Adjuvant treatment improves overall survival in women with high-intermediate risk early-stage endometrial cancer with lymphovascular space invasion.

BACKGROUND: Adjuvant therapy in early-stage endometrial cancer has not shown a clear overall survival benefit, and hence, patient selection remains crucial. OBJECTIVE: To determine whether women with high-intermediate risk, early-stage endometrial cancer with lymphovascular space invasion particularly benefit from adjuvant treatment in improving oncologic outcomes. METHODS: A multi-center retrospective study was conducted in women with stage IA, IB, and II endometrial cancer with lymphovascular space invasion who met criteria for high-intermediate risk by Gynecologic Oncology Group (GOG) 99. Patients were stratified by the type of adjuvant treatment received. Clinical and pathologic features were abstracted. Progression-free and overall survival were evaluated using multivariable analysis. RESULTS: 405 patients were included with the median age of 67 years (range 27-92, IQR 59-73). 75.0% of the patients had full staging with lymphadenectomy, and 8.6% had sentinel lymph node biopsy (total 83.6%). After surgery, 24.9% of the patients underwent observation and 75.1% received adjuvant therapy, which included external beam radiation therapy (15.1%), vaginal brachytherapy (45.4%), and combined brachytherapy + chemotherapy (19.1%). Overall, adjuvant treatment resulted in improved oncologic outcomes for both 5-year progression-free survival (77.2% vs 69.6%, HR 0.55, p=0.01) and overall survival (81.5% vs 60.2%, HR 0.42, p<0.001). After adjusting for stage, grade 2/3, and age, improved progression-free survival and overall survival were observed for the following adjuvant subgroups compared with observation: external beam radiation (overall survival HR 0.47, p=0.047, progression-free survival not significant), vaginal brachytherapy (overall survival HR 0.35, p<0.001; progression-free survival HR 0.42, p=0.003), and brachytherapy + chemotherapy (overall survival HR 0.30 p=0.002; progression-free survival HR 0.35, p=0.006). Compared with vaginal brachytherapy alone, external beam radiation or the addition of chemotherapy did not further improve progression-free survival (p=0.80, p=0.65, respectively) or overall survival (p=0.47, p=0.74, respectively). CONCLUSION: Adjuvant therapy improves both progression-free survival and overall survival in women with early-stage endometrial cancer meeting high-intermediate risk criteria with lymphovascular space invasion. External beam radiation or adding chemotherapy did not confer additional survival advantage compared with vaginal brachytherapy alone.

Are Videos or Text Better for Describing Attributes in Stated-Preference Surveys?

OBJECTIVE: In stated-preference research, the conventional approach to describing study attributes is through text, often with easy-to-understand graphics. More recently, researchers have begun to present attribute descriptions and content in videos. Some experts have expressed concern regarding internalization and retention of information conveyed via video. OBJECTIVE: Our study aimed to compare respondents' understanding of attribute information provided via text versus video. METHODS: Potential respondents were randomized to receive a text or video version of the survey. In the text version, all content was provided in text format along with still graphics. In the video version, text content was interspersed with four video clips, providing the same information as the text version. In both versions, 10 questions were embedded to assess respondents' understanding of the information presented relating to ovarian cancer treatments. Half of the questions were on treatment benefits and the other half were on treatment-related risks. Some questions asked about the decision context and definitions of treatment features, and others asked about the graphic presentation of treatment features. Preferences for ovarian cancer treatments were also compared between respondents receiving text versus video versions. RESULTS: Overall, 150 respondents were recruited. Of the 95 who were eligible and completed the survey, 54 respondents received the text version and 41 received the video version. Median times to completion were 24 and 30 min in the video and text arms, respectively (p < 0.01). Both groups spent an average of 35 min completing the survey. On the first comprehension question, 43% in the text arm and 61% in the video arm provided the correct response (p = 0.08). Although the mean number of correct responses was significantly higher in the video versus text arms (9.1 vs. 8.6, p = 0.02), there were no systematic differences in preferences between arms. CONCLUSIONS: The quality of stated-preference data relies on respondents' understanding of study content. Information provided via video may better engage survey participants and improve their retention of content.

Incidence of venous thromboembolism among patients receiving neoadjuvant chemotherapy for advanced epithelial ovarian cancer.

OBJECTIVES: Neoadjuvant chemotherapy may be considered for women with epithelial ovarian cancer who have poor performance status or a disease burden not amenable to primary cytoreductive surgery. Overlap exists between indications for neoadjuvant chemotherapy and known risk factors for venous thromboembolism, including impaired mobility, increasing age, and advanced malignancy. The objective of this study was to determine the rate of venous thromboembolism among women receiving neoadjuvant chemotherapy for epithelial ovarian cancer. METHODS: A multi-institutional, observational study of patients receiving neoadjuvant chemotherapy for primary epithelial ovarian, fallopian tube, or peritoneal cancer was conducted. Primary outcome was rate of venous thromboembolism during neoadjuvant chemotherapy. Secondary outcomes included rates of venous thromboembolism at other stages of treatment (diagnosis, following interval debulking surgery, during adjuvant chemotherapy, or during treatment for recurrence) and associations between occurrence of venous thromboembolism during neoadjuvant chemotherapy, subject characteristics, and interval debulking outcomes. Venous thromboembolism was defined as deep vein thrombosis in the upper or lower extremities or in association with peripherally inserted central catheters or ports, pulmonary embolism, or concurrent deep vein thrombosis and pulmonary embolism. Both symptomatic and asymptomatic venous thromboembolism were reported. RESULTS: A total of 230 patients receiving neoadjuvant chemotherapy were included; 63 (27%) patients overall experienced a venous thromboembolism. The primary outcome of venous thromboembolism during neoadjuvant chemotherapy occurred in 16 (7.7%) patients. Of the remaining venous thromboembolism events, 22 were at diagnosis (9.6%), six post-operatively (3%), five during adjuvant chemotherapy (3%), and 14 during treatment for recurrence (12%). Patients experiencing a venous thromboembolism during neoadjuvant chemotherapy had a longer mean time to interval debulking and were less likely to undergo optimal cytoreduction (50% vs 80.2%, p=0.02). CONCLUSIONS: Patients with advanced ovarian cancer are at high risk for venous thromboembolism while receiving neoadjuvant chemotherapy. Consideration of thromboprophylaxis may be warranted.

Adjuvant therapy for early stage, endometrial cancer with lymphovascular space invasion: Is there a role for chemotherapy?

OBJECTIVES: Lymphovascular space invasion (LVSI) is an independent risk factor for recurrence and poor survival in early-stage endometrioid endometrial cancer (EEC), but optimal adjuvant treatment is unknown. We aimed to compare the survival of women with early-stage EEC with LVSI treated postoperatively with observation (OBS), radiation (RAD, external beam and/or vaginal brachytherapy), or chemotherapy (CHEMO)+/-RAD. METHODS: This was a multi-institutional, retrospective cohort study of women with stage I or II EEC with LVSI who underwent hysterectomy+/-lymphadenectomy from 2005 to 2015 and received OBS, RAD, or CHEMO+/-RAD postoperatively. Progression-free survival and overall survival were evaluated using Kaplan-Meier estimates and Cox proportional hazards models. RESULTS: In total, 478 women were included; median age was 64 years, median follow-up was 50.3 months. After surgery, 143 (30%) underwent OBS, 232 (48.5%) received RAD, and 103(21.5%) received CHEMO+/-RAD (95% of whom received RAD). Demographics were similar among groups, but those undergoing OBS had lower stage and grade. A total of 101 (21%) women recurred. Progression-free survival (PFS) was improved in both CHEMO+/-RAD (HR = 0.18, 95% CI: 0.09-0.39) and RAD (HR = 0.31, 95% CI: 0.18-0.54) groups compared to OBS, though neither adjuvant therapy was superior to the other. However, in grade 3 tumors, the CHEMO+/-RAD group had superior PFS compared to both RAD (HR 0.25; 95% CI: 0.12-0.52) and OBS cohorts (HR = 0.10, 95% CI: 0.03-0.32). Overall survival did not differ by treatment. CONCLUSIONS: In early-stage EEC with LVSI, adjuvant therapy improved PFS compared to observation alone. In those with grade 3 EEC, adjuvant chemotherapy with or without radiation improved PFS compared to observation or radiation alone.

Patient preferences for maintenance PARP inhibitor therapy in ovarian cancer treatment.

OBJECTIVE: To measure preferences of women with ovarian cancer regarding risks, side effects, costs and benefits afforded by maintenance therapy (MT) with a poly ADP ribose polymerase (PARP) inhibitor. METHODS: A discrete-choice experiment elicited preferences of women with ovarian cancer regarding 6 attributes (levels in parentheses) relevant to decisions for MT versus treatment break: (1) overall survival (OS; 36, 38, 42 months); (2) progression-free survival (PFS; 15, 17, 21 months); (3) nausea (none, mild, moderate); (4) fatigue (none, mild, moderate); (5) probability of death from myelodysplastic syndrome/acute myelogenous leukemia (MDS/AML; 0% to 10%); (6) monthly out-of-pocket cost ($0 to $1000). Participants chose between 2 variable MT scenarios and a static scenario representing treatment break, with multiple iterations. Random-parameters logit regression was applied to model choices as a function of attribute levels. RESULTS: 95 eligible participants completed the survey; mean age was 62, 48% had recurrence, and 17% were ever-PARP inhibitor users. Participants valued OS (average importance weight 24.5 out of 100) and monthly costs (24.6) most highly, followed by risk of death from MDS/AML (17.9), nausea (14.7), PFS (10.5) and fatigue (7.8). Participants would accept 5% risk of MDS/AML if treatment provided 2.2 months additional OS or 4.8 months PFS. Participants would require gains of 2.6 months PFS to accept mild treatment-related fatigue and 4.4 months to accept mild nausea. CONCLUSIONS: When considering MT, women with ovarian cancer are most motivated by gains in OS. Women expect at least 3-4 months of PFS benefit to bear mild side effects of treatment.

Patient preferences for attributes of primary surgical debulking versus neoadjuvant chemotherapy for treatment of newly diagnosed ovarian cancer.

BACKGROUND: Randomized trials have reported conflicting findings on survival for advanced-stage ovarian cancer treated with primary debulking surgery (PDS) versus neoadjuvant chemotherapy with interval debulking; surgical complications and mortality are higher with PDS. We assessed women's preferences for tradeoffs related to this important clinical decision. METHODS: Ovarian cancer patients were recruited to complete a discrete-choice experiment (DCE) consisting of 8 choice tasks presenting experimentally designed treatment alternatives in terms of treatment order, extent of surgery including risk of ostomy, chance of death from surgical complications (1%-10%), readmission for surgical complications (5%-50%), progression-free survival (1-3 years), and overall survival (3-5 years). Random-parameters logit regression was applied to model participants' choices as a function of attribute levels. RESULTS: A total of 101 ovarian cancer survivors completed the DCE survey; of these participants, 30% were receiving chemotherapy at the time, and 33% had prior recurrence. Overall survival was of greatest importance to participants (36/100), followed by risk of readmission due to complications (23/100), progression-free survival (19/100), surgical mortality (16/100), extent of surgery (4/100), and order of surgery and chemotherapy (2/100). Overall, the participants would tolerate a 15-percentage point increase in risk of major complications (95% confidence interval [CI], 3%-29%) or a 4-percentage point increase in the risk of surgical mortality (95% CI, 2%-13%) in order to increase their expected overall survival from 3 to 3.5 years. CONCLUSIONS: Patients would accept a moderately higher risk of perioperative complications and surgical mortality in exchange for substantial gains in survival. These quantitative findings provide clinicians with a framework to discuss preferences with patients and to incorporate preferences into clinical trial design.

Gender variation in Medicare utilization and payments in gynecologic oncology.

OBJECTIVES: The Medicare Provider Utilization and Payment Data: Physician and Other Supplier Public Use File (POSPUF) and Medicare Physician and Other Supplier National Provider Identifier (POS NPI) Aggregate Report are publicly available files from the Center for Medicare and Medicaid Services that include payments to providers who care for fee-for-service Medicare recipients. The aim of this study was to analyze variability in gynecologic oncologists' Medicare reimbursements, with attention to differences in provider gender and time in practice. METHODS: The 2015 POSPUF and POS NPI were analyzed with respect to gynecologic oncologists. We searched external publicly available data sources to confirm subspecialty and to determine each provider's number of years in practice. Evaluation and management (E&M) and procedure/surgery codes were analyzed; drug delivery codes were excluded due to variability in billing by facility/hospital. RESULTS: The POS NPI file included 733 gynecologic oncologist providers receiving $55,626,739 in total payments. Female providers comprised 39% of gynecologic oncologists and received 31% of reimbursements (30% of E&M reimbursements and 24% of surgical reimbursements). During the first ten years in practice, female providers comprised 58% of providers and accounted for 52% of reimbursed services, compared to 38% of providers/26% of reimbursed services (11-20 years), and 18% of providers/19% of reimbursed services (>20 years). CONCLUSION: Male gynecologic oncologists perform more Medicare services than their female counterparts. There is a comparable number of services performed between genders among both the most senior and the most junior providers, with a gender gap in services and reimbursements among mid-career providers.

Associations between lymphovascular space invasion, nodal recurrence, and survival in patients with surgical stage I endometrioid endometrial adenocarcinoma.

OBJECTIVE: To investigate the predictive value of lymphovascular space invasion (LVSI) for nodal recurrence and overall survival (OS) in patients with stage I endometrioid endometrial cancer (EC) following surgical staging that included adequate lymph node sampling. METHODS: Retrospective analyses of patients undergoing surgical staging for FIGO stage I endometrioid EC between 1998 and 2015 were performed using an institutional database and the National Cancer Database (NCDB). Using the institutional database, logistic regression modeling identified predictors of nodal recurrence; Cox proportional hazards modeling was used to predict progression-free survival (PFS). Utilizing NCDB, Cox proportional hazards modeling was used to predict OS. The Kaplan-Meier method was used to estimate hazard ratios (HR). Survival curves were compared using the log-rank test. RESULTS: Among 275 institutional cases, LVSI was present in 48 (17.5%). There were 11 nodal recurrences: 18.8% (9/48) of cases with LVSI had a nodal recurrence compared to 0.88% (2/227) of those without LVSI. In multivariate analysis of institutional data, LVSI was the only significant predictor of nodal recurrence (p = 0.002). Among 28,076 NCDB cases, LVSI was present in 3766 (13.5%). In multivariate analysis of NCDB, grade 3, LVSI, and depth of invasion (all p <  0.001) were prognostic for OS after adjusting for adjuvant radiation. CONCLUSION: LVSI is an independent prognostic factor for nodal recurrence in stage I endometrial cancer with lymph node assessment. LVSI is associated with lower OS in NCDB. Given these findings, adjuvant therapy could be considered in these patients.

A pilot study of lower extremity lymphedema, lower extremity function, and quality of life in women after minimally invasive endometrial cancer staging surgery.

OBJECTIVE: The primary aim of this study was to pilot the use of an objective measurement technique to prospectively evaluate the incidence of lower extremity lymphedema (LEL) after minimally invasive staging surgery for endometrial cancer. Secondary objectives included observation of changes in lower extremity function and quality of life in this patient population. METHODS: A prospective evaluation of LEL was performed in 97 women who underwent minimally invasive staging surgery for endometrial cancer using comparative circumferential volume measurements. Postoperative changes in lower extremity function and global quality of life were also assessed using patient-reported outcome measures. RESULTS: Ninety-seven patients were included for lymphedema analysis. The rate of LEL was 25% at 4-6 weeks, 19% at 6-9 months, and 27% at 12-18 months postoperatively. The presence of LEL was associated with a significant worsening from baseline Lower Extremity Functional Scale (LEFS) scores at 4-6 weeks (-27.0% vs -3.7%, p = 0.02) and 6-9 months (-13.0% vs 0%, p = 0.01). LEL was not associated with a change in patient-reported global quality of life. CONCLUSIONS: Up to one in four women experience lymphedema following surgical staging for endometrial cancer, and its presence is associated with diminished lower extremity function. Larger, prospective trials using the objective methodology piloted in this study should better clarify risk factors and long-term outcomes of this morbidity.

Targeted composite value-based endpoints in platinum-sensitive recurrent ovarian cancer.

OBJECTIVES: FDA-approved treatments for platinum-sensitive recurrent ovarian cancer (PSROC) include bevacizumab and PARP inhibitors (PARPi); clinical decisions regarding therapy must be made prior to initiating chemotherapy. Using the American Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO) value frameworks, we assessed relative values of concurrent/maintenance biologic therapies in PSROC. METHODS: Value scores were calculated for key maintenance therapies based on randomized controlled trials: bevacizumab (OCEANS, GOG 213); olaparib (Study 19, SOLO2); niraparib (NOVA); rucaparib (ARIEL3). Personalized value scorecards were constructed for patients with germline/somatic-BRCA mutations, homologous recombination deficiency (HRD), and wild-type BRCA (wBRCA). ASCO value scores assess clinical benefit, toxicity, long-term survival, symptom palliation, treatment-free interval, and quality of life (QOL). ESMO value scores assess clinical benefit, toxicity, and QOL. RESULTS: ASCO scores were highest for maintenance PARPi in germline/somatic-BRCA mutation cohorts: olaparib (SOLO2) = 47, (Study 19) = 62; niraparib = 50; rucaparib = 54. HRD cohorts had slightly lower scores: niraparib = 46; rucaparib = 37. wBRCA cohorts had the lowest scores: niraparib = 26; rucaparib = 26; and olaparib (Study 19) = 32, as did patients receiving bevacizumab (OCEANS) = 35, (GOG 213) = 26. ESMO scores demonstrated high-value for maintenance PARPi in germline/somatic-BRCA mutation cohorts and low-value for bevacizumab and PARPi in wBRCA cohorts. CONCLUSIONS: The value of maintenance PARPi therapy depends heavily on BRCA status, with the highest value scores in germline/somatic-BRCA mutation cohorts. Personalized value scorecards provide a visual aid to assess the harm-benefit balance of maintenance PARPi for PSROC.

Preferences of women with epithelial ovarian cancer for aspects of genetic testing.

BACKGROUND: Although genetic testing is recommended for women with epithelial ovarian cancer (EOC), little is known about patient preferences for various testing options. We measured relative preferences for attributes of testing in women with EOC referred for genetic counseling. METHODS: Subjects were recruited to participate in a discrete-choice-experiment survey to elicit preferences for attributes of genetic testing: out-of-pocket cost ($0, $100, $250, or $1000), probability of a deleterious mutation (60, 80%, or 88%), probability of a variant of uncertain significance (VUS) result (5, 20%, or 40%), sample requirements (blood or saliva), and turn-around time (1, 2 or 4 weeks). Subjects viewed educational videos followed by a series of choices between pairs of constructed genetic tests with varying attribute levels. Random-parameters logit was used to estimate preference weights for attribute levels. Relative importance weights and money-equivalent values were calculated. RESULTS: Ninety-four patients were enrolled; 68 (76.4%) presented for genetic counseling. Test cost was the most important attribute to subjects (importance weight = 41 out of 100) followed by probability to detect deleterious mutations (36) and probability of a VUS result (20). Sample requirements and turnaround time did not drive test choices. Subjects were willing to pay an additional $155 and $70 for incremental 5% improvements in the probability to detect deleterious mutations and probability of a VUS result. At genetics consultation, 55/68 (80.9%) subjects chose multigene testing. CONCLUSIONS: Low out-of-pocket cost, high probability of detecting deleterious mutations and high probability of a VUS result are preferred by patients with EOC considering genetic testing.

The association between progesterone receptor expression and survival in women with adult granulosa cell tumors.

BACKGROUND: Granulosa cell tumors (GCT) variably express estrogen receptors (ER) and progesterone receptors (PR). The goal of this study is to evaluate the relationship between ER and PR expression patterns and clinical outcomes in women with GCT. METHODS: A multicenter, retrospective analysis was performed of all cases of GCT diagnosed between 1989 and 2012. Immunohistochemical staining for ER and PR was performed on formalin-fixed paraffin embedded (FFPE) tumor tissue and interpreted using a semiquantitative scoring system that incorporated tumor cell staining proportion and intensity. Demographics, disease status, and survival information were collected. Associations between ER and PR staining scores and recurrence-free and overall survival were assessed using univariate Cox proportional hazards models. RESULTS: FFPE tumor blocks were available for 149/186 GCT patients. The majority of the women had clinical stage I disease (76%). ER and PR expression was present in 52% and 98% of subjects, respectively. The median composite scores of ER and PR staining were 1 (range 0-8) and 9 (range 0-15), respectively. In univariate analysis, PR composite score >9 was strongly associated with decreased recurrence-free survival (HR = 2.9, 95% CI = 1.5-5.5) and decreased overall survival (HR = 3.7, CI 1.3-10.2). ER composite score was not a significant predictor of recurrence-free survival or overall survival (p = 0.7, HR = 1.1, 95% CI 0.6-2.0 and p = 0.06, HR = 1.1, 95% CI 0.4-2.9, respectively). CONCLUSIONS: Our results reveal that high PR composite score (≥9) was associated with both decreased recurrence-free and overall survival in patients with GCT while ER expression was not associated with survival outcomes.

Safety and feasibility of contained uterine morcellation in women undergoing laparoscopic hysterectomy.

BACKGROUND: Widespread concerns have been raised regarding the safety of power morcellation of uterine specimens because of the potential to disseminate occult malignancy. We sought to assess the safety and feasibility of contained manual uterine morcellation within a plastic specimen bag among women with uterine neoplasms. METHODS: A retrospective single-institution descriptive cohort study was conducted from 2003 to 2014. Patients with leiomyoma and/or uterine malignancy who underwent minimally invasive surgery with contained uterine manual morcellation were identified from surgical logs. Demographic data, pathology results, operative details and adjuvant treatments were abstracted. RESULTS: Eighty-eight patients were identified; 35 with leiomyoma and 53 with endometrial cancer. The mean age was 48 and 60, respectively. Uterine size/weight was greater in women with leiomyoma compared to those with cancer (15.1 weeks/448 g vs. 10.7 weeks/322 g). Mean operative time was 206 min (range 115-391) for leiomyoma cases and 238 min (range 131-399) for cancer cases. Median length of stay was 1 day (range 0-3 days). There were no cases of occult leiomyosarcoma and all specimens were successfully manually morcellated within a bag. There were no intraoperative complications. Thirty-day postoperative complications occurred in 7 patients, including one readmission for grade (G) 1 vaginal cuff separation after intercourse, G1 port-site hematoma (1), G2 port-site cellulitis (1), G2 vaginal cuff cellulitis (2), G2 bladder infection (2), G2 pulmonary edema (1), and G1 musculoskeletal injury (1). CONCLUSIONS: Contained uterine hand morcellation is a feasible procedure with low peri-operative complication rates that allows for minimally invasive surgical procedures for women with large uterine neoplasms. Further evaluation is needed to assess survival outcomes for uterine malignancies.

Prospective Evaluation of Lymph Node Processing at Staging Surgery for High-grade Endometrial Cancer.

To determine whether the processing of additional adipose tissue collected during lymph node (LN) dissection results in the identification of additional LNs during endometrial cancer (EC) staging and to determine if the division of LNs into nodal basin-specific specimens has an effect on the number of LNs identified during EC staging. A prospective randomized controlled trial was performed on women with high-grade EC undergoing surgical staging. Subjects were randomized to collection of LNs into nodal basin-specific containers on the randomized side versus simple labeling on the nonrandomized side. The total number of LNs and total number of LNs with metastases on the randomized versus the nonrandomized side were compared. The remaining adipose tissue from each LN specimen was submitted for histologic examination. We analyzed the number of LNs with and without metastases identified from additional adipose tissue. Of 120 consented subjects, 56 had sufficient data for analysis. The additional adipose tissue contained 7.5 additional LNs per patient on average (range: 0-26). In 2/54 total cases (3.7%) and 2/5 cases with nodal metastases (40%), the additional adipose contained LNs with metastases. In both cases, metastases were also detected in grossly identified LN candidates. The mean number of LNs identified was not significantly different based on method of collection (P=0.22). The mean number of LNs containing metastases per side was not significantly different (P=0.58). Processing of adipose tissue does increase the total number of LNs identified, however, it does not influence EC stage. No difference in LN counts was noted with basin-specific collection.

Multidisciplinary approach to manage antenatally suspected placenta percreta: updated algorithm and patient outcomes.

BACKGROUND: Due to the significant morbidity and mortality associated with placenta percreta, alternative management options are needed. Beginning in 2005, our institution implemented a multidisciplinary strategy to patients with suspected placenta percreta. The purpose of this study is to present our current strategy, maternal morbidity and outcomes of patients treated by our approach. METHODS: From 2005 to 2014, a retrospective cohort study of patients with suspected placenta percreta at an academic tertiary care institution was performed. Treatment modalities included immediate hysterectomy at the time of cesarean section (CHYS), planned delayed hysterectomy (interval hysterectomy 6 weeks after delivery) (DH), and fertility sparing (uterine conservation) (FS). Prognostic factors of maternal morbidity were identified from medical records. Complications directly related to interventional procedures and DH was recorded. Descriptive statistics were utilized. RESULTS: Of the 21 patients with suspected placenta percreta, 7 underwent CHYS, 13 underwent DH, and 1 had FS with uterine preservation. Of the 20 cases that underwent hysterectomy, final pathology showed 11 increta, 7 percreta, and 2 inconclusive. 19/20 cases underwent interventional radiology (IR) procedures. Selective embolization was utilized in 14 cases (2/7 CHYS; 12/13 DH). The median time from cesarean section (CS) to DH was 41 [26-68] days. There were no cases of emergent hysterectomy, delayed hemorrhage, or sepsis in the DH group. Both estimated blood loss and number of packed red blood cell transfusions were significantly higher in the CHYS group. 3/21 cases required massive transfusion (2 CHYS, 1 FS) with median total blood product transfusion of 13 units [12-15]. The four IR-related complications occurred in the DH group. Incidence of postoperative complications was similar between both groups. Median hospital length of stay (LOS) after CHYS was 4 days [3-8] compared to DH cohort: 7 days [3-33] after CS and 4 days [1 -10] after DH. The DH cohort had a higher rate of hospital readmission of 54% (7/13) compared to 14% (1/7) CHYS, most commonly due to pain. There were no maternal deaths. CONCLUSION: This multidisciplinary strategy may appear feasible; however, further investigation is warranted to evaluate the effectiveness of alternative approaches to cesarean hysterectomy in cases of morbidly adherent placenta.

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

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

Tumor grade and chemotherapy response in endometrioid endometrial cancer.

The objective of this study is to evaluate the association between tumor grade and response to chemotherapy in patients with endometrioid endometrial adenocarcinoma. Patients with advanced or recurrent endometrioid endometrial adenocarcinoma of known tumor grade who received at least 3 cycles of chemotherapy were retrospectively identified at three institutions. RECIST 1.1 criteria were used to assess response to neoadjuvant, postoperative or salvage chemotherapy. Chi-square testing was used to evaluate the association between tumor grade and chemotherapy response. Ninety-one patients met inclusion criteria: 13 with grade 1, 29 with grade 2 and 49 with grade 3 tumors. Eighty-four percent of patients received chemotherapy for recurrence, 12% for postoperative residual disease, and 4% in the neoadjuvant setting. The majority (85%) received carboplatin and paclitaxel. Forty-six percent (6/13) of grade 1, 72% (21/29) of grade 2 and 43% (21/49) of grade 3 tumors achieved an objective response. Grade 2 tumors were more likely to respond to chemotherapy compared to grade 3 tumors (72% vs. 43%, p = 0.02; Table 2), and specifically more likely to respond to carboplatin/paclitaxel (72% vs. 41%, p = 0.016). Median progression-free survival for patients receiving chemotherapy for recurrence or progression was 9 months for grade 1, 8 months for grade 2, and 5 months for grade 3 tumors. Similar results between grade and treatment response were apparent in the subset of 37 patients with a recently re-assigned tumor grade (G2 88% vs. G3 44%, p = 0.032). In this series of endometrioid endometrial cancers, grade 2 tumors had the best measurable response to chemotherapy.

Impact of postoperative nausea and vomiting prophylaxis with dexamethasone on the risk of recurrence of endometrial cancer.

OBJECTIVE: To assess whether antiemetic doses of dexamethasone are associated with an increased risk of cancer recurrence in women who underwent surgery for endometrial cancer. RESEARCH DESIGN AND METHODS: This is a retrospective study at an academic university medical center. Women who underwent surgery for endometrial cancer from 2003 to 2007 were identified from a prospectively collected endometrial cancer database. Perioperative records were reviewed to determine administration of dexamethasone. Patients were divided into two groups: those who received dexamethasone 4-10 mg for postoperative nausea and vomiting prophylaxis and those who did not receive dexamethasone. We collected information on patient demographics, cancer stage, cancer grade, histology, year of surgery, chemotherapy, radiation therapy, duration of surgery, perioperative blood transfusion, receipt of epidural analgesia, dose of dexamethasone given, follow-up time, and co-morbidities. MAIN OUTCOME MEASURES: Primary endpoint was recurrence-free survival. Secondary endpoints included progression-free survival and overall survival. RESULTS: Three hundred and nine patients were included in the analysis. There were no significant differences between dexamethasone exposed (n = 107) and non-exposed patients in recurrence-free survival ([5 year estimate (95% CI)] = 71 (62-82) % vs. 71 (64-78) %, p = 1.0), progression-free survival (57 [47-68] % vs. 60 [53-68] %, p = 0.9), or overall survival (68 [59-79] % vs. 71 [64-79] %, p = 1.0). In univariate analysis, significant predictors of recurrence-free survival were tumor stage (p = 0.02), tumor grade (0.003) and receipt of adjuvant chemotherapy (p < 0.001). In the multivariable model, higher tumor grade (hazard ratio [HR] [95% CI] = 2.3 [1.4-3.9], p = 0.002) and receipt of adjuvant chemotherapy (3.2 [1.8-5.8], p < 0.001), but not dexamethasone (0.9 [0.5-1.5], p = 0.7), were significant predictors of recurrence-free survival. CONCLUSIONS: Dexamethasone administration was not associated with an increased risk of recurrence in women having surgery for endometrial cancer. Limitations of the study include its retrospective single center design and the fact that administration of dexamethasone was not randomized.

Lumbee Native American ancestry and the incidence of aggressive histologic subtypes of endometrial cancer.

OBJECTIVE: The Lumbee Indian tribe is the largest Native American tribe in North Carolina, with about 55,000 enrolled members who mostly reside in southeastern counties. We evaluated whether Lumbee heritage is associated with high-risk histologic subtypes of endometrial cancer. METHODS: We retrospectively analyzed the available records from IRB-approved endometrial cancer databases at two institutions of patients of Lumbee descent (year of diagnosis range 1980-2014). Each Lumbee case was matched by age, year of diagnosis, and BMI to two non-Lumbee controls. Chi-square test was used to compare categorical associations. Kaplan-Meier methods and log-rank test were used to display and compare disease-free survival (DFS) and overall survival (OS). Multivariate Cox proportional hazards regression was used to adjust for age and BMI while testing cohort as a predictor of DFS and OS. RESULTS: Among 108 subjects, 10/35 (29%) Lumbee and 19/72 (26%) non-Lumbee subjects had high-risk (serous/clear cell/carcinosarcoma) histologic types (p = 0.8). 12/35 (34%) Lumbee and 24/72 (33%) non-Lumbee subjects had grade 3 tumors (p = 0.9). 5/33 (15%) Lumbee and 13/72 (18%) non-Lumbee had advanced stage endometrial cancer at diagnosis (p = 0.7). Lumbee ancestry was not associated with worse survival outcomes. OS (p = 0.054) and DFS (p = 0.01) were both worse in Blacks compared to Lumbee and White subjects. CONCLUSION: In this retrospective cohort analysis, Lumbee Native American ancestry was not a significant independent predictor of rates of high-risk histological subtypes of endometrial cancer or poor survival outcomes.

Postoperative Pain Scores and Narcotic Use in Robotic-assisted Versus Laparoscopic Hysterectomy for Endometrial Cancer Staging.

STUDY OBJECTIVE: To retrospectively evaluate perioperative pain and analgesic and antiemetic use in patients who underwent surgical staging for endometrial cancer using traditional versus robotic-assisted laparoscopy. DESIGN: We identified women in a single institution who underwent minimally hysterectomy for endometrial cancer from 2008 to 2012. Patient characteristics and perioperative outcomes, including analgesic and antiemetic use and pain scores, were analyzed. After univariate analysis, a multivariate linear regression model was generated to determine factors associated with narcotic use in the post anesthesia care unit (PACU) (Canadian Task Force Classification II-3). SETTING: A single academic institution in the United States from 2008 to 2012. PATIENTS: Women undergoing total laparoscopic hysterectomy or robotic-assisted laparoscopic hysterectomy for endometrial cancer. INTERVENTIONS: Laparoscopic or robotic-assisted laparoscopic hysterectomy. MEASUREMENTS AND MAIN RESULTS: Three hundred thirty-five women were included (213 laparoscopy and 122 robotic-assisted laparoscopy). There was no difference in pain scores at 0 to 6 and 6 to 12 hours after surgery; at 12 to 24 hours, robotic-assisted surgery was associated with higher median pain scores (5/10 vs 4/10, p = .012). Robotic-assisted surgery was associated with a longer anesthesia time (289 vs 255 minutes, p < .001), similar antiemetic use (p = .40), and lower narcotic use in the postanesthesia care unit (PACU) (1.3 mg vs 2.5 mg morphine equivalents, p = .003). There was no difference in narcotic use on the postoperative floor (p = .46). In multivariate analysis controlling for age, menopausal status, anesthesia duration, and local anesthetic use, hysterectomy type was not a significant predictor of PACU narcotic use (p = .86). CONCLUSIONS: In a retrospective analysis, a robotic-assisted approach to endometrial cancer was not associated with reduced PACU narcotic or antiemetic use compared with the traditional laparoscopic approach. Twenty-four-hour narcotic and antiemetic use was also not different between the 2 approaches.