Biopsy-free versus biopsy-confirmed robot-assisted radical prostatectomy for prostate cancer: a systematic review and meta-analysis of an investigational strategy

Background Routine prostate biopsy before radical prostatectomy (RP) provides histopathological confirmation and information for risk stratification but is associated with procedure-related morbidity. Advances in multiparametric magnetic resonance imaging (mpMRI) and prostate-specific membrane antigen positron emission tomography (PSMA PET) have prompted interest in highly selected biopsy-free pathways. Methods PubMed, Embase, Web of Science, and the Cochrane Library were searched from inception to August 2026 for randomized or non-randomized comparative studies of biopsy-free RP (BF-RP) versus biopsy-confirmed RP (BC-RP). Analyses were stratified by study design, and fixed-effect models were used for design-specific subgroup estimates when at least two studies were available. Results Three comparative studies (one randomized trial and two non-randomized cohorts) contributed 532 analyzed participants. In the randomized trial, BF-RP was associated with shorter operative time (MD −15.06 min, 95% CI −22.11 to −8.01) and lower estimated blood loss (MD −29.80 mL, 95% CI −43.77 to −15.83). In the two non-randomized studies, BF-RP was also associated with shorter operative time (MD −9.89 min, 95% CI −12.29 to −7.49; I²=0%) and lower estimated blood loss (MD −20.56 mL, 95% CI −27.03 to −14.08; I²=47%). Non-randomized evidence favoured BF-RP for study-defined continence at 3 months (RR 1.22, 95% CI 1.11–1.34; I²=0%), but no clear difference was seen at 6 or 12 months. Final pathological grading was incompletely reported. Fu et al. reported one BF-RP patient with high-grade prostatic intraepithelial neoplasia rather than cancer and did not report a final Gleason/Grade Group distribution. Razdan et al. reported clinically significant prostate cancer (csPCa; Grade Group ≥2) in 112/118 (94.9%) BF-RP and 102/117 (87.2%) BC-RP patients; Grade Group 4–5 disease was present in 20/118 (16.9%) and 5/117 (4.3%), respectively. In Yang et al., csPCa was present in 104/108 (96.3%) BF-RP and 105/108 (97.2%) BC-RP patients, while Gleason score ≥8 occurred in 37/108 (34.3%) and 40/108 (37.0%), respectively; two of 111 initially selected BF-RP patients had benign pT0 pathology. The longest reported central follow-up was a median of 20.5 months, which is inadequate to assess long-term biochemical recurrence, metastasis-free survival, cancer-specific survival, or overall survival. Conclusions BF-RP remains a purely investigational strategy supported by a very limited, heterogeneous, and highly selected evidence base. The available evidence is insufficient to establish that imaging can safely replace biopsy, to demonstrate oncological or safety equivalence, or to define an acceptable risk of overtreatment. BF-RP should not be adopted as a routine alternative to biopsy and, if evaluated, should be confined to prospective research protocols or clinical trials with explicit informed consent and prespecified long-term oncological endpoints. Systematic Review Registration PROSPERO CRD420261478267.