Cervical re-injection of indocyanine green to improve sentinel lymph node detection in endometrial cancer.

OBJECTIVES: To evaluate the role of cervical re-injection of indocyanine green (ICG) to increase the detection rate of sentinel lymph node (SLN) in patients with endometrial cancer (EC) who underwent robotic-assisted surgical staging. METHODS: We retrospectively identified consecutive EC patients undergoing robotic-assisted staging with SLN biopsy at our Institution between June 2016 and April 2020. Patients were excluded if they had open abdominal surgical approach, neoadjuvant chemotherapy, and advanced stage [International Federation of Gynecology and Obstetrics (FIGO) stage III-IV] at diagnosis. According to our SLN protocol, in case of either unilateral or no SLN detection, we performed an ipsilateral or bilateral cervical re-injection of ICG. RESULTS: In total, 251 patients meeting inclusion criteria were included in the analysis. At first injection, bilateral detection was achieved in 184 (73.3%), unilateral detection in 57 (22.7%), and no detection in 10 (4.0%) patients. Cervical re-injection was performed in 51 of 67 patients with failed bilateral mapping. After cervical re-injection, bilateral detection rate increased to 94.5% (222/235), while unilateral and no detection were 5.1% (12/235) and 0.4% (1/235), respectively. CONCLUSIONS: Our results suggest that cervical re-injection of ICG, in case of failed bilateral mapping of SLN, brings about a significant improvement in SLN detection rates, therefore reducing the number of side-specific required lymphadenectomies.

Role of lymphadenectomy in endometrial cancer with nonbulky lymph node metastasis: Comparison of comprehensive surgical staging and sentinel lymph node algorithm.

OBJECTIVES: To compare survival and progression outcomes between 2 nodal assessment approaches in patients with nonbulky stage IIIC endometrial cancer (EC). METHODS: Patients with stage IIIC EC treated at 2 institutions were retrospectively identified. At 1 institution, a historical series (2004-2008) was treated with systematic pelvic and para-aortic lymphadenectomy (LND cohort). At the other institution, more contemporary patients (2006-2013) were treated using a sentinel lymph node algorithm (SLN cohort). Outcomes (hazard ratios [HRs]) within the first 5 years after surgery were compared between cohorts using Cox models adjusted for type of adjuvant therapy. RESULTS: The study included 104 patients (48 LND, 56 SLN). The use of chemoradiotherapy was similar in the 2 cohorts (46% LND vs 50% SLN), but the use of chemotherapy alone (19% vs 36%) or radiotherapy alone (15% vs 2%) differed. Although there was evidence of higher risk of cause-specific death (HR, 2.10; 95% CI, 0.79-5.58; P = 0.14) and lower risk of para-aortic progression (HR, 0.27; 95% CI, 0.05-1.42; P = 0.12) for the LND group, the associations did not meet statistical significance. The risk of progression was not significantly different between the groups (HR, 1.27; 95% CI, 0.60-2.67; P =0 .53). In parsimonious multivariable models, high-risk tumor characteristics and nonendometrioid type were independently associated with lower cause-specific survival and progression-free survival. CONCLUSIONS: In EC patients with nonbulky positive lymph nodes, use of the SLN algorithm with limited nodal dissection does not compromise survival compared with LND. Aggressive pathologic features of the primary tumor are the strongest determinants of prognosis.

Pelvic Sentinel lymph node detection in High-Risk Endometrial Cancer (SHREC-trial)-the final step towards a paradigm shift in surgical staging.

STUDY AIMS: To prospectively assess the diagnostic accuracy of a pelvic sentinel lymph node (SLN) algorithm in high-risk endometrial cancer (HREC). PATIENTS AND METHODS: Consecutive women with presumed FIGO stage I-II HREC underwent robotic surgery at two academic centres by five accredited surgeons. An anatomically based algorithm was adhered to, following cervical injection of indocyanine green (ICG), with reinjection of tracer in case of non-display of predefined lymphatic pathways. After removal of SLNs, a pelvic and infrarenal para-aortic lymphadenectomy was performed. Primary end-point was sensitivity of the SLN-ICG algorithm. Secondary end-points were sensitivity of the overall SLN algorithm (including macroscopically suspect nodes as SLNs), SLN mapping rates and morbidity of the SLN procedure. RESULTS: Two hundred fifty-seven women were analysed; 54 had pelvic lymph node metastases (LNMs), and 52 of those were correctly identified by the SLN-ICG algorithm. In two women (one with false-negative ICG-SLNs and one non-mapped woman), the pelvic LNMs were identified by the overall SLN algorithm. The SLN-ICG algorithm had a sensitivity of 98% (95% confidence interval [CI] 89-100) and a negative predictive value of 99.5% (95% CI 97-100). The sensitivity of the overall SLN algorithm was 100% (95% CI 92-100) and the negative predictive value was 100% (95% CI 98-100). The bilateral mapping rate was 95%. Two women (1%) had isolated para-aortic metastases. No adverse events occurred during the SLN procedure. CONCLUSION: With a complete sensitivity to detect pelvic LNMs, the described pelvic SLN algorithm can, in the hands of experienced surgeons, exclude overall nodal involvement in 99% and thereby safely replace a full lymphadenectomy in HREC.

Multicenter study comparing oncologic outcomes between two nodal assessment methods in patients with deeply invasive endometrioid endometrial carcinoma: A sentinel lymph node algorithm versus a comprehensive pelvic and paraaortic lymphadenectomy.

OBJECTIVES: To compare oncologic outcomes in the staging of deeply invasive endometrioid endometrial carcinoma (EEC) using a sentinel lymph node algorithm (SLN) versus pelvic and paraaortic lymphadenectomy to the renal veins (LND); to compare outcomes in node-negative cases. METHODS: At two institutions, patients with deeply invasive (≥50% myometrial invasion) EEC were identified. One institution used LND (2004-2008), the other SLN (2005-2013). FIGO stage IV cases were excluded. Clinical characteristics and follow-up data were recorded. RESULTS: 176 patients were identified (LND, 94; SLN, 82). SLN patients were younger (p = 0.003) and had more LVSI (p < 0.001). 9.8% in the SLN and 29.8% in the LND cohorts, respectively, received no adjuvant therapy (p < 0.001). There was no association between type of assessment and recurrence; adjusted hazard ratio (aHR; LND vs. SLN) 0.87 (95%CI 0.40, 1.89) PFS. After controlling for age and adjuvant therapy, there was no association between assessment method and OS (aHR 2.54; 95%CI 0.81, 7.91). The node-negative cohort demonstrated no association between survival and assessment method: aHR 0.69 (95%CI 0.23, 2.03) PFS, 0.81 (95%CI 0.16, 4.22) OS. In the node-negative cohort, neither adjuvant EBRT+/-IVRT (HR 1.63; 95%CI 0.18, 14.97) nor adjuvant chemotherapy+/-EBRT+/-IVRT (HR 0.49; 95%CI 0.11, 2.22) were associated with OS, compared to no adjuvant therapy or IVRT-only. CONCLUSION: Use of an SLN algorithm in deeply invasive EEC does not impair oncologic outcomes. Survival is excellent in node-negative cases, irrespective of assessment method. Adjuvant chemotherapy in node-negative patients does not appear to impact outcome.

Performance of sentinel lymph node biopsy in high-risk endometrial cancer.

OBJECTIVE: To determine the rate and performance of sentinel lymph node (SLN) mapping among women with high-risk endometrial cancers. METHODS: Patients diagnosed between 2012 and 2015 with uterine cancer of grade 3 endometrioid, clear cell, serous or carcinosarcoma histology and who underwent SLN mapping prior to full pelvic lymph node dissection were included. Subjects underwent methylene blue or ICG injection for laparoscopic (N = 16) or robotic-assisted laparoscopic (N = 20) staging. Outcomes included SLN mapping rates, SLN and non-SLN positive rates, false negative SLN algorithm rate, and the negative predictive value (NPV) of the SLN algorithm. Fisher's exact test was used to compare mapping and node positivity rates. RESULTS: 9/36 (25%) patients with high-risk uterine cancer had at least one metastatic lymph node identified. Successful mapping occurred in 30/36 (83%) patients. SLN mapped to pelvic nodes bilaterally in 20 (56%), unilaterally in 9 (25%), and aortic nodes only in 1 (3%). Malignancy was identified in 14/95 (15%) of all sentinel nodes and 12/775 (1.5%) of all non-sentinel nodes (p < 0.001). The false negative rate of SLN mapping alone was 2/26 (7.7%); the NPV was 92.3%. When the SLN algorithm was applied retrospectively the false negative rate was 0/31 (0%); the NPV was 100%. CONCLUSION: SLN mapping rates for high-risk cancers are slightly lower than in prior reports of lower risk cancers. The NPV of the SLN mapping alone is 92% and rises to 100% when the SLN algorithm is applied. Such results are acceptable and consistent with larger subsets of lower risk endometrial cancers.

Comparison of a sentinel lymph node and a selective lymphadenectomy algorithm in patients with endometrioid endometrial carcinoma and limited myometrial invasion.

OBJECTIVES: To assess clinicopathologic outcomes between two nodal assessment approaches in patients with endometrioid endometrial carcinoma and limited myoinvasion. METHODS: Patients with endometrial cancer at two institutions were reviewed. At one institution, a complete pelvic and para-aortic lymphadenectomy to the renal veins was performed in select cases deemed at risk for nodal metastasis due to grade 3 cancer and/or primary tumor diameter>2cm (LND cohort). This is a historic approach at this institution. At the other institution, a sentinel lymph node mapping algorithm was used per institutional protocol (SLN cohort). Low risk was defined as endometrioid adenocarcinoma with myometrial invasion <50%. Macrometastasis, micrometastasis, and isolated tumor cells were all considered node-positive. RESULTS: Of 1135 cases identified, 642 (57%) were managed with an SLN approach and 493 (43%) with an LND approach. Pelvic nodes (PLNs) were removed in 93% and 58% of patients, respectively (P<0.001); para-aortic nodes (PANs) were removed in 14.5% and 50% of patients, respectively (P<0.001). Median number of PLNs removed was 6 and 34, respectively; median number of PANs removed was 5 and 16, respectively (both P<0.001). Metastasis to PLNs was detected in 5.1% and 2.6% of patients, respectively (P=0.03), and to PANs in 0.8% and 1.0%, respectively (P=0.75). The 3-year disease-free survival rates were 94.9% (95% CI, 92.4-97.5) and 96.8% (95% CI, 95.2-98.5), respectively. CONCLUSIONS: Our findings support the use of either strategy for endometrial cancer staging, with no apparent detriment in adhering to the SLN algorithm. The clinical significance of disease detected on ultrastaging and the role of adjuvant therapy is yet to be determined.