Intermediate risk prostate cancer is the most common indication for focal therapy. Most consensus statements of international groups regarding this topic recommend including patients with ISUP 2 or 3 PCA and a PSA below 15. Minimal amounts of ISUP 1 on the contralateral side is not seen as a contraindication [12, 13]. Most of the current data on focal therapy is collected within this patient cohort.

One of the few comparative studies in the field was published by Shah et al. Using propensity matching they compared 246 focal therapy patients to 246 radical prostatectomy patients [14]. Their primary endpoint was FFS, which was described earlier for focal therapy and was also adapted for RP patients meaning need for salvage whole gland or systemic treatment. Untreated biochemical recurrence after RP was not considered failure, and patients receiving adjuvant radiation therapy (RT) were excluded. There was no significant difference for FFS between RP and focal therapy at 3.5 and 8 years (86% vs 91%, 82% vs 86% and 79% vs 83%). The authors concluded that oncological outcomes were similar between therapies in this collective. However, a major point of critique remains the different nature of failure due to the different nature of therapy, even though “failure” is certainly a very relevant endpoint for patients. Another study by Scheltema et al. compared 50 patients after IRE to 50 patients after RP in a matched-pair analysis with the main endpoint of functional outcomes [15]. They found that IRE was superior in pad-free continence as well as erections sufficient for intercourse at 12 months, however significantly more patients had oncological failure in the IRE group. Overall, 29% of patients with IRE had biopsy proven csPCA at 12 months and 8% (4) fulfilled the previously mentioned definition of FFA (whole gland or systemic therapy). None of the patients in the RP group had recurred using the definition of PSA > 0.2 ng/ml.

A prospective multicenter study on MRI-guided HIFU cohort of 101 intermediate risk PCA patients has been published by Ehdaie et al. [11] with the primary endpoint of absence of csPCA in the target confirmed by biopsy after 24 months. In this study the HIFU procedure was carried out within an MRI-scanner under real-time MRI heat monitoring of the prostate, allowing for the best possible control of energy application. Of 89 patients who underwent biopsy at 24-months, 88% had no csPCA within the target area, however this number was reduced to 60% when considering the entire prostate, as out-of-field recurrence was a common event. Treatment related side-effects were very rare, and also functional outcome was excellent with 100% of patients with continence at baseline showing pad-free continence at 24-months. There were very mild changes in erections, with a mean difference in IIEF‑5 scores at 24 months was −0.16.

Similarly, Wysock et al. [16] reported a prospective cohort of patients undergoing primary focal cryotherapy and biopsy at 6 months. Within their cohort of 83 patients only 5 showed cancer on biopsy at 6 months, and only one had csPCA. The same group of authors also reported 24 months functional outcomes after focal cryotherapy showing preserved potency in 70% of patients [17]. An older retrospective analysis of the international COLD-registry from 2012 did show that in patients undergoing focal cryotherapy pad-free continence was 98.4% and maintenance of spontaneous erections was 58.1% suggesting improvement also in functional outcomes for cryotherapy [18].

The largest single retrospective analysis describes a cohort of 1379 men treated with focal therapy using transrectal HIFU over 15 years [10] They showed a 7-year FFS of 68% and 65% for intermediate- and high-risk cancers. Clavien-Dindo > 2 adverse events occurred in 0.5% (7/1379) patients. The metastasis-free (MFS), and overall survival (OS) within 7 years was 100% and 97%. Functional outcome was not specifically reported in this study.