Focal Therapy for Prostate Cancer: A Patient-Friendly Guide to the Latest Clinical Trials

Table of Contents

• Introduction: A New Direction in Prostate Cancer Care
• How This Review Was Conducted
• Key Findings: A Detailed Look at Ongoing Clinical Trials
• What This Means for Patients: Clinical Implications
• Understanding the Limitations
• Actionable Recommendations for Patients
• Source Information

Introduction: A New Direction in Prostate Cancer Care

If you've been diagnosed with localized prostate cancer (cancer that hasn't spread beyond the prostate), you are likely considering your treatment options. For decades, the main choices have been active surveillance (closely monitoring the cancer), radical prostatectomy (surgical removal of the entire prostate), or radical radiation therapy (targeting the whole prostate with external beams or radioactive seeds). While effective, surgery and full-prostate radiation carry significant risks of side effects, including long-term urinary incontinence (involuntary urine leakage) and erectile dysfunction (difficulty achieving or maintaining an erection).

This has led researchers to explore a middle ground: focal therapy. Focal therapy is defined as the guided destruction of only the image-defined, biopsy-confirmed cancerous lesion along with a small safety margin of surrounding tissue. It primarily uses advanced imaging like multiparametric magnetic resonance imaging (mpMRI), a special type of MRI scan that provides detailed pictures of the prostate, to precisely target the tumor. The goal is to achieve cancer control similar to radical treatments while dramatically reducing the impact on a patient's quality of life.

A variety of energy-based focal therapy modalities now exist, each using a different method to destroy cancer cells:

• High-Intensity Focused Ultrasound (HIFU): Uses concentrated ultrasound waves to heat and destroy tissue.
• Cryoablation (Cryotherapy): Uses extremely cold gas to freeze and kill cancer cells.
• Irreversible Electroporation (IRE): Uses short, high-voltage electrical pulses to permanently create holes in cancer cell membranes, causing cell death.
• Focal Laser Ablation (FLA): Uses laser energy delivered through a thin fiber to heat and destroy the tumor.
• Transurethral Ultrasound Ablation (TULSA): Uses ultrasound energy delivered from a device inserted through the urethra to heat and ablate prostate tissue.
• Water Vapor Ablation (Rezum®): Uses injected steam to destroy targeted tissue.

Despite promising results over the last 10-15 years, current guidelines from the American Urological Association (AUA) and the National Comprehensive Cancer Network (NCCN) do not yet endorse focal therapy for standard use outside of clinical trials. Furthermore, the U.S. Food and Drug Administration (FDA) does not approve focal therapy specifically for cancer treatment, classifying it only as a tissue-destructive procedure.

The drive to research these options is reinforced by major long-term studies on traditional treatments. The PROTECT trial, which followed 1,643 men for a median of 15 years, found no significant difference in prostate cancer-specific death among men who chose active monitoring, surgery, or radiation. While radical treatments reduced cancer progression and spread, this did not translate to a survival advantage for most men, and they came with more side effects. Similarly, the PIVOT trial, with 731 men followed for 12.7 years, found no difference in mortality between surgery and active surveillance, but surgery led to more incontinence and erectile dysfunction. These findings underscore why the medical community is actively seeking effective treatments with fewer life-altering consequences.

How This Review Was Conducted

To provide a clear picture of the current research landscape, the authors of this review performed an exhaustive search of two major databases up to December 1st, 2023: ClinicalTrials.gov (a registry of clinical studies) and PubMed (a database of biomedical literature).

They used a wide range of search terms related to prostate cancer and every major type of focal therapy, including "high-intensity focused ultrasound (HIFU)," "cryoablation," "irreversible electroporation (IRE)," and "focal laser ablation." The focus was on identifying feasibility trials, Phase 2, and Phase 3 clinical trials published from 2015 onward or currently ongoing. The selection process was conducted by two authors, with the entire team reaching a consensus on which trials to include. This narrative review is intended to give patients and clinicians a snapshot of the dynamic and evolving field of focal therapy research.

Key Findings: A Detailed Look at Ongoing Clinical Trials

The review identified numerous clinical trials at various stages: some are actively recruiting, some have finished recruiting but are analyzing results, and others have recently published findings. These trials investigate all the major focal therapy modalities, focusing on both cancer control (oncological outcomes) and patient quality of life. Importantly, several novel trials are studying the added benefit of combining focal therapy with hormonal treatments like androgen deprivation therapy (ADT). Below is a detailed breakdown of the key trials organized by their primary focus.

Trials Comparing Multiple Energy Modalities

The CHRONOS Trial (NCT04049747): This is a large, ambitious prospective study in the UK consisting of two parallel randomized controlled trials (RCTs). An RCT is a study where participants are randomly assigned to different treatment groups, which is the gold standard for comparing treatments.

• CHRONOS-A is a non-inferiority trial. It aims to recruit 1,190 men to test whether focal therapy alone (using either HIFU or cryotherapy) is not worse than radical therapy (surgery, radiation, or brachytherapy) in terms of 5-year progression-free survival (PFS). PFS is defined as the time until the cancer progresses, requires salvage treatment, spreads, or causes death.
• CHRONOS-B is a multi-arm trial aiming to recruit 1,260 men. It will investigate whether adding neoadjuvant (pre-treatment) drugs like finasteride or bicalutamide to focal therapy improves 5-year failure-free survival compared to focal therapy alone.
• Both CHRONOS trials will also closely monitor side effects, quality of life, and economic costs.

The ATLANTA Trial (NCT03763253): This is a unique phase 2 RCT in England for men with metastatic prostate cancer (cancer that has spread). It aims to recruit 399 patients by January 2027 to test if treating the primary prostate tumor with either focal therapy (HIFU/cryo) or radical therapy (surgery/radiation) in addition to standard drug treatments for metastases improves outcomes compared to drug treatments alone. Primary outcomes include biopsy results at 6 months and progression-free survival at 2-4 years.

University of Cincinnati Trial (NCT05790213): This is a phase 2, single-arm study exploring a combination approach for intermediate-risk cancer. It plans to enroll 57 patients to receive focal therapy plus a 6-month course of ADT and a novel hormone drug called Apalutamide. The main goal is to see the proportion of men with no significant cancer in treated and untreated areas at the 6-month biopsy.

Trials Focused on High-Intensity Focused Ultrasound (HIFU)

The PART Trial (ISRCTN99760303): This was a completed feasibility study in the UK that successfully randomized 82 men with intermediate-risk cancer to either surgery (41 men) or HIFU (41 men). While not designed to prove which was better, it confirmed that a large RCT was possible and found that, in the short-to-medium term, men treated with HIFU reported better health-related quality of life scores. This trial paved the way for larger studies like CHRONOS.

The HIFUSA Trial (NCT03531099): This is an ongoing phase 3 RCT in France directly comparing HIFU to active surveillance in men with low-risk prostate cancer. The primary goal is to see how many men in the active surveillance group convert to needing radical treatment within 48 months compared to the HIFU group.

The FOCALE Trial (NCT03568188): This single-arm study in Belgium is assessing the success of HIFU specifically for intermediate-risk cancer. The primary endpoint is the percentage of positive biopsies in the treated area of the prostate at 12 months post-treatment.

The ENHANCE Trial (NCT03845751): This is a small, single-arm phase 2 trial in France testing HIFU combined with a short course of ADT for intermediate-risk cancer. It will measure treatment failure via biopsy at 12 months in 20 patients.

The EMERHIT Trial (NCT05710861): This is a French randomized medical economics trial comparing focal HIFU to total prostatectomy. Its main goal is to evaluate the cost-utility ratio—essentially, the cost per quality-adjusted life year (QALY)—of HIFU compared to surgery at 24 months.

Trials on Other Focal Therapy Modalities

CAPTAIN Trial for TULSA (NCT05027477): This RCT is comparing TULSA-Pro® therapy to radical prostatectomy. It has dual primary endpoints: efficacy (freedom from treatment failure at 36 months) and safety (preservation of urinary continence and erectile function at 12 months).

PRIS Trials for IRE (NCT05513443): These are two planned RCTs. PRIS 1 will compare IRE to radical prostatectomy, with urinary continence at 12 months as the primary goal. PRIS 2 will compare IRE to radiation therapy, focusing on irritative urinary symptoms at 12 months.

PRESERVE Trial for IRE (NCT04972097): This single-arm study is evaluating both the efficacy (negative biopsy at 12 months) and safety of IRE treatment.

Focal Laser Ablation (FLA) Trials: Several single-arm trials are investigating FLA, including one at Mayo Clinic (NCT02600156) and others in San Diego (NCT05826470) and by Avenda Health (NCT06047509). These primarily focus on safety and short-to-medium-term success rates.

VAPOR 2 Trial for Water Vapor Ablation (NCT05683691): This single-arm trial is evaluating the freedom from disease progression or salvage therapy at 36 months, along with urinary incontinence rates at 12 months.

What This Means for Patients: Clinical Implications

The sheer volume and design of these trials signal a major shift in prostate cancer research. The medical community is actively investing time and resources to determine if focal therapy can reliably become a standard treatment option. The implications are significant:

First, there is a clear recognition that for many men with localized disease, preserving quality of life is as important as treating the cancer. Large trials like CHRONOS are directly comparing the quality-of-life outcomes of focal therapy against radical treatments, which is a critical patient-centered focus.

Second, research is becoming more nuanced. Instead of just asking "Is focal therapy effective?", trials are now asking more specific questions: "Is it as good as surgery for certain men?" (CHRONOS-A), "Can we make it better by adding drugs?" (CHRONOS-B, Cincinnati trial), and "Is it a good option for men with more advanced disease?" (ATLANTA trial). This reflects a move toward personalized medicine.

Finally, the variety of energy modalities being tested means that if focal therapy is validated, there may be multiple technical options available. Different energies might be better suited for tumors in different locations or of different sizes, allowing urologists to tailor the treatment to the individual's specific cancer anatomy.

Understanding the Limitations

While the research is promising, it is crucial to understand the current limitations. The most important limitation is that focal therapy remains an investigational treatment according to major U.S. and international guidelines. This is because the long-term data (10-15 years) on cancer control and survival is still maturing.

Many of the most definitive trials, like CHRONOS, will not have results for several years. The trials mentioned often have primary endpoints at 1, 2, or 5 years, but prostate cancer is often slow-growing, and long-term follow-up is essential to ensure cancer does not recur in untreated parts of the gland.

Additionally, focal therapy requires precise tumor identification. Its success is heavily dependent on high-quality mpMRI and accurate targeted biopsies to map the cancer's exact location and extent. Not all cancers are suitable for focal therapy; it is generally considered for men with a single, clearly defined tumor or significant cancer confined to one area of the prostate.

Actionable Recommendations for Patients

1. Discuss All Options: If diagnosed with localized prostate cancer, have a detailed conversation with your urologist about all management strategies, including active surveillance, radical therapies, and the possibility of participating in a clinical trial for focal therapy.
2. Ask About Trial Eligibility: If you are interested in focal therapy, ask your doctor if you might be a candidate for any ongoing clinical trials in your area. You can also search for trials yourself on ClinicalTrials.gov.
3. Understand the "Why": If considering focal therapy, understand the specific rationale for your case. Ask: What is the exact location and size of my tumor? What modality is being recommended and why? What are the short-term and potential long-term risks?
4. Seek a Multidisciplinary Opinion: Prostate cancer care often benefits from a multidisciplinary team. Consider getting opinions from both a urologist who specializes in focal therapy and a radiation oncologist to compare all modern treatment paths, including advanced radiation techniques which also aim to reduce side effects.
5. Focus on Quality of Life Metrics: When reviewing trial results or discussing outcomes with your doctor, pay close attention to quality of life data—specifically rates of pad-free urinary continence and erectile function preservation—in addition to cancer control rates.

Source Information

Original Article Title: A narrative clinical trials review in the realm of focal therapy for localized prostate cancer
Authors: Alon Lazarovich, Vijay Viswanath, Aaron S. Dahmen, Abhinav Sidana
Publication: Translational Cancer Research, Vol 13, No 11, November 2024
DOI: 10.21037/tcr-23-2406
This patient-friendly article is based on peer-reviewed research and aims to comprehensively translate the original scientific content for an educated patient audience, preserving all key data, trial details, and clinical context.