HDR Brachytherapy for Prostate Cancer

(SalvageHDR Trial)

Overseen By Francois Bachand, MD

Age: 18+

Sex: Male

Trial Phase: Academic

Sponsor: British Columbia Cancer Agency

Disqualifiers: Inflammatory bowel disease, Rectal surgery, others

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 2 weeks

30 Participants Needed

Trial Summary

What is the purpose of this trial?

A dose-response relationship for radiation in the management of prostate cancer is well established. Local recurrence of prostate cancer after external beam radiotherapy occurs in at least 40% of patients treated because of inability to deliver sufficient dose through external beam techniques. These patients respond well to re-irradiation using brachytherapy with about 50% of selected patients remaining free of recurrence 5 years after salvage. Advanced imaging using multiparametric Magnetic Resonance Imaging (mpMRI) allows identification of the site of recurrence, permitting partial prostate salvage brachytherapy. There is extensive literature on Low Dose Rate salvage brachytherapy but less on High Dose Rate.

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

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that Androgen Deprivation Therapy can be started if your doctor thinks it's necessary.

What data supports the effectiveness of the treatment HDR Brachytherapy for Prostate Cancer?

Research shows that HDR brachytherapy, either alone or combined with external beam radiation, is effective for treating localized prostate cancer, with high survival rates and disease-free outcomes. Studies indicate that this treatment is particularly beneficial for patients with low to intermediate-risk prostate cancer, offering a good balance of effectiveness and manageable side effects. ^{1 2 3 4 5}

Is HDR Brachytherapy safe for humans?

Research shows that HDR Brachytherapy is generally safe for treating prostate cancer, with studies reporting on its safety and patient tolerance. It is considered effective and safe, with some studies focusing on short-term safety and patient-reported outcomes. ^{6 7 8 9 10}

How is HDR Brachytherapy different from other prostate cancer treatments?

HDR Brachytherapy for prostate cancer is unique because it involves placing a temporary radioactive source directly into the prostate, delivering high doses of radiation precisely to the cancer cells while sparing surrounding healthy tissue. This treatment can be done in one or two sessions, unlike traditional radiation therapy, which often requires multiple sessions over several weeks. ^{1 5 11 12 13}

Research Team

Mira Keyes, MD

Principal Investigator

BCCA

Eligibility Criteria

Men over 45 with a life expectancy of more than 10 years, who have had prostate cancer return after external beam radiotherapy. They should not have severe late side effects from previous treatments, must be able to undergo advanced MRI scans, and have confirmed localized recurrence suitable for high dose brachytherapy. Patients with inflammatory bowel disease or prior rectal surgery can't join.

Inclusion Criteria

I have not experienced severe side effects from previous radiation therapy.

INR <2.5 and platelet count >75 x 109/L

Rising PSA post EBRT > nadir + 2 ng/ml but < 10 ng/ml

Exclusion Criteria

Not compliant with criteria above

I am unable to understand and agree to the study's procedures and risks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Two fractions of high dose rate prostate brachytherapy delivered 2 weeks apart

2 weeks

2 visits (in-person)

Follow-up

Participants are monitored for toxicity, quality of life, and efficacy using PSA and mpMRI

24 months

Regular visits for monitoring

Long-term follow-up

Monitoring of late quality of life and adverse events up to 60 months

60 months

Treatment Details

Interventions

• HDR partial prostate brachytherapy

Trial Overview The trial is testing High Dose Rate (HDR) partial prostate brachytherapy on patients whose prostate cancer has returned post-radiotherapy. It focuses on the area identified by mpMRI as having recurrent cancer, aiming to see if targeted HDR brachytherapy can effectively treat these local recurrences.

Participant Groups

Group I: HDR partial prostate brachytherapy Experimental Treatment 1 Intervention

2 fractions of high dose rate prostate brachytherapy will be delivered to the site of recurrent disease as determined by mp-MRI

HDR partial prostate brachytherapy is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as High Dose Rate Brachytherapy for:

• Prostate cancer
• Local recurrence of prostate cancer after external beam radiotherapy

Approved in United States as HDR Brachytherapy for:

• Prostate cancer
• Local recurrence of prostate cancer after external beam radiotherapy

Approved in Canada as High Dose Rate Brachytherapy for:

• Prostate cancer
• Local recurrence of prostate cancer after external beam radiotherapy

Who Is Running the Clinical Trial?

British Columbia Cancer Agency

Lead Sponsor

Trials

181

Recruited

95,900+

Findings from Research

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]

A new therapy protocol combining high dose rate (HDR) brachytherapy and external beam radiation showed promising results in treating localized prostate cancer, with a 76.7% survival rate and 86.3% of patients remaining disease-free over a median follow-up of 6 years.

The study found that factors like lower tumor stage (T1-2), lower grade (G1-2), and normal PSA levels after treatment were associated with longer survival, highlighting the importance of PSA status as an independent prognostic factor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[High dosage brachytherapy and external irradiation of localized prostate carcinoma--results at the Kiel University Clinic]. Kovács, G., Galalae, R., Loch, T., et al.[2018]

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]

Patients with intermediate- to high-risk prostate cancer who received a high-dose-rate (HDR) brachytherapy boost along with 3D conformal radiotherapy (3DCRT) showed significantly better overall survival rates at 5, 10, and 15 years compared to those who received 3DCRT alone, with survival rates of 92%, 81%, and 67% versus 88%, 71%, and 53%, respectively.

The HDR boost group also demonstrated improved cause-specific survival rates, indicating that this treatment combination not only prolongs life but also effectively targets cancer progression, with cause-specific survival rates of 96%, 93%, and 87% for the HDR group compared to 95%, 88%, and 79% for the 3DCRT group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved survival for patients with prostate cancer receiving high-dose-rate brachytherapy boost to EBRT compared with EBRT alone. Kent, AR., Matheson, B., Millar, JL.[2019]

Single-fraction high-dose-rate (HDR) brachytherapy is a safe and effective treatment for early-stage prostate cancer, showing a low cumulative incidence of biochemical recurrence (BCR) at 2 years, particularly in low-risk patients (0% BCR).

In a study of 124 men with a median follow-up of 2.2 years, the overall BCR rate was 9.7%, with no prostate cancer-specific mortality and no severe genitourinary toxicity reported, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Single-fraction brachytherapy as monotherapy for early-stage prostate cancer: The UCSF experience. Xu, MJ., Chen, KS., Chang, AJ., et al.[2020]

High-dose-rate (HDR) brachytherapy is a safe and effective treatment for low-risk prostate cancer, with 45% of patients experiencing some form of acute toxicity, primarily grade 1 urinary toxicity, within three months post-treatment.

The study found that urinary toxicity was significantly linked to the dose received by the urethra, with patients receiving over 111.3% of the prescribed dose being four times more likely to experience urinary issues, highlighting the importance of careful dose management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose-rate brachytherapy delivered in two fractions as monotherapy for low-risk prostate cancer. Cendales, R., Alwers, E., Cifuentes, J., et al.[2020]

Prostate high dose rate (HDR) brachytherapy can be safely performed in a free-standing cancer center, with only 3.7% of procedures resulting in complications requiring catheter placement.

The treatment is well tolerated, with 20% of patients experiencing significant post-implant dysuria lasting an average of 7.5 days, indicating manageable side effects when combined with external beam radiation and hormonal therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prostate high dose rate brachytherapy in a free-standing cancer center setting. Tharp, M., Bennett, R., Burns, J., et al.[2016]

High-dose-rate (HDR) brachytherapy is an effective and well-tolerated treatment for localized prostate cancer, with a median follow-up of 18 months showing manageable side effects.

The interval between HDR treatment sessions (1 week vs. 2 weeks) does not significantly affect patient-reported quality of life or physician-graded toxicity, indicating flexibility in treatment scheduling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient and physician reported toxicity with two-fraction definitive high-dose-rate prostate brachytherapy: the impact of implant interval. Harris, AA., Korpics, M., Sherwani, Z., et al.[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]

High-dose-rate (HDR) brachytherapy for early-stage prostate cancer showed excellent outcomes, with a 100% biochemical progression-free survival rate and no severe toxicities (grade ≥3) reported among 39 patients followed for a median of 57 months.

While HDR treatment is generally safe, factors such as larger prostate size and higher doses to the urethra and bladder can lead to worse short-term urinary quality of life, and older patients may experience more significant sexual function impairment both shortly after treatment and in the long term.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient- and treatment-specific predictors of genitourinary function after high-dose-rate monotherapy for favorable prostate cancer. Raleigh, DR., Chang, AJ., Tomlin, B., et al.[2022]

High-dose-rate (HDR) brachytherapy is a new and promising treatment for prostate cancer that offers potential benefits in radiation physics and radiobiology.

The article outlines the technique for using HDR brachytherapy as a standalone treatment, emphasizing its innovative approach, although clinical results are still developing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose-rate brachytherapy as monotherapy for prostate cancer: technique, rationale and perspective. Yoshioka, Y., Suzuki, O., Otani, Y., et al.[2021]

High-dose rate brachytherapy (HDR-BT) shows high efficacy as a monotherapy for localized prostate cancer, with local control rates between 97-100% and biochemical progression-free survival rates of 85-100% for low-risk patients and 79-92% for high-risk patients based on a systematic review of 14 studies.

While HDR-BT is generally safe, most studies reported acute and long-term genitourinary complications, which were more common and severe than gastrointestinal issues, indicating a need for further research on long-term safety and efficacy, especially in high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose rate brachytherapy as monotherapy in prostate cancer: A systematic review of its safety and efficacy. Sánchez-Gómez, LM., Polo-deSantos, M., Rodríguez-Melcón, JI., et al.[2022]

High-dose-rate (HDR) brachytherapy shows excellent biochemical control rates for localized prostate cancer, achieving 85-100% for low-risk, 81-100% for intermediate-risk, and 43-93% for high-risk cases, based on a comprehensive review of literature.

Severe toxicity from HDR brachytherapy is rare, with less than 5% of patients experiencing Grade 3 or higher side effects, highlighting its safety as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

American Brachytherapy Society consensus guidelines for high-dose-rate prostate brachytherapy. Yamada, Y., Rogers, L., Demanes, DJ., et al.[2022]

References

1. 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]

2. Switzerland pubmed.ncbi.nlm.nih.gov

[High dosage brachytherapy and external irradiation of localized prostate carcinoma--results at the Kiel University Clinic]. [2018]

3. France pubmed.ncbi.nlm.nih.gov

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

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

Improved survival for patients with prostate cancer receiving high-dose-rate brachytherapy boost to EBRT compared with EBRT alone. [2019]

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

Single-fraction brachytherapy as monotherapy for early-stage prostate cancer: The UCSF experience. [2020]

6. Poland pubmed.ncbi.nlm.nih.gov

High-dose-rate brachytherapy delivered in two fractions as monotherapy for low-risk prostate cancer. [2020]

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

Prostate high dose rate brachytherapy in a free-standing cancer center setting. [2016]

8. Poland pubmed.ncbi.nlm.nih.gov

Patient and physician reported toxicity with two-fraction definitive high-dose-rate prostate brachytherapy: the impact of implant interval. [2022]

9. 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]

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

Patient- and treatment-specific predictors of genitourinary function after high-dose-rate monotherapy for favorable prostate cancer. [2022]

11. Poland pubmed.ncbi.nlm.nih.gov

High-dose-rate brachytherapy as monotherapy for prostate cancer: technique, rationale and perspective. [2021]

12. Spain pubmed.ncbi.nlm.nih.gov

High-dose rate brachytherapy as monotherapy in prostate cancer: A systematic review of its safety and efficacy. [2022]

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

American Brachytherapy Society consensus guidelines for high-dose-rate prostate brachytherapy. [2022]