Endometrial cancer: A society of gynecologic oncology evidence-based review and recommendations, part II.

In 2014, the Society of Gynecologic Oncology's Clinical Practice Committee published a clinical update reviewing the treatment of women with endometrial cancer. At that time, there had been significant advances in the diagnosis, work-up, surgical management, and available treatment options allowing for more optimal care of affected women. This manuscript, Part II in a two-part series, includes specific recommendations on treatment of recurrent disease, post treatment surveillance and survivorship, considerations for younger women, and special situations. Part I covered histopathology and molecular pathology, risk factors, presentation and diagnostic approach, surgical approach and adjuvant therapy.

Endometrial cancer: A society of gynecologic oncology evidence-based review and recommendations.

INTRODUCTION: In 2014, the Society of Gynecologic Oncology's Clinical Practice Committee published a clinical update reviewing the treatment of women with endometrial cancer. At that time, there had been significant advances in the diagnosis, work-up, surgical management, and available treatment options allowing for more optimal care of affected women. Despite these advances, the incidence of endometrial cancer as well as the deaths attributable to the disease have continued to rise; from 1987 to 2014 there has been a 75% increase in cases and almost 300% increase in endometrial cancer deaths. Fortunately, since then, there has been progress in the treatment of patients with endometrial cancer with increased utilization of molecular pathology, greater understanding of genetic predisposition, enhanced methods for lymph node assessment, a broader understanding of the efficacy of radiation and chemotherapy, and a more efficient approach to survivorship and surveillance. The purpose of this document is to present a comprehensive review of this progress. MANUSCRIPT DEVELOPMENT PROCESS: The authors reviewed the available evidence, contributed to the development of this manuscript, provided critical review of the guidelines, and finalized the manuscript recommendations. The review was also presented to and approved by the Society of Gynecologic Oncology (SGO) Clinical Practice Committee, SGO Publications Committee, and the SGO board members prior to submission for publication. The recommendations for this manuscript were developed by a panel of gynecologic oncologists who were members of the SGO Clinical Practice and Education Committees. Panelists reviewed and considered evidence from current uterine cancer literature. The terminology used in these guidelines was adopted from the ASCCP management guidelines [1] using a two-part rating system to grade the strength of recommendation and quality of evidence (Table 1). The rating for each recommendation is given in parentheses.

The risk of female-specific cancer after bariatric surgery in the state of New York.

BACKGROUND: Obesity is a known risk factor for many cancers. Although bariatric surgery has been associated with a decrease in the risk of developing cancer, data on the effect of bariatric surgery on female-specific cancers are limited. This study aimed to assess the impact of bariatric interventions on the development of endometrial, ovarian and breast cancer. METHODS: The New York Statewide Planning and Research Cooperative System database was used to identify all female patients without a pre-existing cancer diagnosis who had a diagnosis of obesity between 2006 and 2012. The risk of having female-specific cancer diagnosis in patients who underwent bariatric surgery were compared with those who had no bariatric interventions using multivariable proportional sub-distribution hazard regression analysis. Subsequent cancer diagnoses were followed up to 2016. RESULTS: We identified 55,781 and 247,102 obese female patients who had and did not have bariatric surgery, respectively. The overall incidence of female-specific cancer was 2.69% and 2.09% for the non-surgery and surgery groups, respectively (p < 0.0001). Surgery patients were less likely to develop female-specific cancers [hazard ratio (HR) 0.78; 95% CI 0.73-0.83; p < 0.0001]. Patients undergoing Roux-en-Y gastric bypass had a lower risk of developing female-specific cancer than laparoscopic sleeve gastrectomy (HR 0.66; 95% CI 0.51-0.87; p = 0.0056) and laparoscopic adjustable gastric banding (HR 0.83; 95% CI 0.69-0.99; p = 0.0056) patients. CONCLUSIONS: Patients undergoing bariatric surgery have a lower incidence of endometrial, female breast and ovarian cancer than non-surgery obese patients. These data suggest that bariatric interventions may reduce the risk of female-specific cancers.

5-HT does not lower blood pressure in the 5-HT7 knockout rat.

The fall in mean arterial pressure (MAP) after 24 h of 5-HT infusion is associated with a dilation of the portal vein (PV) and abdominal inferior vena cava (Ab IVC); all events were blocked by the selective 5-HT7 receptor antagonist SB269970. Few studies have investigated the contribution of the 5-HT7 receptor in long-term cardiovascular control, and this requires an understanding of the chronic activation of the receptor. Using the newly created 5-HT7 receptor knockout (KO) rat, we presently test the hypothesis that continuous activation of the 5-HT7 receptor by 5-HT is necessary for the chronic (1 wk) depressor response and splanchnic venodilation. We also address if the 5-HT7 receptor contributes to endogenous cardiovascular regulation. Conscious MAP (radiotelemeter), splanchnic vessel diameter (ultrasound), and cardiac function (echocardiogram) were measured in ambulatory rats during multiday 5-HT infusion (25 µg·kg-1·min-1 via minipump) and after pump removal. 5-HT infusion reduced MAP and caused splanchnic venodilation of wild-type (WT) but not KO rats at any time point. The efficacy of 5-HT-induced contraction was elevated in the isolated abdominal inferior vena cava from the KO compared with WT rats, supporting loss of a relaxant receptor. Similarly, the efficacy of 5-HT causing an acute pressor response to higher doses of 5-HT in vivo was also increased in the KO vs. WT rat. Our work supports a novel mechanism for the cardiovascular effects of 5-HT, activation of 5-HT7 receptors mediating venodilation in the splanchnic circulation, which could prove useful in the treatment of cardiovascular disease.

Patterns of care and outcomes for women with uterine cancer and ovarian metastases.

OBJECTIVE: For women with uterine cancer with metastases isolated to the adnexa (stage IIIA) optimal adjuvant therapy is unknown. We performed a population-based analysis to examine the use of chemotherapy, vaginal brachytherapy, and external beam therapy (in women with stage IIIA uterine cancer. METHODS: The National Cancer Database was used to identify women with stage IIIA uterine cancer with ovarian metastasis from 2004 to 2012. We explored the use of chemotherapy, vaginal brachytherapy, and external beam therapy over time. Multivariable models were developed to examine factors associated with survival. RESULTS: We identified 4088 women with uterine cancer and ovarian metastases. Overall, 56.2% of women received chemotherapy. Vaginal brachytherapy was used in 11.1%, while 36.6% received external beam therapy. Five-year survival was 64.7 % (95% CI, 62.9% to 66.5%). In a multivariable model, chemotherapy was associated with a 38% decrease in mortality (HR = 0.62; 95% CI, 0.54 to 0.71). Similarly, both external beam therapy (HR = 0.74; 95% CI, 0.65 to 0.85) and vaginal brachytherapy (HR = 0.67; 95% CI, 0.53 to 0.85) were associated with improved survival. When the cohort was limited to women who received chemotherapy, radiation was associated with improved overall survival (HR 0.74, 95% CI 0.61 to 0.90). There was no difference in survival between the use of external beam therapy and vaginal brachytherapy. CONCLUSIONS: Chemotherapy was associated with a decrease in mortality in women with endometrial cancer and ovarian metastases. The addition of radiation therapy was associated with improved overall survival, although there was no difference between external beam therapy and vaginal brachytherapy.

Patient reported outcomes in evaluation of chemotherapy toxicity in women with gynecologic malignancies: A pilot study.

OBJECTIVE: Patient reported outcomes (PRO) relating to treatment toxicities have been demonstrated to reliably evaluate adverse events in clinical trials. We assessed the user satisfaction of implementing a focused PRO questionnaire for patients with gynecologic cancers undergoing chemotherapy. METHODS: Patients with gynecologic cancers undergoing chemotherapy were prospectively identified after IRB approval from April 2017 to August 2017. We administered a 24-symptom questionnaire, adapted from the validated PRO version of the Common Terminology Criteria for Adverse Event, to enrolled participants at the beginning of two outpatient visits. Patient and provider satisfaction with use of PRO was assessed afterwards. Descriptive statistics were performed. RESULTS: A total of 44 patients were enrolled. Patients were racially diverse: 52% Caucasian, 18% African-American, 9% Asian, and 20% other; 27% were of Hispanic origin. The majority of patients had ovarian cancer (54%), followed by uterine (29%) and cervical cancer (15%). Ninety-five percent of patient and 97% of provider satisfaction survey responses indicated the PRO questionnaire addressed important symptoms. Nearly all patient and provider responses indicated the PRO questionnaire was easy to use. Sixty-nine percent of patient and 97% of provider responses indicated the questionnaire positively impacted clinical care; 85% of patients wished to use a similar questionnaire throughout treatment. CONCLUSIONS: We have shown that incorporating a focused patient-reported symptom questionnaire into routine outpatient care of gynecological oncology patients undergoing chemotherapy was met with a high degree of patient and provider satisfaction regarding questionnaire content, feasibility, and perception of care improvement.

Adherence to treatment recommendations and outcomes for women with ovarian cancer at first recurrence.

OBJECTIVE: Treatment selection for recurrent ovarian cancer is typically based on the duration of time between the completion of adjuvant, platinum-based therapy and the time of recurrence, the platinum free interval (PFI). We examined the use of, and outcomes associated with platinum-based chemotherapy based on the PFI in women with recurrent ovarian cancer. METHODS: The Surveillance, Epidemiology, and End Results-Medicare database was used to identify women aged >65years with epithelial ovarian cancer who underwent surgery and platinum-based chemotherapy and who developed a recurrence >3months after the completion of adjuvant therapy. Patients were stratified by PFI into 3 groups: PFI <6months, PFI 7-12months, and PFI >12months. Multivariable models were used to examine predictors of use of platinum-based therapy and survival for each group. RESULTS: A total of 2369 patients were identified. In women with a PFI of ≤6months, treatment consisted of platinum-based combination therapy in 28.2%, single agent platinum in 5.2% and non-platinum therapy in 66.6%. Corresponding rates of these treatments among women with a PFI of 7-12months were 39.7%, 12.4% and 47.9%, respectively; the rates were 57.6%, 13.2% and 29.3% in those with a PFI of >12months, respectively. Median survival was 13, 18, and 27months for patients with a PFI of ≤6months, 7-12months, and >12months, respectively (P<0.0001). For all three groups, platinum combination therapy was associated with decreased risk of death compared to non­platinum based therapy. CONCLUSION: Platinum free interval is a strong predictor of survival in elderly women with recurrent ovarian cancer. There is widespread variation in treatment selection for women with recurrent ovarian cancer with many women receiving non-guideline based regimens.

National Trends in Extended Procedures for Ovarian Cancer Debulking Surgery.

OBJECTIVE: Primary cytoreduction for ovarian cancer often requires extended radical procedures and is associated with significant morbidity. In 2010, neoadjuvant chemotherapy was shown to have similar survival to primary cytoreduction but with less need for radical surgery. We hypothesized that the increased use of neoadjuvant chemotherapy would decrease the use of radical cytoreductive procedures and thus examined trends in the performance of radical cytoreductive procedures. METHODS: We used the Nationwide Inpatient Sample to determine the annual number of extended procedures (colon, small intestine, liver, diaphragm, spleen, and gastric resection, ileostomy, colostomy) performed in women undergoing surgery for ovarian cancer from 1998 to 2013. Estimates were weighted to provide national averages. To account for changes in incidence over time, we used national incidence rates and report procedures performed per 1000 new cases of ovarian cancer. Trends were assessed using Cochrane-Armitage tests. RESULTS: We identified 274,639 ovarian cancer patients who underwent surgery, ranging from 15,720 to 18,714 procedures performed each year. We identified a significant increase in the use of extended procedures over this period. These differences were significant for absolute numbers of procedures, rate per 1000 new ovarian cancer cases, and percent per hysterectomy/bilateral salpingoophorectomy for rectosigmoid resection, diaphragm resection, splenectomy, ileostomy, and liver resection. Specifically, the use of these procedures rose from 1998 to 2010, declined in 2011, and rose again in 2012 and 2013. CONCLUSIONS: Although there was a transient decrease in the use of extended cytoreductive procedures from 2010 to 2011 after the publication of randomized neoadjuvant trial data, use of these procedures again rose in 2012 and 2013.

Unsuspected Uterine Sarcoma in an Urban Hospital: Does Surgical Approach Matter?

STUDY OBJECTIVE: To compare the incidence of unsuspected uterine sarcoma based on surgical approach, open versus minimally invasive, for myomectomy and hysterectomy. DESIGN: Retrospective chart review of demographic data, preoperative characteristics, operative details, and pathology results from the electronic medical record (Canadian Task Force classification II-3). SETTING: A large, urban, academic medical center. PATIENTS: All women undergoing myomectomy or hysterectomy performed for a benign indication via a benign gynecologic surgical procedure between 2010 and 2014. MEASUREMENTS AND MAIN RESULTS: A total of 1959 myomectomies and hysterectomies were performed, among which 4 unsuspected uterine sarcomas were identified, for an incidence of 2.0 per 1000 cases. The incidence of sarcoma was similar in patients undergoing open abdominal surgery and those undergoing minimally invasive surgery (MIS) (3 in 743 [0.40%] vs. 1 in 1216 [0.08%]; p = .16). The mean age, body mass index, and specimen weights were also similar in the 2 groups. Although more than one-quarter of all cases involved morcellation, the majority via power morcellation, no specimens with sarcoma were morcellated. CONCLUSION: The incidence of unsuspected uterine sarcoma during myomectomy or hysterectomy for benign indications is low at our institution, and is similar for open and MIS cases. Patients should be counseled on the risks and benefits of both open surgery and MIS approaches.

Distinct molecular landscapes between endometrioid and nonendometrioid uterine carcinomas.

Endometrial carcinoma (EC) is traditionally characterized as endometrioid and nonendometrioid based on histopathologic phenotypes. Molecular-based classifications have been proposed, but are not widely implemented. Herein we examine molecular profiles between EC histologic subtypes. 3133 ECs were submitted between March 2011 and July 2014: 1634 Type I and 1226 Type II. In situ hybridization and immunohistochemistry were used to assess copy number and protein expression of selected genes. Sequenced variants in 47 genes were analyzed using the Illumina TruSeq Amplicon Cancer Panel. Type II EC included 628 cases of uterine serous cancer (USC), 136 cases of clear cell (CC), 361 cases of carcinosarcoma (CS), 38 cases of mucinous, and 36 cases of squamous cell. PI3K/Akt/mTOR pathway was most frequently dysregulated within Type I and mucinous histologies, least altered in CS and squamous. PD-L1 expression was highest in mucinous, absent in squamous. ER/PR expression was common in Type II, most frequent in USC, mucinous, and squamous. Receptor tyrosine kinase was frequently dysregulated in Type II disease: HER2 amplification highest in USC and CC, EGFR mutations exclusively seen in mucinous EC, KRAS mutations common in mucinous, squamous, and Type I, and c-MET overexpression high in CC and mucinous. BRCA1 and BRCA2 were most frequently mutated in CS. Grade 3 EC shares features of G1 tumor and Type II disease, most notably resembling CS. Endometrial carcinomas are a molecularly heterogeneous group of tumors. A histology-based molecular map can identify rational targets to optimize treatment and guide future clinical trials.

Vulvar and vaginal melanoma: A unique subclass of mucosal melanoma based on a comprehensive molecular analysis of 51 cases compared with 2253 cases of nongynecologic melanoma.

BACKGROUND: Optimal treatments for vulvar and vaginal melanomas (VVMs) have not been identified. Herein, the authors compare molecular profiles between VVM and nongynecologic melanoma (NGM) subtypes with the objective of identifying novel, targetable biomarkers. METHODS: In total, 2304 samples of malignant melanoma that were submitted to Caris Life Sciences between 2009 and 2015 were reviewed. In situ hybridization and immunohistochemistry were used to assess copy numbers and protein expression of selected genes. Sequenced variants were analyzed using a proprietary cancer panel. RESULTS: In total, 51 VVMs (14 vaginal and 37 vulvar melanomas) were compared with 2253 malignant NGMs, including 2127 cutaneous, 105 mucosal, and 21 acral melanomas. In VVMs, B-Raf proto-oncogene serine/threonine kinase (BRAF) was the most frequently mutated gene (26%) compared with 8.3% of mucosal NGMs (P = .008). In BRAF-mutated tumors, fewer VVMs (50%), compared with NGMs (82.1%), had a variant within the valine codon 600 (V600) domain. The KIT mutation rate was highest in VVMs (22%) compared with 3% in cutaneous (P < .001) and 8.8% in mucosal (P = .05) melanoma subtypes. NRAS mutations were rare in VVMs compared with cutaneous (25.9%; P = .009) and acral (40.6%; P = .002) melanoma subtypes. PD-L1 (56%) and PD-1 (75%) were frequently expressed in VVM, whereas PI3KCA pathway mutations and estrogen receptor/progesterone receptor expression were rare. Compared with VVMs that had KIT mutations, wild-type KIT VVMs were more likely to express molecular markers suggestive of platinum resistance (ERCC1), alkylating sensitivity (MGMT), and anthracycline sensitivity (TOP2A). CONCLUSIONS: The unique molecular features of VVM render this disease a distinct subtype of melanoma. Gene-based molecular therapy and immunotherapies may be promising and should be evaluated in clinical trials. Cancer 2017;123:1333-1344. © 2016 American Cancer Society.

Physicians' Perspectives and Practice Patterns Toward Opportunistic Salpingectomy in High- and Low-Risk Women.

BACKGROUND: Opportunistic bilateral salpingectomy (OBS) has been proposed as an ovarian cancer risk-reducing strategy. METHODS: A survey was emailed to 300 members of the American College of Obstetricians and Gynecologists. RESULTS: 125 (42%) surveys were returned: 60% female, 88% generalists, 67% private practice. Only 36% correctly identified the lifetime risk of ovarian cancer, only 23% understood the risk-reducing benefit of bilateral salpingo-oophorectomy. 75% perform salpingectomy during hysterectomy, 26-53% use for sterilization depending on approach. Concerns were increased operative time and complications. For BRCA mutations, 64% recommend BSO, 12% recommend a two-step risk-reducing strategy, and 14% refer to gynecologic oncology. CONCLUSIONS: We identified broad support and factors limiting willingness to perform OBS.

Utility of radiation therapy for early-stage uterine papillary serous carcinoma.

OBJECTIVE: Early-stage uterine papillary serous carcinoma (UPSC) has a poor prognosis and high recurrence rate. While adjuvant chemotherapy is generally recommended, the role of radiation is uncertain. We examined the association between vaginal brachytherapy and whole pelvic radiation and survival in women treated with and without adjuvant chemotherapy. METHODS: The National Cancer Data Base was used to identify women with stage I-II UPSC treated between 1998 and 2012. Trends in use of chemotherapy, brachytherapy, and external beam radiation over time were examined. The association between these treatments and mortality were examined using multivariable Cox proportional hazards models. RESULTS: A total of 7325 patients were identified. Overall, 2779 (37.9%) received chemotherapy. The use of vaginal brachytherapy increased from 7.2% in 1998 to 29.1% in 2012 (P<0.0001), while use of external beam radiation decreased from 18.2% to 11.7% over the same period (P<0.0001). Use of chemotherapy was associated with a 22% reduction in mortality (HR=0.78; 95% CI, 0.69-0.88). While brachytherapy was associated with decreased mortality (HR=0.67; 95% CI, 0.57-0.78), use of external beam radiation was not associated with survival (HR=1.03; 95% CI, 0.92-1.17). Stratified by stage, use of chemotherapy was associated with decreased mortality for women with stage IB and II tumors, but not for stage IA neoplasms. Vaginal brachytherapy was associated with reduced mortality for stage IA and II neoplasms. CONCLUSION: For women with early-stage UPSC, chemotherapy is associated with improved survival. Vaginal brachytherapy was also associated with improved survival, however, there was little benefit to use of external beam radiation.

All-cause mortality in young women with endometrial cancer receiving progesterone therapy.

BACKGROUND: Uterine-preserving therapy with progesterone may be used in young women with endometrial cancer who desire fertility preservation. Such therapy delays definitive treatment with hysterectomy. OBJECTIVE: We examined the use and safety of progestational therapy in young women with endometrial cancer. The primary outcome of the analysis was overall survival. STUDY DESIGN: We identified women ≤49 years of age with stage I endometrial cancer in the National Cancer Database from 2004 through 2014. Women treated with hormonal therapy with or without hysterectomy were compared to women treated with hysterectomy. After propensity score weighting, overall survival was examined using proportional hazards models. RESULTS: A total of 23,231 patients, including 872 (3.8%) women treated with hormonal therapy were identified. Use of hormonal therapy was 2.4% (95% confidence interval, 1.8-3.3%) in 2004 and increased over time to 5.9% (95% confidence interval, 5.0-6.9%) by 2014 (P < .0001). Use of hormonal therapy decreased with older age, higher substage, and increasing grade. Black women were more likely to receive hormonal therapy while Medicaid recipients were less likely to receive hormonal therapy. The 5-year survival for patients treated with hormonal therapy was 96.4% (95% confidence interval, 94.3-98.0%) compared to 97.2% (95% confidence interval, 96.9-97.4%) for hysterectomy. In a multivariable model, women treated with hormonal therapy were 92% (hazard ratio, 1.92; 95% confidence interval, 1.15-3.19) more likely to die compared to women who underwent primary hysterectomy. When stratified by stage, hormonal therapy was associated with increased mortality in women with stage IB and I-not otherwise specified tumors but not for stage IA neoplasms. CONCLUSION: Use of progestational therapy is increasing. Its use was associated with decreased survival, particularly in women with stage IB tumors.

Utilization of gynecologic services in women with breast cancer receiving hormonal therapy.

BACKGROUND: The selective estrogen receptor modulator tamoxifen is now widely used for the treatment and prevention of breast cancer. Tamoxifen use has been associated with a variety of gynecologic problems. Despite the frequency with which hormonal therapy is used for the treatment of breast cancer, limited population-level data are available to describe the occurrence of gynecologic conditions and the use of surveillance testing in women receiving tamoxifen and aromatase inhibitors. OBJECTIVE: We performed a population-based analysis among women with breast cancer receiving hormonal therapy with tamoxifen, a drug commonly used in premenopausal and sometimes postmenopausal women, to determine the frequency of gynecologic abnormalities and use of diagnostic and surveillance testing. We compared these findings to women treated with aromatase inhibitors, agents commonly used in postmenopausal women. STUDY DESIGN: The MarketScan database was used to identify women diagnosed with breast cancer from 2009 through 2013 who underwent mastectomy or lumpectomy. Women receiving tamoxifen (age <50 vs ≥50 years) were compared to women ≥50 years of age treated with aromatase inhibitors. We examined the occurrence of gynecologic symptoms and diseases (vaginal bleeding, endometrial polyps, endometrial hyperplasia, and endometrial cancer) and gynecologic procedures and interventions (transvaginal ultrasound, endometrial biopsy, hysteroscopy/dilation and curettage, and hysterectomy). Time-dependent analyses were performed to examine symptoms and testing. RESULTS: A total of 75,170 women, including 15,735 (20.9%) age <50 years treated with tamoxifen, 13,827 (18.4%) age ≥50 years treated with tamoxifen, and 45,608 (60.7%) age ≥50 years treated with aromatase inhibitors were identified. The cumulative incidence of any gynecologic symptom or pathologic diagnosis during the study period was 20.2%, 12.3%, and 3.5%, respectively (P < .001), while the cumulative incidence of any gynecologic procedure or intervention during the study period was 34.2%, 20.9%, and 9.0%, respectively (P < .0001). Among women without symptoms or pathology, interventions were performed in 20.0%, 11.0%, and 6.8%, respectively (P < .0001). CONCLUSION: Compared to women taking aromatase inhibitors, gynecologic symptoms, procedures, and pathology are higher for both premenopausal and postmenopausal women with breast cancer on tamoxifen. Increased efforts to curb use of gynecologic interventions in asymptomatic women are needed.

Disparities in the management of ectopic pregnancy.

BACKGROUND: Ectopic pregnancy is common among young women. Treatment can consist of either surgery with salpingectomy or salpingostomy or medical management with methotrexate. In addition to acute complications, treatment of ectopic pregnancy can result in long-term sequelae that include decreased fertility. Little is known about the patterns of care and predictors of treatment in women with ectopic pregnancy. Similarly, data on outcomes for various treatments are limited. OBJECTIVE: We examined the patterns of care and outcomes for women with ectopic pregnancy. Specifically, we examined predictors of medical (vs surgical) management of ectopic pregnancy and tubal conservation (salpingostomy vs salpingectomy) among women who underwent surgery. STUDY DESIGN: The Perspective database was used to identify women with a diagnosis of tubal ectopic pregnancy treated from 2006-2015. Perspective is an all-payer database that collects data on patients at hospitals from throughout the United States. Women were classified as having undergone medical treatment, if they received methotrexate, and surgical treatment, if treatment consisted of salpingostomy or salpingectomy. Multivariable models were developed to examine predictors of medical treatment and of tubal conserving salpingostomy among women who were treated surgically. RESULTS: Among the 62,588 women, 49,090 women (78.4%) were treated surgically, and 13,498 women (21.6%) received methotrexate. Use of methotrexate increased from 14.5% in 2006 to 27.3% by 2015 (P<.001). Among women who underwent surgery, salpingostomy decreased over time from 13.0% in 2006 to 6.0% in 2015 (P<.001). Treatment in more recent years, at a teaching hospital and at higher volume centers, were associated with the increased use of methotrexate (P<.05 for all). In contrast, Medicaid recipients (adjusted risk ratio, 0.92; 95% confidence interval, 0.87-0.98) and uninsured women (adjusted risk ratio, 0.87; 95% confidence interval, 0.82-0.93) were less likely to receive methotrexate than commercially insured patients. Among those who underwent surgery, black (adjusted risk ratio, 0.76; 95% confidence interval, 0.69-0.85) and Hispanic (adjusted risk ratio, 0.80; 95% confidence interval, 0.66-0.96) patients were less likely to undergo tubal conserving surgery than white women and Medicaid recipients (adjusted risk ratio, 0.69; 95% confidence interval, 0.64-0.75); uninsured women (adjusted risk ratio, 0.60; 95% confidence interval, 0.55-0.66) less frequently underwent salpingostomy than commercially insured patients. CONCLUSION: There is substantial variation in the management of ectopic pregnancy. There are significant race- and insurance-related disparities associated with treatment.

Utilization of sentinel lymph node biopsy for uterine cancer.

BACKGROUND: To limit the potential short and long-term morbidity of lymphadenectomy, sentinel lymph node biopsy has been proposed for endometrial cancer. The principle of sentinel lymph node biopsy relies on removal of a small number of lymph nodes that are the first drainage basins from a tumor and thus the most likely to harbor tumor cells. While the procedure may reduce morbidity, efficacy data are limited and little is known about how commonly the procedure is performed. OBJECTIVE: We examined the patterns and predictors of use of sentinel lymph node biopsy and outcomes of the procedure in women with endometrial cancer who underwent hysterectomy. STUDY DESIGN: We used the Perspective database to identify women with uterine cancer who underwent hysterectomy from 2011 through 2015. Billing and charge codes were used to classify women as having undergone lymphadenectomy, sentinel lymph node biopsy, or no nodal assessment. Multivariable models were used to examine clinical, demographic, and hospital characteristics with use of sentinel lymph node biopsy. Length of stay and cost were compared among the different methods of nodal assessment. RESULTS: Among 28,362 patients, 9327 (32.9%) did not undergo nodal assessment, 17,669 (62.3%) underwent lymphadenectomy, and 1366 (4.8%) underwent sentinel lymph node biopsy. Sentinel lymph node biopsy was performed in 1.3% (95% confidence interval, 1.0-1.6%) of abdominal hysterectomies, 3.4% (95% confidence interval, 2.7-4.1%) of laparoscopic hysterectomies, and 7.5% (95% confidence interval, 7.0-8.0%) of robotic-assisted hysterectomies. In a multivariable model, more recent year of surgery was associated with performance of sentinel lymph node biopsy. Compared to abdominal hysterectomy, those undergoing laparoscopic (adjusted risk ratio, 2.45; 95% confidence interval, 1.89-3.18) and robotic-assisted (adjusted risk ratio, 2.69; 95% confidence interval, 2.19-3.30) hysterectomy were more likely to undergo sentinel lymph node biopsy. Among women who underwent minimally invasive hysterectomy, length of stay and cost were lower for sentinel lymph node biopsy compared to lymphadenectomy. CONCLUSION: The use of sentinel lymph node biopsy for endometrial cancer increased from 2011 through 2015. The increased use was most notable in women who underwent a robotic-assisted hysterectomy.

Trends in end-of-life care and health care spending in women with uterine cancer.

BACKGROUND: High-intensity care including hospitalizations, chemotherapy, and other interventions at the end of life is costly and often of little value for cancer patients. Little is known about patterns of end-of-life care and resource utilization for women with uterine cancer. OBJECTIVE: We examined the costs and predictors of aggressive end-of-life care for women with uterine cancer. STUDY DESIGN: In this observational cohort study the Surveillance, Epidemiology, and End Results-Medicare linked database was used to identify women age ≥65 years who died from uterine cancer from 2000 through 2011. Resource utilization in the last month of life including ≥2 hospital admissions, >1 emergency department visit, ≥1 intensive care unit admission, or use of chemotherapy in the last 14 days of life was examined. High-intensity care was defined as the occurrence of any of the above outcomes. Logistic regression models were developed to identify factors associated with high-intensity care. Total Medicare expenditures in the last month of life are reported. RESULTS: Of the 5873 patients identified, the majority had stage IV cancer (30.2%), were white (79.9%), and had endometrioid tumors (47.6%). High-intensity care was rendered to 42.5% of women. During the last month of life, 15.0% had ≥2 hospital admissions, 9.0% had a hospitalization >14 days, 15.3% had >1 emergency department visits, 18.3% had an intensive care unit admission, and 6.6% received chemotherapy in the last 14 days of life. The percentage of women who received high-intensity care was stable over the study period. Characteristics of younger age, black race, higher number of comorbidities, stage IV disease, residence in the eastern United States, and more recent diagnosis were associated with high-intensity care. The median Medicare payment during the last month of life was $7645. Total per beneficiary Medicare payments remained stable from $9656 (interquartile range $3190-15,890) in 2000 to $9208 (interquartile range $3309-18,554) by 2011. The median health care expenditure was 4 times as high for those who received high-intensity care compared to those who did not (median $16,173 vs $4099). CONCLUSION: Among women with uterine cancer, high-intensity care is common in the last month of life, associated with substantial monetary expenditures, and does not appear to be decreasing.

Port Site Metastases: A Survey of the Society of Gynecologic Oncology and Commentary on the Clinical Workup and Management of Port Site Metastases.

STUDY OBJECTIVE: Laparoscopic port site metastases (PSMs) have an incidence of .5% to 2%. The management of an isolated PSM (iPSM), without evidence of recurrence elsewhere, remains unclear. The aim of this study was to elucidate practices regarding iPSMs. DESIGN: A 23-item survey was created using commercially available survey software. Over the course of January 2016 the survey was e-mailed to the members of the Society of Gynecologic Oncology with 2 follow-up reminder e-mails. (Canadian Task Force classification III.) SETTING: Online survey. MEASUREMENTS AND MAIN RESULTS: Of the 709 surveys sent, 132 were returned. Providers practicing for <5 years saw fewer PSMs and those who performed more minimally invasive surgeries (MISs) saw more PSMs. Comparing providers who have or have not seen PSMs, no differences in pneumoinsufflation pressure, the mode of delivery of the specimen, the use of local anesthesia at port site incisions, or the method of deflation were seen. If an iPSM was suspected, most providers indicated they would obtain imaging (computed tomography, 51%, or positron emission tomography/computed tomography, 43%) followed by an interventional radiology-guided biopsy (29%) or resection of the mass. Tendency for treatment is to surgically resect the lesion followed by adjuvant therapy. CONCLUSION: After controlling for time in practice, we did not find a strong risk factor for iPSMs other than performing >75% of oncologic surgeries by MIS. Most respondents performed imaging when suspecting iPSMs and use systemic adjuvant therapy after confirming iPSMs.

Radiation Duration in Women with Cervical Cancer Treated with Primary Chemoradiation: A Population-Based Analysis.

This study examines factors associated with prolonged radiation duration and its impact on survival in women with cervical cancer treated with primary chemoradiation. Women in the National Cancer Database with stage IB2-IVA cervical cancer from 2003 to 2011 who received radiation and chemotherapy were included. Of 7209 women, who met inclusion criteria, 3401 (47.1%) and 3808 (52.8%) completed radiation in ≤ 8 and > 8 weeks, respectively. There was no overall survival difference for radiation duration ≤ 8 vs. > 8 weeks. Sensitivity analyses showed that inferior overall survival is only seen with radiation duration of > 10-12 weeks.