LN involvement still remains the most important prognostic factor for women with endometrial and cervical malignancy. However, because early stage disease has a low risk of LN metastasis, in the last few decades, SLN mapping has received increased attention. It is a technique that could potentially result in reducing the morbidity associated with ineffective complete lymphadenectomy.15
Since Ballester et al. published their preliminary SLN mapping experience with cervical injection for women with endometrial cancer, a great amount of valuable literature has been produced.8 There are data supporting its usefulness in detecting micrometastases, thanks to the ultrastaging technique, which allows for a lower complication rate than radical pelvic and/or aortic lymphadenectomy.16,17
In 2015, SLN mapping was incorporated into the National Comprehensive Cancer Network guidelines for both cervical and endometrial cancer in highly specialized centers with extensive experience in SLN mapping and included applying a SLN algorithm to reduce the false-negative rate.18–20 Moreover, in cervical cancer patients, a large retrospective multicenter study showed that the early detection of micrometastasis in patients with cervical cancer has the same impact on survival as in cases of macrometastasis.21
The standard for the most effective SLN mapping in both early stage cervical and endometrial cancers is a dual technique including the combination of 99mTc and blue dye. In the literature, the SLN DR with both blue dye and 99mTc ranges from 80 to 100 %.7 However, the use of a radiolabeled tracer is more demanding for hospitals because it presents many logistic challenges and costs that limit their use worldwide, particularly for countries with limited or no access to radioisotopes.
More recently, the clinical effectiveness of NIR fluorescence using ICG has been evaluated for SLN mapping in gynecologic malignancies, particularly in a minimally invasive, traditionally laparoscopic approach or using a robotic platform.10,22–24 The U.S. Food and Drug Administration has approved ICG for use in humans since 1959 for cardiac and liver functions, but for tissue ICG, its use is off label. Moreover, ICG is widely used particularly for chorioangiography and as a tool to delineate the extrahepatic biliary tree for NIR fluorescence cholangiography.
To date, and including our study, about 400 cases have been published, and globally, the DR and bilateral detection seem to be superior to 99mTc with or without blue dye. We started SLN mapping in October 2010 in our department, and more recently we have introduced real-time fluorescent SLN detection with ICG.13 Many recent studies have demonstrated that NIR fluorescence seems to be safe and feasible, and also allows for real-time observation of lymphatic channels with high DRs and low false-negative rates.
An extensive study using ICG in gynecologic cancers was recently published by Jewell et al.10 The optimal bilateral mapping of ICG alone was 79 % (156 of 197) and for ICG and blue dye was 77 % (23 of 30). The authors concluded that the intracervical injection of ICG has a high bilateral DR and appears to offer an advantage over using blue dye alone, so that the combined use of ICG and blue dye appears unnecessary. To our knowledge, this is the first European experience of SLN mapping with fluorescent ICG, using the Storz ICG SPIES system for the laparoscopic platform and traditional open surgery using the Vitom II system.
The intracervical injection of ICG improved the optimal bilateral mapping (58 % up to 85 %), with a consequent important impact on the management of our cases. In our series of 163 consecutive cases, SLNs mapping using ICG demonstrated the highest DR compared to other modalities (100 %). In addition, florescent mapping with ICG was significantly superior to 99mTc with blue dye or blue dye alone in terms of bilateral mapping in early stage endometrial and cervical cancer (85 % ICG vs. 58 and 50 % of 99mTc with blue dye and blue dye alone, respectively). These differences are particularly evident and statistically significant in the case of endometrial cancer. The higher number of bilateral mappings—if confirmed in prospective trials—may consequently reduce the overall number of complete lymphadenectomies, thereby reducing the duration and additional costs of surgical treatment.
Although it was not the main aim of this study, our experience with ICG resulted in an improvement in the workflow because the SLN mapping procedure can be started directly in the operating room. This approach saves time and can avoid the discomfort for patients that results from the preoperative injection of radiocolloid in the nuclear medicine department. Furthermore, the use of ICG seems to be useful during the surgical procedure after SLN mapping, allowing the surgeon to complete the procedure without staining the operative field, as occasionally occurred with blue dye (Fig. 2). This is particularly useful in the case of obese patients, when bleeding covers the retroperitoneal fat and obscures the SLN, and the blue dye extensively stains the operative field. Moreover, the parametrial/paracervical region can be inspected easily using fluorescent dye without impairing parametrial dissection.
The retrospective European data available regarding the use of ICG for SLN mapping are limited. In 2015 Plante et al. and Imboden et al. presented their pilot experiences with ICG in uterine and cervical cancer.23,25 Among the 379 published cases mapped with ICG, the overall DR and the rate of bilateral mapping was better compared to the available literature using 99mTc radiocolloid and blue dye. By comparing 99mTc, blue dye, and ICG, How et al. recently supported the results of the Memorial Sloan Kettering group suggesting that blue dye may be omitted for SLN mapping in endometrial cancer.26
Our results are similar to those recently published demonstrating that SLN mapping with ICG fluorescence seems to improve SLN mapping and bilateral mapping better than with 99mTc with blue dye or blue dye alone for both cervical and endometrial cancers.
Even if the data were recorded consecutively and if there was no difference in the baseline characteristics within the three groups, our study has some limitations because of the small sample size and because of its nonrandomized nature. No patients with negative SLNs with positive non-SLNs for metastases were found; however, the value of a false-negative rate of 0 could be underestimated because in our study, a systematic pelvic and aortic lymphadenectomy was performed only in the case of failed mapping and in the case of positive PET/CT in the pelvic and/or aortic chains of endometrial cancer patients. However, this approach was based on the results described in the current literature, which shows an estimated risk of almost 2–3 % of isolated aortic metastases in preoperative endometrial stage I disease.27,28 Furthermore, the learning curve associated with the use of a new technique probably decreases the bilateral DR seen at the beginning of our experience using 99mTc and blue dye.13