Focal irreversible electroporation for treatment of primary and radio-recurrent prostate cancer - the evidence is mounting!

Abstract

Focal therapy for localised prostate cancer has gained attention over the last decade as patients and clinicians attempt to find the ‘Holy Grail’ of a cure for localised prostate cancer, with minimal side-effects. The lack of published data on long-term oncological control and functional outcomes has been a concern for acceptance of focal therapy. Additionally, debate remains as to which patients should be considered for focal therapy, although recent guideline recommendations have been published [1]. Three manuscripts published in this month's edition of the BJUI evaluate the medium-term outcomes of focal irreversible electroporation (IRE) as primary treatment for localised prostate cancer and also as salvage for local recurrence after prostate radiotherapy. The IRE procedures were performed at two tertiary referral centres headed by experienced, high-quality, internationally recognised research clinicians. Scheltema et al. [2] presents the median 5-year (interquartile range 40–80 months) outcomes of primary focal IRE for localised prostate cancer. A total of 229 patients were analysed, of which 86% had intermediate-risk cancer and 7% high-grade disease. The metastasis-free survival was 99.6% and 69% of patients had not progressed to secondary treatments at 8 years. Urinary continence was preserved in 98% and only 13% of patients had deterioration of erections suitable for intercourse at 12 months. Salvage IRE (s-IRE) for localised recurrent disease after radiotherapy and brachytherapy was assessed in two manuscripts. In the prospective, multicentre FIRE trial (Australian and New Zealand Clinical Trial Registry [ACTRN]12617000806369), Blazevski et al. [3] analysed 37 consecutive patients with a median follow-up of 29 months and 27 patients (73%) were free of local and systemic recurrence. Four (11%) had local recurrent disease only. Urinary continence decreased from 97% at baseline to 93% at 12 months and erections suitable for intercourse deteriorated from 35% to 15%. In the Geboers et al. [4] manuscript of 74 s-IRE cases, with a median (range) follow-up of 48 (27–68) months, urinary continence was preserved in 93%, while 23% had erectile function suitable for penetration at 12 months. Biopsy-confirmed infield recurrence occurred in only 7%, with out-of-field biopsy-confirmed recurrence identified in 15%. The Kaplan–Meier estimated 5-year progression-free survival was 60%. All authors are to be commended for their commitment to prospective data collection of focal IRE, including undertaking the ambitious project to investigate the role for IRE in the salvage setting. The low biopsy-confirmed infield recurrence of prostate cancer in the primary and salvage setting confirms the effectiveness of IRE as a management option for prostate cancer. Not unique to these studies are the relatively high rates of out-of-field recurrence at the standard 12-month biopsy. This is likely a consequence of the pre-IRE evaluation, rather than the development of a new focus of clinically significant prostate cancer. As the authors have stated, the increasing use of a pre-treatment staging prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/CT could improve the ability to identify a focus of clinically significant cancer not identified on the diagnostic MRI or standard template prostate biopsies. In the primary setting there are still several questions that remain unanswered. Should routine prostate biopsies still be performed as part of ‘active surveillance’ when the post-IRE prostate biopsy is negative? Can we rely on the negative predictive value of MRI to exclude clinically significant prostate cancer? By protocol, one re-do IRE treatment was allowed and not classified as a treatment failure. A re-do IRE was a strong risk factor for progression (hazard ratio 4.44) requiring whole-gland treatment [2]. Although Scheltema et al. [2] point out the favourable functional outcomes after a salvage radical prostatectomy (s-RP) for post-IRE local recurrence, Marconi et al. [5] have identified in-field failure after focal therapy as one of only two risk factors for oncological progression after s-RP. Therefore, for the general urological community, perhaps men with in-field significant recurrence should proceed early to whole-gland salvage treatment, unless they are personally disinclined to do so? Finally, as there is no difference in freedom from progression after focal IRE between the intermediate- and high-grade cohort, more research is required to identify which high-grade cancers are suitable for focal IRE. The poor quality-of-life outcomes following salvage whole-gland treatment of radio-recurrent prostate cancer are well known. Most men in this cohort are treated with palliative androgen-deprivation therapy. While a s-RP is associated with good long-term local control, focal s-IRE appears to demonstrate improved functional outcomes and lower morbidity compared to whole-gland salvage treatment. s-IRE has demonstrated satisfactory short-term biopsy-confirmed local control. However, in the absence of a post-s-IRE prostate biopsy, the definition of local recurrence after s-IRE also needs to be better defined, particularly in the PSMA PET/CT area era, where radiotherapy recurrence can be identified below the Phoenix definition of failure [6]. The author has nothing to disclose.