Sentinel-Node Mapping by Intraoperative Near-Infrared Fluorescence in the Robotic Surgical Treatment of Endometrial Cancer

In recent years sentinel lymph node (SLN) mapping has emerged as an attractive approach for treating gynecologic cancer, and in particular, endometrial cancer (EC), the most common gynecologic malignancy in developed countries.^1,2

The SLN biopsy was first described by Cabanas in 1977, ³ and has gained increasing popularity for staging several cancers, such as melanoma, breast, and vulvar cancers. In the late 1990s, Burke et al. were the first researchers to introduce the concept of SLN biopsy for staging women affected by EC^4,5; regarding this latter specific setting, evidence supporting the performance of SLN biopsy has constantly increased, as demonstrated by more than 100 studies with positive results available in the literature. ⁶

Theoretically, SLN evaluation upholds the effectiveness of standard lymphadenectomy to detect patients with positive lymph nodes, thus minimizing the risk of developing lymphadenectomy-related morbidity in patients not needing it. ¹ In this regard, 2 randomized trials evaluating the performance of hysterectomy plus lymphadenectomy in comparison with that of hysterectomy without additional procedures ¹ suggested that lymphadenectomy increases morbidity without ameliorating oncologic outcomes in patients with early stage EC and low probability of lymph-nodal involvement. Moreover, in an exhaustive meta-analysis, Kang et al. identified 26 trials on SLN biopsy in EC. That study showed a detection rate of 78% and a sensitivity of 93% for SLN biopsy; considering a risk of 10% for having lymph-nodal metastasis, a false–negative rate of 1% was calculated for SLN biopsy. ⁷ Since the publication of the meta-analysis, 2 additional prospective studies on SLN biopsy for EC suggested that the sensitivity and negative predictive value (NPV) of SLN biopsy are both promising.^8,9 Anyway, at the moment, no consensus on the systematic performance of retroperitoneal staging exists for managing patients affected by EC. ¹⁰

In the last decades, performance of SLN for EC staging has gained evidence among gynecologic oncologists in parallel with the emerging role of minimally invasive surgical approaches. Current controversial areas of SLN are related to which are the best techniques and tracers to perform the SLN mapping; in fact, until now, different types of injection sites (cervical, uterine and endometrial) and detection techniques have been evaluated. ⁶

In our opinion, a further development in this field (after conventional dye or radiotracers) has been the introduction of indocyanine-green (ICG), which enables near-infrared fluorescence imaging for open, laparoscopic, and, in particular, robot-assisted laparoscopic surgery. IGC is composed of small particles that show florescence after they are visualized thorough a near-infrared light (range: 700–900 nm); ICG can be injected in the same sites used for the other detection methods directly before starting surgery, is very rarely responsible for allergic reactions, and is visible (which is different than radiotracers, because ICG is in the near-infrared spectrum).

The intraoperative near-infrared fluorescence (INIF) imaging system (Firefly,™; Intuitive Surgical Inc., Sunnyvale, CA) is the main system developed to detect this fluorescent light through a robotic-assisted approach (da Vinci Xi or Si™; Intuitive Surgical Inc.). In particular, the equipment for the robotic-assisted surgical approach includes a fluorescence-capable illuminator, a camera head, and an endoscope. Other systems with similar functions have been developed for laparoscopic single-site and conventional laparoscopy.

Our robotic experience (with the da Vinci Xi) involves the following procedure: Immediately after the anesthesia and the docking, prior to insertion of a uterine manipulator, a total of 4 mL of ICG 1% dye is slowly injected superficially (0.1 cm) and deep (1 cm) into the cervix at the 3 o'clock and 9 o'clock positions through a spinal needle. First, the pelvis is evaluated carefully and a washing is obtained before starting the surgical procedure; then, an accurate dissection is performed by opening the pararectal and paravesical spaces. The various nodal regions (e.g., obturator, external iliac, presacral) are evaluated to identify the fluorescent SLN (∼ after 20 minutes from the tracer injection) via the INIF camera. The SLNs of both pelvic sides are removed to be sent for histologic evaluation according to a standardized ultrastaging protocol.

Overall, the INIF image system enables rapid conversion from the normal robotic view to that which shows the accurate location of the ICG (Fig. 1): in fact, this procedure is performed promptly by holding the camera control pedal at the console and then sliding the finger switch. Moreover, it enables the ability to maintain the usual visualization without any dye in the field (unlike isosulfan blue), and thus enables direct visualization of the SLN (this is different than radioisotope, which requires a Geiger counter to be inserted into the field).

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FIG. 1.

Normal robot-assisted endoscopic view of the pararectal and the paravesical spaces (A) and view by intraoperative near-infrared fluorescence (INIF) imaging system (B). Normal robot-assisted endoscopic view of the sentinel lymph node (C) and view by INIF imaging system (D) after its dissection.

In 2017, the multicenter prospective FIRES trial evaluated 385 patients with apparent stage I EC who were undergoing robotic-assisted surgery. ¹¹ Patients included in that trial underwent hysterectomy with SLN mapping with the INIF system, followed by pelvic (with or without) para-aortic lymphadenectomy. Mapping in at least 1 SLN was observed in 86% of patients, whereas positive nodes were identified in 41 of them (36 of those women had at least 1 mapped SLN). Lymph-nodal metastases were identified into the SLN correctly in 35 cases (97%). Thus, the researchers reported a sensitivity to detect node-positive disease of 97.2% and an NPV of 99.6% when performing the SLN technique. ¹¹ Recently, a retrospective study on SLN biopsy utilizing ICG and robotics (with an INIF system) confirmed the feasibility of this procedure for treatment of stage I EC (SLNs were not identified or the procedure was stopped only in 3.4% of subjects) ¹²

In conclusion, the evidence for the use of the INIF imaging system is still accumulating. However, new clinical researchers are demanding to investigate the use of ICG further along with INIF imaging system; in the near future, our research group is going to confirm the feasibility and the outcomes of SLN biopsy utilizing the robotic platform and near-infrared imaging for treating patients with early stage EC.