The role of focal therapy for localized prostate cancer: From diagnosis to ablation

Abstract

Introduction

Focal therapy (FT) has emerged as an intermediate therapeutic strategy between active surveillance (AS) and radical treatments for the management of localized prostate cancer (PCa) in patients with clinically significant disease and a well-defined index lesion (IL). The development of ablative and imaging techniques has enabled the selective treatment of the IL, preserving healthy tissue and reducing adverse effects.

Objectives

o review the current evidence on FT in localized PCa, including technological modalities, selection criteria, diagnostic tools, post-treatment surveillance strategies, and barriers to its clinical implementation in the Spanish healthcare setting.

Materials and methods

A structured narrative review was conducted through a search in PubMed, Scopus, and Web of Science, including studies published up to April 2025. Original articles, reviews, clinical guidelines, and meta-analyses focusing on FT for localized PCa were selected. Prospective and comparative studies addressing oncological and functional outcomes, as well as associated technologies such as fusion biopsy, multiparametric magnetic resonance imaging (mpMRI), prostate-specific membrane antigen positron emission tomography (PSMA-PET), and artificial intelligence (AI), were prioritized.

Results

FT offers encouraging short- and medium-term oncological outcomes, with notable functional preservation. Modalities such as high-intensity focused ultrasound (HIFU) and cryotherapy are currently the most widely used and have the longest clinical trajectory, while irreversible electroporation (IRE) stands out among emerging techniques with results.

Surveillance after FT should be multifactorial and include serial PSA monitoring, systematic and targeted biopsies, as well as imaging techniques such as mpMRI. Specific tools such as PI-FAB (Prostate Imaging after Focal Ablation) and TARGET (Transatlantic Recommendations for MRI Evaluation after Focal Therapy) systems allow for standardized interpretation of mpMRI after FT. In Spain, its adoption remains limited, reinforcing the need for specific guidelines and multicenter registries.

Resumen

Introducción

La terapia focal (TF) ha emergido como una estrategia terapéutica intermedia entre la vigilancia activa (VA) y los tratamientos radicales en el manejo del cáncer de próstata (CP) localizado, dirigida a pacientes con enfermedad clínicamente significativa y lesión índice (LI) bien definida. Gracias al desarrollo de técnicas ablativas e imagen avanzada, permite tratar selectivamente la LI, preservando tejido sano y reduciendo efectos adversos.

Objetivos

Revisar la evidencia actual sobre la TF en el CP localizado, incluyendo modalidades tecnológicas, criterios de selección, herramientas diagnósticas, estrategias de seguimiento postratamiento y barreras para su implementación clínica en el contexto español.

Material y métodos

Se realizó una revisión narrativa estructurada mediante búsqueda en PubMed®, Scopus® y Web of Science®, incluyendo estudios publicados hasta abril de 2025. Se seleccionaron artículos originales, revisiones, guías clínicas y metaanálisis centrados en TF para CP localizado. Se priorizaron estudios prospectivos y comparativos que abordaran resultados oncológicos, funcionales y tecnologías asociadas como la biopsia por fusión, la resonancia magnética multiparamétrica (RMmp), la tomografía por emisión de positrones con antígeno prostático específico de membrana (PET-PSMA), y la inteligencia artificial (IA).

Resultados

La TF ofrece resultados oncológicos alentadores a corto y medio plazo, con preservación funcional destacada. Modalidades como el ultrasonido focalizado de alta intensidad (HIFU) y la crioterapia, son actualmente las más utilizadas y con mayor trayectoria clínica, junto con la electroporación irreversible (IRE), que destaca entre las técnicas emergentes con resultados prometedores.

El seguimiento post-TF debe ser multifactorial e incluye la monitorización seriada del PSA, la realización de biopsias sistemáticas y dirigidas, y el uso de técnicas de imagen como la RMmp. Herramientas específicas como PI-FAB (Prostate Imaging after Focal Ablation) y TARGET (Transatlantic Recommendations for MRI Evaluation after Focal Therapy) permiten estandarizar la interpretación de la RMmp tras TF. En España, su adopción aún es limitada, lo que refuerza la necesidad de guías adaptadas y registros multicéntricos.

Introduction

The treatment of prostate cancer (PCa) has evolved, but remains controversial due to its high prevalence and the side effects associated with traditional therapies [1]. Focal therapy (FT) has emerged as an intermediate option between active surveillance (AS) and radical treatment, aimed at patients with clinically significant PCa and a well-characterized index lesion (IL). This has been made possible by advances in precision diagnosis, resulting from improvements in imaging techniques (multiparametric magnetic resonance imaging – mpMRI), as well as targeted biopsies of the index lesion, alongside progress in ablative techniques from both a technological and clinical experience standpoint [2–4].

Objective

This narrative review aims to provide an updated, critical, and structured overview of the role of FT in localized PCa. It addresses its conceptual foundations, main technological modalities, patient selection criteria, diagnostic tools, oncological and functional outcomes, post-treatment surveillance strategies, and the challenges and barriers to its clinical implementation in the Spanish setting.

Evidence acquisition

A structured narrative review of the literature was conducted following a reproducible, clinically oriented approach. A bibliographic search was performed in the PubMed, Scopus, and Web of Science databases, covering studies published up to April 2025.

Combinations of MeSH terms and free-text keywords such as: “focal therapy,” “localized prostate cancer,” “systematic review,” “meta-analysis,” “erectile dysfunction,” “urinary incontinence,” “multiparametric MRI,” “micro-ultrasound,” and “PSMA PET,” were used, applying Boolean operators (AND, OR) to optimize the search.

Initially, 428 records were identified. After removing duplicates and studies unrelated to the topic, 127 articles were included in the final qualitative synthesis. The complete process of identification, screening, and selection of studies is summarized in Fig. 1.

Fig. 1.

Adapted PRISMA flow diagram showing the process of identification, selection, and eligibility of studies included in the narrative review on focal therapy for localized prostate cancer.

Original articles, reviews, meta-analyses, and clinical guidelines directly addressing FT for localized PCa were considered, prioritizing prospective and comparative studies evaluating oncological outcomes (PSA reduction, recurrence, treatment-free survival), functional outcomes (erectile dysfunction, urinary incontinence using validated questionnaires), and the use of associated technologies (fusion biopsy, mpMRI, prostate-specific membrane antigen positron emission tomography – PSMA PET, and artificial intelligence – AI).

Preclinical studies, editorials, duplicates, publications without clinical relevance, and articles without data on clinical outcomes were excluded. The selection of studies was performed manually by two independent reviewers, following quality and clinical applicability criteria.

Evidence synthesis

The management of PCa has evolved considerably in recent decades. Treatment options remain a subject of debate, particularly regarding their impact on patients' quality of life. In Spain, PCa was the most frequent male tumor in 2024, with 30,316 new cases diagnosed [5]. Its management has shifted from the radical approach of radical prostatectomy (RP) and radiotherapy (RT) toward less invasive techniques that aim to reduce the impact on urinary and erectile function. In response to the need to balance efficacy in terms of oncological and functional outcomes, therapeutic approaches such as FT [6] have emerged, allowing for the selective ablation of neoplastic areas of the prostate while preserving healthy parenchyma and minimizing risks.

This review analyzes the main FT modalities for localized PCa, along with clinical evidence, oncological and functional outcomes, and recent technological development. It also highlights current challenges and the potential of this strategy as an effective and less invasive option.

Definition of focal therapy (FT) in PCa

FT in PCa is defined as the “guided ablation of an image-defined, biopsy-confirmed, cancerous lesion with a safety margin surrounding the targeted lesion” [7].

Although PCa can be a multifocal disease, there is increasing evidence that the largest lesion with the highest histological grade—known as IL—is the most aggressive and primarily responsible for disease progression [8]. Therefore, aiming at accurately covering the IL is essential for successful focal treatment [9].

Index lesion (IL) theory

The conceptual basis of FT lies in the IL theory, which holds that cancer progression is primarily driven by the most aggressive lesion within the prostate, while secondary foci may play a marginal role in metastatic spread. This IL may account for up to 80% of tumor volume and represent the dominant Gleason grade in up to 92% of cases [10], with the average size of non-index lesions being approximately 0.3 mm.

The FLAME randomized phase III trial presents a strong validation of this model, with localized intermediate- and high-risk PCa patients treated with standard RT (77 Gy) or standard RT with a focal boost (up to 95 Gy) directed at the dominant lesion. The results showed a significant improvement in biochemical progression-free survival without increasing toxicity or compromising quality of life in those who received focal boosting [11].

Similar results were observed by Zhang et al., who compared focal ablation with irreversible electroporation (IRE) versus an extended treatment strategy. Both approaches showed comparable oncological outcomes, but functional preservation was superior in the group treated exclusively on the IL [12].

The role of mpMRI and fusion biopsy in FT

Advances in diagnosis based on mpMRI and the incorporation of fusion biopsy improve patient selection through more accurate localization of the IL. Together with the PI-RADS classification system, mpMRI has optimized diagnosis, achieving a sensitivity of 90% and a specificity of 80.1% for clinically significant PCa (csPCa) [2]. Moreover, mpMRI-visible lesions are associated with more aggressive pathological characteristics and genetic profiles [13].

Although mpMRI-guided biopsies are more effective than conventional systematic biopsies, combining both modalities provides the highest detection rates, minimizing the risk of underdiagnosis and undergrading [14]. This advantage has been widely supported by comparative studies such as the PERFECT and PREVENT trials, which have explored transperineal (TP) and transrectal (TR) routes and their implications regarding diagnostic efficacy and infectious complications [15,16]. Both trials demonstrated similar diagnostic efficacy for TP and TR approaches, with csPCa detection rates close to 50%. Additionally, the TP route offers advantages over the TR route as it reduces the risk of infection and has a higher yield for detecting lesions on the anterior surface of the prostate [17].

Recent research has introduced the concepts of umbra (mpMRI-visible lesions) and penumbra (10-mm radius outside MRI lesions) to describe the distribution of csPCa. It has been observed that 90% of csPCa foci are located within this enlarged region, supporting targeted sampling of the perilesional zone—also referred to as focal saturation—as a strategy to enhance csPCa detection [18].

Moreover, the incorporation of PSMA PET imaging improves diagnostic sensitivity, particularly in high-risk tumors or recurrent disease. Targeted biopsies with ⁶⁸Ga-PSMA PET/CT have shown sensitivity ranging between 84%–100% and specificity between 76–100%, also correlating with tumor aggressiveness [4].

Micro-ultrasound (MUS), operating at a frequency of 29 MHz, is a novel real-time high-resolution imaging tool with a threefold higher resolution than conventional TR ultrasound. Its PRI-MUS scoring system, analogous to PI-RADS, has standardized the evaluation of lesions during targeted biopsies, and recent clinical trials confirm its sensitivity comparable to mpMRI, with the added benefit of immediate guidance during FT procedures [19].

Finally, AI is playing an increasing role in FT—from image analysis and lesion characterization to ablation zone planning [20]. Building on these advances, the results of the PI-CAI study, which analyzed more than 10,000 MRIs from 9,129 patients, were recently published. In a subgroup of 400 cases, the AI system achieved an area under the ROC curve (AUROC) of 0.91, significantly outperforming the average performance of 62 radiologists (AUROC 0.86; P < .0001). These findings reinforce the potential of AI as a support tool in AI-assisted FT workflows [21].

Selection criteria

The success of FT depends fundamentally on adequate and rigorous patient selection, as this largely determines its clinical efficacy. However, standardized guidelines are still lacking, and the criteria used vary considerably among studies and institutions.

According to the international FALCON (FocAL therapy CONsensus) consensus [22], FT is indicated in patients with:

• •

  A visible lesion on mpMRI, confirmed by fusion and systematic biopsy.

• •

  ISUP 2–3 disease → Although no consensus threshold exists regarding the proportion of Gleason pattern 4 to indicate FT, the European Association of Urology (EAU) 2025 guidelines state that AS may be considered in selected cases of ISUP 2 with a pattern 4 component ≤ 10% [23]. This criterion indirectly defines the boundary between patients suitable for AS and those who could benefit from focal or radical treatment.

• •

  No consensus was reached regarding PSA level threshold at diagnosis.

• •

  The presence of disease outside the IL is not a contraindication for FT.

Summary of the main energy sources in FT for PCa

FT represents a minimally invasive approach that can be applied using a wide range of energy sources, each with specific mechanisms of action and advantages.

According to the 2025 EAU guidelines [23], among the most established and widely used modalities, high-intensity focused ultrasound (HIFU) and cryotherapy can be used as focal ablative modalities in the framework of prospective registries. Other emerging techniques showing encouraging results, such as IRE [1], focal laser ablation (FLA), water vapor ablation (WVA), or transurethral ultrasound ablation (TULSA), should be reserved for clinical trials or use within monitored prospective registries.

Fig. 2 illustrates the mechanisms of action, routes of application, anesthetic requirements, and specific advantages of these energy sources [6].

Fig. 2.

Main energy sources used in focal therapy for the treatment of localized prostate cancer. Each modality differs in its mechanism of action (thermal vs. non-thermal), approach, anesthetic requirements, and preferred tumor location.

Abbreviations: IRE, irreversible electroporation; HIFU, high-intensity focused ultrasound; TULSA, transurethral ultrasound ablation; FLA, focal laser ablation; WVA, water vapor ablation; BPH, benign prostatic hyperplasia.

Oncological and functional outcomes of FT

The ProtecT study, which compared active monitoring, RP, and RT in patients with low-risk or favorable intermediate-risk localized PCa, suggested that prostate cancer–specific mortality at 15 years was low regardless of the initial treatment assigned, questioning the need for radical therapies in all cases [24]. However, a considerable proportion of patients initially managed with active monitoring—approximately 60%—eventually undergo radical treatment during follow-up, either due to clinical progression or patient anxiety. In this context, FT could represent an interesting intermediate alternative, offering local control with less functional impact in patients with a low likelihood of dying from the disease. Recent studies highlight the emerging role of mpMRI as a key tool for selecting suitable candidates for FT, allowing better characterization of tumor location, extent, and aggressiveness [25].

When applying FT, it is important to understand the concept of treatment failure, which can be divided into two main categories: recurrence within the treatment field (in-field failure, IFF) or disease outside the treatment field (out-of-field failure, OFF) [6]. These categories allow us to identify the limitations of the procedure and better understand its clinical scope.

In-field recurrences occur when the treated tumor has not been completely eradicated, either due to inadequacies in energy delivery or targeting precision. These failures are considered as real FT failure of the procedure and are also called ablation failures. Conversely, out-of-field disease occurs when lesions persist or develop outside the treated area. This may be due to undetected tumor foci during the initial evaluation or the emergence of new malignancies.

According to the latest systematic review and meta-analysis based on prospective studies, in-field recurrence rates range from 5% to 22%, while out-of-field recurrence rates range from 2% to 29% [26]. Nevertheless, one of the main current challenges in FT is the lack of consensus regarding criteria and methodologies used to assess oncological outcomes and treatment failure.

Table 1 summarizes the oncological and functional outcomes reported in recent systematic reviews and meta-analyses on FT in localized PCa, published between 2018 and 2025 [1,26–30].

Table 1.

Summary of oncologic and functional outcomes from systematic reviews and meta-analyses conducted between 2018 and 2025 on focal therapy for localized prostate cancer, covering a large patient population. The table includes details on the energy sources used, biopsy and imaging assessment methods, PSA reduction after treatment, recurrence-related outcomes, incontinence and erectile dysfunction rates, validated assessment questionnaires, and follow-up duration.

Study	Energy source	Biopsy	Imaging test	PSA reduction	Oncological outcomes	Functional outcomes	Evaluation of functional outcomes	Follow-up (months)
Bakavicius et al. [30] (20 studies, 4209 patients)	HIFU	Targeted and systematic	mpMRI	Median PSA reduction of 53%–84%	In-field recurrence: 5%−22%; out-of-field progression 2%−29%	20% OF	IPSS, ICSmaleSF, IIEF, EPIC, FACT-P	6–56 m
						2% IU
Cribbs et al. [27] (55 studies, 12,655 patients)	IRE and HIFU	–	mpMRI	Mean PSA reduction 74.7% HIFU vs. 57.3% IRE	IRE: lower mean PSA reduction, higher rates of negative in-field biopsy, and better preservation of potency	DE: Less with IRE vs. HIFU.	IPSS, IIEF, EPIC	–
						IU:
						IRE: 94% continent (3 m), 100% (7 m)
						HIFU: 100% continent (3 m)
Hopstaken, et al. [1] (72 studies, 5827 patients)	8 energy sources	Targeted and systematic	mpMRI	Not detailed; PSA monitoring during follow-up	Median in-field csPCa: HIFU 14.7%, IRE 8.5%, PDT 10%, Cryotherapy 15%, FLA 17%	DE 0%−40% depending on energy.	IPSS, ICSmaleSF, IIEF-5, EPIC	Short
						IU < 1% per year.
Nicoletti et al. [28,29] (124 studies, +8000 patients)	10 energy sources	Targeted and systematic	mpMRI	BR range: 2% (Focal Brachytherapy) to 67.5% (HIFU)	Rescue treatment rates from 1% (IRE) to 54% (HIFU)	Continence 92%–100%. ED variable depending on technique: from 0% to 94.4% (cryotherapy).	IPSS, IIEF/IIEF-5, SHIM, EPIC, AUA, ICSmaleSF, FACT-P, CTCAE, Clavien-Dindo	Varies between studies (median of 24 m)
Slusarczyk et al. [26] (50 studies, 4615 patients)	7 energy sources	Targeted and systematic	mpMRI	Not specified; baseline median PSA 6.5 ng/mL	RFS csPCa: 86% at 12 months; 81% at 24 months. Radical or systemic TFS at 5 years: 82%.	De novo ED in 11% (CI 4–18%).	–	Median 21 m (CI 12–34)
						IU 3% (CI 0%–6%)

Abbreviations: FT, focal therapy; PCa, prostate cancer; csPCa, clinically significant prostate cancer; RFS, recurrence-free survival; TFS, treatment-free survival; PSA, prostate-specific antigen; mpMRI, multiparametric magnetic resonance imaging; HIFU, high-intensity focused ultrasound; IRE, irreversible electroporation; FLA, focal laser ablation; PDT, photodynamic therapy; ED, erectile dysfunction; UI, urinary incontinence; IPSS, International Prostate Symptom Score; IIEF/IIEF-5/15, International Index of Erectile Function (short and full versions); ICSmaleSF, International Continence Society male short form; EPIC, Expanded Prostate Cancer Index Composite; FACT-P, Functional Assessment of Cancer Therapy–Prostate; CI, 95% confidence interval; m, months.

Management of FT failure

In selected cases of local recurrence after non-surgical treatment, FT may represent a valid salvage treatment option.

According to a recent systematic review and meta-analysis including 990 patients, salvage FT was associated with acceptable oncological control rates and better functional outcomes, particularly regarding urinary continence, compared with salvage RP and salvage RT [31].

The indication for salvage FT should be discussed within a multidisciplinary team meeting, with careful reassessment of tumor stage using mpMRI, targeted biopsies, and metastatic workup, followed by a detailed discussion with the patient regarding risks, benefits, and available alternatives.

Ideally, these treatments should be performed in centers experienced in FT and included in multicenter prospective registries in order to evaluate long-term outcomes and generate robust evidence.

The role of the immune response in FT

In recent years, interest has grown in the immunological impact of focal ablation beyond tumor destruction. Following FT, tumor cells are destroyed, releasing tumor antigens and damage-associated molecular signals that are captured by antigen-presenting cells. These cells migrate to lymph nodes, promoting the development of tumor-specific T lymphocytes. This process, known as primary activation of the immune system (IS), is an essential step in generating a specific and durable immune response [32].

Recent studies suggest that modalities such as IRE, due to their apoptosis-based mechanism with no thermal damage, avoid denaturation of tumor proteins and antigens, making them ideal for antitumor immune activation. This process could promote immune surveillance and even provide an abscopal effect, causing the regression of distant lesions. Although this phenomenon has been described after RT combined with immunotherapy, it has not been clinically demonstrated after FT in PCa [33].

Another area of development involves the combination of FT with IS modulators to increase the antitumor response. A novel approach uses IRE to facilitate the focal administration of oncolytic viruses, leveraging the altered membrane integrity of ablated tissue. By combining focal ablation with local administration of oncolytic viruses, the aim is to amplify the immunogenic effect of the treated tumor, transforming residual tumors into niches more visible to the IS, thereby inducing a durable and adaptive immune response [34].

Although direct clinical evidence remains limited, the emerging paradigm suggests that FT could act as a local immunostimulant within broader combined treatment strategies. By modifying the tumor microenvironment and increasing infiltration of immune cells, especially cytotoxic T lymphocytes, systemic responses are triggered. This approach is particularly relevant in patients with localized disease but at risk of microscopic spread, where a potential abscopal effect could have added therapeutic value. Thus, FT may not only control the IL but also contribute to immune surveillance against occult or emerging tumor foci [35].

Surveillance after FT

Follow-up of patients who have undergone FT for localized PCa represents one of the main current challenges, due to the lack of standardized criteria and the complexity of interpreting post-treatment changes. Unlike radical therapies, where PSA decline is clear and expected, the presence of residual prostate tissue after FT leads to fluctuating PSA levels, thereby limiting its value as a standalone marker of recurrence [36].

Currently, a combined strategy based on PSA monitoring, mpMRI, and systematic and targeted biopsies is widely recommended for surveillance after FT. Specific tools such as PI-FAB and TARGET systems enable standardized interpretation of mpMRI in this context. Based on these principles, we propose the following structured algorithm, which includes PSA, mpMRI, and biopsy according to post-treatment timing and the patient risk profile (Fig. 3).

Fig. 3.

Proposed algorithm for monitoring after focal therapy for localized prostate cancer, based on the narrative review by Koehler et al. (2025). Follow-up combines serial PSA, MRI imaging, and targeted or systematic biopsies based on clinical and biochemical findings. Criteria for suspicion of recurrence and recommendations for long-term follow-up are also detailed.

Abbreviations: PSA, prostate-specific antigen; MRI, magnetic resonance imaging; Bx, biopsy; ISUP, International Society of Urological Pathology; PI-RADS, Prostate Imaging Reporting and Data System; PI-FAB, Prostate Imaging after Focal Ablation; TARGET, Transatlantic recommendations for prostate gland evaluation with magnetic resonance imaging after focal therapy.

Mp-MRI enables monitoring of treatment efficacy, evaluation of in situ recurrence, and detection of disease foci outside the treated area. However, post-ablation signal patterns (fibrosis, necrosis, hemorrhage) may complicate the distinction between benign changes and residual disease [37]. To overcome these limitations, two radiological scoring systems have been developed specifically for post-focal therapy evaluation: PI-FAB and TARGET, in which dynamic contrast-enhanced (DCE) sequence plays a fundamental role.

PI-FAB: prostate imaging after focal ablation

The PI-FAB system proposes a sequential evaluation based on three key mpMRI sequences: DCE, DWI (including ADC map), and T2-weighted imaging.

Each sequence is scored on a 3-point scale, allowing a structured assessment of the probability of recurrence. The system emphasizes the need of comparison with pre-treatment images and of clinical and PSA data integration [38].

TARGET: transatlantic recommendations for prostate gland evaluation with MRI after focal therapy

TARGET system is based on an international consensus meeting and provides a broader framework for post-FT evaluation. It integrates the three classic mpMRI sequences (DCE, DWI, and T2) with an overall score out of 5, where:

• •

  Lesions within the treated area are scored using the TARGET system.

• •

  Lesions outside the treated area are assessed using PI-RADS v2.1.

TARGET recommends first surveillance mpMRI at 12 months and then annually [39].

Table 2 presents a comparison between the two systems proposed for mpMRI interpretation after FT in PCa: PI-FAB and TARGET.

Table 2.

Comparison between the PI-FAB and TARGET radiological scoring systems used for mpMRI interpretation after FT in PCa. The table summarizes the key differences in terms of dominant sequence, scoring criteria, scope of application, and technical and clinical requirements to be considered during follow-up.

	PI-FAB	Target
Dominant sequence	DCE	DCE
Other sequences evaluated	DWI (high-b-value and ADC), T2	DWI, T2
Scale type	3 points per sequence	Overall score out of 5
Scope of application	Lesions within the treated area	Lesions inside and outside the treated area
Assessment of lesions outside the treated area	Not defined	PI-RADS for lesions outside the ablation area
Need to compare with previous MRI	Yes	Yes
Requires PSA and clinical data	Yes	Yes

Abbreviations: DCE, dynamic contrast-enhanced; DWI, diffusion-weighted imaging; ADC, apparent diffusion coefficient; MRI, magnetic resonance imaging; PI-RADS, Prostate Imaging Reporting and Data System; PSA, prostate-specific antigen.

PSMA PET has gained popularity as a complementary tool to improve post-FT assessment. Although it is not universally approved for this purpose, its high sensitivity and specificity enable detection of local recurrences and early metastases, particularly in cases where mpMRI findings are indeterminate or discordant with PSA. In addition, it could reduce the need for protocolized biopsies, thereby decreasing the risk of complications [40].

Challenges and considerations for implementing a FT program

Despite recent advances, multiple barriers limit the widespread adoption of FT as standard treatment for localized PCa. One of the main challenges is the scarcity of long-term data, as most of the available evidence focuses on short- and medium-term outcomes, which hinders a definitive assessment of its oncological efficacy and durability.

The development of prospective multicenter registries is essential to strengthen the available evidence. In this context, the recent development of a specific FT group within the Spanish Association of Urology represents a key advance, promoting training, generating professional consensus, and laying the foundations for a national registry adapted to local clinical practice.

In Spain, the adoption of FT remains limited and uneven, concentrated mainly in tertiary or private centers with access to technologies such as HIFU, cryotherapy, or IRE. Although there were initial experiences with different ablative techniques based on insufficient information provided by transrectal biopsies, these led to hemiablations or whole-gland treatments. The origin of FT in Spain corresponds to the systematic use of mpMRI and fusion biopsies from the mid-2010s onwards, which made it possible to characterize the IL, with the first Spanish series emerging when they reached a significant median follow-up [41].

The implementation of a FT program requires a structured and multidisciplinary approach, combining imaging expertise, precise selection criteria, and standardized procedures. Key elements include:

• •

  Appropriate case selection (with mpMRI and targeted biopsy).

• •

  Access to validated technological platforms.

• •

  Consistent and reproducible follow-up protocols.

Collaboration between urologists, radiologists, and pathologists is essential to ensure adequate oncological and functional outcomes. It is also essential to define a clear mission and guiding principles, such as a commitment to scientific evidence, collaborative work, patient autonomy through transparent information, and the ethical principle of “do no harm”.

The sustainability of an FT program requires financial planning, knowledge of the regulatory framework, and a clear understanding of the reimbursement model. Since 2024, techniques such as HIFU, IRE, and cryotherapy have been recognized by agencies such as the FDA under the category of “prostate tissue ablation,” both in primary and salvage treatment settings.

Finally, having the necessary tools—including targeted biopsy programs, training in at least one FT technique, and the appropriate care setting—enhances the quality of the program. It is imperative to engage in active participation in scientific societies, training programs, and specialized courses to promote continuous improvement, encourage scientific exchange, and achieve clinical excellence in the field of focal therapy.

Conclusions

FT emerges as an increasingly recognized intermediate therapeutic strategy for the management of localized PCa in patients with well-characterized IL, particularly in intermediate-risk patients. Its implementation has shown to lead to a significant reduction in the adverse effects associated with radical treatments, while maintaining acceptable rates of oncological control in the short and medium term. Advancements in imaging techniques, particularly mpMRI, which has the most substantial evidence and established application, along with the development of specific tools such as PI-RADS v2.1, PI-FAB, and TARGET systems, have improved diagnostic accuracy and surveillance. However, significant challenges persist, including the dearth of long-term data, the absence of standardized guidelines, and logistical and economic barriers to its integration into the public health care system. The consolidation of working groups, the development of multicenter registries, and multidisciplinary training will be pivotal to its establishment in clinical practice, particularly within the framework of the Spanish healthcare system.

Funding statement

This work has not received specific funding from public, commercial, or non-profit agencies.