Simple SummaryFocal therapy is a treatment modality option for select patients with localized intermediate-risk prostate cancer. A rise in its use over recent years has been brought on by its favorable side effect profile, mainly the reduced risk of erectile dysfunction or continence over the current standard of through either radiotherapy or radical prostatectomy. Mainly still in its early stages of use, a notable challenge with this treatment modality is the significant risk of local cancer recurrence requiring subsequent treatments. While patients have several options for further treatment, some will opt to undergo salvage radical prostatectomy. However, the data is lacking for postoperative, oncologic, and functional outcomes for these patients. Thus, we performed a systematic review on patients who underwent radical prostatectomy for prostate cancer recurrence after prior failed primary focal therapy. Our overall findings showed acceptable complication rates and oncologic outcomes, however, with suboptimal functional outcomes for patients undergoing sRP for recurrent PCa after prior FT. Inferior outcomes were also observed for salvage treatment compared to primary radical prostatectomy (pRP). These findings are critical, as it will ultimately determine treatment modality choice after FT failure for future PCa patients.AbstractContext: Focal therapy (FT) has been gaining popularity as a treatment option for localized intermediate-risk prostate cancer (PCa) due to the associated lower morbidity compared to whole-gland treatment. However, there is an increased risk of local cancer recurrence requiring subsequent treatment in a small proportion of patients. Objective: To conduct a systematic review and meta-analysis to better describe and analyze patient postoperative, oncologic, and functional outcomes for those who underwent salvage radical prostatectomy (sRP) to manage their primary FT failure. Evidence acquisition: A systematic review was completed using three databases (PubMed, Embase, and CINAHL) from October to December 2021 to identify data on outcomes in patients who received sRP for cancer recurrence after prior focal treatment. Evidence synthesis: 12 articles (482 patients) were included. Median time to sRP was 24 months. Median follow-up time was 27 months. A meta-analysis revealed a postoperative complication rate of 15% (95% CI: 0.09, 0.24), with 4.6% meeting criteria for a major complication Clavien (CG) grade ≥3. Severe GU toxicity was seen in 3.6% of the patients, and no patients had severe GI toxicity. Positive surgical margins (PSM) were found in 27% (95% CI: 0.19, 0.37). Biochemical recurrence (BCR) after sRP occurred in 23% (95% CI: 0.17, 0.30), indicating a BCR-free probability of 77% at 2 years. Continence (pad-free) and potency (ability to have penetrative sex) were maintained in 67% (95% CI: 0.53, 0.78) and 37% (95% CI: 0.18, 0.62) at 12 months, respectively. Conclusion: Our evidence shows acceptable complication rates and oncologic outcomes; however, with suboptimal functional outcomes for patients undergoing sRP for recurrent PCa after prior FT. Inferior outcomes were observed for salvage treatment compared to primary radical prostatectomy (pRP). More high-quality studies are needed to better characterize outcomes after this sequence of PCa treatments. Patient summary: We looked at treatment outcomes and toxicity for men treated with sRP for prior FT failure. We conclude that these patients will have significant detriment to genitourinary function, with outcomes being worse than those for pRP patients.