Focal Therapy for Prostate Cancer: A Detailed Look at Cryotherapy, HIFU, and IRE

Table of Contents

• Background: Why Focal Therapy Matters
• How This Research Was Conducted
• How Patient Selection for Focal Therapy Has Evolved
• Changes in Treatment Patterns Over Time
• Key Findings: Oncological and Functional Results
• What This Means for Patients
• Understanding the Study's Limitations
• Recommendations for Patients Considering Focal Therapy
• Source Information

Background: Why Focal Therapy Matters

For men diagnosed with localized prostate cancer, radical (whole-gland) therapy with surgery or radiation has long been the standard treatment. While effective, these treatments can significantly impact a man's quality of life, often causing sexual, urinary, and sometimes bowel side effects because they affect the entire prostate gland and surrounding tissues.

Focal therapy (FT) offers a different approach. Instead of treating the whole prostate, it targets and destroys only the area within the prostate that contains the clinically significant cancer. The goal is to control the harmful cancer while sparing the critical nerves, muscles, and structures responsible for sexual and urinary function. This concept has been discussed for decades, but its adoption was limited until recent advances in imaging and biopsy technology made it more feasible.

A key challenge is that prostate cancer is often "multifocal," meaning there can be several small tumors in different parts of the gland. However, research has shown that not all prostate cancer needs immediate treatment. Low-grade cancers are very unlikely to spread or cause harm, while intermediate- and high-grade cancers—known as clinically significant prostate cancer (csPCa)—are the ones that tend to progress. Furthermore, when small, low-grade spots are ignored, a significant portion of men actually have only a single, significant tumor, making them ideal candidates for focal therapy.

The development of multiparametric magnetic resonance imaging (mpMRI) and MRI-guided fusion biopsies has been a game-changer. These tools allow doctors to much more accurately identify, locate, and biopsy the significant cancer lesion, which is the essential first step for successful focal therapy. With many new treatment technologies being developed, this review focuses on the three with the longest track record: cryotherapy (freezing), high-intensity focused ultrasound or HIFU (using sound waves to heat and destroy tissue), and irreversible electroporation or IRE (using electrical pulses to break down cancer cells).

How This Research Was Conducted

This paper is a systematic review and meta-analysis. This is a powerful type of medical research where scientists don't conduct a new experiment but instead comprehensively gather, combine, and statistically analyze all the high-quality studies that have already been published on a specific topic. It provides a broader, more reliable picture than any single study can.

The researchers systematically searched medical databases to find every primary study reporting outcomes for focal therapy using cryotherapy, HIFU, or IRE, from the earliest records up to May 2024. They only included studies where the treatment ablated half the prostate gland or less and that had at least 20 patients. In total, they identified and analyzed data from 49 unique groups (cohorts) of patients treated between 2008 and 2024.

The breakdown of these studies was:

• 21 cohorts (42.9%) used focal cryotherapy.
• 20 cohorts (40.8%) used focal HIFU.
• 8 cohorts (16.3%) used focal IRE.

The team collected detailed information on how patients were selected, what tools were used (like mpMRI), the specific treatment parameters, and the follow-up protocols. They then pooled the results from all these studies to calculate overall averages for key outcomes.

The main outcomes they looked at were:

1. Cancer Control: Overall survival (OS), cancer-specific survival (CSS), metastasis-free survival (MFS), biochemical (PSA) progression, and results from follow-up biopsies.
2. Treatment Failure: The need for a second focal treatment, radical treatment (surgery/radiation), or a composite measure of failure (including starting hormonal therapy or switching to watchful waiting).
3. Quality of Life: Impacts on sexual and urinary function, categorized as low, moderate, or severe based on the degree of change from baseline.

How Patient Selection for Focal Therapy Has Evolved

The criteria for who is a good candidate for focal therapy have changed and improved significantly over the last 15 years. Early on, the studies were less strict, often including a mix of men with both low-risk and higher-risk disease.

Over time, the focus has sharpened on treating only clinically significant prostate cancer (csPCa). The data shows a clear trend: in studies from 2008-2012, only 35-42.5% of patients had csPCa. By the 2021-2024 period, this proportion had risen dramatically, with studies reporting that 66.3% to 85.3% of their patients had csPCa.

The use of advanced imaging has been central to this improvement. In the early period (2008-2012), none of the studies (0%) reported using mpMRI before treatment. From 2013-2016, 57.1% did. From 2017 onward, over 88% of studies utilized mpMRI to help plan treatment. Similarly, the use of targeted biopsies (sampling the specific suspicious area seen on MRI) increased alongside imaging.

Changes in Treatment Patterns Over Time

Not only has patient selection evolved, but the treatment approach itself has become more refined and precise.

Ablation Patterns: The area of the prostate treated has gotten smaller. Early on, "hemi-ablation" (treating one entire half of the prostate) was common. In the 2008-2012 period, 75% of studies used this approach. Over time, more precise "focal ablation" (treating just the tumor and a small margin) has become dominant. By 2021-2024, only 4% of studies were using hemi-ablation.

Technology Use: Cryotherapy was the predominant technology in the earliest studies. More recently, the mix has diversified. In the latest period (2021-2024), the studies analyzed included cryotherapy (32.0%), HIFU (44.0%), and IRE (24.0%), reflecting a broader array of established options.

Key Findings: Oncological and Functional Results

The researchers pooled data from all 49 studies, which followed patients for a median of 27.8 months (ranging from 6 to 63 months). Here are the detailed results:

Cancer Survival and Progression

Survival Rates:

• Overall Survival (OS): 98.0% of patients were alive at follow-up (95% Confidence Interval: 96.9% to 98.7%).
• Cancer-Specific Survival (CSS): 99.3% of patients had not died from prostate cancer (95% CI: 98.8% to 99.6%).
• Metastasis-Free Survival (MFS): 98.5% of patients showed no signs of the cancer spreading (95% CI: 97.7% to 99.0%).

Biochemical (PSA) Progression: PSA is a blood marker for prostate activity. A rising PSA after treatment can suggest cancer recurrence. The pooled average rate of PSA progression was 9.4% per year (95% CI: 7.0% to 12.3%). Again, no difference was seen between the three treatment types.

Follow-Up Biopsy Results

Follow-up biopsies are the most direct way to check if cancer remains. In 73.5% (36/49) of the study cohorts, a repeat biopsy was mandatory within 24 months of treatment. The findings from these biopsies are crucial:

• Any Cancer Found (Anywhere in the prostate): 44.6% of biopsied patients (95% CI: 38.7% to 50.6%).
• Clinically Significant Cancer Found (Anywhere): 22.2% of biopsied patients (95% CI: 17.5% to 27.7%). This is the most important figure.
• Clinically Significant Cancer Found IN the Treated Area ("In-field"): Only 8.9% of biopsied patients (95% CI: 6.2% to 12.5%). This suggests the treatment was effective at destroying the target in over 90% of cases.
• Clinically Significant Cancer Found OUTSIDE the Treated Area ("Out-field"): 12.3% of biopsied patients (95% CI: 8.7% to 17.1%). This represents either a new cancer or a significant cancer that was missed during the initial diagnosis.

Need for Additional Treatment

Based on the pooled data:

• Secondary Focal Therapy: 5.0% of patients underwent a second focal treatment.
• Radical Treatment (Surgery/Radiation): 10.5% of patients required whole-gland treatment.
• Composite Failure (needing salvage therapy, radical treatment, hormonal therapy, or switching to watchful waiting): 14.1% of patients.

Quality of Life: Sexual and Urinary Function

Preserving function is a primary goal of focal therapy. The researchers categorized the impact reported in 35 studies on sexual function and 34 studies on urinary function:

Sexual Function Impact:

• Low Impact (function reduced by less than 10% compared to baseline): 45.7% of studies reported this level.
• Moderate Impact (function reduced by 10-30%): 48.6% of studies.
• Severe Impact (function reduced by more than 30%): 5.7% of studies.

Urinary Function Impact: The results here were very positive. A striking 97.1% of studies reported only a low impact on urinary function. This strongly supports the idea that focal therapy can successfully preserve urinary control.

What This Means for Patients

For men with localized, clinically significant prostate cancer, this large analysis provides strong evidence that focal therapy with cryotherapy, HIFU, or IRE is a viable and effective treatment option in the short to intermediate term (approximately 2-5 years).

The extremely high cancer-specific survival rate (99.3%) and metastasis-free survival rate (98.5%) are very reassuring. The fact that only about 9% of men had significant cancer left in the treated area confirms these technologies are effective at destroying the targeted tumor.

The functional outcomes are equally important. The very low impact on urinary function is a major advantage over whole-gland treatments. The impact on sexual function varies, but severe impacts were rare in the reported studies, suggesting a better preservation of sexual quality of life compared to radical prostatectomy, for example.

Critically, the study found no significant differences in cancer control or functional outcomes between cryotherapy, HIFU, and IRE. This suggests the choice between these "established" modalities may depend more on other factors, such as local expertise, tumor characteristics, and patient preference, rather than one being definitively superior.

Understanding the Study's Limitations

While the results are promising, the researchers highlighted important limitations that patients should be aware of:

Medium-Term Data: The median follow-up was about 28 months. Prostate cancer often progresses slowly, so long-term data (10+ years) is still needed to fully understand the durability of focal therapy. The excellent 5-year survival rates are encouraging, but longer follow-up is essential.

Inconsistent Reporting: The studies included were very different from each other in how they selected patients, performed follow-up, and reported results. For example, less than 60% of studies reported standard risk categories for their patients. This heterogeneity makes it harder to draw firm conclusions for every specific patient scenario.

Selection Bias: The men in these studies were carefully chosen for focal therapy. They typically had tumors that were identified clearly on MRI and believed to be confined. The results may not apply to men with more aggressive, multi-focal, or poorly visualized cancers.

Lack of Comparative Trials: The vast majority of these studies were single-arm cohorts, meaning they only looked at men who got focal therapy. There is a notable lack of large, randomized trials directly comparing focal therapy to radical therapy (surgery/radiation) or active surveillance. Such trials are needed to definitively prove equivalence or superiority.

Recommendations for Patients Considering Focal Therapy

Based on this extensive review, here are key points for patients to discuss with their urologist:

1. Confirm You Are a Good Candidate: Focal therapy is best suited for men with a single, clearly identifiable lesion of clinically significant prostate cancer (typically Gleason Grade Group 2 or 3). A high-quality multiparametric MRI (mpMRI) and a targeted fusion biopsy are essential first steps to confirm this.
2. Understand the Goal: Focal therapy aims for "cancer control with quality of life preservation." It is a treatment, not necessarily a cure, and involves ongoing monitoring. The goal is to manage the significant cancer while minimizing side effects.
3. Commit to Rigorous Follow-Up: Active surveillance after focal therapy is mandatory, not optional. This includes regular PSA tests, repeat MRI scans, and likely a follow-up biopsy 1-2 years after treatment to check the entire prostate, not just the treated area.
4. Discuss All Established Options: If your cancer is focal-therapy-eligible, discuss the pros and cons of cryotherapy, HIFU, and IRE with your doctor. The evidence suggests they have similar effectiveness, so the decision may come down to center experience, specific tumor location, and your personal priorities.
5. Seek a Specialist Center: Focal therapy requires significant expertise in imaging, biopsy, and the treatment technology itself. Seek out urology centers with dedicated focal therapy programs and high volumes of these procedures.
6. Weigh Against Alternatives: Have a balanced discussion about all management options, including active surveillance (for very low-risk disease), radical prostatectomy, and radiation therapy. Understand the different risk/benefit profiles for cancer control and side effects associated with each approach.

Source Information

Original Article Title: "Established focal therapy HIFU, IRE, or cryotherapy where are we now? a systematic review and meta-analysis"
Authors: Kae Jack Tay, Khi Yung Fong, Armando Stabile, Jose Luis Dominguez-Escrig, Osamu Ukimura, Lara Rodriguez-Sanchez, Andreas Blana, Ezequiel Becher, M. Pilar Laguna
Publication: Prostate Cancer and Prostatic Diseases (2025) 28:693–706
Note: This patient-friendly article is based on the peer-reviewed research publication cited above. It is intended to educate and inform patients and should not replace the personalized medical advice of a qualified healthcare professional.