FOCAL THERAPY Whole-gland Ablation of Prostate Cancer: Outcomes Supported by 2 Decades of Real-world Clinical Experience

By: Aaron E. Katz, MD, NYU Winthrop Hospital, NYU Langone Health, New York; Andre Luis Abreu, MD, KUSC Institute of Urology, Center for Image-Guided Surgery, Focal Therapy and Artificial Intelligence for Prostate Cancer, Keck School of Medicine, University of Southern California, Los Angeles; Sriram Deivasigamani, MBBS, Duke Cancer Institute and Duke University Medical Center, Durham, North Carolina; Thomas J. Polascik, MD, Duke Cancer Institute and Duke University Medical Center, Durham, North Carolina | Posted on: 09 Jun 2023

Historically, the treatment of prostate cancer (PCa) has been a radical approach using either radiation therapy or radical prostatectomy. Although effective, no single treatment option is the therapy of choice for localized PCa, and this one-size-fits-all approach exposes all patients to the full range of treatment-related adverse effects. PCa often has a protracted course and better long-term PCa-specific mortality, especially for low-risk disease that has allowed active surveillance as the de facto management of choice to avoid debilitating adverse effects.

The management of PCa needed an approach that can mitigate the risk of treatment-related adverse effects along with cancer control per se, leading to the acceptance and advancement of such alternative in situ methods as ablation therapy. Initially used in poor surgical candidates, technical advancements with ablation using real-time imaging improved its oncologic outcomes while maximally preserving functional outcomes.

Ablative therapies for PCa have been described since the early 1990s. Urologists have embraced ablation and have incorporated them into their treatment offerings, despite a lack of large-scale randomized controlled trials (RCTs). However, there are multiple instances of how we practice medicine that are not guided by level 1 evidence. At present, there are several energy sources that are capable of effectively ablating PCa. Since high-intensity–focused ultrasound (HIFU) and cryoablation have been the 2 most commonly used ablative technologies in clinical practice, we focused on their long-term outcomes. Given at least 25 years of clinical experience, we wished to ascertain the real-world performance of HIFU and cryoablation by comprehensive systematic review to surmount the paucity of RCTs and understand long-term outcomes.

A recent systematic review and meta-analysis included studies with at least 50 patients and followed up on for at least 5 years. Twenty-nine studies were identified, including 14 on cryoablation and 15 on HIFU. Most studies were retrospective (n=23), and 6 prospective studies, including 1 RCT, with IDEAL stage 2b (n=20) being the most common. The median sample size, age, PSA, and follow-up of the included studies were n=261 (range, 70-4,062), 69 (65-82) years, 7.9 (5-26) ng/ml, and 72 (60-181.2) months, respectively. The study included all D’ Amico risk categories: 33% low risk, 45% intermediate risk, and 22% high risk. The Table displays the baseline characteristics of the included studies.

Table. Baseline Clinical Characteristics

Variables Median Range
Sample size (n) 261 70-4,062
Follow-up (mo) 72 60-181.2
Age (y) 69 65-82
PSA (ng/mL) 7.9 5-26
Gleason Score ≤6 (%) 52.45 21-85
Gleason Score 7 (%) 32 14-56.5
Gleason Score ≥8 (%) 12 2-57
Low D’Amico risk (%) 33 8-56
Intermediate D’Amico risk (%) 45 28-65
High D’Amico risk (%) 22 4-62

Overall, the oncologic outcomes at 5 and 10 years were as follows: biochemical recurrence-free survival: 69% (95% CI: 60-76) and 58% (95% CI: 49-65); recurrence-free survival: 77% (95% CI: 71-82); disease-specific survival: 98% (95% CI: 96-99) and 96% (95% CI: 92-97); overall survival (OS): 92% (95% CI: 89-94) and 63% (95% CI: 27-89); metastasis-free survival: 93% (95% CI: 88-96) and 84% (95 CI: 63-94). The Figure depicts a pictorial representation of oncologic outcomes. These findings were competitive with such oncologic outcomes as biochemical recurrence-free survival, disease-specific survival, metastasis-free survival, and OS of radical approaches, such as radical prostatectomy (57.1%, 96.6%, 94%, and 85.5%); external beam radiotherapy (57%, 96.2%, 90.6%, and 75.5%), and brachytherapy (80%, 95.4%, 94%, and 78%) on intermediate-risk PCa at 10 years.1 However, the 10-year OS rate was less comparable to radical approaches, which might be due to the increased age of our study population and their associated medical comorbidities (>50% of cohort were above the age of >70 years).

Figure. Overall oncologic outcomes at 10 years. BCRFS indicates biochemical recurrence–free survival; DSS, disease-specific survival; MFS, metastasis-free survival; OS, overall survival.

The main adverse events reported in the review were stricture (11% [95% CI: 6-19]), urinary retention (10% [95% CI: 6-15]) urinary tract infection (8% [95% CI: 5-13]), and recto-urethral fistula (0.7% [95% CI: 0.6-0.9]). Most of the adverse events are grade 1 or 2 based on Common Terminology Criteria for Adverse Events, Version 5, or Clavien-Dindo criteria. In comparison to other whole-gland therapies, such as radical prostatectomy and radiation therapy, those treated with whole-gland ablation had outstanding preservation of urinary continence where the overall pad-free rates were 96% (95% CI: 94-97), 98% at 12 months, and 96% at 24 months and nearly comparable preserved erectile function of 37%. The main limitation of the review includes the heterogeneity of the included studies.


Both HIFU and cryoablation have at least 2 decades of clinical evidence supporting their use for treating men with localized prostate cancer. This systematic review provides evidence to support ablative therapies showing intermediate- and long-term oncologic control and excellent functional outcomes, especially preserving urinary continence and limiting morbidity. Based on long-term real-world evidence, HIFU and cryoablation are legitimate options for the management of localized PCa in the primary setting after informed and shared decision-making based on acknowledging patient preferences and values. Focal therapy can further preserve erectile performance by ablating only the clinically significant cancer while maintaining uninvolved parenchyma on an active surveillance program. We acknowledge that focal therapy of PCa is now a dominant application of these ablative techniques, but it is important to understand their role as a whole-gland treatment option in the primary setting.

  1. Goy BW, Burchette R, Soper MS, Chang T, Cosmatos HA. Ten-year treatment outcomes of radical prostatectomy vs external beam radiation therapy vs brachytherapy for 1503 patients with intermediate-risk prostate cancer. Urology. 2020;136:180-189.