Assessing the comparative efficacy of sentinel lymph node detection techniques in vulvar cancer: a systematic review and meta-analysis
Vulvar cancer is a rare gynecologic malignancy where lymph node status is the most important prognostic factor. Sentinel lymph node biopsy has replaced complete lymphadenectomy in early-stage disease due to its accuracy and lower morbidity. Although technetium-99m combined with blue dye or indocyanine green is the current standard, emerging tracers like indocyanine green alone and superparamagnetic iron oxide show comparable detection rates with potential logistical advantages. This systematic review compares the detection rates of different sentinel lymph node detection methods, such as, technetium-99m, blue dye, indocyanine green, and superparamagnetic iron oxide in vulvar cancer. 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 sentinel lymph node detection in vulvar cancer. Our analysis included observational and randomized controlled trials. The following population-intervention-comparison-outcome framework was used: P-female patients diagnosed with vulvar cancer undergoing sentinel lymph node biopsy as part of their diagnostic or therapeutic management. I-technetium-99m, indocyanine green, superparamagnetic iron oxide, blue dye, technetium-99m+blue dye, technetium-99m+indocyanine green. C-technetium-99m, indocyanine green, superparamagnetic iron oxide, blue dye, technetium-99m+blue dye, technetium-99m+indocyanine green. O-primary outcome: detection rates. To address heterogeneity in study populations, we used a frequentist random-effects model with 95% confidence intervals for effect size. A three-level multivariate model accounted for correlations in studies examining 1 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 Risk Of Bias In Non-randomised Studies - of Interventions and Risk of Bias 2 tools were utilized to assess bias across various domains, while GRADEpro was employed to evaluate the certainty of evidence. A total of 88 studies comprising 4637 patients were included. Per-patient detection rates were as follows: blue dye 78% (95% confidence interval, 69%; 85%), indocyanine green 88% (95% confidence interval, 76%-95%), superparamagnetic iron oxide 95% (95% confidence interval, 81%-99%), technetium-99m 92% (95% confidence interval, 87%-95%), technetium-99m+blue dye 94% (95% confidence interval, 91%-96%), and technetium-99m+indocyanine green 96% (95% confidence interval , 90%-99%). Per-groin detection rates indicated similar trends calculated with three-level forest plots, indocyanine green, and technetium-99m achieving 87% and 93% when combined. Per-groin detection rate of technetium-99m+blue dye resulted in 87% (95% confidence interval, 83%-91%). Superparamagnetic iron oxide exhibited the second highest per-patient detection rate but lacked sufficient per-groin data. 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.
