The current treatment landscape of advanced and metastatic prostate cancer (PCa) is evolving rapidly toward a personalized targeted approach. However, the guideline-approved treatment options for localized PCa have not had significant changes over the past decades, even though 90% of PCa cases in the United States are diagnosed in the localized stage.¹ Basically, men with localized PCa can be managed with active surveillance (unanimously accepted as preferred management for low-risk disease), radiation therapy with or without androgen depravation therapy, or radical prostatectomy.^2-4 Of course, updates have been made in radiation planning and delivery, as well as surgical techniques, for prostate removal, but in reality, treatment outcomes have not shown significant improvement, especially functional outcomes. This is well documented in several articles reporting high levels of treatment regret among patients undergoing radiation or prostatectomy.⁵

The updated long-term data of the ProtecT trial underscores the importance of adequate patient selection for each treatment modality.⁶ Even though many patients will benefit from monitoring and many others require active radical treatment, there is a significant subset of patients for whom radical treatment results in overtreatment, and monitoring will render them as high risk for progression to metastatic disease. With the objective to fill this void, focal therapy (FT) has emerged to balance adequate cancer control and preservation of urinary and sexual function. Although the concept of FT is not new and the technology to deliver it is not novel either, what has pushed the latest improved outcomes with FT is the ability to better localize the index lesion. Certainly, the improvements in MRI acquisition and interpretation and targeted biopsies are to be acknowledged.

Although certain forms of ablation currently are accepted as guideline-approved treatments for PCa, they are accepted either as whole-gland therapy in the primary setting² or as partial gland ablation in the radio recurrent setting.⁴ Regardless of the increasing adoption of focal therapy in the worldwide community and the growing body of evidence supporting the case of implementation of FT in the primary setting, FT is not yet acknowledged as a guideline-approved valid treatment option for men with localized PCa.

FT is gaining acceptance, not only by patients but also by clinicians. New evidence is showing low levels of treatment regret among patients electing for this treatment method.⁷ Also, the creation of a dedicated FT academic society (the Focal Therapy Society) is helping to motivate the growth of the field in an evidence-based path. However, there is still a long road ahead for FT to make the jump from consensus approved to guideline approved and, thus, be ready for prime time.

Many argue that the wall preventing FT to gain wider acceptance is the lack of prospective randomized trials. This is a significant barrier; however, the biggest existing challenge in FT is the definition of strong and reproducible endpoints, particularly those serving for recurrence outcomes. Definition of biochemical recurrence in patients undergoing either radiation therapy and radical prostatectomy is now widely accepted and externally validated. This is not the case for FT. The definitions of strong endpoints are challenging for this treatment modality because the gland is not treated in its entirety, and the amount of tissue treated varies from patient to patient. To further add to the challenge, the post-treatment PSA kinetics is different depending on the energy source chosen. For example, after performing cryoablation, one can expect an initial steep drop on the PSA curve followed by a slight increase, leading into a plateau, whereas after a successful focal high-intensity focused ultrasound, PSA tends to drop slowly into a plateau.

Another challenge FT must face is the standardization of follow-up. There are multiple follow-up protocols proposed. A consensus led by a panel of experts in the field in 2020 established that follow-up should be done with PSA, imaging (with multiparametric MRI), and protocol biopsy.⁸ However, the timing of said studies is still a matter of debate, and also there is doubt whether PSA screening or MRI serve as valid surrogate markers for recurrence.

There is still work to be done. However, if current ongoing prospective trials succeed to transfer the favorable oncological outcomes obtained on cohort studies while maintaining the low treatment-related morbidity, then FT would take one more step toward broader acceptance. This will also facilitate the discussion and evaluation of valid treatment outcome definitions and standardized follow-up protocols.

Hopefully, stronger evidence will pave the way toward guideline acceptance of FT because this will mean more options and lower morbidity to our patients.