Indocyanine green versus technetium‐99m with blue dye for sentinel lymph node detection in early‐stage cervical cancer: A systematic review and meta‐analysis

Abstract

Background: The fluorescent dye indocyanine green (ICG) has emerged as a promising tracer for intraoperative detection of sentinel lymph nodes (SLNs) in early-stage cervical cancer. Although researchers suggest the SLN detection of ICG is equal to the more conventional combined approach of a radiotracer and blue dye, no consensus has been reached. Aims:We aimed to assess the differences in overall and bilateral SLN detection rates with ICG versus the combined approach, the radiotracer technetium-99m ( 99m Tc) with blue dye. Methods and Results:We searched MEDLINE, Embase, and the Cochrane Library from inception to January 1, 2020 and included studies reporting on a comparison of SLN detection with ICG versus 99m Tc with blue dye in early-stage cervical cancer.The overall and bilateral detection rates were pooled with random-effects metaanalyses.From 118 studies retrieved seven studies (one cross-sectional; six retrospective cohorts) were included, encompassing 589 patients. No significant differences were found in the pooled overall SLN detection rate of ICG versus 99m Tc with blue dye. Meta-analyses of all studies showed ICG to result in a higher bilateral SLN detection rate than 99m Tc with blue dye; 90.3% (95%CI, 79.8-100.0%) with ICG versus 73.5% (95%CI, 66.4-80.6%) with 99mTc with blue dye. This resulted in a significant and clinically relevant risk difference of 16.6% (95%CI, 5.3-28.0%). With sensitivity analysis, the risk difference of the bilateral detection rate maintained in favor of ICG but was no longer significant (13.2%, 95%CI −0.8-27.3%).Conclusion: ICG appears to provide higher bilateral SLN detection rates compared to 99m Tc with blue dye in patients with early-stage cervical cancer. However, in adherence with the Grading of Recommendations, Assessment, Development, and

Feasibility of a drop-in γ-probe for radioguided sentinel lymph detection in early-stage cervical cancer

“…Research suggests preoperative imaging with 99m Tc SPECT/CT can enhance the detection of true SLNs by guiding the surgeon to the right anatomical region, especially when SLNs are present at atypical locations [ 24 , 25 ] Another disadvantage of ICG is its rapid progression toward second echelons nodes, due to ICG’s small hydrodynamic diameter, undesirably leading to a higher number of (non-)SLNs removed compared to using 99m Tc [ 26 , 27 ]. Until now, studies comparing ICG with the more conventional method of a radiotracer and blue dye lack compelling evidence that fluorescence can safely replace the conventional method [ 28 , 29 ]. Hybrid modalities integrating the use of a radiotracer, including preoperative imaging, with real-time intraoperative fluorescence imaging could combine the advantages of both methods and are already being studied in other types of cancer [ 23 , 25 , 30 ].…”

Fluorescent Indocyanine Green versus Technetium-99m and Blue Dye for Bilateral SENTinel Lymph Node Detection in Stage I–IIA Cervical Cancer (FluoreSENT): protocol for a non-inferiority study

“…Retrospective cohort studies reporting on the comparison of ICG versus 99m Tc combined with blue dye exist but are generally of insufficient quality, underpowered and potentially suffer from publication bias. After a systematic review and meta-analysis of the available literature comparing ICG with 99m Tc and blue dye, we found that the pooled bilateral detection rate with ICG appeared to be significantly higher 35. However, in adherence with the Grading of Recommendations, Assessment, Development, and Evaluation guidelines, the quality of evidence was too low to provide strong recommendations and directly omit the combined approach of a radiotracer and blue dye.…”

“…Currently, in both systematic reviews and European guidelines on cervical cancer, no consensus on the use of tracer has been reached, and both methods of SLN detection have been approved. [35][36][37] Before omitting any well-functioning and evidence-based procedure ( 99m Tc combined with blue dye), high-quality evidence on the performance of ICG in cervical cancer SLN mapping is needed. In the FILM trial by Frumovitz et al, it was stated: 'Although the combination of blue dye and radiocolloid might be better than blue dye alone and equivalent to indocyanine green in detecting sentinel nodes, no studies -either prospective or retrospective -have compared the combination of blue dye and radiocolloid with indocyanine green'.…”

“…After a systematic review and meta-analysis of the available literature comparing ICG with 99m Tc and blue dye, we found that the pooled bilateral detection rate with ICG appeared to be significantly higher. 35 However, in adherence with the Grading of Recommendations, Assessment, Development, and Evaluation guidelines, the quality of evidence was too low to provide strong recommendations and directly omit the combined approach of a radiotracer and blue dye. In addition, all included studies reported a higher average number of identified SLNs when using ICG as a tracer, indicating these are not likely to be all SLNs but rather second echelon lymph nodes.…”

Table_1.pdf

“…Recent systematic reviews and meta-analyses (35,(37)(38)(39)(40)(41) on SLN mapping technology concerning gynecological malignant tumors are concluded in Supplementary Table 1.…”