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Objective: To compare two published risk stratification models (Milwaukee Model vs. Mayo Criteria) to predict lymphatic dissemination (LD) in endometrioid endometrial cancer (EC)., Methods: Patients with stage I-III EC undergoing surgery from 1/1/2004-9/30/2013 were retrospectively reviewed and classified as low-risk vs at-risk for LD using two independent risk models. LD was defined as positive nodes at surgery or lymph node recurrence within 2 years of surgery after negative lymph node dissection (LND) or when LND was not performed. False positive (FP) and false negative (FN) rates for each risk model were calculated., Results: Among 1103 patients, 81 (7.3%) had LD (72 positive LN and 9 LN recurrences), and most (90.2%) had stage I EC. The Milwaukee Model yielded a low at-risk rate for LD (38.1%) but a high FN rate (13.6%, 95% CI 7.0-23.0). The traditional Mayo Criteria using a cut-off of 2 cm for tumor diameter (TD) had a higher at-risk rate for LD (69.5%) but a FN rate of 0% (95% CI, 0-4.5). Modifying the Mayo Criteria using a TD cutoff of ≤3 cm identified fewer women at-risk (56.8% vs. 69.5%) and had a lower FP rate (53.6% vs. 67.1%), but had a higher FN rate (3.7%, 95% CI, 0.8-10.4)., Conclusions: The Milwaukee Model had the lowest at-risk rate of LD but an unacceptable FN rate. Modifying the Mayo Criteria by increasing the TD cutoff from the traditional ≤2 cm to ≤3 cm would spare an estimated 13.5% of patients LND, but the accompanying FN rate is unacceptably high. The traditional Mayo Criteria for low-risk EC remains the most sensitive in determining which patients LND can be omitted., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To determine if a sentinel lymph node (SLN) mapping algorithm will detect metastatic nodal disease in patients with intermediate-/high-risk endometrial carcinoma., Methods: Patients were identified and surgically staged at two collaborating institutions. The historical cohort (2004-2008) at one institution included patients undergoing complete pelvic and paraaortic lymphadenectomy to the renal veins (LND cohort). At the second institution an SLN mapping algorithm, including pathologic ultra-staging, was performed (2006-2013) (SLN cohort). Intermediate-risk was defined as endometrioid histology (any grade), ≥50% myometrial invasion; high-risk as serous or clear cell histology (any myometrial invasion). Patients with gross peritoneal disease were excluded. Isolated tumor cells, micro-metastases, and macro-metastases were considered node-positive., Results: We identified 210 patients in the LND cohort, 202 in the SLN cohort. Nodal assessment was performed for most patients. In the intermediate-risk group, stage IIIC disease was diagnosed in 30/107 (28.0%) (LND), 29/82 (35.4%) (SLN) (P=0.28). In the high-risk group, stage IIIC disease was diagnosed in 20/103 (19.4%) (LND), 26 (21.7%) (SLN) (P=0.68). Paraaortic lymph node (LN) assessment was performed significantly more often in intermediate-/high-risk groups in the LND cohort (P<0.001). In the intermediate-risk group, paraaortic LN metastases were detected in 20/96 (20.8%) (LND) vs. 3/28 (10.7%) (SLN) (P=0.23). In the high-risk group, paraaortic LN metastases were detected in 13/82 (15.9%) (LND) and 10/56 (17.9%) (SLN) (%, P=0.76)., Conclusions: SLN mapping algorithm provides similar detection rates of stage IIIC endometrial cancer. The SLN algorithm does not compromise overall detection compared to standard LND., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to determine oncological outcomes and incidence of lymph node (LN) metastases in women who underwent systematic pelvic and paraaortic lymphadenectomy for surgical staging of apparent stage I low-grade epithelial ovarian cancer (LGEOC)., Materials and Methods: A retrospective study was performed at nine institutions across Europe and the US, and patients who underwent surgical staging for presumed stage I LGEOC between 2000 and 2016 were included. To ensure surgical quality, a minimum number of ≥10 pelvic and ≥10 paraaortic LNs was required. Patients with preoperative radiologic or clinical evidence of extraovarian or LN disease, and those with nonepithelial histology, were excluded., Results: The overall incidence of LN metastases was 4.3% in the 163 evaluated patients, and the incidence of LN involvement in serous, endometrioid, and mucinous subtypes was 10.7, 1.5, and 0%, respectively. However, Upstaging due to LN involvement alone occurred in only 2.4% of the patients. Eighty-nine (54.6%) patients received adjuvant chemotherapy due to International Federation of Gynecology and Obstetrics stage IC or higher disease. The 5-year progression-free survival (PFS) and overall survival (OS) were 93.2% (95% confidence interval [CI] 89.4-97.1%) and 94.5% (95% CI 90.9-98.0%), respectively. There was no significant difference in PFS or OS between LN-negative and LN-positive patients. However, fewer patients received adjuvant chemotherapy in the LN-negative group. Multivariate analysis did not identify any independent prognostic factor of survival., Conclusion: The risk of LN involvement in nonserous apparent stage I LGEOC appears low, with a rate of <1% in this retrospective analysis, raising questions about the value of lymphadenectomy in those patients. Larger-scale prospective studies are warranted to evaluate the oncologic safety of omitting systematic LN staging in apparent stage I nonserous LGEOC.

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., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To prospectively define the prevalence of lymph node metastasis (LNM) in at risk endometrial cancer (EC)., Methods: From 2004 to 2008, frozen section based Mayo Criteria prospectively identified patients "not at-risk" of LNM (30% EC population; grade I/II, <50% myometrial invasion and tumor diameter ≤ 2 cm) where lymphadenectomy was not recommended. The remaining 70% EC cohort was considered "at-risk" of LNM; where a systematic pelvic and infrarenal paraaortic lymphadenectomy was recommended. Patients were prospectively followed. The area between renal vein and inferior mesenteric artery (IMA) was labeled as high paraaortic area. For calculating the prevalence of LNM in high paraaortic area, the denominator was the population with known anatomic location of nodal tissue in relation to the IMA., Results: Of the 742 patients, 514 were at risk; of which 89% underwent recommended lymphadenectomy. A mean (± standard deviation) of 36 (± 14) pelvic and 18 (± 9) paraaortic nodes were harvested. The prevalence of pelvic and paraaortic LNM was 17% and 12%, respectively. In presence of pelvic LNM, 51% had paraaortic LNM. In absence of pelvic LNM, 3% had paraaortic LNM; of which 67% was located exclusively in high paraaortic area. Among patients with paraaortic LNM, 88% had high paraaortic LNM; and 35% had only high paraaortic LNM. The cases of paraaortic LNM with negative pelvic nodes seemed to cluster in moderate to high grade endometrioid EC with ≥ 50% myometrial invasion., Conclusion: We present reference data for the prevalence of LNM in at-risk EC patients to guide lymphadenectomy decisions for clinical and research purposes., (© 2013.)

Objective: To determine whether preoperative biopsy (grade and histology) and intraoperative tumor diameter (TD) predict lymph node dissemination (LN+) and lymph node recurrence (LNRec) in endometrial cancer (EC)., Methods: Patients who underwent EC surgery from 2004 to 2008 were stratified into risk categories. Cases with preoperative grade 3 or non-endometrioid histology were classified as high risk (HR). Patients with preoperative FIGO grade 1 or 2, endometrioid histology or complex and/or atypical hyperplasia were classified based on intraoperative findings: (a) intraoperative macroscopic extrauterine disease classified as HR; (b) largest TD>2 cm classified as intermediate risk (IR) and (c) TD ≤ 2 cm classified as low risk (LR). LN+ and LNRec rates were determined., Results: Of 704 patients evaluated, 188 were HR (27%), 350 IR (50%), and 166 LR (23%). P/PA lymphadenectomy was performed in 87% HR, 83% IR and 16% LR patients. LN+ and/or LNRec occurred in 51 HR patients (27%) and 39 IR patients (11%). Only 1 LR patient (0.6%) had LN+ and none had LNRec. Four LR patients (2%) required adjuvant therapy according to permanent section pathology., Conclusions: Preoperative biopsy and intraoperative TD can be used to effectively stratify patients into LR, IR or HR subgroups to tailor surgery. LR patients have a low probability (<1%) of LN+ and/or LNRec and lymphadenectomy can be omitted in this group. HR and IR patients combined (3/4 of population) have a substantial risk of LN+ or LNRec (17%). Lymphadenectomy is proposed to be advantageous in HR and IR patients if accurate frozen section is lacking., (Published by Elsevier Inc.)

Objective: To determine which patients with near midline lesions may safely undergo unilateral groin dissection based on clinical exam and lymphoscintigraphy (LSG) results., Methods: Patients participating in GOG-173 underwent sentinel lymph node (SLN) localization with blue dye, and radiocolloid with optional LSG before definitive inguinal-femoral lymphadenectomy (LND). This analysis interrogates the reliability of LSG alone relative to primary tumor location in those patients who had an interpretable LSG and at least one SLN identified. Primary tumor location was categorized as lateral (>2cm from midline), midline, or lateral ambiguous (LA) if located within 2cm, but not involving the midline., Results: Two-hundred-thirty-four patients met eligibility criteria. Sixty-four had lateral lesions, and underwent unilateral LND. All patients with LA (N=65) and midline (N=105) tumors underwent bilateral LND. Bilateral drainage by LSG was identified in 14/64 (22%) patients with lateral tumors, 38/65 (58%) with LA tumors and in 73/105 (70%) with midline tumors. At mapping, no SLNs were found in contralateral groins among those patients with LA and midline tumors who had unilateral-only LSGs. However, in these patients groin metastases were found in 4/32 patients with midline tumors undergoing contralateral dissection; none were found in 27 patients with LA tumors., Conclusion: The likelihood of detectable bilateral drainage using preoperative LSG decreases as a function of distance from midline. Patients with LA primaries and unilateral drainage on LSG may safely undergo unilateral SLN., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: To determine the safety of sentinel lymph node biopsy as a replacement for inguinal femoral lymphadenectomy in selected women with vulvar cancer., Patients and Methods: Eligible women had squamous cell carcinoma, at least 1-mm invasion, and tumor size ≥ 2 cm and ≤ 6 cm. The primary tumor was limited to the vulva, and there were no groin lymph nodes that were clinically suggestive of cancer. All women underwent intraoperative lymphatic mapping, sentinel lymph node biopsy, and inguinal femoral lymphadenectomy. Histologic ultra staging of the sentinel lymph node was prescribed., Results: In all, 452 women underwent the planned procedures, and 418 had at least one sentinel lymph node identified. There were 132 node-positive women, including 11 (8.3%) with false-negative nodes. Twenty-three percent of the true-positive patients were detected by immunohistochemical analysis of the sentinel lymph node. The sensitivity was 91.7% (90% lower confidence bound, 86.7%) and the false-negative predictive value (1-negative predictive value) was 3.7% (90% upper confidence bound, 6.1%). In women with tumor less than 4 cm, the false-negative predictive value was 2.0% (90% upper confidence bound, 4.5%)., Conclusion: Sentinel lymph node biopsy is a reasonable alternative to inguinal femoral lymphadenectomy in selected women with squamous cell carcinoma of the vulva.

Objective: To determine the impact of surgical guidelines and transparent periodic assessment of surgical quality on endometrial cancer (EC) staging by gynecologic oncologists in a single institution and to identify process-of-care, patient-specific, and disease-specific risk factors that influence surgical quality., Methods: In January 2004, a prospective treatment algorithm was implemented for EC at our institution. The number of nodes harvested was a surrogate, and staging quality from 2004 to 2008 (quality assessment [QA] interval) was compared with the previous 5 years (pre-QA interval). Since 2004, low-risk cases based on frozen section examination had not undergone lymphadenectomy and were excluded. Independent patient-specific, disease-specific, and surgery-related risk factors influencing lymphadenectomy quality during both intervals were identified with multivariable logistic regression analysis., Results: Pelvic and para-aortic lymph node dissection (LND) in surgical EC management before QA (n=420) were 77.9% and 48.8% vs 89.3% and 83.4% during the QA (n=561) (P<.001). The median number of pelvic and para-aortic nodes harvested in LND was 29 and 10 before QA vs 34 and 16 during the QA interval (P<.001). With acceptance of stringent criteria for defining systematic LND (mean node count-1 SD) during the QA, systematic pelvic (≥22 nodes) and para-aortic (≥10 nodes) LNDs occurred in 57.4% and 25.7% of cases before QA vs 77.9% and 70.7% during the QA interval (P<.001). In patients with LND, rates of systematic pelvic and para-aortic LND were 73.7% and 53.0% before vs 87.2% and 84.8% after QA (P<.001). Multivariable logistic regression analysis showed independent factors influencing systematic pelvic and para-aortic LND (P<.01): surgeon and stage during the pre-QA interval vs surgical approach; intraoperative ascites; body mass index; surgeon; patient age; and myometrial invasion after QA implementation., Conclusion: Inclusion of detailed surgical guidelines and transparent periodic assessment of surgical quality translated to dramatic improvement in quality of surgical EC staging. This implementation was associated with a transition to more patient-specific risk factors influencing systematic LND. Although surgical quality metrics were markedly enhanced during QA, persistent variability observed among surgeons and the change in surgical approach render continuous QA and improvement obligatory., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objectives: The extent of lymphadenectomy to be performed in apparent early-stage epithelial ovarian cancer (EOC) is not well defined. We evaluated the patterns of lymphatic spread in apparent early-stage EOC and risk factors for lymph node metastasis, as these have potential implications for clinical decision making., Methods: All cases of apparent early-stage EOC diagnosed at our institution between January 1994 and December 2003 were retrospectively identified. Apparent early-stage EOC was defined as gross disease that appeared confined to the pelvis without abdominal spread at the time of initial exploration. Demographics, pathologic findings, staging procedures performed, and clinical impression at surgery were analyzed. Patterns of lymph node positivity and risk factors associated with upstaging were assessed., Results: One hundred and ninety patients with apparent early-stage EOC undergoing primary surgical staging met criteria for inclusion. All patients had at least some pathologic assessment of lymph nodes, with 115 having both bilateral pelvic and paraaortic lymphadenectomy performed. After review of pathology and operative reports, the final FIGO staging within the cohort was 54 IA (28.4%), 10 IB (5.3%), 51 IC (26.8%), 1 IIA (0.5%), 4 IIB (2.1%), 37 IIC (19.5%), 8 IIIA (4.2%), 25 IIIC (13.2%). Overall 25/190 (13%) had lymph nodes metastasis as follows: 8 (32%) had positive pelvic nodes, 12 (48%) had positive paraaortic nodes, and 5 (20%) had both positive pelvic and paraaortic lymph nodes. Significant risk factors for lymph node metastasis included bilateral vs. unilateral primary lesion (26.8% vs. 7.5%, p<0.001), positive cytologic washings vs. negative (22.4% vs. 9.1%, p=0.012), ascites vs. no ascites (28.2% vs. 9.3%, p=0.002), serous vs. other histology (28% vs. 9%, p=0.001), grade 1 vs. grade 2 vs. grade 3 disease (2.7% vs. 1.9% vs. 23.2%, p<0.001), and preoperative CA 125 levels of >35 vs. ≤ 35 U/ml (22.4% vs.0% p=0.006). No patients with mucinous cancers (n=29) had lymph node metastases. Patterns of LN metastases were largely independent of laterality of primary lesions: among those with unilateral lesions and positive nodes (n=10), 5 (50%) had ipsilateral lymph node involvement, 4 (40%) had bilateral involvement, and 1 (10%) had isolated contralateral lymph nodes positive., Conclusions: Complete surgical staging in EOC patients with gross disease confined to the ovaries and pelvis should include bilateral pelvic and paraaortic lymphadenectomy. Even in patients with unilateral lesions, lymph node metastases are commonly bilateral. Bilateral ovarian lesions, positive cytology, presence of ascites, high grade histology, and serous histology are risk factors for lymph node involvement. This information may be helpful in counseling patients presenting for consideration of re-staging after unexpected findings of malignancy., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Abstract: Objective: Overall survival (OS) in endometrial cancer (EC) is dependent on patient-, disease-, and treatment-specific risk factors. Comprehensive risk-scoring models were developed to estimate OS in low-grade and high-grade EC. Methods: Patients undergoing primary surgery for EC from 1999 through 2008 were stratified histologically according to the International Federation of Gynecology and Obstetrics (FIGO) as either (i) low grade: grades 1 and 2 endometrioid EC or (ii) high grade: grade 3, including non-endometrioid EC. Associations between patient-, pathological-, and treatment-specific risk factors and OS starting on postoperative day 30 were assessed using multivariable Cox regression models. Factors independently associated with OS were used to construct nomograms and risk-scoring models. Results: Eligible patients (N=1281) included 925 low-grade and 356 high-grade patients; estimated 5-year OSs were 87.0% and 51.5%, respectively. Among patients alive at last follow-up, median follow-up was 5.0 (low grade) and 4.6years (high grade), respectively. In low-grade patients, independent factors predictive of compromised OS included age, cardiovascular disease, pulmonary dysfunction, stage, tumor diameter, pelvic lymph node status, and grade 2 or higher 30-day postoperative complications. Among high-grade patients, age, American Society of Anesthesiologists score, stage, lymphovascular space invasion, adjuvant therapy, para-aortic nodal status, and cervical stromal invasion were independent predictors of compromised OS. The two risk-scoring models/nomograms had excellent calibration and discrimination (unbiased c-indices=0.803 and 0.759). Conclusion: Patients with low-grade and high-grade EC can be counseled regarding their predicted OS using the proposed risk-scoring models. This may facilitate institution of personalized treatment algorithms, surveillance strategies, and lifestyle interventions. [Copyright &y& Elsevier]