The Focal Therapy Society (FTS) held its 13th Annual International Symposium on Focal Therapy and Imaging in Prostate and Kidney Cancer in Washington, DC, September 7 to 9, 2023. Before the official start of the symposium, the FTS and the US Food and Drug Administration (FDA) hosted an open workshop to create a forum to discuss standards and identify unique challenges that focal therapy devices face during their regulatory approval process (Figure).

Figure. Mark Brown, MD, Michael Rothberg, MD, and Marc Antonino, MS (left to right): opening remarks for the US Food and Drug Administration (FDA) Workshop at the Focal Therapy Society (FTS) 13th Annual International Symposium, September 7, 2023, Washington, DC.

After the inception of PSA screening for prostate cancer (PCa) in the late 1980s, the overdiagnosis and subsequent overtreatment of PCa has been a long-standing topic of debate.¹ Focal therapy for prostate cancer emerged over 20 years ago amid the realization of widespread overtreatment with radical whole-gland therapies (radical prostatectomy and radiation therapy) and their associated morbidities. While several large retrospective studies have demonstrated an improvement in functional outcomes, the long-term oncologic results for focal therapy have not yet fully matured. This has resulted in varying recommendations from the European Association of Urology, AUA, and the National Comprehensive Cancer Network^2-4 regarding the utility of focal therapy approaches for the treatment of select patients with localized PCa.

The workshop opened with a presentation from Michael Brown, MD, a clinical reviewer on the Urology Devices Team within the FDA Center for Devices and Radiological Health. Dr Brown provided an overview of the 3 risk classes of medical devices recognized by the FDA, highlighting how each class is associated with a different level of regulatory scrutiny for safety and effectiveness. An important distinction was made between class II (intermediate-risk) devices, which are cleared by the FDA for prostate tissue ablation, and class III (high-risk) devices, which undergo a higher level of regulatory scrutiny to obtain FDA approval for the treatment of PCa. Both class II and class III devices require premarket review through one of 3 potential pathways: (1) the premarket notification or 510(k) for devices with the same intended use and often the same technology as a predicate device; (2) the de novo pathway, for innovative yet lower-risk devices; and (3) the premarket approval pathway, when no predicate device can be identified.

Daniel Suzman, MD, a medical oncologist from the FDA Center for Drug Evaluation and Research, provided an overview of the statistical and clinical trial considerations for localized PCa. Dr Suzman noted the FDA strongly favors oncologic end points in scenarios where the standard treatment is radical whole-gland therapy. However, due to the natural history of low- and intermediate-risk PCa, the necessity for long-term follow-up would likely generate obsolete results at the time of maturation. Traditional oncologic end points, such as overall survival and cancer-specific survival, would likely be of minimal utility in these patient populations. Rather, surrogate end points, such as rates of postablation positive in-field biopsies or rates of transition to radical whole-gland therapy, may yield more clinically applicable data.

Furthermore, Dr Suzman noted that any randomized controlled trial (RCT) comparing focal therapy to radical whole-gland therapies would likely be designed as a noninferiority trial, which is inherently challenging. He elaborated that noninferiority trials come with several assumptions, including the constancy of the control effect over time and among different populations, the actual effectiveness of the control, and the ability to reliably estimate that effect. Moreover, noninferiority trials may require larger sample sizes, and end points other than cancer-specific and overall survival can be challenging to interpret.

Representatives from the FDA (Table) were then joined by Thomas Polascik, MD, Art Rastinehad, DO, and Howard Parnes, MD, for a panel discussion to generate dialogue on presented content. A key point of discussion revolved around whether evidence demonstrating the safety and efficacy of focal therapy should necessarily come from RCTs vs real-world data in the form of registries. Advocating for the use of real-world data, Herb Lepor, MD (New York University), said, “Randomized controlled trials are known to be cumbersome, require extensive resources, and are challenging to enroll patients.” Caroline Moore, MD (University College London), provided additional context to the debate, stating, “A randomized controlled trial is not enough to change practice if the people you need to change their practice don’t believe in the results.”

In this sense, Dr Parnes and Dr Peter Pinto indicated that “it is possible to learn and make meaningful changes to clinical practice based on the results of nonrandomized trials (ie, Toronto and Hopkins surveillance cohorts).”

Therefore, assuming that registries may be a good alternative to apparently impractical RCTs for obtaining sufficient scientific evidence to demonstrate the effectiveness and safety of focal therapy, the FTS recently launched the FTS Registry. This registry allows the inclusion of patients from around the world treated with any type of energy, with the aim of achieving results similar to those provided by UK registries like HEAT (HIFU Evaluation and Assessment of Treatment), which currently has more than 15 years of follow-up data.⁵ In this regard, statements from FDA members, such as Dr Brown’s remark, “Real-world data that is sufficiently reliable and robust is considered to be valid scientific evidence. We welcome that and consider it very strongly,” and the sentiment that “the fact that real-world data may come from another country is not a problem if it could be applied to the US population,” offer hope in this direction.

Many questions surrounding the future of focal therapy remain to be resolved, but having open discussions and direct collaborations, such as the FDA and FTS, is crucial to challenging established guidelines and advancing the field. There is much work to be done in defining appropriate patient selection and further maturing long-term data; however, workshops like these are paramount to progress for the shared goals of treatment efficacy and safety.