ncbi.nlm.nih.gov

Treatment patterns of high-dose-rate and low-dose-rate brachytherapy as monotherapy for prostate cancer. [2023]

2. England 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. [2022]

3. Ireland 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. [2020]

4. France pubmed.ncbi.nlm.nih.gov

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

5. Poland pubmed.ncbi.nlm.nih.gov

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

6. United States 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. [2022]

7. Poland 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. [2022]

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

The evolution of brachytherapy for prostate cancer. [2023]

9. Egypt pubmed.ncbi.nlm.nih.gov

HDR Brachytherapy in the Management of High-Risk Prostate Cancer. [2021]

10. Ireland 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. [2021]