Identifying safe diagnostic algorithms for sentinel lymph node mapping in high-risk endometrial cancer: The SENTIREC-endo study.

INTRODUCTION: It is unclear if sentinel node (SLN) mapping can replace pelvic- (PLD) and paraaortic lymphadenectomy (PALD) for high-risk endometrial cancer (EC). A diagnostically safe surgical algorithm, taking failed mapping cases into account, is not defined. We aimed to investigate the diagnostic accuracy of SLN mapping algorithms in women with exclusively high-risk EC. METHODS: We undertook a prospective national diagnostic cohort study of SLN mapping in women with high-risk EC from March 2017 to January 2023. The power calculation was based on the negative predictive value (NPV). Women underwent SLN mapping, PLD and PALD besides removal of suspicious and any FDG/PET-positive lymph nodes. Accuracy analyses were performed for five algorithms. RESULTS: 170/216 included women underwent SLN mapping, PLD and PALD and were included in accuracy analyses. 42/170 (24.7%) had nodal metastasis. The algorithm SLN and PLD in case of failed mapping, demonstrated a sensitivity of 86% (95% CI 74-100) and an NPV of 96% (95% CI 91-100). The sensitivity increased to 93% (95% CI 83-100) and the NPV to 98% (95% CI 94-100) if PLD was combined with removal of any PET-positive lymph nodes. Equivalent results were obtained if PLD and PALD were performed in non-mapping cases; sensitivity 93% (95% CI 83-100) and NPV 98% (95% CI 95-100). CONCLUSION: SLN-mapping is a safe staging procedure in women with high-risk EC if strictly adhering to a surgical algorithm including removal of any PET-positive lymph nodes independent of location and PLD or PLD and PALD in case of failed mapping.

Patient-reported lymphedema after sentinel lymph node mapping in women with low-grade endometrial cancer.

BACKGROUND: Sentinel lymph node mapping is a minimally invasive surgical staging procedure that allows identification of macro- and micrometastases. The implementation of sentinel lymph node mapping to women with low-grade endometrial cancer allows detection of lymph node metastases and avoids the morbidity of radical pelvic lymphadenectomy. The extent of myometrial invasion is highly predictive of lymph node metastases but is hard to determine precisely preoperatively. The exact rate of lymph node metastases in the large group of women with <50% myometrial invasion is low but unknown. The benefit of detecting metastases in this group should balance the risk of lymphedema. There is limited knowledge of early and late lymphedema and its impact on the quality of life in women with low-grade endometrial cancer following sentinel lymph node mapping. OBJECTIVE: The primary objective was to investigate the risk of patient-reported lymphedema after sentinel lymph node mapping in women with low-grade endometrial cancer. In addition, we aimed to evaluate risk factors for lymphedema and the condition-specific quality of life (QoL) among women who reported lymphedema 12 months after surgery. STUDY DESIGN: Women with presumed stage I low-grade endometrial cancer were included in a national prospective cohort study on sentinel lymph node mapping from March 2017 to February 2022. Women completed a package of validated patient-reported outcome measures before surgery, 3 and 12 months after surgery. The primary outcome was the leg lymphedema domain score from the European Organisation for Research and Treatment of Cancer-Endometrial Cancer Module (EORTC QLQ-EN24). The lymphedema assessment was further supplemented by 7 validated single items from the European Organisation for Research and Treatment of Cancer item library addressing lymphedema of legs, genitals, and groin. The disease-specific quality of life was assessed using the validated Lymphedema Quality of Life Tool. Scores were linearly transformed to 0 to 100. A change from baseline of 8 points in leg lymphedema sum-score was considered clinically important. Mean difference scores over time with 95% confidence interval were estimated. Multiple linear regression models evaluated baseline predictors associated with the 12 months postoperative lymphedema score, and if early lymphedema predicted lymphedema at 12 months after surgery. Lymphedema condition-specific quality of life was evaluated for women with lymphedema. RESULTS: Seventy-nine % (486/617) completed patient-reported outcome measures at baseline and 12 months. The mean difference score of leg lymphedema from baseline to 12 months was 5.0, confidence interval [3.3, 6.8], that is, below the threshold for clinical importance. Baseline leg lymphedema score and body mass index were positively associated with the leg lymphedema score at 12 months. The leg lymphedema score at 3 months was associated with a higher 12-month score. High scores of lymphedema at 12 months were negatively associated with the women's daily activities, appearance, emotional functioning, and global quality of life and increased their subjective symptom burden. CONCLUSION: Women with low-grade endometrial cancer have a low risk of lymphedema after sentinel lymph node mapping. Leg swelling at baseline and body mass index predicted more lymphedema at 12 months after surgery. Early lymphedema at 3 months predicted persistent lymphedema. A high leg lymphedema score at 12 months is associated with impairment in several aspects of quality of life.

Oncological long-term outcomes of laparoscopic versus open gastrectomy for cT3-4 gastric cancer at surgical staging: a propensity-score matched cohort study.

BACKGROUND: The oncological efficacy of laparoscopic surgery for advanced gastric cancer (AGC) has been evaluated by several randomized trials. However, the inclusion of earlier-stage disease was a limitation in previous studies. METHODS: Patients with cT3-4 gastric cancer, determined by surgical staging to minimize migration of earlier stages, treated at a tertiary cancer center from 2009 to 2018 were included. Based on the surgical approach, the patients were divided into two groups: the laparoscopic gastrectomy (LG) and the open gastrectomy (OG) and matched for age, sex, macroscopic appearance (type 4 or non-type 4), body mass index, estimated tumor size, clinical stage T3'T4, clinical N stage, pathologic T stage (T3 or T4), and type of surgery (total or distal gastrectomy). RESULTS: 588 patients (221 LG, 367 OG) were included in the analysis. After 1:1 propensity-score matching, 386 patients (193 LG, 193 OG) were assigned for analysis. In the LG group, operation time was longer with lower blood loss. The incidence of postoperative complications (≥ grade III) did not differ significantly between the groups (OG: 8.3%, vs. LG: 9.3%). Overall survival (OS) was longer in the LG group (5-year OS: 79.3 vs. 73% HR 0.66, 95% CI 0.44-0.99, P = 0.0497). Relapse-free survival (RFS) did not show a statistical difference (5-year RFS: 69.5 vs. 68.7 HR 0.88, 95% CI 0.62-1.26, P = 0.487). Subgroup analysis for OS also demonstrated equivalent outcomes. CONCLUSION: LG demonstrates comparable safety and efficacy to OG for advanced gastric cancer at surgical staging, with similar rates of severe complications and long-term oncological outcomes. Further research is needed to validate these findings, particularly for total gastrectomy and for patients from Western populations.

Para-aortic and pelvic lymphadenectomy in locally advanced cervical cancer with pelvic lymph node metastasis.

OBJECTIVE: This study sought to explore the efficiency of para-aortic and pelvic lymphadenectomy in the treatment of locally advanced cervical cancer (LACC) with pelvic lymph node (PLN) metastasis. METHODS: A total of 171 LACC patients with imaging-confirmed pelvic lymph node metastasis were included in this study. These patients were divided into two groups: the surgical staging group, comprising 58 patients who had received para-aortic and pelvic lymphadenectomy (surgical staging) along with concurrent chemoradiation therapy (CCRT), and the imaging staging group, comprising 113 patients who had received only CCRT. The two groups' progression-free survival (PFS), overall survival (OS) and treatment-related complications were compared. RESULTS: The surgical staging group started radiotherapy 10.2 days (range 9-12 days) later than the imaging staging group. The overall incidence of lymphatic cysts was 9.30%. In the surgical staging group, para-aortic lymph node metastasis was identified in 34.48% (20/58) of patients, while pathology-negative PLN was observed in 12.07% (7/58). Over a median follow-up period of 52 months, no significant differences in PFS and OS rates were found between the two groups (p > 0.05). Subgroup analysis of patients with lymph node diameters of ≥ 1.5 cm revealed a five-year PFS rate of 75.0% and an OS rate of 80.0% in the surgical staging group, compared to 41.5% and 50.1% in the imaging staging group, respectively, showing statistically significant differences (p = 0.022, HR:0.34 [0.13, 0.90] and p = 0.038, HR: 0.34 [0.12,0.94], respectively for PFS and OS). Additionally, in patients with two or more metastatic lymph nodes, the five-year PFS and OS rates were 69.2% and 73.1% in the surgical staging group, versus 41.0% and 48.4% in the imaging staging group, with these differences also being statistically significant (p = 0.025, HR: 0.41[0.19,0.93] and p = 0.046, HR: 0.42[0.18,0.98], respectively). CONCLUSION: Performing surgical staging before CCRT is safe and delivers accurate lymph node details crucial for tailoring radiotherapy. This approach merits further investigation, particularly in women with pelvic lymph nodes measuring 1.5 cm or more in diameter or patients with two or more imaging-positive PLNs.

Feasibility of intraoperative injection of radioactive tracer and blue dye for sentinel lymph node biopsy in vulvar cancer.

OBJECTIVE: The objective of this study was to examine the feasibility and success rate of intraoperative injection of radiotracer and blue dye performed by the surgeon without the use of preoperative lymphoscintigraphy for the detection of sentinel lymph nodes in clinically early stage vulvar cancer. METHODS: All patients with clinically early stage vulvar cancer who underwent attempted sentinel lymph node biopsy using intraoperative injection of Technetium-99 m (99mTc) tracer and blue dye performed by the surgeon after induction of anesthesia at single academic institution from 12/2009 to 5/2022 were identified. Demographic and clinicopathologic variables were collected. Data were compared using descriptive statistics. RESULTS: One hundred sixty-four patients (median age 66.4 years) underwent intraoperative injection of radioactive tracer and dye for sentinel lymph node biopsy. Most patients (n = 156, 95.1%) were white. Squamous cell carcinoma accounted for 138 cases (84.1%), melanoma for 10 (6.1%), extra-mammary invasive Paget's disease for 11 (6.7%), and other histologies for 5 (3%). A majority of cases were stage I disease on final pathology (n = 119, 72.6%). Most patients (n = 117, 71%) had tumors located within 2 cm of the midline and underwent planned bilateral groin assessment, while 47 (29%) had well lateralized lesions and underwent unilateral groin assessment. For the patients undergoing unilateral groin assessment, 44 of 47 (93.6%) had successful unilateral mapping. Of the patients who underwent bilateral groin assessment, 87 of 117 (74.4%) had successful bilateral mapping, and 26 of 117 (22.2%) had successful unilateral mapping. Of the 26 patients who underwent bilateral assessment but only had unilateral mapping, 19 had unilateral mapping to ipsilateral groin but failed contralateral mapping, six had midline lesions with successful mapping to one groin but failed mapping to the other groin, and one had unilateral mapping to the contralateral groin but not ipsilateral groin. The total successful sentinel lymph node mapping rate in this cohort was 86.5% (243/281 total sentinel lymph node attempts). CONCLUSION: In this cohort, the overall success rate of sentinel lymph node mapping and biopsy was 86.5%. The high rate of successful sentinel lymph node mapping supports the use of intraoperative radiotracer and blue dye injection by trained providers.

Laparo-endoscopic single-site versus conventional laparoscopic surgery for early-stage endometrial cancer: A randomized controlled non-inferiority trial.

OBJECTIVE: To evaluate the feasibility and safety of laparo-endoscopic single-site surgery (LESS) compared with conventional laparoscopic surgery (CLS) for early-stage endometrial cancer. METHODS: Patients with clinical stage IA, IB, grade 1-3 endometrial cancer were randomly assigned to undergo LESS or CLS. The primary endpoint was the non-inferiority of LESS to CLS in terms of operation time and the number of resected pelvic lymph nodes. We set the non-inferior margin of the operation time as within 15% (24 min) and the number of resected pelvic lymph nodes as within 20% (5.2 lymph nodes). RESULTS: There was no significant difference between the LESS group (n = 53) and the CLS group (n = 54) in terms of age, weight, body mass index, parity, menopausal status, history of abdominal surgery, and preoperative CA-125 levels. The total operation time was comparable between the two groups. On average, 4.6 fewer pelvic lymph nodes were retrieved in the LESS group, which was within the non-inferiority margin. There were no significant differences in the incidence of intra- and postoperative complications, estimated blood loss, and postoperative hospital stay between the two groups. After a median follow-up time of 34 months (range, 2-242), the progression-free survival rates were 96.2% and 98.1% (P = 0.55) in the LESS group and the CLS group, and the overall survival rates were 98.1% and 100.0% (P = 0.31), respectively. CONCLUSION: LESS surgical staging was non-inferior to CLS and had acceptable feasibility, safety, and efficacy for the surgical management of early-stage endometrial cancer. TRIAL REGISTRATION: Clinicaltrial.gov identifier number: NCT01679522.

Is sentinel lymph node assessment useful in patients with a preoperative diagnosis of endometrial intraepithelial neoplasia?

OBJECTIVE: To determine the prevalence of underlying high-intermediate (high-IM) and high-risk endometrial cancer (EC) in patients with preoperative diagnosis of Endometrial intraepithelial neoplasia (EIN) and to assess the impact of the information retrieved from the sentinel lymph node (SLN) on adjuvant therapy. METHODS: Retrospective cohort study of women undergoing hysterectomy, optional bilateral salpingo-oophorectomy (BSO) and lymph nodes assessment for EIN between December 2007 and August 2021. RESULTS: One hundred and sixty two (162) eligible patients were included, of whom 101 (62.3%) had a final diagnosis of EIN, while 61 (37.7%) were ultimately diagnosed with carcinoma. Out of 15 patients with high-IM to high-risk disease (9.25% of all EIN), 12 had grade 2-3 EC including 8 with >50% myometrial invasion, 2 with serous subtype, 1 with cervical invasion and 2 with pelvic lymph nodes involvement. Of the 3 patients with grade 1 EC, one patient had disease involving the adnexa and 2 patients had tumor invading >50% of the myometrium and with lymphovascular space invasion (LVSI). Ten patients received vaginal brachytherapy after surgery, 3 patients with extrauterine spread were treated with systemic chemotherapy followed by vaginal brachytherapy and pelvic external-beam radiotherapy and 2 patients with early-stage serous carcinoma received chemotherapy followed by vaginal brachytherapy. CONCLUSIONS: Information from SLN, even when negative, can be helpful in the management of patients with EC after preoperative EIN, as some patients are found to have high-IM to high-risk disease on final pathology. These patients would require either re-staging surgery or adjuvant external beam radiotherapy, both could be avoided by proper staging.

Lymphatic Mapping and Sentinel Node Biopsy in High-Grade Uterine Cancers.

PURPOSE OF REVIEW: Sentinel lymph node (SLN) mapping has been adopted as an acceptable method of lymph node evaluation in the surgical staging for low-grade endometrial cancer. In this review, we analyze the literature on the utility of SLN mapping in high-grade endometrial cancer. RECENT FINDINGS: SLN mapping in high-grade endometrial cancer demonstrates similar high detection rates and diagnostic accuracy as seen in low-grade endometrial cancers. However, obtaining sufficient operator experience (at least 30 cases) and following SLN mapping algorithm continues to be essential to preserving diagnostic accuracy. Although limited in retrospective study design and short-term follow-up, current studies have not demonstrated inferior survival outcomes of SLN mapping compared to traditional lymphadenectomy. SLN mapping is an acceptable and accurate method of lymph node evaluation in high-grade endometrial cancer. Future prospective studies are needed to evaluate long-term oncologic outcomes between SLN mapping and systematic lymphadenectomy in this patient population.

Laparoscopic Resection of a High Grade Serous Ovarian Cancer that Recurred at the Vaginal Stump with Extensive Pelvic Adhesions after Complete Surgical Staging.

STUDY OBJECTIVE: To show laparoscopic resection of a high grade serous ovarian cancer that recurred at the vaginal stump with extensive pelvic adhesions after complete surgical staging. DESIGN: Stepwise demonstration of the procedure with narrated video footage. SETTING: University hospital. INTERVENTIONS: We reported a case of a 62-year-old woman with a history of complete surgical staging of high grade serous ovarian cancer staged IIB, which consisted of hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymph node dissection, and omentectomy, about 18 months before this admission. She received 6 courses of carboplatin/paclitaxel combination therapy after complete surgical staging and achieved complete remission. About 12 months after the last course of chemotherapy, she visited the local clinic because of irregular vaginal bleeding. Physical examination revealed a 3 × 3 × 2 cm3 mass at the vaginal vault. Biopsy of the mass was performed under colposcopy, and pathological reports showed recurrent high grade serous cancer. Her serum cancer antigen 125 level was in normal range. Positron emission tomographic/computed tomographic imaging (PET/CT) showed no evidence of disease dissemination. A diagnosis of recurrent high grade serous ovarian cancer was made. After the biopsy of the recurrent mass, there were no visible lesions, which made us believe that laparoscopy management would not contribute to intraperitoneal spread of the tumors. Therefore, laparoscopic resection of the vaginal stump was scheduled. The key steps of the procedure were summarized as follows. First, the bowels were released from the side abdominal wall to expose bilateral external iliac vessels. Second, bilateral ureters were identified and mobilized to avoid incidental ureter injuries. Third, we opened the rectovaginal space and detached the rectum from the posterior vaginal wall. Fourth, the posterior vesical wall was separated from the vaginal stump. After exposure of the key anatomic landmarks, laparoscopic resection of the vaginal stump was performed safely. Final pathologic report showed recurrent high grade serous ovarian cancer. The patient received 6 courses of carboplatin/paclitaxel combination therapy, and maintenance therapy with olaparib was suggested, but the patient refused to accept this suggestion. She is still in complete remission 8 months after surgery. CONCLUSION: Laparoscopic resection of a high grade serous ovarian cancer that recurred at the vaginal stump with extensive pelvic adhesions after complete surgical staging was achieved successfully in a logical way. The critical point of the procedure is to expose the key anatomic landmarks of the pelvis to avoid incidental injuries [1].

Laparoscopic Debulking of Enlarged Pelvic Nodes during Surgical Para-aortic Staging in Locally Advanced Cervical Cancer: A Retrospective Comparative Cohort Study.

STUDY OBJECTIVE: To evaluate laparoscopic pelvic lymph node debulking during extraperitoneal aortic lymphadenectomy in diagnosis, therapeutic planning, and prognosis of patients with locally advanced cervical cancer and enlarged lymph nodes on imaging before chemoradiotherapy. DESIGN: Retrospective, multicenter, comparative cohort study. SETTING: The study was carried out at 11 hospitals with specialized gynecologic oncology units in Spain. PATIENTS: Total of 381 women with locally advanced cervical cancer and International Federation of Gynecology and Obstetrics 2018 stage IIIC 1r (radiologic) and higher who received primary treatment with chemoradiotherapy. INTERVENTIONS: Patients underwent pelvic lymph node debulking and para-aortic lymphadenectomy (group 1), only para-aortic lymphadenectomy (group 2), or no lymph node surgical staging (group 3). On the basis of pelvic node histology, group 1 was subdivided as negative (group 1A) or positive (group 1B). MEASUREMENTS AND MAIN RESULTS: False positives and negatives of imaging tests, disease-free survival, overall survival, and postoperative complications were evaluated. In group 1, pelvic lymph node involvement was 43.3% (71 of 164), and aortic involvement was 24.4% (40 of 164). In group 2, aortic nodes were positive in 29.7% (33 of 111). Disease-free survival and overall survival were similar in the 3 groups (p = .95) and in groups 1A and 1B (p = .25). No differences were found between groups 1 and 2 in intraoperative (3.7% vs 2.7%, p = .744), early postoperative (8.0% vs 6.3%, p = .776), or late postoperative complications (6.1% vs 2.7%, p = .252). Fewer early and late complications were attributed to radiotherapy in group 1A than in the others (p = .022). CONCLUSION: Laparoscopic pelvic lymph node debulking during para-aortic staging surgery in patients with locally advanced cervical cancer with suspicious nodes allows for the confirmation of metastatic lymph nodes without affecting survival or increasing surgical complications. This information improves the selection of patients requiring boost irradiation, thus avoiding overtreatment of patients with negative nodes.

Dedicated MRI staging versus surgical staging of peritoneal metastases in colorectal cancer patients considered for CRS-HIPEC; the DISCO randomized multicenter trial.

BACKGROUND: Selecting patients with peritoneal metastases from colorectal cancer (CRCPM) who might benefit from cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) is challenging. Computed tomography generally underestimates the peritoneal tumor load. Diagnostic laparoscopy is often used to determine whether patients are amenable for surgery. Magnetic resonance imaging (MRI) has shown to be accurate in predicting completeness of CRS. The aim of this study is to determine whether MRI can effectively reduce the need for surgical staging. METHODS: The study is designed as a multicenter randomized controlled trial (RCT) of colorectal cancer patients who are deemed eligible for CRS-HIPEC after conventional CT staging. Patients are randomly assigned to either MRI based staging (arm A) or to standard surgical staging with or without laparoscopy (arm B). In arm A, MRI assessment will determine whether patients are eligible for CRS-HIPEC. In borderline cases, an additional diagnostic laparoscopy is advised. The primary outcome is the number of unnecessary surgical procedures in both arms defined as: all surgeries in patients with definitely inoperable disease (PCI > 24) or explorative surgeries in patients with limited disease (PCI < 15). Secondary outcomes include correlations between surgical findings and MRI findings, cost-effectiveness, and quality of life (QOL) analysis. CONCLUSION: This randomized trial determines whether MRI can effectively replace surgical staging in patients with CRCPM considered for CRS-HIPEC. TRIAL REGISTRATION: Registered in the clinical trials registry of U.S. National Library of Medicine under NCT04231175 .

Re-thinking the prognostic significance of positive peritoneal cytology in endometrial cancer.

BACKGROUND: Whether abnormal peritoneal cytology (PC) is an independent prognostic factor in endometrial cancer (EC) remains controversial. This study aimed to re-think the prognostic significance of PC in not only all EC patients but also in various subgroups with similar clinicopathological and biological characteristics. METHODS: EC patients who underwent primary surgery of at least a hysterectomy and were pathologically diagnosed with EC in four hospitals affiliated with the Jikei University School of Medicine were retrospectively reviewed. The prognostic significance of PC was evaluated with univariate and multivariate analyses in the entire cohort and subgroups stratified by surgical stages (early/advanced stages), tumor types (types 1/2), and risk classifications (low/intermediate/high). RESULTS: Of 1963 EC cases, 1616 met the inclusion criteria. Positive PC was identified as an adverse prognostic factor in analyses of all EC cases and in all subgroup analyses stratified by surgical stages and tumor types. In survival curve comparisons, the progression-free survival (PFS) and disease-specific survival in early-stage patients with positive PC were clearly located between those of stage II patients with negative PC and stage III patients. In the subgroup analyses stratified by risk classification in early-stage EC, positive PC was related to poorer PFS in the intermediate- and high-risk groups but not in the low-risk group. CONCLUSION: PC status was an independent prognostic factor of EC in all stages and tumor types. Early PC-positive cases, except for the low-risk group, may be recommended for upstaging and should be carefully managed compared with PC-negative cases.

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.

Is there any therapeutic role of pelvic and para-aortic lymphadenectomy in apparent early stage epithelial ovarian cancer?

OBJECTIVE: The therapeutic role of pelvic and para-aortic lymphadenectomy in surgical staging of apparent early-stage epithelial ovarian cancer (eEOC) is still under debate. The aim of this study was to evaluate the potential therapeutic role of systematic lymphadenectomy in patients with eEOC. METHODS: Multi-center retrospective cohort study, comparing women with apparent eEOC who underwent comprehensive bilateral pelvic and para-aortic lymphadenectomy (defined as ≥20 lymph nodes) versus patients receiving no lymphadenectomy or lymph node sampling, from 05/1985 to 12/2016. Patients with bulky nodes at CT-scan and those without complete intra-peritoneal surgical staging were excluded. Only patients who received at least 3 cycles of platinum-based adjuvant chemotherapy were included. RESULTS: Out of 2559 patients with FIGO stage IA-IIIA1 ovarian cancer, 639 (25.0%) met inclusion criteria. 360 (56.3%) underwent comprehensive lymphadenectomy, 150 (23.5%) lymph node sampling and 129 (20.2%) no lymphadenectomy. Patients who underwent comprehensive lymphadenectomy were younger (p < 0.001), experienced a higher number of severe post-operative complications (p = 0.008) and had a longer time to start chemotherapy (p = 0.034). There was no difference in intra-operative complications. Median follow-up was 63 months (range, 5-342). The 5-year disease-free survival (DFS) was 79.7% vs. 76.5% vs. 68.3% (p = 0.006), and 5-year overall survival (OS) was 92.3% vs. 94.5% vs. 89.8% (p = 0.165) in women who received comprehensive lymphadenectomy vs. lymph node sampling vs. no lymphadenectomy, respectively. Lymphadenectomy represented an independent factor for DFS improvement, HR 0.52 (95%CI 0.37-0.73) (p < 0.001). CONCLUSION: Pelvic and para-aortic lymphadenectomy in surgical staging of eEOC improves DFS for the price of increasing post-operative complications and time to chemotherapy but does not affect OS. Better understanding of tumor biology may help to identify those patients in whom lymphadenectomy should still play a role.

Comparison of Perioperative Outcomes between Minimally Invasive Sentinel Node Biopsy and Full Lymphadenectomy for Endometrial Cancer.

STUDY OBJECTIVE: To review the perioperative differences between patients undergoing a minimally invasive sentinel lymph node dissection and those undergoing a full lymphadenectomy. DESIGN: Retrospective review. SETTING: Teaching hospital. PATIENTS: All patients undergoing a minimally invasive procedure for endometrial cancer that included nodal evaluation. INTERVENTIONS: Patients who underwent a sentinel lymph node biopsy were compared with those who underwent a full lymphadenectomy at the time of minimally invasive surgery by either laparoscopic or robot-assisted surgery. MEASUREMENTS AND MAIN RESULTS: A total of 241 minimally invasive surgery procedures for endometrial cancer were performed during the 20-month study period. Nodal dissection was indicated and performed in 156 (65%) of these patients, with 93 undergoing a sentinel lymph node biopsy and 63 a full lymphadenectomy. There was no difference between the sentinel group and the lymphadenectomy group with respect to age, estimated blood loss (p = .23), use of a preoperative enhanced recovery after surgery program (p = .82), or body mass index (34.0 kg/m2 vs 33.7 kg/m2; p = .87). The use of full lymphadenectomy was very dependent on the surgeon (p <.001). There was no difference in narcotic use in milligram intravenous equivalents of morphine in surgery (20.9 vs 22.2; p = .37), recovery (4.6 vs 4.9; p = .73), or total dose (25.4 vs 27.0; p = .33). The surgical procedure was longer with lymphadenectomy (185.2 minutes vs 214.2 minutes; p <.001) and the relative risk of discharge from recovery was lower (0.71; 95% confidence interval, 0.51-0.97; p = .03). The hospital stay was longer with lymphadenectomy (16.3 hours vs 25.5 hours; p <.001) and same-day discharge less frequent (48.5% vs 13.8%; p <.001). A multivariate analysis confirmed that sentinel node biopsy was associated with an increased relative risk of discharge of 1.68 (95% confidence interval 1.11-2.53; p = .01) CONCLUSION: Total narcotic requirements are similar between sentinel node biopsy and lymphadenectomy. However, sentinel node biopsy is associated with a shorter surgical time, recovery time, and hospital stay.

Surgical Technique for Sentinel Lymph Node Sampling in Presumed Early-stage Ovarian Cancer.

STUDY OBJECTIVE: Surgical staging for apparent early-stage ovarian cancer includes systematic pelvic and para-aortic lymph node evaluation to detect occult stage III disease [1]. Although, lymphadenectomy procedure is associated with increased duration of surgery and a 13% risk of lymphocyst formation [2]. Sentinel lymph node (SLN) biopsy is still investigational, and no standardized approach has been studied. Recent mounting evidence has approved the applicability of SLN technique in early-stage ovarian cancer [3,4]. The objective of this video is to demonstrate a surgical technique for robotic performance of SLN biopsy in presumed early-stage ovarian cancer. DESIGN: Stepwise demonstration of the robotic technique for SLN sampling in presumed early-stage ovarian cancer. This video report is part of an institutional, investigational review board-approved study. SETTING: Academic tertiary referral center. INTERVENTIONS: This video presents our team's robotic technique for SLN sampling in a 37-year-old woman who presented to our center with a 10-cm right complex adnexal mass, suspicious for malignancy. A 27-gauge spinal needle was inserted through the abdominal wall under direct visualization. We injected 0.5 mL of dilute indocyanine green solution (Novadaq Technologies, Mississauga, Ontario, Canada) (1.25 mg/mL) subperitoneally into the utero-ovarian ligament. The SLN was checked with the fluorescence-guided camera of the Xi DaVinci robotic system (Sunnyvale, CA). Eight to 10 minutes after the injection, a right para-aortic SLN was identified, and dissection was performed. After dissection, the node was extracted and sent to pathology for evaluation by ultra-staging. The final pathology revealed a stage IA low-grade serous ovarian cancer. CONCLUSION: SLN sampling appears to be feasible in presumed early-stage ovarian cancer and may allow the avoidance of systematic lymph node dissection in this set of patients.

Accuracy of intra-operative frozen section in guiding surgical staging of endometrial cancer.

PURPOSE: Surgery consists the main treatment of endometrial cancer; however, decision of lypmhadenectomy is controversial. Intra-operative frozen section (FS) is commonly used in guiding surgical staging; nevertheless, there are different reports regarding its adequacy and reliability. Aim of this study is to assess accuracy of FS in predicting paraffin section (PS) results in patients with endometrium cancer. METHODS: Data of 223 cases, who were operated for endometrial cancer at a tertiary hospital in 2012-2019, were analyzed retrospectively. Histological type, grade, tumor diameter, depth of myometrial invasion, and cervical and adnexal involvement in frozen and paraffin section were evaluated. Positive and negative predictive values and accuracy of frozen results in predicting paraffin results for each parameter was assessed. Statistical significance was taken as 0.05 in all tests. RESULTS: Accuracy of FS in predicting PS results were 76.23% for histology, 75.45% for grade, 85.31% for depth of myometrial invasion, and 95.45% for tumor diameter. Surgery, based on FS results, caused undertreatment in 4 patients, while metastatic lymph node ratios were found in only 35.3-50.0% of cases who had high risk parameters at FS. CONCLUSION: Our FS results have reasonable accuracy rates in predicting PS results, in comparison with the previous literature. However, even if the high risk parameters detected in FS predict PS accurately, absence of lymph node involvement in all cases with high risk parameters indicates that FS-based triage cannot prevent unnecessary lymphadenectomies.

Pre-surgical staging in endometrial cancer: An opportunity for risk stratification and triage?

BACKGROUND: Endometrial cancer (EC) is treated by comprehensive surgical staging that includes a systematic lymphadenectomy. The low rates of lymph node metastasis (LNM) in early stages question the benefit of routine lymphadenectomy in low-risk disease, but the absence of a reliable method to identify these patients in whom lymphadenectomy could be omitted makes complete staging the standard of care. This study evaluated a method of preoperative staging in EC to identify patients at low risk of LNM and adjuvant treatment. METHODS: This prospective observational study compared the presurgical staging and risk triage based on endometrial biopsy (EB) and imaging (magnetic resonance imaging [MRI], Positron Emission Tomography [PET] scan) in 94 cases of EC with the final surgicopathological staging and evaluated the role of each modality in presurgical evaluation and triage. RESULTS: Ninety-four cases were triaged into 42 low-risk and 52 non-low-risk cases preoperatively. EB showed a sensitivity, specificity, and accuracy of 51.55%, 89.83%, and 75.53%, respectively, in identifying high-risk grade and histology. MRI was effective for local staging and identified tumor size, myometrial invasion, and cervical involvement with accuracy ranging from 82.20% to 97.78% for these parameters. MRI detected LNM with an accuracy of 85.11%, whereas PET exhibited an accuracy of 86.17%. The combined presurgical staging could identify low-risk disease with a sensitivity, specificity, and accuracy of 85.37%, 86.79%, and 86.17%, respectively. CONCLUSION: Preoperative staging may triage patients into low-risk and non-low-risk cases, thereby facilitating a conscious decision to omit lymphadenectomy in low-risk cases, thus avoiding unnecessary morbidity without compromising oncological safety.

Evaluating the diagnostic performance of preoperative endometrial biopsies in patients diagnosed with high grade endometrial cancer: A study of the Society of Gynecologic Oncology (GOC) Community of Practice (CoP).

BACKGROUND: High grade cancers account for a disproportionate number of recurrences in patients with endometrial cancer. Accurately identifying these cases on endometrial biopsies allows for better surgical planning. This study evaluates the diagnostic accuracy of general pathologists (GP) compared to gynecological pathologists (GYNP) in interpreting preoperative biopsies. METHODS: A retrospective cohort study was conducted of patients diagnosed with high grade endometrial cancer (HGEC) between 2012 and 2016 at eight Canadian cancer centres. Data was collected from medical records. Pre-operative biopsies were categorized into groups; biopsies read by GP, GYNP and GP reviewed by GYNP. Rates of HGEC on pre-operative biopsy were calculated. Fisher exact test was used to compare differences between the groups. Univariate logistic regression analysis was conducted for HGEC prediction. RESULTS: Of 1237 patients diagnosed with HGEC, 245 (19.8%) did not have a preoperative diagnosis of high-grade disease. Discordancy was identified in 91/287 (31.71%) of biopsies reported by GP, and in 114/910 (12.53%) of biopsies reported by a GYNP (p < 0.0001). Compared to GP, GYNP were 3.24 (CI 2.36-4.45) times more likely to identify high grade disease on preoperative biopsy. Patients whose biopsy was reported by a GYNP were more likely to have a comprehensive staging procedure (OR 1.77 CI 1.33-2.38) and less likely to receive adjuvant therapy (OR 0.71 CI 0.52-0.96). CONCLUSION: GYNP are more likely to identify HGEC on pre-operative biopsies. Due to high rates of overall discordancy, it is possible that surgical staging procedures should not be based solely on preoperative biopsy. Further strategies to improve pre-operative biopsies' accuracy are needed.

The added value of sentinel node mapping in endometrial cancer.

OBJECTIVE: To evaluate long-term oncological outcomes and the added value of sentinel lymph node sampling (SLN) compared to pelvic lymph node dissection (LND) in patients with endometrial cancer (EC). METHODS: During the evaluation phase of SLN for EC, we performed LND and SLN and retrospectively compared the oncologic outcome with the immediate non-overlapping historical era during which patients underwent LND. RESULTS: From 2007 to 2010, 193 patients underwent LND and from December 2010 to 2014, 250 patients had SLN mapping with completion LND. Both groups had similar clinical characteristics. During a median follow-up period of 6.9 years, addition of SLN was associated with more favorable oncological outcomes compared to LND with 6-year overall survival (OS) of 90% compared to 81% (p = 0.009), and progression free survival (PFS) of 85% compared to 75% (p = 0.01) respectively. SLN was associated with improved OS (HR 0.5, 95% CI 0.3-0.8, p = 0.004), and PFS (HR 0.6, 95% CI 0.4-0.9, p = 0.03) in a multivariable analysis, adjusted for age, ASA score, stage, grade, non-endometrioid histology, and LVSI. Patients who were staged with SLN were less likely to have a recurrence in the pelvis or lymph node basins compared to patients who underwent LND only (6-year recurrence-free survival 95% vs 90%, p = 0.04). CONCLUSION: Addition of SLN to LND was ultimately associated with improved clinical outcomes compared to LND alone in patients with endometrial cancer undergoing surgical staging, suggesting that the data provided by the analysis of the SLN added relevant clinical information, and improved the decision on adjuvant therapy.