Combined Radiation Therapy for Prostate Cancer

(OPTiMAL Trial)

Overseen By Michael Peacock, MD

Age: 18+

Sex: Male

Trial Phase: Academic

Sponsor: British Columbia Cancer Agency

Must be taking: LHRH agonists

Must not be taking: Anticoagulants

Disqualifiers: Prior prostate surgery, Prior radiation, 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: Unknown

Duration: Varies, with androgen deprivation therapy lasting at least 1 year

105 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to reduce side effects in prostate cancer treatment by using advanced imaging and biopsy techniques for precise radiation therapy. It targets men with locally advanced prostate cancer, particularly those with high-risk or certain intermediate-risk features. The trial combines low-dose-rate brachytherapy (a type of internal radiation) with external beam radiation therapy to determine if this approach maintains high cure rates while minimizing side effects. Ideal participants are men diagnosed with prostate cancer who meet specific risk criteria and have not undergone prior treatments like surgery or radiation to the prostate. As an unphased trial, this study allows participants to contribute to innovative 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 if you are on blood thinners, you must be able to stop them safely for at least 5 days.

What prior data suggests that this combined radiation treatment is safe for prostate cancer patients?

Studies have shown that LDR (low-dose-rate) brachytherapy is a safe and effective treatment for prostate cancer. Patients generally tolerate it well, and the side effects remain manageable. One study noted the short treatment time, which many patients appreciate. Another study highlighted its success in controlling the disease while keeping side effects minimal. Importantly, it carries a low risk of causing new cancers from radiation.

Research has also shown that external beam radiation therapy (EBRT) is safe and effective. Patients usually tolerate it well, and it offers good results, especially when combined with brachytherapy. Some studies report its effectiveness even for patients with a higher risk.

Both treatments have strong safety records and are commonly used for prostate cancer, providing reassurance about their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the combined radiation treatment for prostate cancer because it integrates low-dose-rate (LDR) brachytherapy with external beam radiation therapy. Unlike traditional treatments, such as surgery or hormone therapy, this approach delivers targeted radiation both internally and externally. This dual delivery method enhances precision, potentially increasing the effectiveness of the treatment while minimizing damage to surrounding healthy tissues. The anticipation is that this method could offer improved outcomes with fewer side effects, making it a promising option for patients.

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

This trial will evaluate the combined use of low-dose-rate (LDR) brachytherapy and external beam radiation therapy (EBRT) for prostate cancer. Studies have shown that LDR brachytherapy effectively treats prostate cancer, controlling the disease in 75–95% of cases for patients with an intermediate risk level. It helps stop cancer growth, making it a strong option for many. EBRT also effectively treats prostate cancer, often yielding good results. By combining these treatments, the trial aims to improve outcomes by delivering a high dose to the prostate while protecting other organs. Overall, these treatments offer reliable options for effectively managing prostate cancer. ^{1 6 7 8 9}

Who Is on the Research Team?

Michael Peacock, MD

Principal Investigator

BCCANCER

Are You a Good Fit for This Trial?

Men with advanced local prostate cancer who have not received prior treatments like surgery or hormone therapy, and are fit enough for the trial (ECOG performance status 0-2). They must have a life expectancy over 5 years and be able to undergo MRI and PET/CT scans. The trial is specifically for those with high-risk disease as defined by NCCN or intermediate-risk disease meeting certain criteria.

Inclusion Criteria

My prostate cancer is considered high-risk or intermediate-risk with at least 3 points based on specific criteria.

My prostate cancer diagnosis was confirmed through a tissue sample.

My scans show no cancer spread to bones or lymph nodes.

Exclusion Criteria

You are unable to undergo a PET/CT scan.

I am a cancer survivor considered at low risk of recurrence, with no signs of cancer for at least 5 years.

I cannot have an MRI due to certain medical devices or conditions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Re-staging

Participants undergo advanced imaging and trans-perineal biopsy to determine appropriate multi-modality therapy components

4-6 weeks

Multiple visits for imaging and biopsy

Treatment

Participants receive a combination of 125 iodine LDR-PB implant followed by EBRT, with possible androgen deprivation therapy

Varies, with androgen deprivation therapy lasting at least 1 year

Regular visits for radiation therapy sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment, focusing on GU adverse effects

2 years

Periodic follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• External Beam Radiation Therapy
• LDR Brachytherapy

Trial Overview The OPTiMAL trial tests whether precision radiation therapy using advanced imaging techniques can reduce side effects in treating locally advanced prostate cancer. It aims to maintain high cure rates seen in previous studies while minimizing harm through targeted brachytherapy combined with external beam radiation.

How Is the Trial Designed?

Group I: Combined radiation treatment Experimental Treatment 1 Intervention

Combined low-dose-rate brachytherapy and external beam radiation therapy

LDR Brachytherapy is already approved in United States, European Union, Canada for the following indications:

Approved in United States as LDR Brachytherapy for:

• Prostate cancer

Approved in European Union as LDR Brachytherapy for:

• Prostate cancer

Approved in Canada as LDR Brachytherapy for:

• Prostate cancer

Who Is Running the Clinical Trial?

British Columbia Cancer Agency

Lead Sponsor

Trials

181

Recruited

95,900+

Published Research Related to This Trial

Low dose-rate prostate brachytherapy is effective for patients with favorable and select intermediate-risk prostate cancer, achieving a 10-year biochemical control rate of nearly 90%, comparable to surgery and external beam radiation.

While urinary toxicity is common, with 5-15% of patients experiencing acute urinary retention, sexual activity is preserved in about 60% of patients, making brachytherapy a viable treatment option alongside other methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prostate brachytherapy: indications and outcomes]. Hennequin, C., Cormier, L., Richaud, P., et al.[2013]

Low-dose-rate (LDR) brachytherapy can achieve a biochemically relapse-free outcome of up to 90% in low-risk prostate cancer patients over a 10-year follow-up, highlighting its efficacy as a curative treatment.

For intermediate- and high-risk prostate cancer, combined high-dose-rate (HDR) tele- and brachytherapy can also achieve a biochemically relapse-free outcome of 80-90%, indicating its effectiveness in more aggressive cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Brachytherapy of the prostate cancer]. Stübinger, SH., Wilhelm, R., Kaufmann, S., et al.[2021]

Low dose rate (LDR) permanent seed brachytherapy is an effective treatment option for low-risk and favorable intermediate-risk prostate cancer, and it can also be used as a boost in combination with external beam radiation for unfavorable intermediate and high-risk cases.

While LDR brachytherapy can lead to increased urinary symptoms initially, these typically resolve within 6 to 12 months, and the treatment is generally well-tolerated, making it a convenient option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low dose rate brachytherapy for primary treatment of localized prostate cancer: A systemic review and executive summary of an evidence-based consensus statement. King, MT., Keyes, M., Frank, SJ., et al.[2022]

In a study of 50 high-risk prostate cancer patients treated with low dose rate (LDR) brachytherapy, 72% achieved biochemical control, with a 3-year BCR-free survival rate of 92% for those with Gleason scores ≤ 8, indicating effective long-term outcomes for lower-risk patients.

Gleason score ≥ 9 was identified as a significant predictor of biochemical recurrence, highlighting the need for careful patient selection and monitoring in high-risk prostate cancer cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of Gleason Score ≤ 8 among high risk prostate cancer treated with 125I low dose rate brachytherapy based multimodal therapy. Park, DS., Gong, IH., Choi, DK., 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]

In a study of 32 patients with localized prostate cancer, those treated with low-dose rate brachytherapy experienced a significant decline in erectile function over time, with the most notable decrease occurring 36 months post-treatment.

Patients who initially had no or mild erectile dysfunction before treatment saw a greater drop in erectile function scores compared to those with moderate or severe dysfunction, indicating that even mild cases can worsen significantly after brachytherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The chronological process of erectile function after low-dose rate prostate brachytherapy for localised prostate cancer]. Bannowsky, A., Bäurle, L., Ataniyasov, R., et al.[2022]

Low-dose-rate (LDR) brachytherapy for localized prostate cancer shows excellent long-term efficacy, with a 15-year overall survival probability of 81% and a prostate cancer-specific survival probability of 95% based on a study of 2936 patients followed for a median of 10 years.

Key predictors of prostate cancer-related mortality include older age at treatment, advanced clinical stages (T2b and T2c-T3b), and a prostate-specific antigen (PSA) level greater than 1.0 ng/mL at 48 months post-implant, indicating that these factors can help assess patient prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term survival after low-dose-rate brachytherapy for prostate cancer: the Royal Surrey experience. Uribe-Lewis, S., Uribe, J., Bourke, V., et al.[2022]

In a study of 800 patients treated with Low Dose Rate (LDR) Brachytherapy for localized prostate cancer over 7.5 years, the procedure demonstrated a low urinary complication rate of 3% for acute urinary retention and only 0.2% for urinary incontinence.

The study also reported manageable digestive complications, with 12% experiencing intermittent bleeding, 2% proctitis, and a very low rate of 0.3% for rectal fistulas, indicating that LDR brachytherapy is a relatively safe option for prostate cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Brachyterapy in localized prostate cancer]. Abascal Junquera, JM., Hevia Suarez, M., Abascal García, JM., et al.[2019]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7492102/

Comparison of Patient-reported Outcomes After External ... In this prospective comparative effectiveness study, men with localized prostate cancer who received EB-LDR reported worse urinary function after treatment than ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7528218/

Comparison of outcomes and toxicities among radiation ... EBRT is a cornerstone of curative management of localized prostate cancer. External beam RT is used in about 25% of patients younger than 65 years, and almost ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa2214122

Fifteen-Year Outcomes after Monitoring, Surgery, or ... After median follow-up of 15 years, 45 patients (2.7%) had died of prostate cancer: 17 (3.1%) in the active-monitoring group, 12 (2.2%) in the ...

4. mskcc.org mskcc.org/news/what-every-man-should-know-about-radiation-therapy-prostate-cancer

The Latest Radiation Therapy for Prostate Cancer Excellent outcomes: Multiple randomized clinical trials have shown that SBRT is very effective at controlling cancer. Few side effects: SBRT has ...

5. e-roj.org e-roj.org/journal/view.php?number=1500

Comparison of radical prostatectomy and external beam ... Based on recent data and the results from this study, EBRT and RP seemed to have similar effects on controlling high-risk prostate cancer in the ...

6. redjournal.org redjournal.org/article/S0360-3016(25)03353-X/fulltext

Safety and Early Outcomes of External Beam Radiation ... Between 1999 and 2024, 307 patients received EBRT and LDR. Of the 307 patients, 117 patients (38%) had NCCN intermediate-risk prostate cancer ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S036030162503353X

Safety and Early Outcomes of External Beam Radiation ... Here, we retrospectively report the safety and early efficacy of using EBRT and low-dose-rate (LDR) brachytherapy boost with or without androgen deprivation ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9602254/

Prostate only radiotherapy using external beam ... However, favorable results have been reported for SBRT in high-risk patients. Lee et al[42] reported a safe and good result of SBRT using Cyberknife, with a ...

9. cancernetwork.com cancernetwork.com/view/ebrt-regimens-elicit-15-year-prostate-cancer-survival-outcomes

EBRT Regimens Elicit 15-Year Prostate Cancer Survival ... Additionally, the 15-year overall survival (OS) rate was 53% for those undergoing STAD plus EBRT and 51% for those undergoing EBRT alone (P = .