The widespread adoption of multiparametric magnetic resonance imaging (mpMRI) in most urology departments, together with the development of fusion biopsy (FB) techniques, has led to a growing number of early-stage prostate cancer (PCa) diagnoses—often at less aggressive stages. As observed in other solid organ tumors (kidney, breast, liver,…), focal treatment of localized lesions has become an established approach.

However, due to the multifocal nature of PCa, the clinical implementation of focal therapy (FT) has progressed more slowly. The increasing recognition of the index lesion—the largest and most aggressive tumor focus—as the key driver of PCa progression has expanded the indications for FT (1) ( Figure 1 ).

Advances in technology have equipped urologists with highly precise and safe tissue- destructive techniques, which minimize side effects. These include cryotherapy, high-intensity focused ultrasound (HIFU), irreversible electroporation (IRE), radiofrequency ablation, and laser therapy.

Since the 1990s, focal therapy for prostate cancer has advanced through progressively sophisticated strategies. Initially, focal cryotherapy offered a minimally invasive option, followed in the 2000s by high-intensity focused ultrasound (HIFU) and phototherapy for precise, lower-morbidity treatment. Between 2010 and 2014, techniques such as laser ablation guided by fusion biopsy and irreversible electroporation enhanced lesion targeting and non- thermal ablation. Histotripsy emerged in 2015, enabling ultrasound-based tumor destruction without heat, while the 2017 TULSA system integrated MRI-guided transurethral ablation with intraoperative control. Most recently, PSMA PET (2020) has refined lesion detection and post- treatment monitoring, underscoring the critical role of molecular imaging in focal therapy strategies.

Level I scientific evidence has already demonstrated that combining radiotherapy for intermediate- and high-risk localized PCa with androgen deprivation therapy (ADT) for at least six months significantly improves cancer-specific survival (2).

Given the growing role of FT and the aim to enhance cancer-specific survival without increasing toxicity, there is rising interest in investigating whether combining FT with ADT could improve oncologic outcomes—mirroring the established benefit seen with radiotherapy.

This review summarizes current indications for FT based on mpMRI findings and FB results, describes the different energy modalities currently available for prostate tissue ablation, and reviews published and ongoing clinical trials exploring the potential of ADT as an adjunct to FT for prostate cancer tissue destruction.

This narrative review was conducted in June 2024 using the PubMed database with the following search terms: “prostate cancer,” “focal therapy,” “magnetic resonance imaging,” “ablative therapies,” and “androgen deprivation.”

Human studies published in English or Spanish between January 2010 and June 2024 were included, with no additional restrictions applied.

Just as the introduction of PSA testing marked a distinct era in PCa management, the integration of MRI is likely to define a new pre- and post-mpMRI era (3). The combination of mpMRI with image-guided FB has revolutionized PCa diagnostics, enhancing detection rates, enabling precise local tumor staging, improving follow-up for patients under active surveillance (4), and assessing local recurrence after FT (5).

Focal therapy for PCa encompasses a range of energy modalities designed to ablate cancerous tissue while preserving surrounding functional structures. The most extensively evaluated techniques include HIFU, cryotherapy, IRE, vascular-targeted photodynamic therapy (VTP), and interstitial laser therapy (ILT). Less commonly used approaches include radiofrequency or microwave ablation. While high- and low-dose-rate brachytherapy can be applied focally, these have been excluded here because they rely on radiation-induced DNA damage rather than direct tissue ablation via thermal, electrical, or photodynamic mechanisms, making them non-ablative therapies.

Currently, no direct comparative studies have systematically assessed the efficacy or safety profiles between these energy modalities, highlighting the need for prospective trials (15). Except for HIFU, most techniques are applied via the transperineal route under TRUS guidance, with careful preservation of critical structures such as the urethra, neurovascular bundles, sphincter, and rectum. Most modalities have been evaluated in IDEAL stages 2a, 2b, and 3, reflecting early development, refinement, or case series experiences (15). Reported functional outcomes are generally favorable, with continence preservation rates above 90% and erectile function maintained in 70–100% of patients, with the highest rates observed for non-thermal mechanisms (15, 16) ( Tables 1 , 2 ).

Focal therapy in PCa is justified by its potential to reduce physical and psychological morbidity while limiting disease progression (20, 21). Optimal patient selection remains crucial, as variability in age, comorbidities, tumor type, and diagnostic approach complicates cross-study comparisons. Most published data are retrospective, phase II, single-arm studies, with only one phase III trial identified (16, 22).

A prospective randomized study comparing FT with active surveillance (AS) in low-risk patients using photodynamic therapy demonstrated that, after four years, disease progression occurred in 28% of FT patients versus 58% in the AS group, with a lower need for salvage treatment (6% vs. 29%) and no significant differences in adverse effects (22). [Improvement comment: Integrated FT vs AS comparison in a continuous narrative for clarity.] ADT was not administered in this cohort. Most studies continue to focus on ISUP grades 1–3 without systematic evaluation of ADT, highlighting a current gap in evidence.

There is a theoretical rationale for combining FT with ADT. Tissue injury from FT, particularly in the peripheral zone, may increase microcirculation density, and transient ADT could reduce vascularity, potentially decreasing recurrence risk (23). The ENHANCE study demonstrated that HIFU combined with ADT improved oncological outcomes without increasing toxicity (13), providing early support for this approach.

Registry studies further illustrate FT outcomes across risk categories. In a cohort including high-risk (32%) and T2b–T3 patients treated primarily with HIFU, five-year follow-up showed metastasis-free survival in all patients, cancer-specific survival of 98–100%, and 98% maintained full continence (24). Similarly, a comparison of 12,433 radical prostatectomies with 442 patients undergoing laser ablation for low-risk disease revealed no significant differences in cancer-specific mortality over 60 months, though ADT use was not clearly defined (25).

These data emphasize the importance of integrating patient selection, tumor characteristics, and procedural precision to optimize outcomes.

FT has also been applied as salvage therapy following progression post-FT or radiotherapy, using cryotherapy, brachytherapy, or HIFU. In these scenarios, ADT has often been included, achieving acceptable biochemical control and low incidence of grade ≥3 genitourinary toxicities (26–28). Imaging guidance, particularly mpMRI, enhances lesion targeting, reduces functional compromise, and may further improve outcomes, especially when combined with ADT.

Current clinical trials remain predominantly phase II, focusing on low-risk populations without ADT, with only six phase II–III trials actively recruiting, four investigating HIFU and one evaluating electroporation (6, 16). Evidence suggests FT is a viable alternative for localized prostate cancer, particularly for low-risk and select intermediate-risk (ISUP 2) tumors (16, 20, 29).

The role of ADT in FT, either to enhance oncological control or expand indications, remains investigational. ADT may reduce prostate volume by approximately 30% and improve urinary symptoms, potentially broadening the candidate pool for FT (30, 31). Combining FT and ADT is particularly relevant for patients with large prostates, significant lower urinary tract symptoms, or high-risk features, although definitive evidence is lacking.

In summary, FT offers favorable functional outcomes and may reduce disease progression compared to AS. The combination with ADT is promising, particularly in high-risk, salvage, or gland-enlarged patients, but high-quality trials are essential to define optimal patient selection, treatment intensification, follow-up strategies, and the precise role of ADT in focal therapy.

Multiparametric MRI combined with fusion biopsy is essential for accurate patient selection, precise targeting, and effective follow-up in focal therapy for prostate cancer. A range of energy modalities demonstrates comparable ablative efficacy and functional preservation, although direct comparative studies are lacking.

The integration of androgen deprivation therapy (ADT) with focal techniques represents a promising strategy to expand treatment indications, particularly for higher-risk or anatomically challenging cases. Well-designed prospective trials are urgently needed to define optimal patient selection, evaluate combination strategies, and establish long-term oncological and functional outcomes.