Challenges of Salvage Holmium Laser Enucleation of the Prostate Following Contemporary Minimally Invasive Surgical Therapies for Benign Prostatic Hyperplasia: A Mixed-Methods Systematic Review with Meta-Analysis

Background/Objectives: Contemporary minimally invasive surgical therapies (MISTs) for benign prostatic hyperplasia carry retreatment rates up to 32%, with holmium laser enucleation of the prostate (HoLEP) increasingly used as salvage therapy. Prior reviews focused on salvage HoLEP (sHoLEP) following transurethral resection; however, technical challenges specific to the post-MIST field remain uncharacterised. We aimed to characterise technical barriers during sHoLEP following contemporary MISTs, with secondary evaluation of efficacy, safety and feasibility. Methods: Following preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines (PROSPERO: CRD420261321711), five databases were searched from inception to February 2026. Studies reporting sHoLEP outcomes in adults with prior MIST were included. Qualitative findings were synthesised thematically; quantitative outcomes reported by three or more studies underwent random-effects meta-analysis. Risk of bias was assessed using methodological index for non-randomized studies methodological index for non-randomized studies (MINORS) and certainty of evidence using grading of recommendations, assessment, development, and evaluation (GRADE). Results: Ten studies (354 sHoLEP, 3618 primary HoLEP (pHoLEP) patients) were included. Technical difficulty was MIST-type dependent: thermoablative procedures and prostatic artery embolisation preserved the enucleation plane, while prostatic urethral lift (PUL) introduced morcellation-specific challenges including blade jamming and staged procedures. Meta-analysis revealed no difference in operative time or tissue weight, but reduced enucleation efficiency (weighted mean difference; WMD −0.11 g/min, p = 0.027) and peak urinary flow improvement (WMD −3.0 mL/s, p < 0.001). Both findings were sensitive to analysis, losing significance on restriction to predominantly MIST cohorts, and the enucleation efficiency result additionally lost significance on removal of the most heavily weighted study (p = 0.94). Complication rates were equivalent (odds ratio (OR) 0.92, p = 0.787). Conclusions: sHoLEP is safe and efficacious following contemporary MIST. Surgeons should anticipate MIST-specific challenges, particularly morcellation difficulties after PUL requiring tailored instrumentation. Prospective MIST-specific studies are needed.