Can mismatch repair status be added to sentinel lymph node mapping algorithm in endometrioid endometrial cancer?

To evaluate the relation between mismatch repair (MMR) status and the risk of lymph node metastasis in endometrial cancer, and whether this additional data can be incorporated to current SLN (sentinel lymph node) algorithm. We included a series of 332 women that underwent SLN mapping ± systematic lymphadenectomy from January 2013 to December 2021. Protein expressions of MLH1, MSH2, MSH6, PMS2 were examined by immuno-histochemistry and considered MMRd (deficient) when at least one protein was not expressed. MMRd was noted in 20.8% of cases and correlated to grade 3 (p = 0.018) and presence of lymphovascular space invasion (p = 0.032). Moreover, MMRd was an independent risk factor for lymph node metastasis (OR 2.76, 95% CI 1.36-5.62). Notably, 21.7% (15/69) cases with MMRd had lymph node metastasis compared to 9.5% (25/263) of cases with MMRp (proficient) (p = 0.005). The overall and bilateral SLN detection rates were 91.9% and 75.9%, respectively. Of the 80 (24%) cases of non-bilateral SLN detection, 66.2% had low-grade tumors (G1/G2) and myometrial invasion <50%. Considering MMR status an independent prognostic factor for lymph node metastasis, a systematic lymphadenectomy (side specific or bilateral) would forgo in 53.7% (43/80) of cases with non-bilateral detection, representing 13% (43/332) of all endometroid tumors. MMR status was independently related to lymph node metastasis in endometrioid EC. Moreover, MMR status may help to select patients that can forgo systematic lymphadenectomy in case of undetected SLN.

Diniz TP ，Menezes JN ，Goncalves BT ，Faloppa CC ，Mantoan H ，Kumagai LY ，Badiglian-Filho L ，Bovolim G ，Guimaraes APG ，De Brot L ，Baiocchi G ... -  《-》

Combination of sentinel lymph node mapping and uterine frozen section examination to reduce side-specific lymphadenectomy rate in endometrial cancer: a Turkish Gynecologic Oncology Group study (TRSGO-SLN-002).

This study aimed to find out whether side-specific pelvic lymphadenectomy can be omitted without compromising diagnostic efficacy according to "reflex frozen section" analysis of the uterus in case of sentinel lymph node (SLN) mapping failure. Patients who underwent surgery for endometrial cancer with an SLN algorithm were stratified as low-risk or high-risk according to the uterine features on the final pathology reports. Two models for low-risk patients were defined to omit side-specific pelvic lymphadenectomy: strategy A included patients with endometrioid histology, grade 1-2, and <50% myometrial invasion irrespective of the tumor diameter; strategy B included all factors of strategy A with the addition of tumor diameter ≤2 cm. Theoretical side-specific pelvic lymphadenectomy rates were calculated for the two strategies, assuming side-specific pelvic lymphadenectomy was omitted if low-risk features were present on reflex uterine frozen examination, and compared with the standard National Comprehensive Cancer Network (NCCN) SLN algorithm. 372 endometrial cancer patients were analyzed. 230 patients (61.8%) had endometrioid grade 1 or 2 tumors with <50% myometrial invasion (strategy A), and in 123 (53.4%) of these patients the tumor diameter was ≤2 cm (strategy B); 8 (3.5%) of the 230 cases had lymphatic metastasis. None of them were detected by side-specific pelvic lymphadenectomy and metastases were limited to SLNs in 7 patients. At least one pelvic side was not mapped in 107 (28.8%) cases in the entire cohort, and all of these cases would require a side-specific pelvic lymphadenectomy based on the NCCN SLN algorithm. This rate could have been significantly decreased to 11.8% and 19.4% by applying reflex frozen section examination of the uterus using strategy A and strategy B, respectively. Reflex frozen section examination of the uterus can be a feasible option to decide whether side-specific pelvic lymphadenectomy is necessary for all the patients who failed to map with an SLN algorithm. If low-risk factors are found on frozen section examination, side-specific pelvic lymphadenectomy can be omitted without compromising diagnostic efficacy for lymphatic spread.

Altin D ，Taşkın S ，Kahramanoglu I ，Vatansever D ，Tokgozoglu N ，Karabük E ，Turan H ，Takmaz Ö ，Naki MM ，Güngör M ，Köse MF ，Ortac F ，Arvas M ，Ayhan A ，Taskiran C ... -  《-》

Sentinel lymph nodes (SLN) in endometrial cancer: The relationship between primary tumor histology, SLN metastasis size, and non-sentinel node metastasis.

To examine sentinel lymph node pathology and describe relationships to uterine pathology, non-sentinel pelvic lymph nodes, and para-aortic lymph nodes. Patients with apparent uterine-confined endometrial cancer underwent robotic hysterectomy, SLN mapping, completion pelvic lymphadenectomy (LND), and para-aortic (PaLND) directed by frozen section. Patients were risk stratified by histology: low-risk (LR) endometrioid <50% depth-of-invasion (DOI), intermediate-risk (IR) endometrioid ≥50% DOI, and high-risk (HR) type II histology for comparison to other pelvic/aortic metastases. 414 patients were stratified: 275 LR, 80 IR, and 59 HR cases. PaLND was performed in 84.2% of IR/HR patients and 25.1% LR patients. Pelvic node metastasis was detected in 11.6% LR, 50.0% IR, and 39.0% HR patients. PaLN metastasis was detected in 2.9% LR, 11.3% IR, and 16.9% HR patients. Proportionally, isolated tumor cells (ITC) SLNs were more common in LR or IR vs. HR group (51.6% and 44.7% vs. 15.0%, p < 0.05). The SLN false negative rates (FNR) were 0% LR, 2.5% IR, and 5.1% HR. Non-sentinel pelvic node metastases were present in 28(31.5%) of all SLN+ cases, but only 3(8.3%) of SLN with ITC. PaLN metastasis was found in 18.8% LR, 11.8% IR, and 33.3% HR cases with ITC SLNs. After controlling for DOI, LVSI, and grade, ITC-positive SLNs had a significant association with non-sentinel pelvic and aortic metastasis (p = 0.03 and p = 0.008, respectively). Patients with HR histology have more micro/macro-metastases in both SLNs and non-SLN metastases compared to LR/IR patients. SLN ITCs were associated with a clinically significant incidence of PaLN metastasis across all histology risk groups. There were no cases of isolated aortic node metastasis in this study. SLN mapping had an increased, although clinically acceptable FNR in the HR cohort compared to LR patients.

Kennard JA ，Stephens AJ ，Ahmad S ，Zhu X ，Singh C ，McKenzie ND ，Kendrick JE ，Holloway RW ... -  《-》

Value and best way for detection of Sentinel lymph node in early stage endometrial cancer: Selective lymphadenectomy algorithm.

The cornerstone of treatment for endometrial carcinoma is total abdominal hysterectomy and bilateral salpingo-oophoprectomy. Pelvic lymphadenectomy, with or without para-aortic lymphadenectomy, plays an important role in the surgical staging of endometrial carcinoma, and provides more accurate prognostic information. We aimed to evaluate the value and techniques for SLN mapping in early stage endometrial cancer with low risk for lymph node metastasis and whether selective or systematic lymphadenectomy is needed according to the results of proposed algorithm. Between June 2016 and June 2017, 120 patients with early stage endometrial cancer with low risk for nodal metastasis underwent surgical staging. Patients were classified equally according to SLN mapping technique used for injecting the methylene blue dye. Group A included hysteroscopic guided methylene blue injection, Group B included transcervical injection, Group C included subserosal uterine injection and Group D included combined transcervical and subserosal injection. Blue lymph nodes and enlarged suspicious whether stained or non stained ones were dissected for frozen section evaluation done then bilateral pelvic node dissection was done and tissues were sent for pathological examination. Clinical and pathological SLN detection were more with hysteroscopic technique than others and pathological detection was lower than clinical detection in all techniques. Metastatic disease was more common in nodes with suspicious appearance. About 10% of negative suspicious and mapped nodes were associated with positive other nodes for metastasis. SLN in endometrial cancer has a role in staging of endometrial cancer with best technique for detection, hysteroscopic guided blue dye injection. SLN can be used in patients with low risk for lymph node metastasis for selective lymphadenectomy. Blue dye labelling using methylene blue dye is good in low resource countries as it is cheap. We recommended the following algorithm for surgical staging in early endometrial cancer with better results than using SLN alone. Stage I type 1, grade 1,2 endometrial cancer should undergo surgical staging with initial evaluation of the peritoneum which if affected, it is stage III with no need for lymphadenectomy. Then, dissection of the blue and suspicious nodes which if any is positive on frozen section, selective same side pelvic and paraaortic nodal dissection should be done. If they are negative, no need for lymphadenectomy. This approach can help patients to avoid the side effects associated with a complete lymphadenectomy. The higher rate of detection using this algorithm is related to combining the suspicions nodes with the stained ones.

El-Agwany AS ，Meleis MH 《-》

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

To assess clinicopathologic outcomes between two nodal assessment approaches in patients with endometrioid endometrial carcinoma and limited myoinvasion. 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. 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. 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.

Zahl Eriksson AG ，Ducie J ，Ali N ，McGree ME ，Weaver AL ，Bogani G ，Cliby WA ，Dowdy SC ，Bakkum-Gamez JN ，Abu-Rustum NR ，Mariani A ，Leitao MM Jr ... -  《-》