Objective: This systematic review compares the detection rates of different sentinel lymph node detection methods, such as, technetium-99m (Tc99m), blue dye, indocyanine green (ICG) and superparamagnetic iron oxide (SPIO) in vulvar cancer. 2.
Data sources: A systematic search of PubMed, Scopus, Embase, MEDLINE, and Web of Science was conducted up to August 2024. Eligible studies included randomized controlled trials and observational studies evaluating SLN detection in vulvar cancer. 3.
Study eligibility criteria: Our analysis included observational and randomized controlled trials. The following population-intervention-control-outcome (PICO) framework was used: P – female patients diagnosed with vulvar cancer undergoing sentinel lymph node biopsy as part of their diagnostic or therapeutic management. I – Tc99m, ICG, SPIO, Blue dye, Tc99m + blue dye, Tc99m + ICG; C – Tc99m, ICG, SPIO, Blue dye, Tc99m + blue dye, Tc99m + ICG. O – Primary outcome: Detection rates 4.
Study appraisal and synthesis methods: To address heterogeneity in study populations, we used a frequentist random-effects model with 95% CIs for effect size. A three-level multivariate model accounted for correlations in studies examining one or multiple methods. Classical two-level meta-analyses were performed to assess publication bias, with Funnel-plots and Peters’ test used for bias detection. The ROBINS-I and RoB 2 tools were utilized to assess bias across various domains, while GRADE-Pro was employed to evaluate the certainty of evidence. 5.
Results: A total of 88 studies comprising 4,637 patients were included. Per-patient detection rates were as follows: blue dye 78% (95% CI: 69%; 85%), ICG 88% (95% CI: 76-95%), SPIO 95% (95% CI: 81-99%), Tc99m 92% (95% CI: 87-95%), Tc99m + blue dye 94% (95% CI: 91-96%), and Tc99m + ICG 96% (95% CI: 90-99%). Per-groin detection rates indicated similar trends calculated with three-level forest plots, ICG, and Tc99m achieving 87% and 93% when combined. Per-groin detection rate of Tc99m + blue dye resulted in 87% (95% CI: 83-91%). SPIO exhibited the second highest per-patient detection rate but lacked sufficient per-groin data.
Conclusions: Indocyanine green provides detection rates comparable to technetium-99m combined with blue dye or indocyanine green, with fewer logistical constraints, while superparamagnetic iron oxide shows remarkable potential but requires further validation in larger, diverse cohorts. These findings suggest that single use of indocyanine green could replace Technetium-99m and indocyanine green or blue dye in sentinel lymph node mapping for vulvar cancer, and superparamagnetic iron oxide offers promising detection rates over radioactive isotopes.
