As the treatment landscape for prostate cancer evolves, men with localized disease have management options beyond whole gland therapy. Partial gland ablation or focal therapy refers to subtotal, targeted treatment of a prostate zone or lesion. Focal therapy as primary treatment offers great appeal but many questions remain. Which patients are most appropriate? What is the optimal ablative modality today? What advancements are on the horizon?

Focal therapy aims to eliminate disease while preserving urinary and sexual function. Multiparametric MRI allows for reliable identification of clinically significant cancer, reducing the risk of upstaging at radical prostatectomy, and limiting undersampling of the prostate with targeted biopsy. Focal therapy technologies utilize MRI findings to guide treatment. While prostate cancer is often multi-focal in nature, increasing evidence suggests that a dominant (“index”) lesion may be responsible for the clinical course of the disease, making focal therapy an attractive alternative to standard whole gland therapies.

The most appropriate population for focal therapy has not been clearly defined. Many focal therapy early adopters treated low-risk patients, but most patients stratified as low-risk (and some with intermediate risk) should be encouraged to pursue active surveillance, per guidelines. Often men with unilateral foci of intermediate-risk disease are considered reasonable candidates. Further investigation in larger prospective trials is warranted prior to recommending focal ablation in high-risk patients. Jaipuria et al suggest ideal patients for focal prostate cancer ablation have >10-year life expectancy, multiparametric MRI visible lesions (ie Prostate Imaging–Reporting and Data System® ≥3), clinically significant disease within this area (Gleason grade group 2 or 3), and no signs of significant disease elsewhere.¹

Several important challenges exist. First, there are variable definitions of treatment success, related to limitations of available data. PSA is unreliable following focal therapy. Post-ablation MRI and prostate biopsy are used to evaluate for disease persistence or recurrence. Furthermore, there is no universally agreed-upon followup regimen. Finally, each ablative technique has its own unique treatment challenges related to prostate and pelvic anatomy, tumor location, and surgeon learning curve.

What Is Currently Available?

The most well-studied and widely utilized focal ablative therapies include cryotherapy and high-intensity focused ultrasound (HIFU). Cryotherapy causes cellular damage and tissue destruction through freeze/thaw cycles and has long been utilized in treatment of urological and nonurological disease. The technology has undergone several evolutions with marked improvements in energy delivery and treatment monitoring with favorable short-term oncologic and functional outcomes.² In 2015, the U.S Food and Drug Administration approved HIFU for ablation of prostate tissue. Transrectal delivery of ultrasound waves rapidly heats the prostate tissue causing coagulative necrosis with relative precision. Multicenter prospective data suggest reasonable failure-free survival at 5 years among men with clinically significant cancer with limited impact on functional outcomes.³ Another thermal ultrasound technology, transurethral ultrasound ablation, delivers thermal coagulation under image guidance with results suggesting this is a safe and effective option for select patients.⁴ Overall, focal cryotherapy and HIFU are associated with similar oncologic efficacy and treatment toxicities.

Recently there has been a marked increase in focal therapy publication. A recent systematic review highlighted this literature and noted 6 alternatives to cryotherapy and HIFU.⁵ Irreversible electroporation is nonthermal tissue ablation via focal delivery of pulsatile electric current which ultimately results in cell death. While this is approved for tissue destruction, a multicenter trial is currently underway to assess safety and effectiveness in intermediate-risk prostate cancer patients (NCT0497097). Vascular targeted photodynamic therapy, a novel therapy where patients receive intravenous padeliporfin followed by activation with selective ablation via optical fibers placed in prostatic region of interest, was compared to active surveillance in low-risk patients in a multicenter randomized trial. Results indicated that half of the treated patients had no detectable disease on biopsy following therapy.⁶ Focal laser ablation is thermal energy delivered transrectally via diode laser in an MRI suite where real-time tracking of ablation occurs. Short-term followup indicates low retreatment rates with favorable quality of life outcomes.⁷ Focal brachytherapy data indicate treatment is well-tolerated with reasonable 2-year oncologic efficacy.⁸ Less well studied alternatives include radiofrequency ablation and prostatic artery embolization.

What May be Coming Soon?

Gold-silica nanoshells are among the newest technology, capturing light intensity via collective electronic excitation which can aim strong energy currents directly at cancerous tissue while sparing surrounding tissue. When compared to current focal therapy modalities, gold-silica nanoshells were found to have a similar efficacy with 1 paper showing negative biopsy in 88% at 12 months.⁹ Water vapor ablation, established as therapy for benign tissue destruction, is now being investigated to deliver transurethral thermal energy as a means of destroying malignant tissue (NCT04087980).

Additional areas of investigation and development merit mention. Novel imaging modalities are being evaluated for their ability to improve identification of clinically significant cancer and assess response to treatment in real-time and post therapy, including micro-ultrasound, contrast-enhanced ultrasound, and positron emission tomography scan. Other investigations will evaluate use of neoadjuvant therapy in focal therapy hypothesizing improved local control.¹⁰ Finally, as our understanding of prostate cancer genomics grows, biomarkers may help inform decisions regarding focal therapy.

With so many new technologies on the horizon, one can foresee a future with higher utilization of focal therapy for our prostate cancer patients. Many of these treatments show even more localized ablative power and more research is needed to select best candidates and optimize outcomes. Regardless of which focal ablative modality is offered, thorough counseling for patients considering focal therapy is paramount. Patients must understand that focal therapy may leave areas of cancer untreated, and that additional therapy may be required for adequate cancer control. Furthermore, patients must be informed of the need for continued close monitoring. The promise of focal therapy is exciting, and undoubtedly prostate cancer treatment will look different in the years to come.