Targeted biopsy with or without systematic biopsy in PI-RADS-stratified prostate biopsy: a risk-adapted narrative review and clinical proposal

Multiparametric magnetic resonance imaging (mpMRI)-guided targeted biopsy has transformed the diagnostic pathway for prostate cancer. However, the need for routine systematic biopsy in addition to targeted biopsy remains a subject of active controversy. This narrative review synthesizes evidence from prospective cohorts, meta-analyses, and randomized trials published between 2015 and 2026 to evaluate the diagnostic yield and risk trade-offs of targeted biopsy combined with systematic biopsy versus targeted biopsy alone across PI-RADS categories and to propose a risk-adapted biopsy protocol. The available evidence supports a strong dose-response relationship between PI-RADS score and the detection of clinically significant prostate cancer (csPCa). At the same time, this relationship is substantially modified by PSA density (PSAD), prostate volume, lesion size, lesion location, biopsy route, race, and biological markers. Combined targeted plus systematic biopsy still provides the highest overall csPCa detection rate, particularly for PI-RADS 4 lesions and small or equivocal lesions. However, targeted biopsy alone or targeted biopsy with limited perilesional systematic sampling may be cautiously considered for selected high-risk patients, especially those with PI-RADS 5 lesions, lesion size ≥1 cm, or high PSAD. However, this recommendation is based on indirect evidence from non-randomized studies and should be interpreted with caution pending results from ongoing randomized trials. In the indeterminate PI-RADS 3 category, no single imaging criterion is sufficient; PSAD thresholds, urinary biomarkers, and zone-specific risk estimates should be integrated to avoid unnecessary biopsy. A revised three-tiered decision framework is proposed: Selective Omission, conditional optimization, and standard coverage. The manuscript emphasizes that this is a structured narrative review and that de-escalation recommendations are not uniform across all PI-RADS 4–5 lesions. Future randomized trials should move beyond detection rates and evaluate adverse pathology, long-term oncologic outcomes, and patient-reported outcomes.