Multimodal treatment in focal therapy for localized prostate cancer using concomitant short-term androgen deprivation therapy: The ENHANCE prospective pilot study

Focal therapy (FT) for localized prostate cancer (PCa) is emerging to reduce adverse effects of radical treatments, while maintaining comparable oncological outcomes. However, an area for improvement still exists and a gap in cancer control needs to be filled by complementing FT with additional forms of treatment to minimize failures. Part of the recurrences/persistences after FT may be related to PCa microenvironment favouring tumorigenesis of benign tissue or indolent PCa left untreated. FT-induced inflammation may alter microenvironment in a pro-tumorigenic fashion. On the contrary, androgen deprivation therapy (ADT) modifies PCa microenvironment and suppresses PCa tumorigenesis. So far, ADT has proven effective in combination with radiotherapy, has been evaluated in the context of AS and to reduce prostate volume in the context of whole-gland high-intensity focused ultrasound (HIFU). However, no prospective data exist evaluating FT/ADT combination in terms of cancer control for the treatment of localized PCa. We will perform the ENHANCE pilot study (EvaluatioN of HIFU Hemiablation and short-term AndrogeN deprivation therapy Combination to Enhance prostate cancer control). Twenty men with localized unilateral csPCa will receive HIFU hemi-ablation and concomitant short-term ADT. Oncologic efficacy will be assessed 1-year post-treatment considering the persistence/recurrence of csPCa. Complications and functional outcomes will be evaluated using internationally validated questionnaires. If the hypothesis of an oncological benefit together with no relevant additional toxicity is confirmed, the ENHANCE study will allow an evidence-based starting point for a large randomized controlled trial against the standard of care and/or HIFU hemiablation alone.