Focal therapy has emerged as an innovative, and controversial, treatment paradigm for early stage, localized prostate cancer. While focal therapy is often considered an attempt to apply the concept of partial organ resection to prostate cancer, akin to partial nephrectomy or thyroidectomy, it is in some ways very distinct from such treatment approaches due to the multifocal nature of prostate cancer, and the poorly defined extent of local tumor within the prostate. The general view of prostate cancer as multifocal continues to draw concern from urologists regarding the safety and durability of the focal therapy paradigm.

The 2025 AUA Annual Meeting will include a plenary discussion of the current status of focal therapy, along with a spirited, evidence-based debate regarding the utility and safety of prostate cancer focal therapy in current practice. The session will open with a State-of-the-Art Lecture by Dr Samir Taneja, professor of urology and radiology at NYU Langone Health, titled “Focal Therapy in Prostate Cancer: Prime Time or Not?” The lecture will review the current data supporting the rationale for and implementation of focal therapy in practice, as well as the limitations of available data, potential risks, and concerns regarding lack of standardization in candidate selection, patient follow-up, and management of recurrence.

The lecture will be followed by a crossfire debate titled “Intermediate-Risk Prostate Cancer: Is Focal Therapy a Suitable Option for All Cases?” The debate will feature Dr Hashim Ahmed, chair and professor of urology at Imperial College London, and Dr Lara Rodriquez-Sanchez, urology faculty at Institut Mutualiste Montsouris, presenting the “pro” viewpoint. Dr Edward Schaeffer, professor and chair of urology at the Northwestern University Feinberg School of Medicine, and Dr Himanshu Nagar, director of genitourinary oncology in the Department of Radiation Oncology at Memorial Sloan Kettering Cancer Center, are presenting the “con” arguments.

To accept the focal therapy paradigm, an understanding of its rationale is critically important. Historically, histologic evaluation of resected prostates has demonstrated that a number of cases harbor clinically significant disease within a dominant tumor location, or index lesion, while remaining sites of multifocality are most often low grade, small, and rarely demonstrate extraprostatic extension.¹ Follow-up studies in which mutation analysis of metastatic sites, harvested at the time of death, were mapped to a single cell origin within the prostate, supported the idea that identification and destruction of the index tumor in men with early stage disease may mitigate, or abolish altogether, the metastatic potential of the cancer.² Subsequent studies have challenged this conceptual framework, suggesting that metastases may arise from multiple cell populations in the prostate.³ Whether such observations are related to tumor stage, or distinct biology, remains unanswered.

In view of the underlying goal of mitigating metastatic risk, focal therapy has evolved as a management strategy, which leverages the known long natural history of early stage prostate cancer, and, perhaps, seeks to lengthen the natural history of the disease, thereby avoiding the need for radical therapeutic interventions within the patient’s lifetime, secondarily avoiding the impact of treatment on quality of life. Further support of this approach comes from recent 15-year reported outcomes of the ProtecT trial, in which it was demonstrated that upon randomization of men with localized prostate cancer (primarily of favorable risk) to surveillance, surgery, or radiation, disease-specific mortality rates were exceedingly low at 15 years of follow-up, regardless of initial management approach.⁴ As such, the impact of treatment on short-term quality of life must be weighed against the true benefit of radical therapy.

The early experience with focal ablative therapy in a number of studies reporting up to 5-year follow-up demonstrates that regardless of ablative energy sources, locoregional disease control rates, defined by absence of clinically significant cancer on biopsy, are consistently within the 65% to 75% range.^5,6 Upon recurrence, a number of men are eligible for a second ablative session, which appears to increase the durable response rate in follow-up. What is clear from published studies is a relatively favorable rate of urinary and sexual side effects as compared with conventional therapy.^6,7

Despite the promising early data, a number of concerns remain among critics of the focal therapy paradigm. While early locoregional control, defined by imaging and biopsy, is helpful in determining ablative efficacy, it is not clear it is a reasonable surrogate measure of long-term disease control or reduction in prostate cancer mortality risk. In the absence of comparative studies of radical therapy to partial gland treatment, relative benefit or risk is difficult to determine. To date, under Food and Drug Administration guidance, most comparative studies have focused upon a comparison of focal therapy to active surveillance, in a favorable risk cohort, to measure reduction in reclassification and conversion to radical therapy.⁸ Such studies may have greater impact upon preservation of quality of life than reduction of mortality, and leave the question of treatment efficacy unanswered to some extent.

Further fueling the debate is an absence of consensus on candidate selection, extent of treatment, measurement of treatment outcome, management of recurrence, and long-term follow-up. Organizations such as the Focal Therapy Society, among others, seek to provide guidance on such issues in the future in order to avoid abuse and misuse of the treatment paradigm upon growing implementation in the urologic community. The planned lecture and debate in the upcoming AUA2025 plenary session will certainly be thought provoking, and may allow the attendees to formulate their own informed opinion on whether focal therapy for prostate cancer is “ready for prime time, or not.”

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