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Objective: To compare clinical and pathologic characteristics of women with surgical stage I endometrial carcinoma by location of first recurrence and describe characteristics of isolated vaginal recurrence., Methods: Patients with 2009 International Federation of Obstetrics and Gynecology (FIGO) stage I endometrial carcinoma treated at two large cancer centers from 1/1/2009-12/31/2017 were identified. Sarcoma histology was excluded. Recurrences were grouped into isolated vaginal or extravaginal. Isolated vaginal recurrences were localized by anatomic location within the vaginal vault. Clinical and pathologic variables were compared with chi-square analysis, and Kaplan-Meier curves with log-rank tests., Results: Of 2815 women identified, 278 (10%) experienced a recurrence. Sixty-one patients (2%) had an isolated vaginal recurrence, including 42 (69%) at the vaginal apex; 217 (8%) had an extravaginal recurrence, including 18 with a vaginal component. Median time to recurrence was 11 months (range, 1-68) for isolated vaginal recurrence and 20 months (range, 1-98) for extravaginal recurrence (P < .004). Of 960 patients (34%) treated with adjuvant vaginal brachytherapy (VBT), 156 (16%) recurred; 19 (2%) had an isolated vaginal recurrence, including 16 (84%) at the vaginal apex. Three-year PFS rates for isolated vaginal recurrence were 97.6% (SE ± 0.4%) with minimally invasive surgery (MIS) versus 96.9% (SE ± 1.1%) with open (P = .8), and for extravaginal recurrence were 91.8% (SE ± 0.7%) with MIS versus 90.8% (SE ± 1.8%) with open (P = .8)., Conclusions: Isolated vaginal recurrences in stage I endometrial cancer are detected earlier than non-vaginal recurrences. Surgical approach does not appear to impact recurrence. Adjuvant VBT after primary surgery carries a 1%-2% risk of isolated vaginal apex recurrence., Competing Interests: Declaration of Competing Interest Outside the submitted work, N.R. Abu-Rustum reports Stryker/Novadaq and GRAIL grants paid to the institution. V. Makker reports meeting/travel support by Eisai and Merck; participation on a Data Safety Monitoring or Advisory Board of Duality, Merck, Karyopharm, Exelexis, Eisai, Karyopharm, BMS, Clovis, Faeth Immunocore, Morphosys, AstraZeneca, Novartis, GSK, Bayer (all unpaid), and study support to the institution by Merck, Eisai, AstraZeneca, Faeth, Karyopharm, Zymeworks, Duality, Clovis, Bayer, and Takeda. M.M. Leitao Jr. reports research funding paid to the institution from KCI/Acelity, ad-hoc speaker for Intuitive Surgical, Inc., and advisory board participation for JnJ/Ethicon and Takeda. Y. Lakhman serves as a consultant for Calyx Clinical Trial Solutions. A. Jhingran reports a consulting agreement and advisory board participation with Genentech, and a patent (adaptive intracavitary brachytherapy applicator for cervical cancer). The other authors do not have potential conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Using next generation sequencing (NGS), The Cancer Genome Atlas (TCGA) found that endometrial carcinomas (ECs) fall under one of four molecular subtypes, and a POLE mutation status, mismatch repair (MMR) and p53 immunohistochemistry (IHC)-based surrogate has been developed. We sought to retrospectively classify and characterize a large series of unselected ECs that were prospectively subjected to clinical sequencing by utilizing clinical molecular and IHC data., Experimental Design: All patients with EC with clinical tumor-normal MSK-IMPACT NGS from 2014 to 2020 (n = 2115) were classified by integrating molecular data (i.e., POLE mutation, TP53 mutation, MSIsensor score) and MMR and p53 IHC results. Survival analysis was performed for primary EC patients with upfront surgery at our institution., Results: Utilizing our integrated approach, significantly more ECs were molecularly classified (1834/2115, 87%) as compared to the surrogate (1387/2115, 66%, p < 0.001), with an almost perfect agreement for classifiable cases (Kappa 0.962, 95% CI 0.949-0.975). Discrepancies were primarily due to TP53 mutations in p53-IHC-normal ECs. Of the 1834 ECs, most were of copy number (CN)-high molecular subtype (40%), followed by CN-low (32%), MSI-high (23%) and POLE (5%). Histologic and genomic variability was present amongst all molecular subtypes. Molecular classification was prognostic in early- and advanced-stage disease, including early-stage endometrioid EC., Conclusions: The integration of clinical NGS and IHC data allows for an algorithmic approach to molecularly classifying newly diagnosed EC, while overcoming issues of IHC-based genetic alteration detection. Such integrated approach will be important moving forward given the prognostic and potentially predictive information afforded by this classification., Competing Interests: Conflicts of interest N.R. Abu-Rustum reports Stryker/Novadaq and GRAIL grants paid to the institution, outside the current study. C.F. Friedman reports institutional research support from Seagen, Merck, BMS, AstraZeneca, Mersana and Hotspot Therapeutics; consulting fees from BMS, Seagen and Aadi Biosciences; honoraria for lectures from Onclive; meeting/ travel support by Puma; participation on Data Safety Monitoring or Advisory Board of Merck, Genentech and Marengo (all uncompensated). D. Zamarin reports institutional research support from AstraZeneca, Merck, Plexxikon Synthekine and Genentech; consulting fees from AstraZeneca, Synthekine, Astellas, Tessa Therapeutics, Memgen, Celldex, Crown Biosciences, Hookipa Biotech, Kalivir, Xencor and GSK; royalties from Merck; and stock options from Accurius Therapeutics, ImmunOS Therapeutics and Calidi Biotherapeutics, all outside the submitted work. V. Makker reports meeting/travel support by Eisai and Merck; participation on Data Safety Monitoring or Advisory Board of Duality, Merck, Karyopharm, Exelexis, Eisai, Karyopharm, BMS, Clovis, Faeth Immunocore, Morphosys, AstraZeneca, Novartis, GSK, Bayer (all unpaid), and study support to the institution by Merck, Eisai, AztraZeneca, Faeth, Karyopharm, Zymeworks, Duality, Clovis, Bayer and Takeda. Y. Liu reports institutional research funding from Repare Therapeutics, AstraZeneca and GSK; honoraria from Total Health and Sarah Lawrence College; and travel/meeting support by AstraZeneca, outside the submitted work. B. Weigelt reports a research grant from REPARE Therapeutics paid to the institution, outside the submitted work. D.S. Chi reports personal fees from Apyx Medical, Verthermia Inc., Biom ‘Up, and AstraZeneca, as well as recent or current stock/options ownership of Apyx Medical, Verthemia, Intuitive Surgical, Inc., TransEnterix, Inc., Doximity, Moderna, and BioNTech SE. E.L. Jewell reports personal fees from Covidien/Medtronic. M. M. Leitao is an ad hoc speaker for Intuitive Surgical, Inc.; outside the submitted work, he is on the Advisory Board of Ethicon/Johnson & Johnson and Takeda; and reports grants paid to the institution by KCI/Acelity. C. Aghajanian reports clinical trial funding paid to the institution from AstraZeneca; consulting fees (advisory board) from Eisai/Merck, Roche/Genentech, Abbvie, AstraZeneca/Merck, and Repare Therapeutics; advisory board participation (no fee) for Blueprint Medicine; and leadership/fiduciary roles for the GOG Foundation Board of Directors (travel cost reimbursement) and NRG Oncology Board of Directors (unpaid). The remaining authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objectives: To compare outcomes of patients with premalignant endometrial pathology undergoing hysterectomy with or without sentinel lymph node (SLN) removal. Outcomes of interest included surgical adverse events (AEs), cancer status on final pathology, postoperative treatment, and The Cancer Genome Atlas (TCGA) molecular risk profiles., Methods: We retrospectively identified patients with premalignant pathology on preoperative endometrial biopsy who underwent hysterectomy with or without SLN mapping/excision at our institution from 01/01/2017-12/31/2021. Clinical, pathologic, surgical, and TCGA profiling data were abstracted. Appropriate statistical tests were used., Results: Of 221 patients identified, 161 (73%) underwent hysterectomy with SLN excision and 60 (27%) underwent hysterectomy without SLN excision. Median age and body mass index were similar between groups. Median operative time was 130 min for those who underwent SLN mapping/excision versus 136 min for those who did not (p = 0.6). Thirty-day postoperative AE rates were 9% (n = 15/161) and 13% (n = 8/60), respectively (p = 0.9). Ninety-eight (44%) of 221 patients had grade 1-2 endometrioid endometrial cancer on final pathology (4 [4%] were stage IB or higher). Ten (10%) of 98 patients, all within the SLN group, received adjuvant treatment. Among all patients, of 33 (15%) with TCGA molecular classification data, 27 (82%) had copy number-low, 3 (9%) microsatellite instability-high, 2 (6%) POLE-ultramutated, and 1 (3%) copy number-high disease., Conclusions: SLN assessment appears safe, detects a small number of occult nodal metastases for those upstaged, and provides additional staging information that can guide adjuvant treatment. SLN mapping should be discussed in preoperative counseling and offered using a shared decision-making approach., Competing Interests: Declaration of Competing Interest Outside the submitted work, Dr. Jewell reports personal fee from Covidien/Medtronic; Dr. Abu-Rustum reports grant money from GRAIL paid to the institution; and Dr. Leitao reports personal fees from Medtronic, Intuitive Surgical, Inc., and JnJ/Ethicon., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: Gastric-type endocervical adenocarcinoma (GEA) is a rare form of cervical cancer not associated with human papilloma virus (HPV) infection. We summarize our experience with GEA at a large cancer center., Methods: Clinical and demographic information on all patients diagnosed with GEA between June 1, 2002 and July 1, 2019 was obtained retrospectively from clinical charts. Kaplan-Meier survival analysis was performed to describe progression-free survival (PFS) and overall survival (OS). Tumors from a subset of patients underwent next generation sequencing (NGS) analysis., Results: A total of 70 women with GEA were identified, including 43 who received initial treatment at our institution: of these 4 (9%) underwent surgery alone, 15 (35%) underwent surgery followed by adjuvant therapy, 10 (23%) were treated with definitive concurrent chemoradiation (CCRT), 7 (16%) with chemotherapy alone, and 3 (7%) with neoadjuvant CCRT and hysterectomy with or without chemotherapy. One-third (n = 14) of patients experienced disease progression, of whom 86% (n = 12) had prior CCRT. The median PFS and OS for patients with stage I GEA were 107 months (95% CI 14.8-199.2 months) and 111 months (95% CI 17-205.1 months) respectively, compared to 17 months (95% CI 5.6-28.4 months) and 33 months (95% CI 28.2-37.8 months) for patients with stages II-IV, respectively. On NGS, 4 patients (14%) had ERBB2 alterations, including 2 patients who received trastuzumab., Conclusions: GEA is an aggressive form of cervical cancer with poor PFS and OS when diagnosed at stage II or later. Further investigation is needed to identify the optimal management approach for this rare subtype., Competing Interests: Declaration of Competing Interest Outside the submitted work, B. Weigelt reports ad hoc membership in the scientific advisory board of Repare Therapeutics, outside the scope of the study. C. Friedman reports participation in the scientific advisory boards for Merck (LYNK-002) and Genentech (MyPathway) without compensation, consulting for Seagen and Bristol Myers Squibb, and institutional research funds from Genentech/Roche, Bristol Myers Squibb, Merck, AstraZeneca, and Daiichi. E. Jewell reports personal fee from Covidien/Medtronic. K. Cadoo reports grant funding from the Irish Cancer Society, MSD, and Immunogen; consulting fees from Nextcure, MJH Life Sciences, and GSK; payments/honoraria from GSK, AstraZeneca, and MSD; financial support to attend meetings from Roche, Pfizer, and MSD; advisory board participation at MSD, AstraZeneca, GSK, and Eisai; a voluntary advisory role at the National Cancer Control Programme Ireland; and a voluntary board member at ARC Cancer Support Centers. N. Abu-Rustum reports grant funding from GRAIL paid to the institution. S. issa Bhaloo reports stock or stock options in BioNTech, Moderna, Inc., Inovio, Relief Therapeutics Holding SA, Cansino Biologics, Inc., and Pfizer, Inc. M. Leitao reports personal fees from Medtronic, Intuitive Surgical, Inc., and JnJ/Ethicon. C. Aghajanian has received research grants from Abbvie, Clovis, Genentech, and Astra Zeneca and served on advisory boards for Abbvie, AstraZeneca/Merck, Eisai/Merck, Mersana Therapeutics, Repare Therapeutics, and Roche/Genentech. R. O'Cearbhaill reports honoraria from GSK, Bayer, Regeneron, SeaGen, Fresenius Kabi, Immunogen, MJH Life Sciences and Curio. C. Kyi reports grant funding from Conquer Cancer Foundation; grant funding paid to the institution from Merus, Gritstone, and BMS; and consulting fees from Scenic Immunology B.V. and OncLive. D. Zamarin is an inventor on a patent related to the use of oncolytic Newcastle Disease Virus for cancer therapy, and reports grant funding paid to the institution from AstraZeneca, Roche, Plexxikon, and Synthekine; consulting fees from Memgen, Celldex, Agenus, Astellas, AstraZeneca, Crown Biosciences, Roche, GSK, Hookpia, ImmunOS, Kalvir, Synlogic Therapeutics, Synthekine, Takeda, Targovax, Tessa Therapeutics, and Xencor; stock options in Accurius Therapeutics, Immunos Therapeutics and Calidi Biotherapeutics; and a Merck licensed patent (with personal payments and payments to the institution). All other authors have no potential conflicts of interest to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To assess survival among patients diagnosed with uterine carcinosarcoma (CS) who underwent sentinel lymph node (SLN) biopsy alone vs. systematic lymph node dissection (LND)., Methods: We identified newly diagnosed CS patients who underwent primary surgical management from January 1996-December 2019. The SLN cohort underwent SLN biopsy alone with bilateral SLNs identified. The systematic LND cohort did not undergo SLN biopsy., Results: Ninety-nine patients underwent SLN biopsy, and 100 patients underwent systematic LND. There was no difference by age, stage, body mass index, myoinvasion (<50%, ≥50%), lymphovascular space invasion, or positive washings. Eighty-five SLN (85.9%) and 15 LND (15%) underwent minimally invasive surgery (P < 0.001). The median total node count was four (range, 1-13) for SLN and 19 (range, 2-50) for LND (P < 0.001). Nodal metastasis occurred in 23 (23.2%) SLN and in 22 (22%) LND (P = 0.4). Postoperative therapy was administered to 85 (85.9%) SLN and 71 (71%) LND (P = 0.02). Median follow-up was 33 months (range, 1-205) for SLN and 55.3 months (range, 1-269) for LND (P = 0.001). The three-year progression-free survival (PFS) was 62.9% (SE 5.2%) for SLN and 52.3% (SE 5.3%) for LND (P = 0.13). The three-year overall survival (OS) was 72.1% (SE 5.1%) for SLN and 71.6% (SE 4.6%) for LND (P = 0.68). An isolated nodal recurrence occurred in two (2%) SLN and four (4%) LND (P = 0.26)., Conclusions: There is no difference in PFS or OS among CS patients who undergo SLN biopsy vs. systematic LND. SLN biopsy detects nodal metastasis without compromising oncologic outcomes., Competing Interests: Declaration of Competing Interest Outside the submitted work, Dr. Makker reports industry support and unpaid consultant fees from Astra Zeneca, Eisai, Merck, Lilly, Karyopharm, Takeda, Genentech, Clovis, Novartis, Faeth, Zymeworks, GSK, and Moreo. Dr. Makker also discloses personal fees from IBM Watson. Dr. Abu-Rustum reports institutional grants from Stryker/Novadaq and GRAIL. Dr. Leitao reports grants from KCI/Acelity, personal fees from Takeda, J&J/Ethicon, and Intuitive Surgical. All other authors declare no conflicts of interest., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To examine the role of non-exenterative secondary cytoreductive surgery (SCS) compared with non-surgical treatments and identify predictors of improved survival for patients with recurrent endometrial cancer (EC)., Methods: All patients undergoing primary surgical management for EC 1/1/2009-12/31/2017 who subsequently developed recurrence were retrospectively identified. Survival was determined from date of diagnosis of first recurrence to last follow-up and estimated using Kaplan-Meier method. Differences in survival were analyzed using Log-rank and Wald tests, based on Cox Proportional Hazards model., Results: Among 376 patients with recurrent EC, median time to recurrence was 14.3 months (range, 0.2-102.2), post-recurrence median survival 29 months, median follow-up 29.2 months (range, 0-116). Sixty-one patients (16.2%) received SCS, 257 (68.4%) medical management (MM) (chemotherapy and/or radiation therapy), 32 (8.5%) hormonal therapy, 26 (6.9%) no further therapy. Patients selected for SCS were younger, had more endometrioid histology, more stage I disease at initial diagnosis, no residual disease after primary surgery, longer interval to first recurrence or progression, and the longest OS (57.6 months) (95% CI, 33.3-not reached). On multivariate analysis SCS was an independent predictor of improved survival. Among the 61 SCS patients, age < 70 at time of initial diagnosis, and endometrioid histology, were associated with improved post-relapse survival univariately (p = 0.008, 0.03, respectively)., Conclusions: While MM was the most common treatment for first recurrence of EC, patients selected for surgery demonstrated the greatest survival benefit even after controlling for tumor size, site, histology, stage, time to recurrence. Careful patient selection and favorable tumor factors likely play a major role in improved outcomes. Surgical management should be considered whenever feasible in medically eligible patients, with additional consideration given to our suggested criteria., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: Gaps in access to appropriate cancer care, and associated cancer mortality, have widened across socioeconomic groups. We examined whether demographic and socioeconomic factors influenced receipt of adjuvant radiation therapy (RT) in patients with high-risk, early-stage endometrial cancer., Methods: A retrospective study cohort was selected from 349,404 endometrial carcinoma patients from the National Cancer Database in whom adjuvant RT would be recommended per national guidelines. The study included surgically treated patients with endometrioid endometrial cancer with one of the following criteria: 1) FIGO 2009 stage IB, grade 1/2 disease, age ≥ 60 years; 2) stage IB, grade 3 disease; or 3) stage II disease. Logistic regression analysis was performed to identify factors associated with omission of adjuvant RT. Association between adjuvant RT, covariables, and overall survival (OS) was assessed with multivariable Cox proportional hazards models., Results: 19,594 patients were eligible for analysis; 47% did not receive adjuvant RT. Omission of adjuvant RT was more prevalent among African-American, Hispanic, and Asian compared to non-Hispanic white patients (OR 0.79, 95%CI: 0.69-0.91; OR 0.75, 95%CI: 0.64-0.87; OR 0.75, 95%CI: 0.60-0.94, respectively). Lower median household income of patient's area of residence, lack of health insurance, treatment at non-academic hospitals, farther distance to treatment facilities, and residence in metropolitan counties were associated with omission of adjuvant RT. Such omission was independently associated with worse OS (HR1.43, p < 0.001)., Conclusion: Adjuvant RT is omitted in 47% of patients with early-stage, high-risk endometrial cancer, which is associated with poor access to appropriate, high-quality care and worse outcome., Competing Interests: Declaration of Competing Interest C. Jillian Tsai reports consulting for Varian outside the submitted work. Dr. Abu-Rustum reports grants paid to his institution from Stryker/Novadaq, Olympus, and GRAIL outside the submitted work. The other authors have no conflict of interest to report., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To assess the efficacy of non-hormonal, hyaluronic acid (HLA)-based vaginal gel in improving vulvovaginal estrogen-deprivation symptoms in women with a history of endometrial cancer., Methods: For this single-arm, prospective, longitudinal trial, we enrolled disease-free women with a history of endometrial cancer who underwent surgery (total hysterectomy) and postoperative radiation. Participants used HLA daily for the first 2 weeks, and then 3×/week until weeks 12-14; dosage was then increased to 5×/week for non-responders. Vulvovaginal symptoms and pH were assessed at 4 time points (baseline [T1]; 4-6 weeks [T2]; 12-14 weeks [T3]; 22-24 weeks [T4]) with clinical evaluation, the Vaginal Assessment Scale (VAS), Vulvar Assessment Scale (VuAS), Female Sexual Function Index (FSFI), and Menopausal Symptom Checklist (MSCL)., Results: Of 43 patients, mean age was 59 years (range, 38-78); 54% (23/43) were partnered; and 49% (21/43) were sexually active. VAS, VuAS, MSCL, and SAQ (Sexual Activity Questionnaire) scores significantly improved from baseline to each assessment point (all p < .002). FSFI total mean scores significantly increased from T1 to T2 (p < .05) and from T1 to T4 (p < .03). At T1, 41% (16/39) felt confident about future sexual activity compared to 68% (17/25) at T4 (p = .096). Severely elevated vaginal pH (>6.5) decreased from 30% (13/43) at T1 to 19% (5/26) at T4 (p = .41)., Conclusion: The HLA-based gel improved vulvovaginal health and sexual function of endometrial cancer survivors in perceived symptoms and clinical exam outcomes. HLA administration 1-2×/week is recommended for women in natural menopause; a 3-5×/week schedule appears more effective for symptom relief in cancer survivors., Competing Interests: Declaration of competing interest Outside the submitted work, Dr. Jewell reports personal fees from Covidien/Medtronic. All other authors have no conflicts of interest to report., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: We report the incidence of occult nodal metastasis in patients who underwent primary surgical staging for apparent early endometrioid or serous endometrial cancer with bilateral SLN mapping and enhanced pathology. Occult ovarian metastasis rates were also reported., Methods: Patients with clinical stage I serous or endometrioid endometrial cancer who underwent primary staging surgery with successful bilateral SLN mapping from 1/2005-12/2018 were retrospectively evaluated. Rates of isolated tumor cells (ITCs), micro- and macrometastatic nodal disease, and occult ovarian involvement were reported., Results: Of 1044 patients, 959 had endometrioid and 85 serous carcinoma. There were no positive SLNs among 510 patients with noninvasive FIGO grade 1/2 endometrioid carcinoma and < 1%ITCs. Grade 1: 4.5%(9/202) with inner-half and 10%(6/62) with outer-half myoinvasion had positive SLNs. Grade 2: rates were 4%(3/76) and 20%(8/41), respectively. Grade 3: 5%(1/20) with noninvasive, 3%(1/31) with inner-half, and 24%(4/17) with outer-half myoinvasion had positive SLNs. ITC incidence increased with depth of myoinvasion-25% of deeply invasive grade 1/2 and 18% of deeply invasive grade 3 tumors. Four (10%) of 41 patients with noninvasive serous endometrial carcinoma had ITCs or positive SLNs. There were no occult ovarian metastases with grades 1/2 disease, 2/68 (3%) with grade 3 disease, and 2/85 (2%) with serous endometrial carcinoma., Conclusion: Ultrastaging SLNs may be unwarranted in low-grade noninvasive endometrioid cancer but valuable in noninvasive serous carcinoma. Occult ovarian metastasis is uncommon in early endometrial carcinoma and occurs in 2-3% of high-risk histologies. Further research is needed to determine ITC significance, particularly with regard to adjuvant treatment., Competing Interests: Declaration of competing interest Outside the submitted work, the authors claim the following potential disclosures: Dr. Leitao is an ad-hoc speaker for Intuitive Surgical, Inc. and is on the advisory board of JNJ/Ethicon. Dr. Aghajanian reports personal fees from Tesaro, Immunogen, Eisai/Merck, Mersana Therapeutics, Roche, Clovis, and Mateon Therapeutics, as well as grants from Clovis, Genentech, AbbVie, and AstraZeneca. Dr. Abu-Rustum reports grants from Stryker/Novadaq, Olympus, and GRAIL., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: The objective of our study was to assess survival among patients with uterine serous carcinoma (USC) undergoing sentinel lymph node (SLN) mapping alone versus patients undergoing systematic lymphadenectomy (LND)., Methods: We retrospectively reviewed patients undergoing primary surgical treatment for newly diagnosed USC at our institution from 1/1/1996-12/31/2017. Patients were assigned to either SLN mapping alone (SLN cohort) or systematic LND without SLN mapping (LND cohort). Progression-free (PFS) and overall survival (OS) were estimated using Kaplan-Meier method, compared using Logrank test., Results: 245 patients were available for analysis: 79 (32.2%) underwent SLN, 166 (67.7%) LND. 132 (79.5%) in the LND cohort had paraaortic LND (PALND) versus none in the SLN cohort. Median age: 66 and 68 years in the SLN and LND cohorts, respectively (p>0.05). Proportion of stage I/II disease: 67.1% (n = 53) and 64.5% (n = 107) in the SLN and LND cohorts, respectively (p>0.05). Median follow-up: 23 (range, 1-96) and 66 months (range, 4-265) in the SLN and LND cohorts, respectively (p < 0.001). Two-year OS in stage I/II disease (n = 160, 60.1%): 96.6% (SE ± 3.4) and 89.6% (SE ± 2.2) in the SLN and LND cohorts, respectively (p = 0.8). Two-year OS in stage III disease (n = 77): 73.6% (SE ± 10.2) and 77.3% (SE ± 5.8) in the SLN and LND cohorts, respectively (p = 0.8)., Conclusions: SLN mapping alone and systematic LND yielded similar survival outcomes in stage I-III USC. In our practice, the SLN algorithm has replaced systematic LND as the primary staging modality in this setting., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: Assess outcomes of a clinical cohort of patients with endometrioid endometrial cancer (EEC) harboring somatic POLE exonuclease domain mutations (EDMs)., Methods: Patients were consented to a protocol of tumor-normal massively parallel sequencing of 410-468 cancer related genes. EECs subjected to sequencing from 2014 to 2018 were reviewed. Tumors with somatic POLE EDMs were identified. EECs were assessed for microsatellite instability (MSI) using MSIsensor and immunohistochemical analysis for mismatch repair (MMR) proteins., Results: Of the 451 EECs sequenced, 23 had a POLE EDM (5%): 20 primary and 3 recurrent tumors sequenced. Nineteen cases (83%) were stage I/II and 4 (17%) were stages III/IV. Thirteen EECs (57%) were of FIGO grades 1/2, 10 (43%) grade 3. All patients were treated with surgery and 17 (89%) received adjuvant therapy. Five (22%) demonstrated loss of DNA MMR protein expression, none were due to Lynch syndrome. MSIsensor scores were conclusive for 21 samples: 19 were microsatellite stable and 2 MSI-high. After median follow-up of 30 months, 4/23 (17%) developed recurrences: 3 with initial grade 3 stage I and 1 with grade 1 stage III disease. One patient with grade 2 stage IV EEC had progressive disease after treatment., Conclusions: Patients with POLE EDM EEC have been shown to have a favorable prognosis. In this real-world cohort of patients, de novo metastatic disease and recurrences in initially uterine-confined cases were observed. Further research is warranted before incorporating the presence of POLE EDM into decision-making regarding adjuvant therapy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: To assess outcomes after secondary surgical resection in patients with recurrent uterine leiomyosarcoma (uLMS)., Methods: We retrospectively identified all patients who had no evidence of disease after initial surgery for uLMS, who underwent surgery for a first recurrence at our institution between 1/1991 and 10/2013. We excluded patients who received any therapy for recurrence prior to secondary resection, and patients who underwent surgery soon after morcellation [of presumed benign fibroids] showed widespread disease. Overall survival (OS) was determined from time of first recurrence to death or last follow-up., Results: We identified 62 patients: 29 with abdominal/pelvic recurrence only, 30 with lung recurrence only, 3 with both. Median time to first recurrence was 18 months (95% CI: 13.3-23.3): 15.8 months (95% CI: 13.0-18.6) abdominal/pelvic recurrence; 24.1 months (95% CI: 14.5-33.7) lung-only recurrence (p = 0.03). Median OS was 37.7 months (95% CI: 25.9-49.6) abdominal/pelvic recurrence; 78.1 months (95% CI: 44.8-11.4) lung recurrence (p = 0.02). Complete gross resection (CGR) was achieved in 58 cases (93%), with gross residual ≤1 cm in 2 (3.5%) and >1 cm in 2 (3.5%). Median OS based on residual disease was 54.1 months (95% CI: 24.9-83.3), 38.7 months (95% CI: NE), 1.7 months (95% CI: NE), respectively (p < 0.001). In cases with CGR, neither adjuvant radiation (N = 9), chemotherapy (N = 8) nor hormonal therapy (N = 10) was associated with improved OS., Conclusions: Secondary surgical resection of recurrent uLMS is reasonable in patients with a high probability of achieving CGR. Lung-only recurrences were associated with more favorable outcome. Following CGR, additional therapy may not offer benefit., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To evaluate clinical outcomes of patients with BRCA-associated ovarian cancer who developed brain metastases (BM)., Methods: Patients with epithelial ovarian, fallopian tube, and primary peritoneal cancer (EOC) and BM, treated at a single institution from 1/1/2008-7/1/2018, were identified from two institutional databases. Charts and medical records were retrospectively reviewed for clinical characteristics and germline BRCA mutation status. Appropriate statistics were used., Results: Of 3649 patients with EOC, 91 had BM (2.5%). Germline mutation status was available for 63 (69%) cases; 21 (35%) of these harbored a BRCA1/2 mutation (15 BRCA1, 6 BRCA2). Clinical characteristics were similar between groups. BM were diagnosed at a median of 31 months (95% CI, 22.6-39.4) in BRCA-mutated (mBRCA) and 32 months (95% CI, 23.7-40.3) in wild-type BRCA (wtBRCA) (p = 0.78) patients. Brain metastases were the only evidence of disease at time of BM diagnoses in 48% (n = 10) mBRCA and 19% (n = 8) wtBRCA (p = 0.02) patients. There was no difference in treatment of BM by mutation status (p = 0.84). Survival from time of BM diagnosis was 29 months (95%CI, 15.5-42.5) in mBRCA and 9 months (95% CI, 5.5-12.5) in wtBRCA patients, with an adjusted hazard ratio (HR) of 0.53, p = 0.09; 95% CI, 0.25-1.11. HR was adjusted for presence of systemic disease at time of BM diagnosis., Conclusion: This is the largest study to date comparing outcomes in patients with EOC and BM by mutation status. mBRCA patients were more likely to have isolated BM, which may be a factor in their long survival. This supports the pursuit of aggressive treatment for mBRCA EOC patients with BM. Additional studies examining the correlation of BRCA mutational status with BM are warranted., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To assess the rates and distribution of first recurrence in patients with FIGO stage IIIC1 endometrial cancer (EC) who did not undergo paraaortic dissection at surgical staging., Methods: We retrospectively selected all (n = 207) stage IIIC1 patients treated at a single institution from 5/1993-1/2017. Sites of first recurrence were identified, disease-free (DFS) and overall survival (OS) calculated, multivariate logistic regression performed to identify factors associated with recurrence., Results: Three-year DFS and OS were 66.5% and 85.7%, respectively. The most common histology was endometroid (64.2%). Three-year DFS was 81% (SE±3.8%) endometrioid vs. 39.5% (SE±6.6%) non-endometrioid (P < 0.001). Three-year OS was 96.9% (SE±1.8%) endometrioid vs. 65.6% (SE±6.7%) non-endometrioid (P < 0.001). Sixty-two (30.1%) patients recurred. Patterns of recurrence were: 14 (8.3%) multiple sites, 17 (8.2%) abdominal, 14 (6.8%) extra-abdominal, 17 (8.3%) isolated nodal (8 of these (3.9%) paraaortic). Patients with isolated tumor cells (ITCs) in lymph nodes only had 12/71 (17%) recurrence rate vs. 50/135 (37%) for patients with micro-/macrometastasis. On univariate analysis, grade (HR 4.67 95%CI 1.5-14.5, P = 0.008), histology (HR 4.9 95%CI 2.6-9.3, P < 0.001), myometrial invasion (HR 1.9 95%CI 1.04-3.5, P = 0.04), pelvic washing (HR 2.2 95%CI 1.1-4.5, P = 0.03), tumor volume in pelvic LNs (ITC vs. micro-/macrometastasis; HR 0.3 95%CI 0.2-0.7, P = 0.003) were associated with recurrence. On multivariate analysis, only histology was associated with recurrence (HR 7.88 95%CI 3.43-18.13, P < 0.001)., Conclusions: Isolated paraaortic recurrence in stage IIIC1 EC is uncommon. Micro-/macrometastasis were associated with twice the recurrence rate compared to ITC. These data will help clinicians counsel patients with stage IIIC1 EC regarding paraaortic assessment., (Copyright © 2018 Elsevier Inc. All rights reserved.)

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., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: The purpose was to determine the potential impact of IMRT on the rate of bowel obstruction (BO), in patients with gynecologic malignancies undergoing postoperative pelvic RT., Methods: We performed a retrospective review of all patients with endometrial or cervical cancer who received postoperative pelvic RT at our institution from 2000 to 2012. Patients who received definitive or palliative RT, or those with BO due to disease progression, were excluded. Standard two-sided statistical tests were used to evaluate for associated risk factors. Kaplan-Meier, Log rank and Cox proportional hazards regression analysis tests were performed for actuarial analysis., Results: A total of 224 patients were identified, 120 (54%) received postoperative pelvic IMRT and 104 (46%) 3-dimentional (3-D) RT. Median follow-up time was 67months. BO was grade 1 (asymptomatic) in 2/228 (0.9%), grade 2 (conservative management) in 4 (1.8%), and grade 3≥ in 4 (1.8%). Overall, the 5-year actuarial rate of BO was 4.8%. The 5-year rate of BO in the IMRT group was 0.9% compared to 9.3% for 3-D RT (p=0.006). Patients with BMI≥30kg/m(2) were less likely to develop BO (2.6% vs. 8.3; p=0.03). On multivariate analysis, only IMRT retained its significance as an independent predictor of less BO (p=0.022)., Conclusions: The use of postoperative IMRT for cervical and endometrial cancer was associated with significant reduction in the rate of bowel obstruction. This difference maintained its statistical significance on multivariate analysis. Such finding if confirmed by others will help further solidify the benefit of IMRT in gynecologic cancers., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objective: To assess whether contemporary adjuvant management of early stage uterine carcinosarcoma (CS) produces equal outcomes as in uterine serous carcinoma (USC)., Methods: We reviewed 172 women treated from 2000 to 2011 for stage I-II USC (n=112, 65%) or CS (n=60, 35%). Adjuvant therapy was initiated in 154 (90%) patients, with 111 patients receiving intravaginal radiotherapy (IVRT)/chemotherapy. Median follow up was 4.6 years for surviving patients., Results: Characteristics for USC vs. CS did not differ significantly by age ≥60, pelvic or para-aortic node sampling, stage, lymphovascular invasion, chemotherapy use, RT use or omission of adjuvant therapy. Outcomes were better for USC vs. CS in 5-year actuarial rates of recurrence [17% (C.I. 10-25%) vs. 45% (C.I. 31-59%), p<0.001],disease-related mortality (DRM) [11% (5-17%) vs. 30% (16-44%), p=0.016], and all-cause mortality [12% (C.I. 6-18%) vs. 34% (C.I. 20-48%), p=0.007]. In multivariable analysis, CS histology remained a significant predictor of risk for recurrence [HR 3.1 (C.I. 1.7-5.7), p<0.001], DRM [HR 2.4 (C.I. 1.1-5.1), p=0.024], and all-cause mortality [HR 2.4 (C.I. 1.2-4.8), p=0.012]. On sub-group analysis of 111 patients (77 USC, 34 CS) able to receive IVRT/chemotherapy, CS no longer was associated significantly with increased recurrence (29% vs. 15%, p=0.18), DRM (22% vs. 10%, p=0.39), or all-cause mortality (22% vs. 10%, p=0.45)., Conclusions: CS was associated with worse outcomes than USC. However, that difference was not maintained in patients able to receive IVRT and chemotherapy. While intriguing, this result may be due in part to selection against rapid early relapsing CS patients in this group., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: Advanced endometrial cancer patients comprise a heterogeneous group. This study assessed the association of clinicopathological factors with relapse and death from endometrial cancer., Methods: Eligible patients were treated for stage III (FIGO 2009) endometrial adenocarcinoma, had peritoneal cytology performed, and had no gross residual disease post-operatively., Results: Of 192 patients, 59% were ≥60 years old, 48% had ≥50% myometrial invasion, 71% lymphovascular invasion, 25% cervical stromal invasion, 37% adnexal involvement, and 23% positive peritoneal cytology. High-grade histology (serous, clear cell, undifferentiated, or grade 3 endometrioid) was present in 45%. Pelvic lymphadenectomy was performed in 93% and para-aortic lymphadenectomy in 73%. Adjuvant chemotherapy and/or radiation therapy was administered to 93%. At a median follow-up of 42 months, the 5-year rate of relapse was 37% and of death from endometrial cancer was 30%. On multivariate analysis, both outcomes were associated with high-grade histology, positive peritoneal cytology, and deep myometrial invasion (p≤0.04). The cohort was divided into subgroups of patients with 0 (n=46), 1 (n=83), or ≥2 (n=63) of these high-risk characteristics. The 5-year relapse rate for patients with 0 risk factors was 13%, 1 risk factor was 27%, and ≥2 risk factors was 62% (p<0.001). The corresponding 5-year rates of death from endometrial cancer were 11%, 20%, and 56%, respectively (p<0.001)., Conclusions: Stratification of stage III endometrial cancer according to high-grade histology, positive peritoneal cytology, and deep myometrial invasion is useful for prognostication and may grant insight into the optimal treatment for specific subgroups of patients., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Objective: To evaluate patterns of relapse in early stage uterine papillary carcinoma (UPSC) patients receiving adjuvant intravaginal radiotherapy (IVRT) with or without chemotherapy., Methods: From 1/1996 to 12/2010, 77 women with stage I-II UPSC underwent surgery followed by IVRT (median 21Gy). Stage IA patients without residual disease at surgery were excluded. IVRT and chemotherapy (carboplatin/taxane) was given to 61 (79%) patients and IVRT alone to 16 (21%). The median follow-up was 62 months for surviving patients., Results: Of the 77 patients, 11 (14%) relapsed as follows: vaginal 2 (3%), pelvic 5 (6%), para-aortic 5 (6%), peritoneal 6 (8%), and other distant sites 8 (10%). Of the 5 pelvic relapses, 2 were isolated and were salvaged. In those treated without chemotherapy, only 1/16 developed recurrence (mediastinal). The 5-year vaginal, pelvic, para-aortic, peritoneal, and distant recurrence rates were 2.7% (C.I. 0-6.2%), 5.8% (C.I. 0.6-11.0%), 5.4% (C.I. 0.6-10.1%), 5.3% (C.I. 0.5-10.1%) and 6.6% (C.I. 1.4-11.8%), respectively. The 5-year disease-free survival (DFS), and overall survival (OS) were 88% (C.I. 81-95%), and 91% (C.I. 84-97%), respectively. The only predictor of worse 5-year pelvic control was stage (96.2% stage IA vs 87.7% for stage IB-II, p=0.043)., Conclusions: In stage I-II UPSC patients who predominantly receive adjuvant chemotherapy, IVRT as the sole form of adjuvant RT provides excellent locoregional control. The risk of isolated pelvic recurrence is too low to warrant routine use of external pelvic RT., (© 2013.)

Objective: To report the incidence of nodal metastases in patients presenting with presumed low-grade endometrioid adenocarcinomas using a sentinel lymph node (SLN) mapping protocol including pathologic ultrastaging., Methods: All patients from 9/2005 to 12/2011 who underwent endometrial cancer staging surgery with attempted SLN mapping for preoperative grade 1 (G1) or grade 2 (G2) tumors with <50% invasion on final pathology, were included. All lymph nodes were examined with hematoxylin and eosin (H&E). Negative SLNs were further examined using an ultrastaging protocol to detect micrometastases and isolated tumor cells., Results: Of 425 patients, lymph node metastasis was found in 25 patients (5.9%) on final pathology-13 cases on routine H&E, 12 cases after ultrastaging. Patients whose tumors had a DMI <50% were more likely to have positive SLNs on routine H&E (p<0.005) or after ultrastaging (p=0.01) compared to those without myoinvasion., Conclusions: Applying a standardized SLN mapping algorithm with ultrastaging allows for the detection of nodal disease in a presumably low-risk group of patients who in some practices may not undergo any nodal evaluation. Ultrastaging of SLNs can likely be eliminated in endometrioid adenocarcinoma with no myoinvasion. The long-term clinical significance of ultrastage-detected nodal disease requires further investigation as recurrences were noted in some of these cases., (© 2013.)

Objective: The objectives of the study are to evaluate which clinicopathologic factors influenced overall survival (OS) in endometrial carcinoma and to determine if the surgical effort to assess para-aortic (PA) lymph nodes (LNs) at initial staging surgery impacts OS., Methods: All patients diagnosed with endometrial cancer from 1/1993-12/2011 who had LNs excised were included. PALN assessment was defined by the identification of one or more PALNs on final pathology. A multivariate analysis was performed to assess the effect of PALNs on OS. A form of recursive partitioning called classification and regression tree (CART) analysis was implemented. Variables included: age, stage, tumor subtype, grade, myometrial invasion, total LNs removed, evaluation of PALNs, and adjuvant chemotherapy., Results: The cohort included 1920 patients, with a median age of 62 years. The median number of LNs removed was 16 (range, 1-99). The removal of PALNs was not associated with OS (P=0.450). Using the CART hierarchically, stage I vs. stages II-IV and grades 1-2 vs. grade 3 emerged as predictors of OS. If the tree was allowed to grow, further branching was based on age and myometrial invasion. Total number of LNs removed and assessment of PALNs as defined in this study were not predictive of OS., Conclusion: This innovative CART analysis emphasized the importance of proper stage assignment and a binary grading system in impacting OS. Notably, the total number of LNs removed and specific evaluation of PALNs as defined in this study were not important predictors of OS., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: The optimal adjuvant therapy in advanced endometrial cancer is controversial. One regimen is concurrent external beam pelvic irradiation (RT) and cisplatin, then carboplatin/paclitaxel. This study reports an institutional experience using this approach in stage III (FIGO 2009) endometrial cancer., Methods: Patients with stage III (FIGO 2009) endometrial cancer who underwent total hysterectomy and bilateral salpingo-oophorectomy at a single institution from 01/2004 to 12/2009 were identified retrospectively. Those treated with adjuvant RT/cisplatin, followed by carboplatin/paclitaxel comprised the study population., Results: Of the 40 eligible patients, 7 (18%) were stage IIIA and 33 (82%) IIIC. Nineteen patients (48%) were ≥ 60 years of age. Twenty-three (58%) had ≥ 50% myometrial invasion, 30 (75%) lymphovascular invasion, 11 (28%) cervical stromal invasion, and 5 (12%) positive peritoneal cytology. Histology was endometrioid in 32 (80%), serous in 6 (15%), and clear cell in 2 (5%). At a median follow-up of 49 months, the 5-year freedom from relapse was 79% and overall survival 85%. The 5-year rate of vaginal recurrence was 3%, non-vaginal pelvic recurrence 3%, para-aortic recurrence 11%, peritoneal recurrence 5%, and other distant recurrence 11%. Thirty-one patients (78%) were able to complete the planned RT/cisplatin and 4 cycles of carboplatin/paclitaxel. Acute grade 3 toxicity occurred in 10 patients (4 neutropenia, 2 anemia, 1 fatigue, 2 diarrhea). No late toxicity was grade ≥ 3., Conclusion: These favorable outcomes corroborate those of RTOG 9708. Until prospective data that compare adjuvant therapy regimens mature, concurrent chemoradiation should be strongly considered in stage III endometrial cancer., (Copyright © 2013. Published by Elsevier Inc.)

Objectives: According to the updated FIGO system, positive peritoneal cytology does not affect endometrial cancer stage. This revision may reduce rates of obtaining cytology, with unclear implications in advanced disease. This study evaluates the significance of positive cytology in stage III (FIGO 2009) endometrial cancer., Methods: Eligible patients received treatment for stage III endometrial cancer at a single institution and had peritoneal cytology performed., Results: Of 196 patients, 58% were ≥ 60 years old, 48% had deep myometrial invasion, 71% lymphovascular invasion, 25% cervical invasion, 37% adnexal involvement, 79% nodal involvement, and 46% aggressive histology. Positive cytology was present in 23% (45/196) and significantly associated with cervical stromal invasion, adnexal involvement, and aggressive histology (P ≤ 0.03). There was no significant difference in rates of lymphadenectomy, chemotherapy, or radiation between negative and positive cytology groups. At a median follow-up of 47 months, the 5-year freedom from relapse was 39% for positive cytology vs. 69% for negative, disease-specific survival 42% vs. 77%, and overall survival 34% vs. 72% (P < 0.001). Positive cytology correlated with higher recurrence rates in the para-aortic nodes and peritoneum (30% vs. 9%, 23% vs. 4%; P ≤ 0.008). When controlling for adverse features including aggressive histology, positive cytology was associated with an increased hazard for relapse (HR 2.3; P = 0.002) and death (HR 2.9; P < 0.001)., Conclusions: In stage III endometrial cancer, positive cytology independently predicts outcome and is associated with distinct relapse patterns. Obtaining peritoneal cytology in stage III endometrial cancer is critical., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: To determine whether the frequency of cases diagnosed with stage IIIC endometrial cancer is affected by the incorporation of a modified surgical lymph node assessment., Methods: Since 2008, we have increasingly utilized a modified nodal assessment using an algorithm that incorporates SLN mapping. For this analysis, we identified all cases of newly diagnosed endometrial cancers undergoing a minimally invasive staging procedure not requiring conversion to laparotomy from 1/1/08 to 12/31/10. Procedures were categorized as standard, modified, and hysterectomy only. Differences were based on time period: 2008 (Y1), 2009 (Y2), and 2010 (Y3). Appropriate statistical tests were used., Results: We identified a total of 507 cases. The distribution of cases was 143 (Y1), 190 (Y2), and 174 (Y3). Tumor grade (P=0.05) and high-risk histologies (P=0.8) did not differ during the 3 time periods. A standard staging procedure was performed in the following cases: Y1 (93/143; 65%), Y2 (66/166; 35%), and Y3 (40/164; 23%) (P<0.001). Median operative times were as follows: Y1 (218 min), Y2 (198 min), and Y3 (176.5 min) (P<0.001). The median numbers of total lymph nodes removed among cases with at least 1 node retrieved were: Y1 (20); Y2 (10); Y3 (7) (P<0.001). Cases diagnosed as stage IIIC were as follows: Y1 (10/143; 7%), Y2 (15/166; 7.9%), and Y3 (13/164; 7.5%) (P=1.0)., Conclusions: The incorporation of a modified staging approach utilizing the SLN mapping algorithm reduces the need for standard lymphadenectomy and does not appear to adversely affect the rate of stage IIIC detection., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: There is an increased awareness of pelvic insufficiency fractures (PIF) as a potential morbidity of pelvic radiotherapy (RT). The purpose of this study was to determine the incidence of PIF and assess prognostic factors, including intensity-modulated RT (IMRT), in gynecologic oncology patients treated with postoperative pelvic RT., Methods: We performed a retrospective review of all patients with endometrial or cervical carcinoma who received postoperative pelvic RT at our institution during 2000-2008. Patients who received definitive or palliative RT were excluded., Results: A total of 222 patients were identified, of whom 11 (5%) developed PIF at a median time of 11.5months (range, 5.5-87.3months) from RT completion. The 5-year actuarial rate was 5.1% (95% CI 3.3-6.9). In patients with osteoporosis, the 5-year rate was 15.6% compared with 2.9% for those without (P=0.01). Similarly, patients who were on prior hormone-replacement therapy (HRT) had a higher rate (14.8% vs 4.1%, P=0.009). The median body-mass index (BMI) for patients who developed PIF was significantly lower than those who didn't (25.9 vs 27.2, P=0.016). The rate of PIF was 4.9% whether patients received IMRT or conventional RT., Conclusions: The 5-year risk of PIF for postoperative pelvic RT in cervical and endometrial cancer is 5.1%. Women with history of osteoporosis, prior HRT, or low BMI need to be counseled about the risk of PIF. The use of IMRT did not decrease PIF, but further studies are needed to determine if a dose/volume relationship exists between RT and PIF., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: According to national surveys, the use of intensity-modulated radiation therapy (IMRT) in gynecologic cancers is on the rise, yet there is still some reluctance to adopt adjuvant IMRT as standard practice. The purpose of this study is to report a single-institution experience using postoperative pelvic IMRT with or without chemotherapy in high-risk endometrial cancer., Methods: From 11/2004 to 12/2009, 46 patients underwent hysterectomy/bilateral salpingo-oophorectomy for stage I-III (22% stage I/II and 78% stage III) endometrial cancer. Median IMRT dose was 50.4Gy. Adjuvant chemotherapy was given to 30 (65%) patients., Results: With a median follow-up of 52months, 4 patients recurred: 1 vaginal plus lung metastasis, 2 isolated para-aortic recurrences, and 1 lungs and liver metastasis. Five-year relapse rate was 9% (95% CI, 0-13.6%). Five-year disease-free survival (DFS) was 88% (95% CI, 77-98%) and overall survival (OS) was 97% (95% CI, 90-100%). There were 2 patients with non-hematological grade 3 toxicity: 1 (2%) acute and 1 (2%) chronic gastrointestinal toxicity. In patients treated with IMRT and chemotherapy (n=30), 5 had grade 3 leukopenia, 8 grade 2 anemia, and 2 grade 2 thrombocytopenia., Conclusions: Oncologic outcomes with postoperative IMRT were very good, with DFS and OS rates of >88% at median follow-up of 52months, despite a preponderance (78%) of stage III disease. Toxicity was minimal even in the setting of an aggressive trimodality (65% of patients) approach. Data from this study and emerging data from RTOG trial 0418 demonstrate the advantages of IMRT in high-risk endometrial cancer., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: According to national surveys, the use of intensity-modulated radiation therapy (IMRT) in gynecologic cancers is on the rise, yet there is still some reluctance to adopt adjuvant IMRT as standard practice. The purpose of this study is to report a single-institution experience using postoperative pelvic IMRT with concurrent chemotherapy in intermediate- and high-risk early stage cervical cancer., Methods: From 1/2004 to 12/2009, 34 patients underwent radical hysterectomy and pelvic lymph node dissection (28 median nodes were removed) for early stage cervical cancer. Median dose of postoperative pelvic IMRT was 50.4 Gy (range, 45-50.4). All patients received concurrent cisplatin., Results: With a median follow-up of 44 months, 3 patients have recurred; 1 vaginal recurrence, 1 regional and distant, and 1 distant. The 3- and 5-year disease-free survival (DFS) was 91.2% (95% CI, 81.4-100%) and overall survival (OS) was 91.1% (95% CI, 81.3-100%). All failures and all deaths were in the high-risk group (n=3/26). There was 32.3% G3-4 hematologic toxicity, 2.9% acute G3 gastrointestinal toxicity, and no acute G3 or higher genitourinary toxicity. There were no chronic G3 or higher toxicities., Conclusions: Oncologic outcomes with postoperative IMRT were very good, with DFS and OS rates of >90% at median follow-up of 44 months, despite a preponderance (76.5%) of high-risk features. Toxicity was minimal even in the setting of an aggressive trimodality approach. Data from this study and emerging data from the Phase II RTOG study (0418) demonstrate the advantages of postoperative IMRT in early stage cervical cancer., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: The purpose of this study is to report our single-institution experience with concurrent adjuvant intravaginal radiation (IVRT) and carboplatin/paclitaxel chemotherapy for early stage uterine papillary serous carcinoma (UPSC)., Methods: From 10/2000 to 12/2009, 41 women with stage I-II UPSC underwent surgery followed by IVRT (median dose of 21 Gy in 3 fractions) and concurrent carboplatin (AUC=5-6) and paclitaxel (175 mg/m(2)) for six planned cycles. IVRT was administered on non-chemotherapy weeks. The Kaplan-Meier method was used to estimate survival, and the log-rank test was used for comparisons., Results: Median patient age was 67 years (51-80 years). Surgery included hysterectomy, bilateral salpingo-oophorectomy, peritoneal washings, omental biopsy, and pelvic and paraaortic lymph node sampling. FIGO 2009 stage was IA in 73%, IB in 10%, and II in 17%. Histology was pure serous in 71% of cases. Thirty-five patients (85%) completed all planned treatment. With a median follow-up time of 58 months, the 5-year disease-free (DFS) and overall survival (OS) rates were 85% (95%CI, 73-96%) and 90% (95%CI, 80-100%). The 5-year pelvic, para-aortic, and distant recurrence rates were 9%, 5%, and 10%, respectively. There were no vaginal recurrences. Of the 4 pelvic recurrences, 2 were isolated and were successfully salvaged. Patients with stage II disease had lower DFS (71% vs. 88%; p=0.017) and OS (71% vs. 93%; p=0.001) than patients with stage I disease., Conclusions: Concurrent adjuvant carboplatin/paclitaxel chemotherapy and IVRT provide excellent outcomes for early stage UPSC. Whether this regimen is superior to pelvic radiation will require confirmation from the ongoing randomized trial., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To update our report on the outcome of patients who underwent extended pelvic resection (EPR) for recurrent or persistent uterine and cervical malignancies., Methods: We reviewed the records of all patients who underwent EPR between 6/2000 and 07/2011. EPR was defined as an en-bloc resection of a pelvic tumor with sidewall muscle, bone, major nerve, and/or major vascular structure. Complications up to 180 days post surgery were analyzed. Survivals were estimated using the Kaplan-Meier method., Results: We identified 22 patients. Median age at the time of EPR was 58 years (range, 36-74). Median tumor diameter was 5.4 cm (range, 1.5-11.2). Primary tumor sites included: uterus, 13; cervix, 7; synchronous uterus/cervix, 1; and synchronous uterus/ovary, 1. The EPR structures were: muscle, 13; nerve, 10; bone, 8; vessel, 5. Complete gross resection with microscopically negative margins (R0 resection) was achieved in 17 patients (77%). There were no perioperative mortalities. Major postoperative complications occurred in 14 patients (64%). The two most common morbidities were pelvic abscesses and peripheral neuropathies. Median follow-up time was 28 months (range, 6-99). The 5-year overall survival (OS) for the entire cohort was 34% (95% CI, 13-57). For the 17 patients who had an R0 resection, the 5-year OS was 48% (95% CI, 19-73). In patients with positive pathologic margins (n=5), the 5-year OS was 0%., Conclusion: EPR was associated with prolonged survival when an R0 resection was achieved. The high rate of postoperative complications remains a hallmark of these procedures and properly selected patients should be extensively counseled preoperatively., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objectives: To evaluate patterns of recurrence in 1988 FIGO stage IC endometrioid endometrial adenocarcinoma., Methods: A prospectively maintained endometrial cancer database was utilized to identify all patients with stage IC endometrioid endometrial adenocarcinoma treated between 2/93 and 6/09. Patterns of recurrence and risk factors were analyzed., Results: One hundred thirty-four patients with stage IC endometrial cancer were identified. Median age was 66 years (range, 31-91 years). All patients were initially treated surgically, and 79% underwent comprehensive surgical staging with lymphadenectomy. Median number of lymph nodes removed was 18 (range, 1-45). Fifty-one patients (38%) had FIGO grade 1 tumors, 55 (41%) had grade 2 tumors, and 28 (21%) had grade 3 tumors. The majority of patients (91%) received adjuvant radiation therapy. With a median follow-up of 36 months (range, 0.6-141.4 months), 10 patients recurred. Of these, 2 (20%) were grade 1, 2 (20%) were grade 2, and 6 (60%) were grade 3. Nine (90%) of these recurrences had a distant component and 7 (70%) were fatal. Overall, the 3 year cumulative incidence failure rate for grade 1/2 tumors was 5.4%; for grade 3 tumors it was 28.9% (P<0.001). Age, BMI, and lymphovascular invasion were not associated with an increased risk of recurrence., Conclusions: Patients with stage IC, grade 3 endometrial cancer had a significantly increased risk of recurrence (28.9%). All of these recurrences had a distant component and the majority were fatal. Further investigation into the addition of adjuvant systemic therapy in these high-risk patients is warranted., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To evaluate the outcomes observed with pelvic exenteration with curative intent for recurrent uterine malignancies in the modern era., Methods: We reviewed the records of all patients who underwent this procedure at our institution between 1/1997 and 03/2011. Postoperative complications up to 90 days after surgery were analyzed and graded as per our institution grading system. Survivals were estimated using the Kaplan-Meier method., Results: During the study period, 21 patients were identified. Median age at the time of exenteration was 57 years (range, 36-75). Median tumor size was 6 cm (range, microscopic - 14.5). Tumor histology was: endometrioid, 10 cases; mixed, serous, and carcinosarcoma, 7 cases; and sarcomas, 4 cases. The type of exenteration was: total, 14 cases; anterior, 6 cases and posterior, 1 case. There were no intra- or postoperative mortalities. Seven patients (33%) developed at least one grade 2 complication, and 10 patients (48%) developed at least one grade 3 complication. Five (24%) patients had to be re-operated on in the first 90 days post surgery. The median follow up time after exenteration was 39 months (range, 5-112). The 5-year survival of the entire cohort was 40% (95% CI: 18-63). An improved survival was observed in patients with endometrioid tumors and sarcomas (5-year survival rates of 50% and 66%, respectively). The presence of pelvic sidewall involvement and/or hydronephrosis did not negatively affect survival., Conclusion: Pelvic exenteration for recurrent uterine malignancies can be associated with long-term survival in properly selected patients. A high rate of postoperative complications remains a hallmark of this procedure and should be discussed carefully with patients facing this decision., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To compare the incidence of metastatic cancer cells in sentinel lymph nodes (SLN) vs. non-sentinel nodes in patients who had lymphatic mapping for endometrial cancer and to determine the contribution of metastases detected on ultrastaging to the overall nodal metastasis rate., Methods: All patients who underwent lymphatic mapping for endometrial cancer were reviewed. Cervical injection of blue dye was used in all cases. Sentinel nodes were examined by routine hematoxylin and eosin (H&E), and if negative, by standardized institutional pathology protocol that included additional sections and immunohistochemistry (IHC)., Results: Between 09/2005 and 03/2010, 266 patients with endometrial cancer underwent lymphatic mapping. Sentinel node identification was successful in 223 (84%) cases. Positive nodes were diagnosed in 32/266 (12%) patients. Of those, 8/266 patients (3%) had the metastasis detected only by additional section or IHC as part of SLN ultrastaging. Excluding the 8 cases with positive SLN on ultrastaging only, 24/801 (2.99%) SLN and 30/2698 (1.11%) non-SLN were positive for metastatic disease (p=0.0003)., Conclusion: Using a cervical injection for mapping, metastatic cells from endometrial cancer are three times as likely to be detected in SLN than in the non-sentinel nodes. This finding strongly supports the concept of lymphatic mapping in endometrial cancer to fine tune the nodal dissection topography. By adding SLN mapping to our current surgical staging procedures we may increase the likelihood of detecting metastatic cancer cells in regional lymph nodes. An additional benefit of incorporating pathologic ultrastaging of SLN is the detection of micrometastasis, which may be the only evidence of extrauterine spread., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objective: To determine the incidence of adnexal and lymph node (LN) metastasis in newly diagnosed endometrial stromal sarcoma (ESS)., Methods: We identified all cases with a diagnosis of ESS evaluated at our institution from January 1, 1980 to October 31, 2009. All uterine pathology was reviewed at our center. High-grade or undifferentiated tumors and ESS arising in extrauterine sites were excluded. Pertinent clinical data were abstracted from electronic medical records. Appropriate statistical tests were performed using SPSS16.0., Results: We identified 94 cases of ESS. LN metastasis was identified in 7 (19%) of 36 patients who underwent LN evaluation. Six of the 7 cases with LN metastasis had lymphovascular invasion (LVI). LVI status was not reported in the other case. Five of the 7 patients with LN metastasis had grossly positive LNs with or without other gross extrauterine disease. Of 20 patients with disease grossly limited to the uterus and grossly normal LNs, 2 (10%) had LN metastasis. Both of these cases had LVI and extensive myoinvasion. Eighty-seven cases (93%) underwent salpingo-oophorectomy. Adnexal metastasis was identified in 11 (13%) of 87 cases, all manifested by gross adnexal tumor and occurring in patients with other gross pelvic extrauterine disease., Conclusion: The incidence of LN metastasis in ESS is commonly associated with gross extrauterine disease, extensive myoinvasion, and LVI. Since myoinvasion and LVI status often are not assessable at the time of hysterectomy, LN dissection remains a reasonable option at primary surgery. The rate of adnexal metastasis appears to be negligible in the absence of gross adnexal and extrauterine tumor., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Objectives: Traditionally we have relied mainly on final FIGO stage to estimate overall oncologic outcome in endometrial cancer patients. However, it is well known that other patient factors may play equally important roles in outcome. Our objective was to develop a clinically useful nomogram in the hope of providing a more individualized and accurate estimation of overall survival (OS) following primary therapy., Methods: Using a prospectively maintained endometrial cancer database, 1735 patients treated between 1993 and 2008 were analyzed. Characteristics known to predict OS were collected. For each patient, points were assigned to each of these 5 variables. A total score was calculated. The association between each predictor and the outcome was assessed by multivariable modeling. The corresponding 3-year OS probabilities were then determined from the nomogram., Results: The median age was 62 years (range, 25-96). Final grade included: G1 (471), G2 (622), G3 (634), and missing (8). Stage included: IA (501), IB (590), IC (141), IIA (36), IIB (75), IIIA (116), IIIB (6), IIIC (135), IVA (7), and IVB (128). Histology included: adenocarcinoma (1376), carcinosarcoma (100), clear cell (62), and serous (197). Median follow-up for survivors was 29.2 months (0-162.2 months). Concordance probability estimator for the nomogram is 0.746+/-0.011., Conclusion: We developed a nomogram based on 5 easily available clinical characteristics to predict OS with a high concordance probability. This nomogram incorporates other individualized patient variables beyond FIGO stage to more accurately predict outcome. This new tool may be useful to clinicians in assessing patient risk when deciding on follow-up strategies.

Objective: To describe the incidence of isolated paraaortic nodal metastasis in surgically staged endometrial cancer patients with negative pelvic lymph nodes., Methods: Using a prospectively maintained database we identified all cases of endometrial cancer that had both pelvic and aortic nodal dissection and determined the rate of isolated paraaortic nodal metastasis in the setting of negative pelvic nodes. For this report a satisfactory pelvic node dissection meant the identification of 8 or more pelvic nodes on final pathology., Results: 1942 endometrial cancer patients were surgically treated at our institution from 1/93 to 1/08. 847 had both pelvic and paraaortic nodes removed during surgery and identified by pathology. 734 had negative pelvic nodes with at least one paraaortic node identified. Only 12 (1.6%) had positive paraaortic nodes with negative pelvic nodes. Seven (1%) of 640 cases with 8 or more negative pelvic nodes had positive paraaortic nodes. Final grade for these cases included: G1 (2), G2 (2), G3 (1), papillary serous (1), and undifferentiated (1). Of the 570 cases with a final diagnosis of grade 1 endometrial cancer, 187 had both pelvic and aortic node dissection during the same operation, and 2/187 (1%) had a positive paraaortic node with negative pelvic nodes., Conclusions: Isolated paraaortic nodal metastasis in the setting of negative pelvic nodes occurs in approximately 1% of surgically staged endometrial cancer cases. This low rate seems consistent for low- and high-grade lesions. Future studies looking at the incidence of isolated paraaortic nodal metastasis in the setting of negative sentinel pelvic nodes are warranted.

Objective: To report a single institution experience in surgical stage I-II serous endometrial cancer using combined carboplatin/paclitaxel and intravaginal radiation (IVRT)., Methods: Between 10/00 and 12/06, 25 stage I-II patients with serous endometrial cancer were treated at our institution with surgery, postoperative IVRT, and concurrent chemotherapy (CT)., Results: The mean age was 67 years old (range, 53-80 years). Surgery consisted of hysterectomy (TAH/BSO, 64%, LAVH/BSO, 36%), peritoneal washing, omental biopsy, and pelvic lymph-node dissection (median 14 nodes). Para-aortic node sampling was done in 88% (median, 6). IVRT median dose was 21 Gy (range, 18-21 Gy, in 3 fractions) and concurrent CT consisted of carboplatin to AUC=5 and taxol to 175 mg/m(2) given every 3 weeks for 6 cycles. CT was well tolerated with 22/25 (88%) receiving 6 cycles. Three patients received

Objective: The treatment of FIGO stage IB2 cervical cancer is controversial. Our aim was to assess treatment patterns, outcomes, and complications in patients with stage IB2 cervical cancer., Methods: A retrospective study of patients with stage IB2 cervical carcinoma at a single institution between January 1982 and September 2006 was performed. To adequately control treatment variables, we only included patients who underwent their entire treatment at our institution. Toxicity was assessed using NCI Common Toxicity Criteria (CTC)., Results: We identified 82 patients, of whom 47 met the strict inclusion criteria. Of these, 27 patients (57%) underwent primary radical hysterectomy (RH) and 20 (43%) were treated with definitive radiation/chemoradiation therapy (RT/CRT). Patients selected for RT/CRT had a higher American Society of Anesthesiologist (ASA) score than those selected for surgery (P=0.037). The 3-year progression free survival rate was 52% for the RH group and 55% for the RT/CRT group (P=0.977). The 3-year overall survival rates were 72% and 55%, respectively (P=0.161). Overall, 52% of patients in the RH group received postoperative radiation therapy as part of their adjuvant treatment. CTC grade 3, 4, and 5 complications affected 5 patients (19%) in the RH group and 3 (15%) in the RT/CRT group., Conclusion: Both RH and definitive RT/CRT are adequate management strategies for patients with FIGO stage IB2 cervical cancer. However, there was a subset of patients in whom RH as monotherapy was appropriate. Further studies are needed to evaluate the role of new preoperative models that will accurately identify these patients.

Purpose: To determine the progression-free survival (PFS) and overall survival (OS) in a cohort of patients who received either platinum-based chemotherapy with or without radiation therapy (pelvic or WAI), or RT alone., Methods: Memorial Sloan-Kettering Cancer Center (MSKCC) electronic medical records from 8/1/1995 to 10/3/2007 were reviewed for patient age, diagnosis date, type of primary surgery, residual disease at the completion of primary surgery, FIGO stage, treatment details, dates of progression and death, and site(s) of first recurrence. PFS and OS by stage (I/II v III/IV) and by treatment type (chemotherapy with or without RT v RT alone) were determined using landmark analyses 8 weeks after surgery. Patients who received chemotherapy with or without RT (pelvic or abdominal) or RT alone (pelvic or abdominal) were included in the analysis. Both groups were allowed to have received intravaginal radiation therapy (IVRT)., Results: Forty-nine patients met study criteria. Thirty-eight/49 patients received chemotherapy: 23/38 (60.5%) received paclitaxel-carboplatin; 7/38 (18.4%) received ifosfamide-platinum; 8/38 (21.0%) received other chemotherapy. FIGO stage was: I=15 (31%); II=5 (10%); III=21 (43%); IV=8 (16%). Three-year PFS for the entire cohort was 24%. Three-year OS for the entire cohort was 60%. Three-year median PFS time for the entire cohort was 15 months (95% CI: 11-25 months). Three-year median OS time for the entire cohort was 67 months (95% CI: 23-89 months). Three-year PFS for stages I-II was 43% v 14% for stages III-IV (HR=1.98 [0.9-4.33]); P=0.082. Three-year OS for stages I-II was 68% v 55% for stages III-IV (HR=1.26 [0.47-3.41]); P=0.648. Three-year PFS for chemotherapy with or without RT was 35% v 9% for RT alone (HR=1.74 [0.79-3.85]); P=0.164. Three-year OS for chemotherapy with or without RT was 66% v 34% for RT alone (HR=2.02 [0.77-5.33]); P=0.146., Conclusions: Our study corroborates GOG 150 results, and shows that paclitaxel-carboplatin appears to be an efficacious adjuvant chemotherapy regimen for completely resected uterine carcinosarcoma. The role of adjuvant RT in addition to chemotherapy warrants further investigation.

Objectives: To describe the surgical and pathologic findings of fertility-sparing radical abdominal trachelectomy using a standardized surgical technique, and report the rate of post-trachelectomy adjuvant therapy that results in permanent sterility., Methods: A prospectively maintained database of all patients with FIGO stage IB1 cervical cancer admitted to the operating room for planned fertility-sparing radical abdominal trachelectomy was analyzed. Sentinel node mapping was performed via cervical injection of Technetium and blue dye., Results: Between 6/2005 and 5/2008, 22 consecutive patients with FIGO stage IB1 cervical cancer underwent laparotomy for planned fertility-sparing radical abdominal trachelectomy. Median age was 33 years (range, 23-43). Histology included 13 (59%) with adenocarcinoma and 9 (41%) with squamous carcinoma. Lymph-vascular invasion was seen in 9 (41%) cases. Only 3 (14%) needed immediate completion radical hysterectomy due to intraoperative findings (2 for positive nodes, 1 for positive endocervical margin). Median number of nodes evaluated was 23 (range, 11-44); and 6 (27%) patients had positive pelvic nodes on final pathology - all received postoperative chemoradiation. Sixteen (73%) patients agreed to participate in sentinel node mapping which yielded a detection rate of 100%, sensitivity of 83%, specificity of 100% and false-negative rate of 17%. Eighteen of 19 (95%) patients who completed trachelectomy had a cerclage placed, and 9/22 (41%) patients had no residual cervical carcinoma on final pathology. Median time in the operating room was 298 min (range, 180-425). Median estimated blood loss was 250 ml (range, 50-700), and median hospital stay was 4 days (range, 3-6). No recurrences were noted at the time of this report., Conclusions: Cervical adenocarcinoma and lymph-vascular invasion are common features of patients selected for radical abdominal trachelectomy. The majority of patients can undergo the operation successfully; however, nearly 32% of all selected cases will require hysterectomy or postoperative chemoradiation for oncologic reasons. Sentinel node mapping is useful but until lower false-negative rates are achieved total lymphadenectomy remains the gold standard. Investigating alternative fertility-sparing adjuvant therapy in node positive patients is needed., Competing Interests: statement YS has received research support from Plasma Surgical, has served as a consultant for Covidien and a speaker for Genzyme. All other authors have no conflicts of interest to declare.

Objective: To determine the impact of the decrease in use of postoperative pelvic external beam radiation (EBRT) in favor of intravaginal RT (IVRT) alone in patients with early stage endometrial cancer who had lymphovascular invasion (LVI)., Methods: Between 11/1988 and 5/2005, 126 patients treated with simple hysterectomy and postoperative RT had a final pathologic diagnosis of stage IB-IIB adenocarcinoma of endometrioid histology with documented LVI. The patients were divided into two groups based on the era of treatment, (early era: 1988-1996, vs. late era: 1997-2005), in order to best capture the shift away from the routine use of EBRT in favor of surgical staging and IVRT., Results: Of the 126 patients, 35% (n=44) were treated in the early era and 65% (n=82) in the late era. The two groups were balanced in regards to age, race, depth of myometrial invasion, histologic grade, and cervical involvement. Significantly more patients had surgical staging and received IVRT alone in the late than early era (p=0.0001, 0.004, respectively). The rate of pelvic control was 93% for the early era compared to 97% for latter era (p=0.3). There was no significant impact of the treatment era on vaginal control, disease-free survival, or overall survival., Conclusions: These data suggest that the mere presence of LVI need not trigger the use of pelvic EBRT. Instead, the decision on whether to omit EBRT in patients with LVI should be made in the context of a patient's competing risk factors and comorbid conditions.

Objectives: To describe the incidence of isolated paraaortic nodal recurrences in patients with a final diagnosis of grade 1 endometrial carcinoma initially treated with surgery., Methods: Records from a prospectively maintained endometrial carcinoma database were reviewed to identify sites of recurrence. Patients with any papillary serous or clear cell carcinoma, leiomyosarcoma, endometrial stromal sarcoma, squamous carcinoma, or adenosarcoma were excluded. Recurrence sites were classified into 4 main categories: 1) pelvic (including vaginal and other soft tissue pelvic sites); 2) abdominal (including peritoneum, omentum and liver); 3) distant (including lung, brain, supraclavicular, and groins); and 4) isolated paraaortic nodal recurrence (including any nodal recurrence between the midcommon iliac to renal vessels)., Results: Between 1/93 and 5/06, 1453 patients with endometrial carcinoma met the study inclusion criteria. Final grade distribution included: grade 1 endometrial adenocarcinoma, 310 (21%); grade 2, 578 (40%); grade 3, 481 (33%); and incomplete, 84 (5.8%). In all, 154 patients (11%) had documented recurrences. Recurrence sites for all patients/all grades included: pelvis, 52 (34%); abdomen, 51 (33%); distant, 41 (27%), and isolated paraaortic, 10 (6%). None of the isolated paraaortic recurrences occurred in patients with a final diagnosis of grade 1 carcinoma. Furthermore, 9/10 (90%) isolated paraaortic nodal recurrences were in grade 3 tumors. Only 8 (2.6%) of 310 patients with grade 1 tumors recurred. Sites of recurrence for grade 1 tumors included: abdomen, 3; pelvis, 3; and distant, 2., Conclusions: This large series of endometrial carcinoma patients initially treated with surgery confirms that isolated paraaortic nodal recurrence in women with a final diagnosis of grade 1 endometrial carcinoma is extremely rare. These rare isolated paraaortic nodal recurrences appear to be limited to high-grade endometrial carcinomas.

Objective: Over the past 12 years, the primary management of endometrial cancer at a comprehensive cancer center has undergone changes characterized by the increased use of laparoscopic surgery with comprehensive staging resulting in a decreased reliance on postoperative adjuvant whole pelvic radiation therapy (WPRT). The purpose of this study was to analyze the results of these changes., Materials and Methods: Between 1/93 and 12/04, 1312 patients underwent surgery for endometrial cancer consisting of either abdominal or laparoscopic hysterectomy/bilateral salpingo-oophorectomy (TAH/BSO or LAVH/BSO). Pelvic and para-aortic lymph node dissection was performed at the discretion of the attending physician. Postoperative adjuvant treatment employed in patients with high-risk features consisted mainly of WPRT+/-intravaginal radiation therapy (IVRT). Total direct medical charges incurred from 10 days prior to surgery through 75 days after surgery were determined with charges converted to direct medical costs, taking into account inflationary changes., Results: The median age at diagnosis for all patients was 62 years (range, 21-93 years), with a median follow-up of 31.6 months (range, 0-140 months). There was a significant increase in LAVH/BSO versus TAH/BSO (P<0.001) until 2001 when we began participating in a national randomized trial of laparoscopic versus abdominal surgery. In addition, there was a significant increase in the percentage of patients undergoing lymph node dissection as well as the median number of nodes removed (P<0.001). This was associated with a significant decrease in the use of WPRT during 1993-1998 versus 1999-2004 (P<0.001). The use of IVRT remained the same during these time periods. There was no significant difference in 1-, 2-, or 5-year survival for patients treated in either time period. Cost data were available from 1995 to 2004. There was a significant increase in the median total direct medical costs when comparing periods 1995-1998 with 1999-2004 (P<0.001), although the median cost of pelvic radiation therapy was lower in the later time period., Conclusion: Over a 12-year period, the primary management of endometrial cancer changed to include an increased use of laparoscopy and comprehensive surgical staging and a decrease in the use of postoperative adjuvant WPRT, with no appreciable negative effect on overall survival.

Purpose: To determine overall survival and progression-free survival among patients with high-risk, stage III and IV endometrial cancer who receive paclitaxel and carboplatin (TC) after complete tumor resection., Patients and Methods: Patients with stage III/IV endometrial cancer with less than 2 cm of disease after surgical resection who received TC in the adjuvant setting were retrospectively identified and are the subject of this analysis. Data were extracted from electronic medical records. Disease recurrence was documented by radiologic progression or pathologic tissue review. We obtained Institutional Review Board approval before initiating this study., Results: Forty-eight patients were eligible for analysis--24 (50%) with stage IV disease, 29 (60%) with serous or clear cell tumor histology and 43 (90%) with FIGO grade 3 tumors. All patients underwent surgical resection; 10 (21%) of the 48 patients received adjuvant radiation therapy in addition to chemotherapy. Forty-three patients (90%) received 6 cycles of paclitaxel (175 mg/m(2)) and carboplatin (area under the curve of 5-6) every 3 or 4 weeks, and 44 (92%) completed all planned cycles of treatment. With a median follow-up of 20 months (range, 6-92), 29 patients (60%) recurred, with a 3-year overall survival rate of 56%. The median time to progression for all patients was 13 months (95% CI 10, 18) with a median OS of 47 months (95% CI, 30--upper limit not achieved)., Conclusion: TC is a well tolerated, active regimen in the treatment of resected, high-risk stage III and IV endometrial cancer that warrants further investigation.

Objective: Chances of survival after the diagnosis of recurrent endometrial cancer are poor. Although total pelvic exenteration has been described as a treatment for a select subset of patients with recurrent endometrial cancer, the use of other surgical procedures in this setting has not been well described. The objective of this study was to review our experience with non-exenterative surgery for recurrent endometrial cancer., Methods: We reviewed the medical records of all patients who underwent non-exenterative surgery for recurrent endometrial cancer between 1/91 and 1/03. Survival was determined from the time of surgery for recurrence to last follow-up. Survival was estimated using Kaplan-Meier methods. Differences in survival were analyzed using the log-rank test. The Fisher's exact test was used to compare optimal versus suboptimal cytoreduction against possible predictive factors., Results: Twenty-seven patients were identified. Fifteen patients (56%) had disease limited to the retroperitoneum, 10 patients (37%) had intraperitoneal disease, and 2 patients (7%) had both intra- and retroperitoneal disease. Cytoreduction to 2 cm. There were no major perioperative complications or mortalities. The median hospital stay was 7 days (range, 1-18 days). Additional therapies included intraoperative radiation therapy in 9 patients (33%), radiation therapy in 12 patients (44%), and chemotherapy in 10 patients (37%). The median follow-up for the entire cohort was 24 months (range, 5-84 months). The median progression-free survival was 14 months (95% CI, 6-23), and the median disease-specific survival was 35 months (95% CI, 24-not reached). Size of residual disease was the only significant predictor for both progression-free and disease-specific survival. Patients with residual disease 2 cm residual (P = 0.01)., Conclusions: Surgical resection for recurrent endometrial cancer may provide an opportunity for long-term survival in a select patient population. The only factor associated with improved long-term outcome was the size of residual disease remaining at the end of surgical resection.

Objectives: To determine the incidence and prognostic implications of positive mesorectal lymph nodes in patients undergoing total pelvic exenteration for recurrent gynecologic malignancies., Methods: We performed a retrospective chart review of all patients who had undergone total pelvic exenteration for a gynecologic malignancy between July 1992 and December 2003. Patient charts were reviewed for information regarding demographics, site of cancer, histology, pathology report, and time to recurrence., Results: Fifty-eight women had undergone total pelvic exenteration for recurrent gynecologic malignancies during the study period and 57 were available for analysis. Primary cancer site was as follows: cervix, 37 (65%); vagina, 8 (14%); vulva, 5 (9%); and uterine corpus, 7 (12%). In 30 patients (53%), the mesorectal lymph node status was pathologically evaluated. Of these 30 patients, 3 (10%) had positive mesorectal lymph nodes at the time of total pelvic exenteration. All 3 patients had rectal wall involvement (rectal submucosa, 2; rectal mucosa, 1), and all 3 patients recurred within 4 months of pelvic exenteration. The median time to recurrence after surgery was 2.4 months in those patients with positive mesorectal lymph nodes compared with 7.3 months in those with negative mesorectal lymph nodes (P = 0.005). When individually adjusted for other prognostic variables, such as margin status, tumor grade, lymphovascular space involvement, primary cancer site, and histologic type, a finding of positive mesorectal lymph nodes was associated with a shorter time to recurrence of disease (all P < 0.05)., Conclusions: Mesorectal lymph node involvement is a common finding at total pelvic exenteration, particularly in patients with rectal wall involvement. Patients with positive mesorectal lymph nodes appear to have a worse outcome with a shorter time to recurrence of disease.