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

Trial Summary

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 data supports the effectiveness of this treatment for prostate cancer?

Research shows that low-dose-rate (LDR) brachytherapy, a part of the combined radiation therapy, is effective for treating localized prostate cancer, achieving up to 90% relapse-free outcomes in low-risk cases over 10 years. Additionally, combining LDR brachytherapy with external radiation therapy can lead to 80-90% relapse-free outcomes in intermediate- and high-risk cases. ^{1 2 3 4 5}

Is combined radiation therapy for prostate cancer safe for humans?

Low-dose-rate brachytherapy, a type of radiation therapy for prostate cancer, is generally considered safe, with studies showing it as a minimally invasive option with good long-term outcomes. However, it may affect erectile function over time, which is an important consideration for patients. ^{1 3 5 6 7}

How is LDR Brachytherapy different from other prostate cancer treatments?

LDR Brachytherapy for prostate cancer involves implanting small radioactive seeds directly into the prostate, providing targeted radiation over a long period, which is different from external radiation that targets the prostate from outside the body. This method is minimally invasive and can be used alone for low-risk tumors or combined with other therapies for higher-risk cases, offering a high chance of long-term cancer control. ^{1 2 4 6 8}

What is the purpose of this trial?

Multi-modality therapy that includes a brachytherapy implant improves outcomes in locally advanced prostate cancer when compared to other radiation-based treatments, but is also associated with more adverse side effects. The goal of the OPTiMAL trial is to reduce these side effects by using advanced imaging and biopsy techniques to locate cancer and deliver precision radiation therapy, while not compromising the unprecedented high cure rates obtained for the brachytherapy arm of the Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (ASCENDE-RT) randomized control trial. Additionally, some applied research in genetics, pathology and medical imaging is included. Novel medical imaging methods, namely, multi-parametric magnetic resonance imaging (MRI), multi-parametric trans-rectal ultrasound (TRUS), prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) are used for re-staging of prostate cancer. This is followed by trans-perineal biopsy to locate cancerous areas of the prostate with greater precision compared to conventional biopsy. Results from imaging are compared to those from biopsy to develop image-based cancer detection methods.

Research Team

Michael Peacock, MD

Principal Investigator

BCCANCER

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

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 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]

References

1. United States 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. [2022]

2. Korea (South) 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. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Long-term survival after low-dose-rate brachytherapy for prostate cancer: the Royal Surrey experience. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

[Brachytherapy of the prostate cancer]. [2021]

5. 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]

6. Spain pubmed.ncbi.nlm.nih.gov

[Brachyterapy in localized prostate cancer]. [2019]

7. Germany pubmed.ncbi.nlm.nih.gov

[The chronological process of erectile function after low-dose rate prostate brachytherapy for localised prostate cancer]. [2022]

8. France pubmed.ncbi.nlm.nih.gov

[Prostate brachytherapy: indications and outcomes]. [2013]