Focal Therapy for Prostate Cancer in Canada: A Patient's Guide to the Evidence

Table of Contents

• Introduction: The Promise of Focal Therapy
• How This Review Was Conducted
• How Focal Therapies Were Approved: The Regulatory Pathway
• The Current State of Evidence for Focal Therapy
• Detailed Oncologic Outcomes: What Does the Data Show?
• Functional Outcomes and Side Effects
• Canadian Involvement and Current Landscape
• The Future: Ongoing Clinical Trials in Canada
• Conclusions and Key Takeaways for Patients
• Source Information

Introduction: The Promise of Focal Therapy

Prostate cancer is the most common cancer among Canadian men, with about 26,000 new cases diagnosed each year. For men with cancer that is still confined to the prostate (localized), traditional treatment options include active surveillance (monitoring), radical prostatectomy (surgical removal of the entire prostate), or radiation therapy. A major long-term study found that while these treatments have similar survival rates over 15 years, they come with different trade-offs. About a quarter of men on active surveillance avoided treatment entirely, but this group had more cancer progression and spread. Conversely, men who had radical surgery or radiation had more side effects, including urinary incontinence, erectile dysfunction (ED), and bowel problems.

This creates a dilemma known as "overtreatment"—where the side effects of radical therapy may be unnecessary for some men whose cancer may never become life-threatening, but it's difficult to predict who those men are. Focal therapy (FT) aims to fill this gap. The goal is to precisely destroy the main tumor (called the index lesion) thought to drive the disease, while preserving the rest of the healthy prostate gland. This strategy seeks to control the cancer while minimizing damage to nerves and structures responsible for urinary and sexual function.

Different energy sources can be used to destroy the targeted tissue, including:

• High-Intensity Focused Ultrasound (HIFU): Uses focused sound waves to heat and destroy tissue.
• Irreversible Electroporation (IRE): Uses electrical pulses to create tiny holes in cancer cell membranes.
• Cryotherapy: Freezes and destroys tissue.
• Photodynamic Therapy (PDT): Uses a light-activated drug to produce toxic compounds that kill cells.
• Focal Laser Ablation (FLA): Uses laser energy to heat and destroy tissue.
• Transurethral Ultrasound Ablation (TULSA): Delivers ultrasound energy via the urethra to ablate tissue.

Despite approval from Health Canada and the U.S. Food and Drug Administration (FDA), focal therapies are not yet standard, guideline-recommended options in North America. Major urology associations recommend that FT should be offered primarily within clinical trials or prospective registries so that outcomes can be carefully tracked. This review was written to answer three key questions for patients and doctors: How were these therapies approved? What does the current evidence say about their safety and effectiveness? And what options are currently available to Canadians?

How This Review Was Conducted

The authors performed a structured scoping review of the medical literature to gather all relevant studies on focal therapy for prostate cancer published between January 2021 and January 2024. They searched major databases like PubMed and Embase, focusing on studies that reported either functional outcomes (like side effects and quality of life) or oncologic outcomes (like cancer control and survival). The review included various study designs, from single-arm studies to randomized controlled trials (RCTs).

They also examined the FDA database to understand exactly how each focal therapy device was approved for use. Finally, they searched for ongoing clinical trials in Canada using ClinicalTrials.gov and identified private clinics offering FT services.

How Focal Therapies Were Approved: The Regulatory Pathway

Understanding how these devices were approved is crucial. In the U.S., the FDA regulates medical devices through its Center for Devices and Radiologic Health (CDRH). Devices are classified by risk: Class I (low risk, like a tongue depressor), Class II (moderate risk), and Class III (high risk, like a pacemaker). Most focal therapy devices are considered Class II.

Class II devices often get approved through a pathway called 510(k). In this process, a manufacturer must show that their new device is "substantially equivalent" to an already legally marketed device (called a predicate). This can allow a new technology to bypass the need for extensive new clinical trials to prove it treats cancer effectively.

In 2015, HIFU was the first FT device approved, but it took a different route called the "de novo" pathway. This is for novel devices without an existing predicate. The approval was based on a study of 117 men with recurrent prostate cancer after radiation. The data showed HIFU could reduce prostate volume and PSA levels, with negative biopsies in 61% of patients. There were, however, 27 serious adverse events reported in that study.

Every other focal therapy technology (like IRE, cryotherapy, TULSA) has since been approved through the 510(k) pathway, claiming substantial equivalence to an existing device like the HIFU system. A critical point for patients is that these submissions did not require data proving the device's effectiveness at curing or controlling prostate cancer; they only needed to show it could safely ablate (destroy) prostate tissue.

The Current State of Evidence for Focal Therapy

The quality of research for any new surgical procedure evolves through stages. The early stages (IDEAL stages 1-2b) involve small studies figuring out how to do the procedure and checking for safety. Later stages (3-4) involve larger studies that compare the new treatment to the current standard, often through randomized trials.

A major systematic review published in 2020 analyzed 72 studies involving 5,827 patients. It found that the vast majority of evidence for focal therapy is in these early research stages (IDEAL 2a and 2b). Most studies were single-arm, meaning all patients got FT and there was no comparison group. Only five studies had reached the more advanced stages (3 or 4) where proper comparisons can be made. Of the 15 new studies included in this 2024 review, only one was an advanced IDEAL stage 3 study.

This means the current body of evidence, while growing, lacks the high-quality comparative data (especially from RCTs) that doctors and patients rely on to make definitive treatment decisions between FT, surgery, and radiation.

Detailed Oncologic Outcomes: What Does the Data Show?

Measuring success after focal therapy is tricky. PSA levels can remain detectable because healthy prostate tissue is left behind. MRI scans might miss small areas of remaining cancer. Therefore, the most common way to check if FT worked is to perform a follow-up biopsy of the treated area about 12 months later to look for clinically significant cancer (CSC).

Based on the 2020 review, here is what the data shows about finding cancer in the treated area after FT:

• HIFU: Median rate of 14.7%
• IRE: Median rate of 8.5%
• Photodynamic Therapy (PDT): Median rate of 10%
• Cryotherapy: Median rate of 15%
• Focal Laser Ablation (FLA): Median rate of 17%

Cancer can also be found in the untreated part of the prostate. The rates for this were:

• HIFU: 2% to 21% across studies
• IRE: 12.7% to 25% across studies

Other important cancer control metrics include:

• Biochemical Recurrence: (A rising PSA after treatment). Rates varied widely: 1–28% for HIFU, 7–70% for brachytherapy.
• Salvage Therapy: (Needing additional treatment like surgery or radiation later). Rates were: 2–26% for HIFU, 0–25% for IRE.
• Recurrence-Free Survival (RFS) at ~4 years: 58% for HIFU, 92% for focal brachytherapy, 56% for cryotherapy.
• Overall Survival: Was very high (96-100%) across all modalities, but follow-up times were relatively short (median 29 months).

Newer, Notable Studies:

• A large IRE study of 411 patients found 24.1% had clinically significant cancer on follow-up biopsy after a median of 24 months.
• A longer-term IRE study of 229 patients showed 17% needed radical treatment by 35 months. Recurrence-free survival was 84% at 5 years and 69% at 8 years. Crucially, metastasis-free survival was 99.6% and cancer-specific survival was 100% at 5 years.
• A 2023 systematic review comparing IRE to HIFU suggested IRE might lead to better potency preservation and higher rates of negative follow-up biopsies.

Functional Outcomes and Side Effects

The potential to preserve quality of life is a major driving force behind interest in focal therapy.

Serious Adverse Events: The rate of serious complications (Grade III or higher) is generally low. Across 19 HIFU studies, the median rate was 2%, with a range of 0–14%. These events can include urinary tract infections, significant bleeding, or very rarely, fistulas (an abnormal connection between the urethra and rectum). A large review of HIFU patients found urethral strictures (scarring) in 10.3% and urinary fistulas in 1.3% of cases.

Urinary Continence: This is a major strength of FT. Pad-free continence rates (not needing protective pads for leakage) are consistently reported as greater than 95% after treatment, with many studies showing no change from a patient's baseline function before treatment.

Erectile Function: Outcomes are more variable here. Many studies show no significant decline in patient-reported erectile function scores. However, some treatments do have an impact:

• Focal brachytherapy studies showed new-onset erectile dysfunction rates as high as 50%.
• HIFU studies estimated erectile dysfunction rates around 20%, with increased use of erection medication (PDE5 inhibitors like Viagra) in up to 17% of men.
• IRE studies generally show better erectile preservation, with one analysis showing it was superior to robotic prostatectomy.

Treatment Decision Regret: A recent study is a sobering reminder that FT is not perfect for everyone. It found that after a median of 43 months, 19.6% of patients treated with FT regretted their decision. Factors linked to regret included a higher PSA after treatment, finding cancer on a follow-up biopsy, bothersome urinary symptoms, and erectile dysfunction.

Canadian Involvement and Current Landscape

Canada has played a significant role in developing focal therapy evidence. Canadian centers pioneered prostate cryoablation research in the 1990s and have contributed to early studies on laser ablation, ultrasound therapy, and photodynamic therapy. Canadian researchers have also emphasized the importance of doing systematic biopsies after FT to accurately assess treatment success, regardless of what MRI or PSA shows.

Currently in Canada, aside from provincial support for cryoablation in Alberta, focal therapies are primarily accessible in two ways:

1. Clinical Trials: Through participating academic hospitals.
2. Private Payment: The review identified five private clinics across the country offering HIFU, IRE, or TULSA for a fee.

The Future: Ongoing Clinical Trials in Canada

Generating better evidence is the priority. There are several important clinical trials actively recruiting patients in Canada:

• CAPTAIN Trial: A randomized controlled trial directly comparing Radical Prostatectomy to TULSA for intermediate-risk prostate cancer. This is the gold-standard study design needed.
• HDR Focal Study: Exploring the use of focal high-dose-rate (HDR) brachytherapy.
• MR-guided Focal Laser Ablation Study: A single-arm study using MRI to guide laser treatment.
• PSMA-PET for FT Trial: A randomized trial testing if a new, sensitive PET scan can improve patient selection for FT to reduce recurrence.
• WIRED Trial: A pan-Canadian, non-randomized trial examining the benefits and safety of IRE for intermediate-risk cancer.

In the U.S., the pivotal PRESERVE trial for IRE has finished enrolling. Early results show a 67.6% reduction in PSA at 6 months and an 8.3% rate of serious (Grade 3) side effects.

Conclusions and Key Takeaways for Patients

Focal therapy represents a promising middle ground for selected men with localized prostate cancer, aiming to balance cancer control with quality of life preservation. The technologies have regulatory approval for destroying prostate tissue, but in Canada, access is largely through clinical trials or private clinics.

The evidence to date shows:

• Promising Cancer Control: Short- to medium-term data shows many men avoid disease progression, with recurrence-free survival rates between 58% and 92% at four years depending on the technology.
• Excellent Functional Outcomes: Preservation of urinary continence is a standout success, with >95% of men remaining pad-free. Erectile function outcomes are more variable but generally better than with whole-gland treatments.
• Low Serious Complication Rates: Major side effects are uncommon but can occur.

However, significant limitations remain:

• Lack of Long-Term Data: Most studies have follow-up periods under 5 years. Prostate cancer often progresses slowly, so 10- and 15-year data are essential.
• Lack of Comparative Studies: There are very few high-quality randomized trials comparing FT directly to active surveillance, surgery, or radiation.
• Heterogeneous Data: Studies use different patient selection criteria and definitions of success, making it hard to draw simple conclusions.

The most important recommendation from this review is clear: If you are considering focal therapy, you should prioritize enrolling in a clinical trial or a prospective registry. This is the only way to ensure your experience contributes to the evidence needed to properly integrate FT into prostate cancer care and to determine which men benefit from it most.

Source Information

Original Article Title: The use of focal therapy for the treatment of prostate cancer in Canada: Where are we, how did we get here, and where are we going?
Authors: Ravi Kumar, Sangeet Ghai, Antonio Finelli, Laurence Klotz, Adam Kinnaird, Miles Mannas, Bimal Bhindi, Rafael Sanchez-Salas, Maurice Anidjar, Ardalanejaz Ahmad, Joseph Chin, Brant Inman, Nathan Perlis.
Publication: Canadian Urological Association Journal (CUAJ), February 2025, Volume 19, Issue 2, pages 63-72.
This patient-friendly article is based on the peer-reviewed research and analysis presented in the original publication.