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Objective: To estimate the effects of a laparoscopic scoring algorithm to triage patients with advanced ovarian cancer to immediate or delayed debulking to improve complete gross surgical resection rates and determine the resulting clinical outcomes., Methods: We prospectively performed laparoscopic assessment on patients with suspected advanced-stage ovarian cancer from April 2013 to December 2016 to determine primary resectability at tumor reductive surgery. Patients with medically inoperable or distant metastatic disease received neoadjuvant chemotherapy. Two-surgeon scoring was performed in a blinded fashion using a validated scoring method. Patients with predictive index value scores less than 8 were offered primary surgery and those with scores 8 or greater received neoadjuvant chemotherapy. Univariate and multivariate analysis was performed for effects on progression-free survival., Results: Six hundred twenty-one patients presenting with presumed advanced ovarian cancer were evaluated during the study period and 488 patients met inclusion criteria. Two hundred fifteen patients underwent laparoscopic scoring, of whom 125 had predictive index value scores less than 8 and 84 had predictive index value scores 8 or greater. Blinded two-surgeon predictive index value scoring resulted in bivariate discordance in only 2% of patients. Tumor cytoreduction led to no gross residual disease (R0 resection) in 88% of patients in the primary surgery group and 74% in the neoadjuvant chemotherapy group. Patients triaged to primary surgery had an improved progression-free survival of 21.4 months versus 12.9 months in those patients undergoing neoadjuvant chemotherapy (P<.001). Median progression-free survival by treatment group and residual disease status was as follows: primary surgery-R0 23.5 months; primary surgery-R1 (any gross residual disease) 17.6 months; neoadjuvant chemotherapy-R0 15.5 months; and neoadjuvant chemotherapy-R1 12.9 months (P<.001). On multivariate analysis for progression-free survival, baseline CA 125 (P=.001) and gross residual disease at tumor reductive surgery (P=.01) were significantly associated with progression-free survival., Conclusion: Laparoscopic triage assessment allowed for a personalized approach to the management of patients with advanced ovarian cancer and resulted in high complete surgical resection rates at tumor reductive surgery.

Objective: To evaluate the cost-utility of three lymphadenectomy strategies in the management of low-risk endometrial carcinoma., Methods: A decision analysis model compared three lymphadenectomy strategies in women undergoing minimally invasive surgery for low-risk endometrial carcinoma: 1) routine lymphadenectomy in all patients, 2) selective lymphadenectomy based on intraoperative frozen section criteria, and 3) sentinel lymph node mapping. Costs and outcomes were obtained from published literature and Medicare reimbursement rates. Costs categories consisted of hospital, physician, operating room, pathology, and lymphedema treatment. Effectiveness was defined as 3-year disease-specific survival adjusted for the effect of lymphedema (utility=0.8) on quality of life. A cost-utility analysis was performed comparing the different strategies. Multiple deterministic sensitivity analyses were done., Results: In the base-case scenario, routine lymphadenectomy had a cost of $18,041 and an effectiveness of 2.79 quality-adjusted life-years (QALYs). Selective lymphadenectomy had a cost of $17,036 and an effectiveness of 2.81 QALYs, whereas sentinel lymph node mapping had a cost of $16,401 and an effectiveness of 2.87 QALYs. With a difference of $1,005 and 0.02 QALYs, selective lymphadenectomy was both less costly and more effective than routine lymphadenectomy, dominating it. However, with the lowest cost and highest effectiveness, sentinel lymph node mapping dominated the other modalities and was the most cost-effective strategy. These findings were robust to multiple sensitivity analyses varying the rates of lymphedema and lymphadenectomy, surgical approach (open or minimally invasive surgery), lymphedema utility, and costs. For the estimated 40,000 women undergoing surgery for low-risk endometrial carcinoma each year in the United States, the annual cost of routine lymphadenectomy, selective lymphadenectomy, and sentinel lymph node mapping would be $722 million, $681 million, and $656 million, respectively., Conclusion: Compared with routine and selective lymphadenectomy, sentinel lymph node mapping had the lowest costs and highest quality-adjusted survival, making it the most cost-effective strategy in the management of low-risk endometrial carcinoma.

Objective: To assess efficacy of the levonorgestrel-releasing intrauterine device (LNG-IUD) for treatment of complex atypical hyperplasia or low-grade endometrial cancer., Methods: This retrospective case series included all patients treated with the LNG-IUD for complex atypical hyperplasia or early-grade endometrial cancer from January 2003 to June 2013. Response rates were calculated and the association of response with clinicopathologic factors, including age, body mass index, and uterine size, was determined., Results: Forty-six patients diagnosed with complex atypical hyperplasia or early-grade endometrial cancer were treated with the LNG-IUD. Of 32 evaluable patients at the 6-month time point, 15 had complex atypical hyperplasia (47%), nine had G1 endometrial cancer (28%), and eight had grade 2 endometrial cancer (25%). Overall response rate was 75% (95% CI 57-89) at 6 months; 80% (95% CI 52-96) in complex atypical hyperplasia, 67% (95% CI 30-93) in grade 1 endometrial cancer, and 75% (CI 35-97) in grade 2 endometrial cancer. Of the clinicopathologic features evaluated, there was a trend toward the association of lack of exogenous progesterone effect in the pathology specimen with nonresponse to the IUD (P=.05). Median uterine diameter was 1.3 cm larger in women who did not respond to the IUD (P=.04)., Conclusion: Levonorgestrel-releasing IUD therapy for the conservative treatment of complex atypical hyperplasia or early-grade endometrial cancer resulted in return to normal histology in a majority of patients.

Objective: To examine the cumulative incidence of subsequent ovarian cancer among young women with stage I endometrioid endometrial cancer who had ovarian conservation at surgical treatment., Methods: This retrospective study examined the Surveillance, Epidemiology, and End Results Program to identify women aged younger than 50 years who underwent hysterectomy with ovarian conservation for stage I endometrioid endometrial cancer between 1983 and 2013. Time-dependent risk of ovarian cancer diagnosed during the follow-up after endometrial cancer diagnosis was examined., Results: Among 1,322 women in the study cohort, 16 women developed subsequent ovarian cancer with 5- and 10-year cumulative incidences of 1.0% and 1.3%, respectively. Median time to develop subsequent ovarian cancer was 2.4 years, and the majority of subsequent ovarian cancer was diagnosed within the first 3 years from the diagnosis of endometrial cancer (68.8%). The majority of subsequent ovarian cancer was endometrioid type (81.3%) and stage I disease (75.0%). With a median follow-up time of 11.6 years, there were no ovarian cancer deaths. Younger age at endometrial cancer diagnosis was significantly associated with increased risk of subsequent ovarian cancer (10-year cumulative incidences: age younger than 40 compared with 40-49 years, 2.6% compared with 0.4%, hazard ratio 5.00, 95% confidence interval [CI] 1.60-15.7, P=.002)., Conclusion: Young women with stage I endometrioid endometrial cancer have an approximately 1% risk of developing subsequent ovarian cancer after ovarian conservation at the time of hysterectomy that was associated with favorable tumor factors resulting in good ovarian cancer-specific survival. Our results endorse the importance of genetic testing and close follow-up when counseling about this procedure, especially for those who are younger than 40 years.

Objective: To assess whether obesity is an independent predictor of mortality in women with cervical cancer., Methods: This retrospective cohort study of patients with stages IB1-IVA cervical cancer treated with curative intent at MD Anderson Cancer Center from 1980 through 2007 categorized these women as underweight, normal weight, overweight, obese, or morbidly obese according to National Institutes of Health definitions. In addition to weight category, known prognostic factors for survival after a diagnosis of cervical cancer were included in a multivariate model. These known prognostic factors included age, smoking status, race or ethnicity (self-reported), socioeconomic status, comorbidities, tumor histologic subtype, tumor stage, tumor size, presence or absence of hydronephrosis, radiologic evidence of nodal metastasis, and the addition of concurrent chemotherapy with definitive radiation., Results: A total of 3,086 patients met the inclusion criteria. The median survival for the entire cohort was 81 months (range 0-365 months). The presence of lymph node spread and advancing stage were the most significant predictors of survival. Compared with normal-weight women, morbidly obese women had a significantly higher hazard ratio for both all-cause death (hazard ratio 1.26, 95% confidence interval [CI] 1.10-1.45) and disease-specific death (hazard ratio 1.24, 95% CI 1.06-1.47). Underweight, overweight, and obese women did not have an increased risk for death compared with normal-weight women., Conclusion: After controlling for all previously known prognostic factors, morbid obesity remains an independent risk factor for death from cervical cancer. Overweight and obese women have the same prognosis as normal-weight women.

Objective: Selection of physicians for fellowships in obstetrics and gynecology subspecialties has become increasingly competitive. The number and quality of research publications is an important factor in the selection process. We sought to estimate the incidence of unverifiable publications among gynecologic oncology fellowship applicants., Methods: We reviewed the applications to a single gynecologic oncology fellowship program during 2004-2008. Articles and book chapters reported as published, in press, submitted, or in progress were searched for systematically by three reviewers using PubMed and Google. χ2 analysis was used to evaluate associations between demographic factors and unverifiable publications., Results: Two hundred forty-three applications met the inclusion criteria. Of the 35 applicants who listed membership in Alpha Omega Alpha, four (11%) were not listed on the organization's web site as inductees. Of the 464 articles reported as published or in press, only 387 (83%) could be verified. Of the 148 applicants who reported at least one published or in press article, 44 (30%) had at least one unverifiable publication. On multivariable analysis, only male gender increased the likelihood of unverifiable ("ghost") publications (odds ratio 2.1, 95% confidence interval 1.1-4.1). Of the 282 manuscripts reported as submitted or in progress, only 126 (45%) were published. Of the 124 applicants who reported at least one submitted or in progress manuscript, 88 (71%) had at least one unverifiable manuscript., Conclusion: The proportion of unverifiable publications listed on gynecologic oncology fellowship applications is concerning. Stringent review of applications before interview invitations and match list submission is warranted.

Objective: To describe the clinical and pathologic features of vaginal melanoma and to determine predictors of outcome in patients with this disease., Methods: Thirty-seven women with clinical and radiographic stage I vaginal melanoma treated at one institution between 1980 and 2009 were included in this retrospective study. Treatment modalities were assigned to one of three categories: pelvic exenteration, wide excision, and nonsurgical (primary radiation therapy, chemotherapy, or both). Overall survival and progression-free survival were calculated from the date of the surgical diagnosis., Results: The median age was 60.6 years. Eighty-four percent of patients were white. Vaginal bleeding was the most common presenting symptom. Lesions were located in the distal third of the vagina in the majority (65%) of patients. Initial management included a wide local or radical excision (76% of patients); pelvic exenteration (14%); and radiotherapy, chemotherapy, or radiotherapy and chemotherapy (10%). At a median follow-up of 17.4 months, 33 women experienced disease recurrence. Recurrence was local only in seven patients (22%), distant only in 20 (63%), and both in five (15%). The most common sites of distant recurrence were lungs and liver. Median progression-free survival was 11.4 months, and median overall survival was 19 months. The 5-year progression-free and overall survival rates were 9.5% and 20.0%, respectively. Patients treated surgically had significantly longer survival than those treated nonsurgically (P=.01). Radiotherapy after wide excision reduced local recurrence risk and increased survival from 16.1 months to 29.4 months, although the increase was not significant (P=.46)., Conclusion: Malignant vaginal melanoma, even when localized at presentation, has a very poor prognosis. Patients treated surgically have longer survival than those treated nonsurgically. Radiotherapy after wide excision reduces local but not distant recurrences.

Objective: To estimate the incidence of venous thromboembolism among patients undergoing gynecologic laparoscopy and characterize the risk of venous thromboembolism among patients with gynecologic malignancy., Methods: Data were collected for patients who underwent laparoscopic gynecologic surgery from January 2000 to January 2009. Incidence of deep vein thrombosis (DVT) or pulmonary embolism diagnosed within 6 weeks of surgery was estimated. Fisher's exact test was used to estimate the association between the presence of perioperative venous thromboembolism and categorical variables., Results: Six (of 849) patients developed symptomatic venous thromboembolism (0.7%, 95% confidence interval: 0.024-1.44%). The median time to diagnosis of venous thromboembolism was postoperative day 15.5 (range, 1-41 days), median body mass index was 25.4 kg/m (range, 18.4-50 kg/m), median operative time was 176 minutes (range, 53-358 minutes), and median estimated blood loss was 125 mL (range, 10-250 mL). Five of 430 (1.2%) patients with a history of gynecologic malignancy developed postoperative thromboembolic events. Venous thromboembolism was diagnosed in three of 662 (0.5%) patients undergoing intermediate complexity procedures and three of 106 (2.8%) patients undergoing high-complexity procedures. Three patients with venous thromboembolism (50%) had a history of at least one previous modality of cancer treatment before laparoscopy. One patient (17%) had DVT only, four (67%) had pulmonary emboli without an identified DVT, and one (17%) had both. There were no associated mortalities., Conclusion: The incidence of thromboembolism in patients undergoing low- and intermediate-complexity, minimally invasive surgery was low, even among patients with a gynecologic malignancy. Patients undergoing high-complexity, minimally invasive procedures may benefit from postoperative anticoagulation., Level of Evidence: II.

Background: Women with Lynch syndrome or hereditary nonpolyposis colorectal carcinoma (HNPCC) have a 40-60% lifetime risk of endometrial cancer and a 7-12% lifetime risk of ovarian cancer. Risk-reducing surgery, including hysterectomy and bilateral salpingo-oophorectomy (BSO), is currently recommended once child bearing is complete. We describe two cases of primary peritoneal cancer after BSO in women with Lynch syndrome or HNPCC., Cases: The first patient was a 44-year-old woman who underwent hysterectomy with BSO for benign disease. She presented 12 years later with a pelvic mass and was diagnosed with a high-grade serous primary peritoneal cancer. Genetic testing showed a mutation in the MSH2 DNA mismatch repair gene. The second case was a 58-year-old woman who had a hysterectomy and BSO for endometrial cancer. She developed a high-grade serous primary peritoneal cancer 8 years later and was found to have a mutation in the PMS2 DNA mismatch repair gene., Conclusion: Women with Lynch syndrome or HNPCC should be counseled that they may be at risk for developing primary peritoneal cancer despite undergoing gynecologic cancer risk-reducing surgery. The magnitude of this risk remains to be determined.

Objective: To compare intraoperative and postoperative outcomes, pathologic findings, cancer recurrence, and death rates in normal-weight, overweight, obese, and morbidly obese women undergoing radical hysterectomy and pelvic lymphadenectomy for early-stage cervical cancer., Methods: A review of patients who underwent radical hysterectomy and pelvic lymphadenectomy for invasive cervical cancer between 1990 and 2006 was performed. On the basis of body mass index (BMI) (calculated as weight [kg]/[height (m)](2)), women were categorized as normal weight (BMI 18.5-24.9), overweight (BMI 25.0-29.9), obese (BMI 30.0-34.9), or morbidly obese (BMI at least 35.0)., Results: Four hundred eight women met the inclusion criteria. Of these, 155 (38%) were normal weight, 126 (31%) were overweight, 77 (19%) were obese, and 50 (12%) were morbidly obese. There were no statistically significant differences between these four groups in age, Charlson comorbidity score, smoking history, stage, histologic grade or subtype, tumor size, depth of invasion, transfusion rate, operative time, or intraoperative complications. Higher BMI was significantly correlated with higher estimated operative blood loss (P=.001). There were no statistically significant differences between the groups in pathologic findings, length of postoperative hospital stay, postoperative complications, readmission rate, or proportion of women receiving adjuvant radiotherapy. At a median follow-up time of 64 months, there were no differences between groups in rates of recurrence or death from disease., Conclusion: Radical hysterectomy and pelvic lymphadenectomy is feasible for obese and morbidly obese women with cervical cancer. Obesity alone should not be a contraindication to radical hysterectomy in women with cervical cancer.

Objective: To estimate if women in the general population are aware of the relationship between obesity and cancer risk, and to identify groups who may benefit from educational programs., Methods: A self-administered survey was distributed to women in the Houston community. The questions were taken from a bank of validated questions published by the Center for Disease Control, Behavioral Risk Factor Surveillance System, and the Harvard Forums on Health Survey. Demographic information and participant knowledge of obesity-related cancer risk was collected. Logistic regression and Cochran-Armitage tests for trend were use to assess the association between predictor variables and knowledge., Results: One thousand five hundred forty-five women completed the survey; 28% were normal weight (body mass index [BMI] less than 25 kg/m(2)), 24% were overweight (BMI 25-30 kg/m(2)), and 45% were obese (BMI at least 30 kg/m(2)). Fifty-eight percent (95% confidence interval 56-61%) were not aware that obesity increased risk for endometrial cancer. There was no difference in knowledge of endometrial cancer risk associated with any of the demographic characteristics studied. Black women were the most likely to respond that they did not know about the relationship between obesity and cancer. There was no association between personal weight and knowledge of obesity-associated risk., Conclusion: There is limited knowledge of the relationship between obesity and cancer risk, particularly among black women. Patient education regarding these risks may increase awareness of the relationship between obesity and endometrial cancer among women.

Objective: The objective of this study was to evaluate clinical factors associated with choosing prophylactic bilateral salpingo-oophorectomy (BSO) over surveillance in women with a BRCA1 or BRCA2 mutation., Methods: Between 1996 and 2005, 139 women who tested positive for a BRCA1 or BRCA2 mutation were identified. Thirty-three women were excluded due to a personal history of ovarian or fallopian tube cancer before genetic testing, resulting in 106 women for the final analysis. The characteristics of women who underwent prophylactic BSO were compared with those choosing surveillance., Results: Sixty-five of the BRCA mutation carriers (61%) underwent prophylactic BSO. Median age at BSO was 45.6 years. Median time from disclosure of genetic test results to surgery was 4.6 months. Eighty-five percent of women who underwent prophylactic BSO were parous compared with 66% of women who chose surveillance (P = .03). A previous diagnosis of breast cancer was noted in 72% of women who underwent prophylactic BSO compared with 46% of women undergoing surveillance (P < .01). Fifty-two women (80%) had hysterectomy performed at the time of BSO. Two women had incidental ovarian cancer diagnosed at time of surgery., Conclusion: Age greater than 40 years, parity, and a personal history of breast cancer were associated with choosing prophylactic BSO in our cohort. A short time interval was noted from the time of receiving positive genetic test results to undergoing prophylactic surgery.

Objective: Endometrial cancer is the most common gynecologic malignancy in the United States. The mean age at diagnosis is 61 years; however, 5-30% of women are aged younger than 50 years at the time of diagnosis. The objective of this study was to conduct a clinical and pathologic review of endometrial cancers diagnosed in premenopausal women aged younger than 50 years, to better identify the risk factors for this subgroup of women., Methods: We conducted a retrospective cohort study of patients with histologically confirmed endometrial cancer treated at the University of Texas, M. D. Anderson Cancer Center from 1989 to 2003. Clinical characteristics including age, body mass index (BMI), parity, diabetes, and personal or family history of cancer were obtained from the medical record. Pathologic information was obtained from pathology reports., Results: Twelve percent (188/1531) of all patients with endometrial adenocarcinoma were aged younger than 50 years. The mean age at diagnosis was 41 years (range 21-49 years). Mean BMI was 34 kg/m(2) (range 18-68); 58% of patients had a BMI of 30 or greater. Fifty-five percent were nulliparous and 39% reported irregular menstrual cycles. The incidence of both diabetes and hypertension was 23%. Thirty-six patients (19%) had synchronous ovarian cancers., Conclusion: We found that the majority of patients diagnosed with endometrial cancer at a young age were obese and nulliparous. In addition, we found a high incidence of synchronous primary ovarian cancers in this cohort of young, premenopausal women.