Preoperative ultrasound before sentinel lymph node biopsy in melanoma in the era of neoadjuvant treatment: a systematic review and meta-analysis of diagnostic performance and cost analysis.

Background: Neoadjuvant immunotherapy improves outcomes compared to adjuvant therapy in stage III melanoma and reduces costs when adjuvant therapy is omitted following a major pathological response (MPR). However, adjuvant therapy remains the sole systemic treatment for patients identified as stage III by sentinel lymph node biopsy (SLNB). Detecting nodal metastases prior to this procedure could be beneficial. Methods: We conducted a systematic review and meta-analysis to determine the accuracy of preoperative ultrasound and fine-needle aspiration cytology (FNAC) and the healthcare costs of implementing this strategy. PubMed, Embase, and Web of Science were searched up to March 21, 2025. Diagnostic cohort studies were included when preoperative ultrasound and/or FNAC were performed in patients with cutaneous melanoma eligible for SLNB, with histopathological confirmation. Studies that lacked individual patient-level diagnostic data were excluded. Two reviewers independently screened and extracted data. The pooled sensitivity and specificity were calculated using bivariate or univariate random-effects models. The associated healthcare costs for each strategy were calculated using the pooled estimates, costs of the procedure, therapies and follow-up. Findings: Of 1315 records screened, 19 diagnostic studies comprising 7396 patients were included. For ultrasound, pooled sensitivity was 33.6% (95% CI: 23.5-45.5%) and specificity 92.4% (87.3-95.6%). For FNAC, pooled sensitivity and specificity were 92.6% (15.9-99.9%) and 99.1% (96.6-99.8%). Most studies had unclear risk of bias in patient selection and index test domains, while applicability concerns were generally low. Substantial heterogeneity was observed across studies. Ultrasound-FNAC was estimated to detect approximately 31% (8/25.5) of nodal metastases preoperatively. Implementation of this strategy was cost saving across multiple scenarios where adjuvant immunotherapy was omitted following MPR. Interpretation: Implementation of ultrasound-FNAC prior to sentinel lymph node biopsy enables neoadjuvant immunotherapy and is cost saving, indicating potential value in routine clinical practice. Funding: None.