Is Robotic-Assisted Surgery Safe in the Elderly Population? An Analysis of Gynecologic Procedures in Patients ≥ 65 Years Old.

BACKGROUND: The elderly population is expanding worldwide but is underrepresented in clinical trials. We sought to assess the safety of robotic gynecologic surgery in an elderly cohort and to identify factors associated with unfavorable outcomes. METHODS: All patients ≥ 65 years who underwent a robotically assisted procedure at a single institution between May 2007 to December 2016 were divided into three age groups: 65-74 (Group 1); 75-84 (Group 2); ≥ 85 (Group 3). Perioperative outcomes were recorded in patients who did not require conversion to laparotomy. We compared clinical variables among groups and performed multivariate logistic regression to detect variables associated with major complications (≥ Grade 3) or 90-day mortality. RESULTS: We retrospectively identified 982 cases: 685 in Group 1; 249 in Group 2; 48 in Group 3. Median age = 71 years. Median BMI = 28.9. Malignancy was documented in 72.8% of cases; the majority were endometrial cancer (61.8%). Thirty-four patients (3.5%) were readmitted within 30 days. Seventy-seven (7.8%) had a postoperative complication, and 23 (2.3%) had a major complication. Ninety-day mortality was 0.5%. There was significant difference between groups with respect to body mass index (P = 0.026), ECOG PS (P ≤ 0.001), > 5 comorbidities (P = 0.005), hospital stay (P < 0.001), major complications (P = 0.001), and 90-day mortality (P < 0.001). On multivariable logistic regression, age ≥ 85 years was associated with major complications. Body mass index, age ≥ 85 years, and major complications were significantly associated with 90-day mortality. CONCLUSIONS: Robotic-assisted surgery appears to be safe in an elderly cohort. The incidence of overall and major complications is consistent with those reported in the literature. Patients ≥ 85 years old appear to be at higher risk of unfavorable outcomes.

Less versus more radical surgery in stage IB1 cervical cancer: A population-based study of long-term survival.

BACKGROUND: Standard surgical treatment for women with stage IB1 cervical cancer consists of radical hysterectomy. This study assesses survival outcomes of those treated with less radical surgery (LRS; conization, trachelectomy, simple hysterectomy) compared to more radical surgery (MRS; modified radical, radical hysterectomy). METHODS: Using the Surveillance, Epidemiology and End Results database, we identified women <45 years with FIGO stage IB1 cervical cancer diagnosed from 1/1998 to 12/2012. Only those who underwent lymph node (LN) assessment were analyzed. Disease-specific survivals (DSSs) of LRS were compared with those of MRS. RESULTS: Of 2571 patients, 807 underwent LRS and 1764 underwent MRS, all with LN assessment. For LRS vs. MRS, 28% vs. 23% were diagnosed with adenocarcinoma (p = 0.024), 31% vs. 39% had G3 disease (p < 0.001), 40% vs. 45% had tumor size >2 cm (p < 0.001), and 27% vs. 29% received adjuvant radiation therapy (p = 0.005). Median follow-up was 79 months (range, 0-179). Ten-year DSS for LRS vs. MRS was 93.5% vs. 92.3% (p = 0.511). There was no difference in 10-year DSS when stratified by tumor size ≤2 cm (LRS 95.1% vs. MRS 95.6%, p = 0.80) or > 2 cm (LRS 90.1% vs. MRS 88.2%, p = 0.48). Factors independently associated with increased risk of death included adenosquamous histology (HR 2.37), G3 disease (HR 2.86), tumors >2 cm (HR 1.82), and LN positivity (HR 2.42). Compared to MRS, LRS was not associated with a higher risk of death. CONCLUSIONS: In a select group of young women with stage IB1 cervical cancer, LRS compared to MRS does not appear to compromise DSS.

Patterns of FIRST recurrence of stage IIIC1 endometrial cancer with no PARAAORTIC nodal assessment.

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

Perioperative epidural use and survival outcomes in patients undergoing primary debulking surgery for advanced ovarian cancer.

OBJECTIVE: Epidurals are associated with improved outcomes in some solid tumors, presumably due to their effect on surgical stress response. There are limited data on the prognostic significance of epidural anesthesia in patients undergoing primary debulking surgery (PDS) for advanced ovarian cancer. We sought to assess the impact of epidural anesthesia on the survival outcomes of patients undergoing PDS for advanced ovarian cancer. METHODS: In this retrospective study, consecutive patients with stage IIIB-IV epithelial ovarian, fallopian tube, or peritoneal carcinoma who underwent PDS at our institution from 01/2005-12/2013 were identified. Progression-free survival (PFS) and overall survival (OS) with regard to epidural use were analyzed. RESULTS: Of 648 patients, 435 received an epidural and 213 did not. Patients in the former group were more likely to have higher stage disease (stage IV disease, 26% vs. 16%, respectively; P = .005), carcinomatosis (87% vs. 80%, respectively; P = .027), and bulky upper abdominal disease (66% vs. 58%, respectively; P = .046). Complete gross resection was achieved in 48% and 32%, respectively (P < .001). For the epidural vs. non-epidural groups, median PFS was 20.8 months and 13.9 months, respectively (P = .021); median OS was 62.4 months and 41.9 months, respectively (P < .001). After controlling for confounding factors, including residual disease, epidural use was independently associated with a decreased risk of progression (HR = 1.327; 95% CI, 1.066-1.653) and death (HR = 1.588; 95% CI, 1.224-2.06). CONCLUSIONS: Perioperative epidural use was independently associated with improved PFS and OS in these patients. Epidural anesthesia at the time of PDS may be warranted in this setting.

Continuous improvement in primary Debulking surgery for advanced ovarian cancer: Do increased complete gross resection rates independently lead to increased progression-free and overall survival?

OBJECTIVES: To assess complete gross resection (CGR) rates and survival outcomes in patients with advanced ovarian cancer who underwent primary debulking surgery (PDS) during a 13-year period in which specific changes to surgical paradigm were implemented. METHODS: We identified all patients with stage IIIB-IV high-grade ovarian carcinoma who underwent PDS at our institution, with the intent of maximal cytoreduction, from 1/2001-12/2013. Patients were categorized by year of PDS based on the implementation of surgical changes to our approach to ovarian cancer debulking (Group 1, 2001-2005; Group 2, 2006-2009; Group 3, 2010-2013). RESULTS: Among 978 patients, 78% had stage IIIC disease and 89% had disease of serous histology. Carcinomatosis was found in 81%, and 60% had bulky upper abdominal disease (UAD). Compared to Group 1, those who underwent PDS during the latter 2 time periods had higher ASA scores (p < 0.001), higher-stage disease (p < 0.001), and more often had carcinomatosis (p = 0.015) and bulky UAD (p = 0.009). CGR rates for Groups 1-3 increased from 29% to 40% to 55%, respectively (p < 0.001). Five-year progression-free survival (PFS) rates increased over time (15%, 16%, and 20%, respectively; p = 0.199), as did 5-year overall survival (OS) rates (40%, 44%, and 56%, respectively; p < 0.001). On multivariable analysis, CGR was independently associated with PFS (p < 0.001) and OS (p < 0.001). CONCLUSIONS: Despite higher-stage disease and greater tumor burden, CGR rates, PFS and OS for patients who underwent PDS increased over a 13-year period. Surgical paradigm shifts implemented specifically to achieve more complete surgical cytoreduction are likely the reason for these improvements.

Long-Term Oncologic Outcomes of Uterine-Preserving Surgery in Young Women With Stage Ib1 Cervical Cancer.

OBJECTIVE: This study aimed to evaluate oncologic outcomes of women with stage IB1 cervical cancer treated with uterine-preserving surgery (UPS) (defined as conization or trachelectomy) versus non-UPS (defined as hysterectomy of any type). METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify women younger than 45 years diagnosed with stage IB1 cervical cancer from 1998 to 2012. Only those who underwent lymph node (LN) assessment were included. Outcomes of UPS versus non-UPS were analyzed. RESULTS: Among 2717 patients, 125 were treated with UPS and 2592 were treated with non-UPS. Those in the UPS group were younger (median age 33 vs 37 years, P < 0.001), less commonly had tumor size greater than 2 cm (27% vs 45%, P < 0.001), and less commonly received adjuvant radiation therapy (18% vs 29%, P = 0.006). There was no difference in distribution of tumor grade, histology, or rate of LN positivity. Median follow-up was 79 months (range, 0-179). There was no difference in 5-year disease-specific survival (DSS) between the UPS versus non-UPS groups (93% vs 94%, respectively, P = 0.755). When stratified by tumor size, DSS for UPS versus non-UPS was as follows: tumors 2 cm or less, 96.8% versus 96.3% (P = 0.683); tumors greater than 2 cm, 82.4% versus 90.4% (P = 0.112). Factors independently associated with worsened survival included adenosquamous histology (hazard ratio [HR] 2.29, 95% confidence interval [CI]1.51-3.47), G3 disease (HR 2.44, 95% CI 1.01-5.89), tumor size greater than 2 cm (HR 1.93, 95% CI 1.36-2.75) and LN positivity (HR 2.29, 95% CI 1.64-3.22). The UPS was not associated with a higher risk of death. CONCLUSIONS: The UPS does not seem to compromise oncologic outcomes in a select group of young women with stage IB1 cervical cancer, especially in the setting of tumors 2 cm or less. Further studies are needed to clarify the role of UPS in tumors greater than 2 cm.

Diverting ileostomy during primary debulking surgery for ovarian cancer: Associated factors and postoperative outcomes.

OBJECTIVE: To examine the use, as well as postoperative and long-term oncologic outcomes of diverting loop ileostomy (DI) during primary debulking surgery (PDS) for ovarian cancer. METHODS: Patients with stage II-IV ovarian, fallopian tube, or primary peritoneal carcinoma who underwent colon resection during PDS from 1/2005-1/2014 were identified. Demographic and clinical data were analyzed. RESULTS: Of 331 patients, 320 (97%) had stage III/IV disease and 278 (84%) had disease of high-grade serous histology. Forty-four (13%) underwent a DI. There were no significant differences in age, comorbidity index, smoking status, serum albumin, or attending surgeon between the DI and non-DI groups. Operative time (OR=1.21; 95% CI, 1.03-1.42; p=0.02) and length of rectosigmoid resection (OR=1.04; 95% CI, 1.01-1.08; p=0.02) were predictors of DI on multivariable analysis. The overall anastomotic leak rate was 6%. A comparison of groups (DI vs non-DI) showed no significant differences in major complications (30% vs 23%; p=0.41), anastomotic leak rate (5% vs 7%; p=0.60), hospital length of stay (10 vs 9days; p=0.25), readmission rate (23% vs 17%; p=0.33), or interval to postoperative chemotherapy (41 vs 40days; p=0.20), respectively. Ileostomy reversal was successful in 89% of patients. Median follow-up was 52.6months. There were no differences in median progression-free (17.9 vs 18.6months; p=0.88) and overall survival (48.7 vs 63.8months; p=0.25) between the groups. CONCLUSIONS: In patients undergoing PDS, those with longer operative time and greater length of rectosigmoid resection more commonly underwent DI. DI does not appear to compromise postoperative outcomes or long-term survival.

Lifestyle and Weight Management Counseling in Uterine Cancer Survivors: A Study of the Uterine Cancer Action Network.

OBJECTIVE: The purpose of this study was to examine the experiences, attitudes, and preferences of uterine cancer survivors with regard to weight and lifestyle counseling. MATERIALS AND METHODS: Members of the US Uterine Cancer Action Network of the Foundation for Women's Cancer were invited to complete a 45-item, Web-based survey. Standard descriptive statistical methods and χ tests were used to analyze responses. RESULTS: One hundred eighty (28.3%) uterine cancer survivors completed the survey. Median age was 58 years, 85% were white, and median survivorship period was 4.4 years. Most had stage I-II disease (69%) and were overweight or obese (65%). Eighty-nine percent of respondents received care by a gynecologic oncologist. Increased respondent body mass index was associated with decreased exercise frequency (P = 0.016). Only 50% of respondents underwent any weight/lifestyle counseling, with those living in the West and Southwest reporting the highest rates (70.8% and 69.2%, P = 0.011). Most who received counseling felt that discussions were motivating, performed in a sensitive manner, and did not undermine the patient-physician relationship. Specific recommendations were rarely offered; there were no reported referrals to weight loss programs or bariatric specialists, and few (6%) reported referrals to nutritionists. Respondents (85%) preferred their gynecologic oncologist address weight using direct, face-to-face counseling with specific recommendations regarding interventions and referral to specialists. Finally, self-reported overweight respondents experienced greater success with weight loss compared to those reporting obesity or morbid obesity (30.8% vs 15.8% vs 12.5%, P = 0.011). CONCLUSIONS: Uterine cancer survivors reported high obesity, low activity rates, and a desire for substantive weight loss counseling from their gynecologic oncologists. Respondents suggested that current counseling practices are inadequate and incongruent with their needs. Further research to define optimal timing, interventional strategies, and specific recommendations for successful lifestyle changes in this population is warranted.

Impact of race and ethnicity on treatment and survival of women with vulvar cancer in the United States.

OBJECTIVE: To examine racial/ethnic differences in treatment and survival in women diagnosed with invasive vulvar cancer in the United States. METHODS: Women with invasive vulvar cancer were identified from the Surveillance, Epidemiology, and End Results database from 1/1/92 to 12/31/02. Statistical analysis using Chi-square, Fisher's Exact Test, Kaplan-Meier survival methods, and Cox regression proportional hazards models was performed. RESULTS: Of the 2357 cases of invasive vulvar cancer included in this study, 1974 (83.8%) were non-Hispanic white, 209 (8.9%) were non-Hispanic black, 119 (5.0%) were Hispanic, and 55 (2.3%) women were of another race/ethnicity. After adjustment for stage, black women were half as likely (OR=0.48, 95% CI 0.31-0. 74) to undergo surgery and 1.7 times more likely (OR=1.67, 95% CI 1.18-2.36) to receive radiation than white women. In multivariable analysis, surgical treatment reduced the risk of death from vulvar cancer by 46% (HR 0.54, 95% CI 0.43-0.67), whereas radiation was not shown to impact the risk of death (HR 0.99, 95% CI 0.84-1.19), after adjusting for age, race, stage, and grade. There was no significant difference in risk of death by race/ethnicity group after adjusting for the previously described variables. CONCLUSIONS: Based on this study, race/ethnicity is not an independent risk factor for poor prognosis in women diagnosed with invasive vulvar cancer, despite differences in treatment modality by race/ethnicity. Further research to define the factors contributing to differences in treatment selection according to race/ethnicity and the resulting impact on quality of life is warranted.

A Phase III Study of Pafolacianine Injection (OTL38) for Intraoperative Imaging of Folate Receptor-Positive Ovarian Cancer (Study 006).

PURPOSE: The adjunctive use of intraoperative molecular imaging (IMI) is gaining acceptance as a potential means to improve outcomes for surgical resection of targetable tumors. This confirmatory study examined the use of pafolacianine for real-time detection of folate receptor-positive ovarian cancer. METHODS: This phase III, open-label, 11-center study included subjects with known or suspected ovarian cancer, scheduled to undergo cytoreductive surgery. The objectives were to confirm safety and efficacy of pafolacianine (0.025 mg/kg IV), given ≥ 1 hour before intraoperative near-infrared imaging to detect macroscopic lesions not detected by palpation and normal white light. RESULTS: From March 2018 through April 2020, 150 patients received a single infusion of pafolacianine (safety analysis set); 109 patients with folate receptor-positive ovarian cancer comprised the full analysis set for efficacy. In 33.0% of patients (95% CI, 24.3 to 42.7; P < .001), pafolacianine with near-infrared imaging identified additional cancer on tissue not planned for resection and not detected by white light assessment and palpation, exceeding the prespecified threshold of 10%. Among patients who underwent interval debulking surgery, the rate was 39.7% (95% CI, 27.0 to 53.4; P < .001). The sensitivity to detect ovarian cancer was 83%, and the patient false-positive rate was 24.8%. Investigators reported achieving complete R0 resection in 62.4% (68 of 109) of patients. Drug-related adverse events were reported by 30% of patients (45 of 150) and most commonly included nausea, vomiting, and abdominal pain. No drug-related serious adverse events or deaths were reported. CONCLUSION: This phase III study of pafolacianine met its primary efficacy end point, identifying additional cancers not otherwise identified or planned for resection. Pafolacianine may offer an important real-time adjunct to current surgical approaches for ovarian cancer.

Vaginal metastasis of gestational trophoblastic neoplasia resulting in hemorrhage: A case report.

Complete molar pregnancies complicate approximately 1 in 1500 pregnancies in the United States and result in gestational trophoblastic neoplasia in about 15-20% of these cases. Vaginal metastasis is the second most common site of metastasis and may present with vaginal bleeding and hemorrhage. This report describes a case of a 19-year-old Hispanic primigravida who presented with hemorrhage from an anterior vaginal wall metastasis two weeks after dilation and curettage for complete molar pregnancy. Hemorrhage resolved after extrusion of the lesion from the anterior vaginal wall. Pathology showed markedly atypical trophoblastic tissue from the lesion. Vaginal involvement of gestational trophoblastic neoplasia can present with life-threatening hemorrhage.

miR-200c-driven Mesenchymal-To-Epithelial Transition is a Therapeutic Target in Uterine Carcinosarcomas.

Uterine carcinosarcomas (UCSs) are highly aggressive malignancies associated with poor prognoses and limited treatment options. These tumors are hypothesized to develop from the endometrial adenocarcinoma (EAC) through epithelial-mesenchymal transition (EMT). We test this long-standing hypothesis by depleting miR-200, a family of microRNAs critical for EMT, in EAC cell lines. Our data suggest that UCSs do not develop from EACs via EMT. Clinically more relevant, we show that miR-200 expression in UCS cells induces a robust mesenchymal-epithelial transition (MET). Using in vitro and murine xenograft models, we demonstrate decreased growth and aggressiveness of miR-200-overexpressing UCS cell lines. Whole transcriptome analysis confirmed changes consistent with an MET and also revealed changes in angiogenic genes expression. Finally, by treatment of UCS-xenografted mice with miR-200c incorporated in DOPC nanoliposomes, we demonstrate anti-tumor activities. These findings suggest that ectopic miR-200 expression using advanced microRNA therapeutics may be a potential treatment approach for patients with UCS.

Ovarian carcinosarcoma: effects of cytoreductive status and platinum-based chemotherapy on survival.

Objective. To define survival patterns of women with ovarian carcinosarcoma based on patient, tumor, and treatment characteristics. Methods/Materials. A single-institution, retrospective analysis of women diagnosed with ovarian carcinosarcoma from February 1993 to May 2009 was performed. Survival was analyzed with Cox proportional hazards ratios and Kaplan Meier tests. Results. Forty-seven cases of primary ovarian carcinosarcoma were identified. Age conveyed an HR 3.28 (95% CI 1.51-7.11, P = 0.003) for death. Compared to Stages I-II, Stage III carried an HR for death of 4.75 (95% CI 1.16-19.4, P = 0.03) and Stage IV disease an HR of 9.13 (95% CI 1.76-47.45, P = 0.009). Compared to those with microscopic residual, women with >1 cm diameter of residual disease after primary cytoreductive surgery had an HR for death of 4.71 (95% CI 1.84-12.09, P = 0.001). At analysis, 59.1% of those who received platinum-based chemotherapy were alive, compared to 23.1% of those who received nonplatinum-based chemotherapy (P = 0.08). Conclusions. Age, stage, and cytoreduction to no gross residual disease are associated with improved survival in women with ovarian carcinosarcoma. Complete surgical cytoreduction should be the goal of surgical management when possible, but the ideal adjuvant treatment regimen remains unclear.