Focal therapy (FT) is emerging as a middle-ground treatment option for men with localized prostate cancer, offering the potential to destroy only the cancerous portion of the prostate while sparing healthy tissue and reducing the side effects commonly associated with whole-gland treatments like surgery or radiation. However, the success of this approach hinges entirely on selecting the right patients. This comprehensive review, published in Prostate Cancer and Prostatic Diseases, analyzed 11 international consensus statements and expert recommendations to define the optimal criteria for identifying the best candidates for focal therapy. The researchers found that ideal candidates are men with clinically localized, intermediate-risk prostate cancer (Gleason 3+4 or 4+3), preferably with a single (unifocal) lesion, a PSA level below 20 ng/mL (ideally below 10), and a life expectancy of at least 8–10 years. Crucially, the review emphasizes that men with larger prostates or pre-existing erectile dysfunction should not be automatically excluded, and that multiparametric MRI followed by targeted and systematic biopsy is the mandatory standard for evaluating all potential candidates.
Prostate cancer is one of the most common cancers affecting men worldwide. For decades, men diagnosed with localized prostate cancer—cancer that hasn't spread beyond the prostate gland—have faced a difficult choice between aggressive whole-gland treatments (like radical prostatectomy or radiation therapy) and active surveillance (monitoring the cancer without immediate treatment). Whole-gland treatments offer strong cancer control but often come with significant side effects, including urinary incontinence and erectile dysfunction. Active surveillance avoids these side effects but can cause anxiety and carries a small risk of the cancer progressing undetected.
Focal therapy (FT) has emerged as a "third way" — a middle-ground treatment option designed to destroy only the cancerous portion of the prostate while leaving the rest of the gland intact. The goal is to mitigate the side effects commonly associated with more aggressive treatments without compromising cancer control. Several FT modalities are currently available, including high-intensity focused ultrasound (HIFU), cryotherapy (freezing), irreversible electroporation (IRE, which uses electrical pulses), laser ablation, photodynamic therapy (PDT, which uses light-activated drugs), and brachytherapy (BT, which involves placing radioactive seeds).
Numerous single-center and multi-institutional studies have reported on the outcomes of these novel therapies. However, the American Urological Association (AUA) guidelines currently consider FT only in select, appropriately informed patients with intermediate-risk prostate cancer, with an emphasis on prioritizing enrollment in clinical trials. Patients should be informed that high-quality data comparing the outcomes of FT to other prostate cancer management options—including radiation therapy, surgery, and active surveillance—are currently lacking.
Despite the evidence supporting the use of FT in patients with localized prostate cancer, reported studies exhibit considerable variability in patient selection criteria. This variability makes it difficult for doctors to know exactly who benefits most from FT and who might be better served by other approaches. The identification of the best candidate has evolved dynamically over the past two decades alongside increasing comprehension of FT's capabilities and limitations. This review aims to synthesize the most recent evidence concerning the optimal approach to patient selection for FT in prostate cancer.
The researchers performed a systematic review of the medical literature using the PubMed database, searching for studies published before December 31, 2023. The search was conducted according to the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) statement, a standardized guideline for conducting and reporting systematic reviews.
The initial search identified 934 records. After excluding unrelated articles, letters, editorial comments, replies from authors, non-human studies, and non-English language articles, 26 full-text articles were assessed for eligibility. After critical appraisal of the full texts, 15 more articles were excluded, leaving a final total of 11 articles included in the qualitative synthesis.
Two investigators independently assessed the data and extracted the following information from each study: first author, year of publication, consensus method used, consensus threshold, number of expert participants, response rates, characteristics of participants, summary of recommendations for imaging and biopsy in FT, and summary of consensus statements on patient selection for FT. Because the included studies were consensus statements and expert opinions rather than randomized controlled trials, the results were described qualitatively rather than combined in a statistical meta-analysis.
The first step in assessing whether a patient might be eligible for FT is to characterize the prostate cancer lesion(s) accurately. In the early days of FT, doctors relied on transrectal ultrasound (TRUS)-guided biopsies to map the cancer. However, the introduction of multiparametric magnetic resonance imaging (mpMRI) has revolutionized cancer detection and consequently improved the process of patient selection for FT.
The use of mpMRI in FT candidates was first presented in a consensus statement by experts in this field in 2010. Subsequently, panels of experts re-emphasized the importance of mpMRI as the preferred approach for accomplishing the necessary objectives in FT. Recent consensus panels on patient selection for FT have consensually concurred that mpMRI stands as the preferred imaging modality for preoperative evaluation.
mpMRI has a high sensitivity in detecting clinically significant prostate cancer. In a Cochrane meta-analysis comparing MRI to template biopsies in biopsy-naïve and repeat-biopsy settings, MRI had a pooled sensitivity of 0.91 and specificity of 0.37 for International Society of Urological Pathology (ISUP) grade >2 cancers. For grade >3 cancers, the pooled sensitivity of MRI was 0.95, and the specificity was 0.35. In plain language, this means that MRI is very good at finding aggressive cancers (it correctly identifies about 91–95% of them), but it also produces false positives—about 35–37% of the time it flags a suspicious area that turns out not to be high-grade cancer.
MRI-TRUS fusion is the recommended technique to perform biopsies following mpMRI. The findings of the PRECISION trial (Prostate Evaluation for Clinically Important Disease: Sampling Using Image-guidance Or Not?) demonstrated that an mpMRI-guided biopsy leads to higher detection of clinically significant prostate cancer while avoiding detection of insignificant disease. According to an International Delphi Consensus, in the presence of an mpMRI-suspicious lesion (i.e., Prostate Imaging Reporting & Data System: PIRADS 4 or 5), histological confirmation using MRI-TRUS-fusion biopsy is necessary prior to treatment with FT.
Systematic biopsy is still required in this setting to assess mpMRI-negative areas prior to treating a histologically confirmed mpMRI lesion. However, the minimum standard for the extent of systematic biopsy outside of the mpMRI lesion (i.e., number of cores/approach) remains indeterminate. When mpMRI is unavailable, three-dimensional (3D) mapping biopsies are recommended. Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) scan, an effective imaging modality in patients with prostate cancer, may be used more frequently in the future as experience increases with its use in the field of FT.
Prostate biopsy can be performed using the transrectal (TR) or transperineal (TP) approach. The TR approach has been traditionally favored due to its less invasive nature and feasibility under local anesthesia. However, a significant drawback of this approach is its relatively high rate of infectious complications. In a systematic review of 165 articles, TR, compared to TP approach, was associated with a significantly higher incidence of sepsis (0.8% vs 0.1%) and hospitalization (1.1% vs 0.9%). Recent prospective studies have demonstrated that the TP approach can safely omit antibiotics without increasing the risk of infection, while maintaining comparable detection rates of prostate cancer to the TR approach. Consequently, the TP approach is now preferred for patients undergoing prostate biopsy.
Overall health and clinical features of the patients are important points that should be considered during appropriate candidate selection for FT. According to the Delphi Consensus by Tay et al., life expectancy considerations are similar to those stated in major guidelines, with no upper or lower boundary beyond which FT is contraindicated. According to the current guidelines, a minimum estimated life expectancy of 8–10 years is required in order for treatment to result in a reduction in the risk of death. Nevertheless, Tan et al. considered the age range of 60–80 when considering FT for patients who are discontinuing active surveillance. Additionally, similar to other surgical procedures, those with fewer comorbidities (other health conditions) are more appropriate candidates for FT compared to sicker patients.
Genitourinary symptoms are also important when considering a patient for FT. Although preservation of erectile function is an important reason for choosing FT over radical treatments, the lack of erectile function at baseline should not exclude a patient from FT. This is a crucial point for patients who already have erectile dysfunction—they should not be denied the potential benefits of FT simply because they can't benefit from erectile function preservation. In addition, the presence of mild to moderate lower urinary tract symptoms (such as frequent urination, urgency, or weak stream) are not contraindications for FT.
Men with prostate volumes of less than 50 ml (about the size of a walnut) are more suitable for FT compared to those with prostate volumes greater than 50 ml. Patients with larger prostates should not be excluded from FT, but they need to be counseled with caution. FT in these patients depends on the location of the index lesion (the main cancerous lesion), the amount of tissue requiring ablation, and the type of ablative energy used. For instance, in the case of HIFU treatment for a large prostate, ultrasound waves may dissipate over longer focal points, resulting in prostatic edema (swelling). This could potentially displace the treatment target from the firing zone, especially in lesions located in the anterior (front) zone of the prostate. On the contrary, FT of posterior (back) lesions is not affected by the prostate size.
Initial consensus statements for FT patient selection have excluded salvage cases—patients who have had previous treatment of the primary cancer within the prostate, recent hormone treatment for prostate cancer, or previous radiation to the pelvis. In recent years, more experience has been gained with salvage FT. The recent AUA guidelines recommend offering cryoablation and HIFU to patients with biopsy-documented prostate cancer recurrence after primary radiation as part of a shared decision-making approach. Nevertheless, data regarding salvage FT following primary prostate cancer ablation is limited. Salvage FT should preferably be performed in experienced centers as part of a clinical trial or well-designed prospective cohort study. In addition, patients should be made aware of the potential complications and functional outcomes associated with this procedure.
Finally, patients should understand the lack of randomized clinical trial and long-term outcomes data following FT. In addition, due to the slight risk of infield recurrence (cancer returning at the treatment site) resulting from incomplete ablation, or outfield recurrence (cancer appearing elsewhere in the prostate) caused by small, overlooked satellite lesions, or the de novo occurrence of prostate cancer in the untreated gland, the patient must be compliant for close surveillance after treatment. Patients may require re-treatments (e.g., repeat FT, radiation, or radical prostatectomy), which could lead to suboptimal outcomes when compared to primary treatments.
Gleason grade is an important factor to be considered in the evaluation of a patient with prostate cancer for FT. The Gleason grading system is a pathological scoring system that ranges from 6 (low-grade, least aggressive) to 10 (high-grade, most aggressive). In the past decade, there has been a shift from low-grade cancers toward higher-grade cancers being considered for FT.
In the earlier days, FT was only considered for low-risk patients, and the presence of Gleason 4 in the biopsy was among the exclusion criteria. In 2010, the consensus statement by de la Rosette et al. was the first to include patients with Gleason pattern 4 prostate cancer for FT. The advancement of imaging and biopsy techniques has led to wide acceptance of these new criteria among focal therapists.
Currently, major guidelines recommend active surveillance as the preferred management option for patients with low-risk (i.e., Gleason 3+3) prostate cancer. This recommendation is based on the high-level evidence from the ProtecT trial, which demonstrated no significant differences in long-term all-cause mortality among patients with localized prostate cancer who underwent radical prostatectomy, radiation therapy, or active monitoring. In other words, for men with low-risk cancer, watching and waiting is just as safe as aggressive treatment in terms of overall survival.
FT is currently accepted for patients with intermediate-risk prostate cancer, and those having Gleason 3+4 cancer represent the ideal candidates. Given the limited evidence supporting the use of FT in patients with Gleason grade greater than 7 (i.e., Gleason 4+3 or higher), this treatment should be offered with caution and only to those in whom additional diagnostic evaluations have confirmed the absence of extraprostatic disease (cancer that has spread outside the prostate capsule). This is based on expert opinion rather than high-level evidence.
In cases where a patient presents with a single core of Gleason 8, accompanied by multiple cores of Gleason 6 and 7 in surrounding areas, the single Gleason 8 core may disproportionately represent the disease burden. In such cases, whole-mount pathology (examining the entire prostate after surgical removal) may reveal the predominant presence of Gleason ≤7 following gland extirpation. This means that a single high-grade core on biopsy doesn't necessarily mean the whole tumor is high-grade—sometimes it's just a small aggressive focus within a predominantly moderate-grade cancer.
It is important to note that various consensus statements have employed different criteria for calculating prostate cancer risk groups (e.g., D'Amico vs. National Comprehensive Cancer Network: NCCN). However, this discrepancy has minimal impact on the selection criteria for FT.
Patients with prostate cancer who are candidates for FT should have a clinically localized (clinical stage ≤T2c) disease—meaning the cancer is confined to the prostate gland. While select patients with extra-prostatic extension (T3a, meaning the cancer has just barely started to poke through the prostate capsule) may be considered for FT, those with seminal vesicle invasion (T3b) and bladder neck invasion (T3b) should be counseled with caution. FT in such a high-risk group of patients should only be performed by highly experienced urologists.
It is worth noting that FT in patients with T3 disease may be associated with a higher failure rate. In a prospective study of 625 consecutive patients with non-metastatic clinically significant prostate cancer undergoing focal HIFU, stage T3 was a significant predictor of failure, with a multivariable hazard ratio of 3.06 (95% CI 1.11–8.44; p=0.03). In plain language, this means that patients with T3 disease were about three times more likely to experience treatment failure compared to patients with organ-confined disease, and this result was statistically significant (p=0.03, meaning there's only a 3% chance this finding was due to random chance).
The tumor volume in both imaging and needle biopsies was a limitation to FT during the period when random biopsies were used for the detection of prostate cancer. In the initial consensus statement for FT by Eggener et al., the inclusion criteria consisted of a single lesion with a maximum size of 12mm in the imaging, as well as maximal cancer percentage in core less than 20%, maximal cancer length in each core less than 7mm, and maximal cores with cancer less than 33%. Nowadays, with the availability of mpMRI, evaluation of cancer size is calculated more accurately. According to recent consensus statements, visible cancer foci less than 1.5 ml on mpMRI are suitable for FT.
This comprehensive review has several important implications for patients diagnosed with localized prostate cancer who are exploring their treatment options. First and foremost, it confirms that focal therapy is a legitimate treatment option for a specific subset of patients—but not for everyone. The ideal candidate profile that emerges from this synthesis of expert consensus includes:
For patients who fit this profile, FT offers a potentially attractive option that may preserve quality of life while providing cancer control. However, patients must understand that the evidence base for FT is still evolving. There is no level I evidence (the highest tier of medical evidence, typically from large randomized controlled trials) regarding the best patient selection approach for FT. The only randomized trial reported to date in the field of FT included patients with low-risk prostate cancer who underwent focal PDT—a group that current guidelines would now recommend for active surveillance rather than treatment.
The review also underscores the critical importance of proper diagnostic evaluation before considering FT. Every patient being evaluated for FT should undergo mpMRI followed by both MRI-targeted and systematic biopsy. This is not optional—it's the standard of care. The mpMRI helps identify suspicious lesions, and the targeted biopsy confirms whether those lesions contain clinically significant cancer. The systematic biopsy ensures that no significant cancer is hiding in areas that look normal on MRI. Skipping either step could lead to undertreating a more extensive cancer than initially appreciated.
Patients should also be aware that FT requires a commitment to close follow-up after treatment. Because FT leaves most of the prostate gland intact, there is a risk of cancer recurrence either at the treatment site (infield recurrence) or elsewhere in the gland (outfield recurrence). Patients must be willing to undergo regular PSA testing, follow-up MRI, and potentially repeat biopsies. Some patients may ultimately require additional treatment, which could include repeat FT, radiation therapy, or radical prostatectomy.
It's important for patients to understand the limitations of the evidence supporting FT and the patient selection criteria described in this review. First and foremost, there is no level I evidence—the highest tier of medical evidence, typically derived from large, randomized controlled trials—regarding the best patient selection approach for FT. The recommendations in this review are based primarily on expert consensus statements and opinion, not on head-to-head comparative trials.
The only randomized trial reported to date in the field of FT included patients with low-risk prostate cancer who underwent focal PDT. This is notable because current guidelines recommend active surveillance for low-risk patients, meaning the trial population may not reflect the patients who are actually receiving FT in clinical practice today. Furthermore, the trial did not compare FT to surgery, radiation, or active surveillance—the standard treatment options.
Several single-center and multicenter reports on FT with different sources of energy have been reported during the past two decades, with the majority being small-sample size single-arm phase I or II studies. These study designs lack a comparison group, making it difficult to determine whether FT outcomes are truly comparable to standard treatments. With increasing experience in this field, multicenter reports and larger sample size studies have been recently published, but these are still predominantly observational rather than randomized.
The consensus statements themselves have limitations. Different consensus panels used different methods (Delphi processes, RAND/UCLA appropriateness method, informal consensus) and different thresholds for agreement (ranging from 50% to 95% consent). The number of expert participants varied widely, from 14 to 90, and the response rates for multi-round Delphi processes ranged from 54% to 100%. This variability means that the strength of consensus behind each recommendation may differ.
Additionally, the utility of molecular and genomic biomarkers in patient selection for FT remains unknown. While there is optimism that novel genomic markers could help refine risk stratification for patients with prostate cancer, the evidence is not yet sufficient to incorporate them into routine clinical decision-making for FT candidacy.
Finally, long-term oncological outcomes for FT are still maturing. The review notes that patients should understand the lack of randomized clinical trial and long-term outcomes data following FT. While short-term and intermediate-term results are encouraging, the field awaits longer follow-up to confirm that FT provides durable cancer control comparable to whole-gland treatments.
Based on this comprehensive review, the following recommendations emerge for patients considering focal therapy for prostate cancer:
In summary, focal therapy represents a promising middle ground for well-selected patients with localized prostate cancer. The ideal candidate has intermediate-risk, unifocal disease, a PSA below 20 ng/mL, and a life expectancy of at least 8–10 years. Proper patient selection—based on high-quality mpMRI, targeted and systematic biopsy, and careful consideration of patient and disease features—is the cornerstone of achieving optimal outcomes. As the field continues to evolve and more long-term data become available, the criteria for patient selection will likely continue to be refined. For now, patients and their doctors should use the consensus-based criteria outlined in this review as a framework for shared decision-making.
Focal therapy is a treatment that destroys only the cancerous part of the prostate, leaving healthy tissue intact. It aims to reduce side effects like incontinence and erectile dysfunction compared to whole-gland treatments. It is considered a middle-ground option for certain men with localized prostate cancer.
Yes, these are not absolute exclusions. Men with prostates larger than 50 ml or pre-existing erectile dysfunction should not be automatically ruled out. However, larger prostates require caution, and the decision depends on lesion location and treatment type. Erectile dysfunction does not prevent you from benefiting from focal therapy.
There is a risk of cancer recurrence at the treatment site (infield) or elsewhere in the prostate (outfield). You may need additional treatments, such as repeat focal therapy, radiation, or surgery. Close follow-up with PSA tests, MRI, and possibly repeat biopsies is required after treatment.
High-quality data directly comparing focal therapy to surgery, radiation, or active surveillance is lacking. Most studies are small and not randomized. While short-term results are encouraging, long-term outcomes are still maturing. Discuss the risks and benefits with your healthcare team.
Gleason 3+4 is intermediate-risk prostate cancer, which is the ideal category for focal therapy. Men with low-risk (Gleason 3+3) are usually recommended active surveillance, while those with Gleason 8 or higher should approach focal therapy with caution and only after confirming no cancer spread outside the prostate.
Original Article Title: Identifying the best candidate for focal therapy- a comprehensive review
Authors: Alireza Ghoreifi, Leonard Gomella, Jim C. Hu, Badrinath Konety, Luca Lunelli, Ardeshir R. Rastinehad, Georg Salomon, Samir Taneja, Rafael Tourinho-Barbosa, and Amir H. Lebastchi
Journal: Prostate Cancer and Prostatic Diseases (2025) 28:684–692
Publication Date: Published online October 23, 2024
DOI: https://doi.org/10.1038/s41391-024-00907-y
Affiliations: Department of Urology, University of Southern California, Los Angeles, CA; Department of Urology, Thomas Jefferson University, Philadelphia, PA; Department of Urology, Weill Cornell Medicine, New York-Presbyterian Hospital, New York, NY; Allina Health Cancer Institute, Minneapolis, MN; Department of Urology, Hospital Louis Pasteur, Chartres, France; The Smith Institute for Urology at Lenox Hill, New York, NY; Martini Clinic, Prostate Cancer Center Hamburg-Eppendorf, Hamburg, Germany; Department of Urology, NYU Langone Health, New York, NY; Department of Urology, Institut Mutualiste Montsouris, Université Paris-Descartes, Paris, France.
Note: This patient-friendly article is based on peer-reviewed research. It is intended for educational purposes and should not replace professional medical advice. Patients should always consult with their healthcare providers about their individual treatment options.
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