Nivolumab with or without ipilimumab in patients with recurrent or metastatic cervical cancer (CheckMate 358): a phase 1-2, open-label, multicohort trial.

BACKGROUND: In preliminary findings from the recurrent or metastatic cervical cancer cohort of CheckMate 358, nivolumab showed durable anti-tumour responses, and the combination of nivolumab plus ipilimumab showed promising clinical activity. Here, we report long-term outcomes from this cohort. METHODS: CheckMate 358 was a phase 1-2, open-label, multicohort trial. The metastatic cervical cancer cohort enrolled patients from 30 hospitals and cancer centres across ten countries. Female patients aged 18 years or older with a histologically confirmed diagnosis of squamous cell carcinoma of the cervix with recurrent or metastatic disease, an Eastern Cooperative Oncology Group performance status of 0 or 1, and up to two previous systemic therapies were enrolled into the nivolumab 240 mg every 2 weeks group, the randomised groups (nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks [NIVO3 plus IPI1] or nivolumab 1 mg/kg every 3 weeks plus ipilimumab 3 mg/kg every 3 weeks for four cycles then nivolumab 240 mg every 2 weeks [NIVO1 plus IPI3]), or the NIVO1 plus IPI3 expansion group. All doses were given intravenously. Patients were randomly assigned (1:1) to NIVO3 plus IPI1 or NIVO1 plus IPI3 via an interactive voice response system. Treatment continued until disease progression, unacceptable toxicity, or consent withdrawal, or for up to 24 months. The primary endpoint was investigator-assessed objective response rate. Anti-tumour activity and safety were analysed in all treated patients. This study is registered with ClinicalTrials.gov (NCT02488759) and is now completed. FINDINGS: Between October, 2015, and March, 2020, 193 patients were recruited in the recurrent or metastatic cervical cancer cohort of CheckMate 358, of whom 176 were treated. 19 patients received nivolumab monotherapy, 45 received NIVO3 plus IPI1, and 112 received NIVO1 plus IPI3 (45 in the randomised group and 67 in the expansion group). Median follow-up times were 19·9 months (IQR 8·2-44·8) with nivolumab, 12·6 months (7·8-37·1) with NIVO3 plus IPI1, and 16·7 months (7·2-27·5) with pooled NIVO1 plus IPI3. Objective response rates were 26% (95% CI 9-51; five of 19 patients) with nivolumab, 31% (18-47; 14 of 45 patients) with NIVO3 plus IPI1, 40% (26-56; 18 of 45 patients) with randomised NIVO1 plus IPI3, and 38% (29-48; 43 of 112 patients) with pooled NIVO1 plus IPI3. The most common grade 3-4 treatment-related adverse events were diarrhoea, hepatic cytolysis, hyponatraemia, pneumonitis, and syncope (one [5%] patient each; nivolumab group), diarrhoea, increased gamma-glutamyl transferase, increased lipase, and vomiting (two [4%] patients each; NIVO3 plus IPI1 group), and increased lipase (nine [8%] patients) and anaemia (seven [6%] patients; pooled NIVO1 plus IPI3 group). Serious treatment-related adverse events were reported in three (16%) patients in the nivolumab group, 12 (27%) patients in the NIVO3 plus IPI1 group, and 47 (42%) patients in the pooled NIVO1 plus IPI3 group. There was one treatment-related death due to immune-mediated colitis in the NIVO1 plus IPI3 group. INTERPRETATION: Nivolumab monotherapy and nivolumab plus ipilimumab combination therapy showed promise in the CheckMate 358 study as potential treatment options for recurrent or metastatic cervical cancer. Future randomised controlled trials of nivolumab plus ipilimumab or other dual immunotherapy regimens are warranted to confirm treatment benefit in this patient population. FUNDING: Bristol Myers Squibb and Ono Pharmaceutical.

Improved Rates of Same-day Discharge in Patients Undergoing Surgery for Endometrial Cancer Following the COVID-19 Pandemic.

STUDY OBJECTIVE: To determine the effect of the coronavirus disease 2019 (COVID-19) pandemic on the rate of same-day discharge (SDD) after minimally invasive surgery for endometrial cancer. DESIGN: Retrospective cohort. SETTING: Teaching hospital. PATIENTS: A total of 166 patients underwent a minimally invasive surgery procedure for the indication of endometrial cancer at a large academic institution from September 1, 2019, to October 1, 2020-80 patients before the implementation of the COVID-19 restrictions and 86 patients after. INTERVENTIONS: COVID-19 pandemic with visitor restrictions and hospital policy changes placed on March 17, 2020. MEASUREMENTS AND MAIN RESULTS: SDD rate was increased by 18% after the start of the COVID-19 pandemic (40% vs 58%, p = .02). There were no differences between the 2 groups with regard to operative time (p = .07), estimated blood loss (p = .21), uterine weight (p = .12), age (p = .06), body mass index (p = .42), or surgery start time (p = .15). In a multivariable logistic regression model, subjects in the COVID-19 group had 3.08 times (95% confidence interval, 1.40-6.74; p = .01) higher odds of SDD than those in the pre-COVID-19 group. There was no difference in 30-day readmission rates (7.5% vs 5.8%, p = .66). CONCLUSION: There was a significant increase in the SDD of patients with endometrial cancer since the start of the COVID-19 pandemic. The pandemic has strained hospital resources and motivated patients and physicians to avoid hospitalization. This shows that with proper motivation, an increase in SDD rates is possible without an increase in complications or rehospitalization.

The MEMORY Study: MulticentEr study of Minimally invasive surgery versus Open Radical hYsterectomy in the management of early-stage cervical cancer: Survival outcomes.

OBJECTIVE: The Laparoscopic Approach to Cervical Cancer (LACC) trial found that minimally invasive radical hysterectomy compared to open radical hysterectomy compromised oncologic outcomes and was associated with worse progression-free survival (PFS) and overall survival (OS) in early-stage cervical carcinoma. We sought to assess oncologic outcomes at multiple centers between minimally invasive (MIS) radical hysterectomy and OPEN radical hysterectomy. METHODS: This is a multi-institutional, retrospective cohort study of patients with 2009 FIGO stage IA1 (with lymphovascular space invasion) to IB1 cervical carcinoma from 1/2007-12/2016. Patients who underwent preoperative therapy were excluded. Squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinomas were included. Appropriate statistical tests were used. RESULTS: We identified 1093 cases for analysis-715 MIS (558 robotic [78%]) and 378. OPEN procedures. The OPEN cohort had more patients with tumors >2 cm, residual disease in the hysterectomy specimen, and more likely to have had adjuvant therapy. Median follow-up for the MIS and OPEN cohorts were 38.5 months (range, 0.03-149.51) and 54.98 months (range, 0.03-145.20), respectively. Three-year PFS rates were 87.9% (95% CI: 84.9-90.4%) and 89% (95% CI: 84.9-92%), respectively (P = 0.6). On multivariate analysis, the adjusted HR for recurrence/death was 0.70 (95% CI: 0.47-1.03; P = 0.07). Three-year OS rates were 95.8% (95% CI: 93.6-97.2%) and 96.6% (95% CI: 93.8-98.2%), respectively (P = 0.8). On multivariate analysis, the adjusted HR for death was 0.81 (95% CI: 0.43-1.52; P = 0.5). CONCLUSION: This multi-institutional analysis showed that an MIS compared to OPEN radical hysterectomy for cervical cancer did not appear to compromise oncologic outcomes, with similar PFS and OS.

Impact of a Clinical Genomics Program on Trial Accrual for Targeted Treatments: Practical Approach Overcoming Barriers to Accrual for Underserved Patients.

PURPOSE: Clinical trials of novel and targeted agents increasingly require biomarkers for eligibility. Precision oncology continues to evolve, but challenges hamper broad use of molecular profiling (MP) that could increase the number of patients benefiting from targeted therapy. We implemented an integrated clinical genomics program (CGP), including a virtual Molecular Tumor Board (MTB), and examined its impact on MP use and impact on clinical trial accrual in a multisite regional-based cancer system with an emphasis on effects for isolated clinicians. METHODS: We assessed MP and MTB use from 2010 to 2020 by practice location, physician experience, and patient characteristics. Use of MTB-recommended treatments was assessed. Clinical trial enrollment was evaluated for patients with MP versus MP and MTB review. RESULTS: After CGP implementation, the number of physicians using MP and the number of MP tests increased ≥ 10-fold. The proportion of Hispanic patients with MP was the same as that in the system (both 2%) with marginal differences observed in the proportion of African Americans tested compared with the system population (16% v 19%). Physicians followed MTB treatment recommendations in 74% of cases. Rapid clinical decline was the most common reason why physicians did not follow MTB recommendations. Clinical trial accrual was 15% (669 of 4,459) for patients with MP alone and 28% (94 of 334) with both MP and MTB review. Clinical trial availability and patient out-of-pocket costs affected MP use. CONCLUSION: Integrating CGP into clinical workflow with decision support tools, trial matching, and management of patient costs led to increased use of MP by physicians with all levels of experience, enhanced clinical trial accrual, and has the potential to reduce disparities in MP.

Enhanced recovery after surgery (ERAS) protocol is associated with lower post-operative opioid use and a reduced office burden after minimally invasive surgery.

OBJECTIVE: Enhanced recovery after surgery (ERAS) has decreased hospital opioid use, but less attention has been directed towards its impact on clinic burden with respect to post-operative care. Our objective was to determine the impact of an ERAS protocol on post-operative opioid prescribing, and the subsequent number of pain medication refill requests and unscheduled patient-provider interactions in the 30-day post-operative period. METHODS: IRB-approved retrospective study comparing post-operative opioid prescription practices 10 months before and 10 months after ERAS protocol implementation after minimally invasive gynecologic surgery. Opioid doses in morphine milligram equivalents (MMEs), number of unscheduled visits, and phone calls were compared before and after ERAS implementation. RESULTS: A total of 791 patients were included; 445 without and 346 with ERAS implementation. ERAS was associated with higher rates of same day discharge (49% vs 39%, p = 0.003) and lower readmission rates (2.0% vs 5.6%, p = 0.011). Post-operatively, patients who received the ERAS protocol were prescribed less opioids (197.8 vs. 223.5 MMEs, p = 0.0087). There was a trend towards less refill requests with ERAS (1.7% vs 3.6%, p = 0.11). ERAS was associated with a decreased number of post-operative phone calls (38% vs 46%, p = 0.023), including calls for pain (10% vs 16%, p = 0.021), and fewer unscheduled visits related to pain (1.5% vs 5.8%, p = 0.001). CONCLUSIONS: Implementation of the ERAS protocol resulted in a decrease in post-operative opioid prescribing. Despite the lower amount of prescribed post-operative opioids, the ERAS protocol translated into a decrease in the need for post-operative interactions with the clinic staff, specifically encounters associated with pain.

Phase Ib Study of Navicixizumab Plus Paclitaxel in Patients With Platinum-Resistant Ovarian, Primary Peritoneal, or Fallopian Tube Cancer.

PURPOSE: This phase Ib study evaluated the safety and efficacy of paclitaxel plus navicixizumab, a bispecific antiangiogenic antibody to vascular endothelial growth factor and delta-like ligand 4, against platinum-resistant ovarian cancer. PATIENTS AND METHODS: This open-label, nonrandomized, dose-escalation and -expansion study included 44 patients with previously treated, recurrent, platinum-resistant grade 2/3 ovarian cancer. Treatment was intravenous navicixizumab (3 mg/kg or 4 mg/kg once every 2 weeks) plus paclitaxel (80 mg/m2 intravenously on days 0, 7, and 14 of 28-day cycles). The primary and secondary objectives were to evaluate the safety and efficacy of navicixizumab plus paclitaxel. An RNA-based diagnostic panel was retrospectively used to test the hypothesis that tumors with high angiogenesis or immune-suppressed tumor microenvironment (TME) subtypes (biomarker-positive) are more likely to respond to navicixizumab than those with immune-active/-desert TME subtypes (biomarker-negative). RNA expression was analyzed in available pretreatment tumor tissue to classify 33 patients' TME subtypes, and TME panel findings were correlated with tumor response. RESULTS: The dose-escalation cohorts enrolled patients at navicixizumab doses of 3 mg/kg once every 2 weeks (n = 3) and 4 mg/kg once every 2 weeks (n = 2); 3 mg/kg was selected for expansion (n = 39). No dose-limiting toxicities occurred. The most common grade 3/4 treatment-related adverse events were hypertension (40.9%), neutropenia (6.8%), and thrombocytopenia (4.5%). Pulmonary hypertension occurred in 18.2% (grade 1-2). The overall objective response rate was 43.2% (95% CI, 28.3 to 59.0): 33.3% (95% CI, 17.3 to 52.8) in patients previously treated with bevacizumab, 64.3% (95% CI, 35.1 to 87.2) in bevacizumab-naive patients, and 62% (95% CI, 31.6 to 86.1) in biomarker-positive patients. The median duration of response was 6 months (95% CI, 5.4 months to not estimable). CONCLUSION: Navicixizumab plus paclitaxel demonstrated promising clinical activity in bevacizumab-treated and -naive patients with platinum-resistant ovarian cancer, with manageable toxicity.

Factors Associated with Same Day Discharge after Laparoscopic Surgery in Gynecologic Oncology.

STUDY OBJECTIVE: To identify factors associated with same day discharge (SDD) after laparoscopic surgery in gynecologic oncology. DESIGN: Retrospective cohort. SETTING: Teaching hospital. PATIENTS: Total of 800 patients having minimally invasive surgery in the division of gynecologic oncology during a 20-month period. INTERVENTION: Minimally invasive surgery cases were reviewed for determinants of SDD to identify factors that could improve the SDD rate. MEASUREMENTS AND MAIN RESULTS: During the study period, 800 minimally invasive procedures were performed with a 43.0% SDD rate. Patients who had SDD were younger (52.3 years vs 58.0 years; p <.001), had a lower body mass index (31.1 kg/m2 vs 33.7 kg/m2; p <.001), were less likely to have a malignancy (28.2% vs 55.5%; p <.001), had a lower estimated blood loss (36 vs 72 mL; p <.001), and were more likely to have received an enhanced recovery after surgery protocol (49.8% vs 39.3%; p <.003). Total surgical time was shorter in women with SDD (156 minutes vs 208 minutes) as was total narcotic use in morphine equivalents (MEq) (milligram intravenous MEq, 23.1 mg MEq vs 28.8 mg MEq). SDD was also associated with earlier start time (p <.001). Laparoscopic cases were most likely to have SDD (51.4%) as compared with robotic assisted surgery (16.1%) or minilaparotomy (10.5%). There was a wide range of SDD among surgeons ranging from 19.8% to 56.2% (p <.001). In a multivariate analysis, the factors predicting SDD in order of predictive factors were surgical time (p <.001), recovery time (p <.001), start time (p <.001), surgeon (p <.001), age (p <.001), estimated blood loss (p <.001), and type of surgery (p = .005). CONCLUSION: Multiple factors affect SDD. Modifiable factors for SDD include the start time, surgeon preference, and patient expectations for SDD. Given these data, centers should prioritize surgical order by which patients are more likely to go home, and surgeons should analyze their own data with respect to achieving higher SDD rates.

RaPiDS (GOG-3028): randomized Phase II study of balstilimab alone or in combination with zalifrelimab in cervical cancer.

Balstilimab (anti-programmed death 1) and zalifrelimab (anti-CTLA-4) are two new checkpoint inhibitors that have emerged as promising investigational agents for the treatment of cervical cancer, particularly in the setting of previously-treated, recurrent/metastatic disease. Here we describe the rationale and design of RaPiDS (NCT03894215), a two-arm Phase II study evaluating the safety, tolerability and efficacy of balstilimab administered alone or in combination with zalifrelimab in patients with advanced cervical cancer who progressed after first-line, platinum-based chemotherapy. Patients will be randomized in a 1:1 ratio. The primary end point is objective response rate, and key secondary objectives include safety, duration of response, progression-free survival, overall survival and quality of life outcomes.

Lay abstract Current treatment options for women with recurrent/metastatic cervical cancer are limited. Immunotherapy is altering the therapeutic landscape in this setting yet opportunities remain to improve on current outcomes. Dual blockade of different immune checkpoints is an approach shown to be highly effective in other cancers. Balstilimab (anti-programmed death 1) and zalifrelimab (anti-CTLA-4) are two new checkpoint inhibitors showing promise in patients with advanced cervical cancer. The RaPiDS trial is designed to characterize the safety and activity of balstilimab, alone and in combination with zalifrelimab, in patients with recurrent/metastatic cervical cancer who progressed after prior platinum-based chemotherapy. Clinical trial registration: NCT03894215 (ClinicalTrials.gov).

Perioperative Recovery and Narcotic Use in Laparoscopic versus Robotic Surgery for Endometrial Cancer.

STUDY OBJECTIVE: To compare intraoperative and perioperative narcotic use, recovery room time, and total hospital stay for patients treated with robotic vs laparoscopic surgery for endometrial cancer. DESIGN: Retrospective cohort. SETTING: Teaching hospital. PATIENTS: All patients having minimally invasive surgery in the division of gynecologic oncology during a 20-month period. INTERVENTION: Laparoscopic cases were compared with robot-assisted cases with respect to perioperative outcome. MEASUREMENT AND MAIN RESULTS: Hospital billing records were used to identify all patients with endometrial cancer treated from January 1, 2018 through July 31, 2019 undergoing either laparoscopic or robotic surgery. Data were collected including total narcotic use converted to intravenous morphine milligram equivalent (MME), total amount of time in recovery, and length of hospital stay. A total of 139 laparoscopic and 101 robotic surgeries were eligible for analysis. There was no difference between the groups with respect to blood loss, alcohol use, or smoking. Patients undergoing laparoscopy had a significantly lower body mass index compared with patients undergoing robotic surgery (32.9 vs 38.0 kg/m2; p <.001). Univariate analysis showed no difference between the 2 groups with respect to narcotic use in surgery (21.7 vs 21.1 MME; p = .64), recovery (4.3 vs 4.5 MME; p = .70), or total dose (26.0 vs 25.6 MME; p = .78). However, patients who underwent a robotic approach had a longer recovery room time (128 minutes vs 163 minutes; p <.001 and a longer surgical time (288 minutes vs 204 minutes; p = .001). Patients in the robotic group were also more likely to undergo full lymphadenectomy than patients in the laparoscopy group (38.0% vs 20.8% p <.001). In a multivariate analysis, the only significant factors for predicting total narcotic dose were age, use of a preoperative enhanced recovery after surgery program, and surgical time. Patients who had laparoscopy were more likely to achieve same-day discharge (39.3% vs 17.8%; p <.001), but in the multivariate analysis, the type of surgery did not predict same-day discharge. CONCLUSION: There was no difference in narcotic use in the perioperative period with robotic surgery compared with laparoscopy. Recovery time was longer for robotic surgery, but this was not significant in multivariate analysis. Same-day discharges were less frequent with robotics, which may be more related to the physician's choice rather than the procedure.

The impact of opportunistic salpingectomy on ovarian cancer mortality and healthcare costs: a call for universal insurance coverage.

BACKGROUND: Opportunistic salpingectomy at the time of hysterectomy or as an alternative to bilateral tubal ligation may reduce the incidence of ovarian cancer, because it has been demonstrated that most serous ovarian cancers begin in the fallopian tubes. However, salpingectomy at the time of sterilization is not always financially covered by third-party payers, and this represents a barrier to adoption. Routine salpingectomy has become more common but is not always practiced at the time of hysterectomy. OBJECTIVE: This study aimed to determine the impact of opportunistic salpingectomy as an alternative tubal ligation and routine salpingectomy at the time of hysterectomy on ovarian cancer mortality and overall cost. STUDY DESIGN: An 8-state Markov state transition model was constructed, including hysterectomy, tubal ligation, and ovarian cancer. Transition probabilities were informed by previously reported population data and include age-adjusted rates of elective sterilization and hysterectomy. This model was used to predict ovarian cancer incidence and the cost effectiveness of opportunistic salpingectomy. Testing of this model suggested that it accurately predicted overall life expectancy and closely predicted the rate of hysterectomy in the population. The model may underestimate the rate of tubal sterilization, making it conservative with respect to the benefits of salpingectomy. RESULTS: The recursive Markov model was run from ages 20 to 85 years in 1-year intervals with a half step correction and included age-adjusted rates of tubal ligation, hysterectomy (with and without oophorectomy), and ovarian cancer. The model predicts that opportunistic salpingectomy at the time of tubal ligation will reduce ovarian cancer mortality by 8.13%. Opportunistic salpingectomy at the time of hysterectomy will reduce ovarian cancer mortality by 6.34% for a combined decrease of 14.5%. Both strategies are cost effective when considering only the cost of the opportunistic salpingectomy. The excess cost of opportunistic salpingectomy at the time of tubal ligation was $433.91 with an incremental cost-effective ratio of $6401 per life-year and $5469 per quality-adjusted life year gained when adjusting for ovarian cancer with a utility of 0.64. The incremental cost-effective ratio for opportunistic salpingectomy during hysterectomy at a cost of $124.70 was $2006 per life-year and $1667 per quality-adjusted life year. When considering the impact of ovarian cancer prevention with respect to the cost of ovarian cancer treatment, opportunistic salpingectomy may produce a substantial healthcare savings. Utilizing a 3% discount rate, it is estimated that the total savings for universal salpingectomy could be as high as $445 million annually in the United States. A sensitivity analysis around the benefit of opportunistic salpingectomy suggests that this procedure will be cost effective even if salpingectomy provides only a modest reduction in the risk of ovarian cancer. CONCLUSION: It is estimated that universal opportunistic salpingectomy may prevent 1854 deaths per year from ovarian cancer and may reduce healthcare costs. Given these data, universal opportunistic salpingectomy should be considered at the time of tubal ligation and hysterectomy and covered by third-party payers.

Comparison of Perioperative Outcomes between Minimally Invasive Sentinel Node Biopsy and Full Lymphadenectomy for Endometrial Cancer.

STUDY OBJECTIVE: To review the perioperative differences between patients undergoing a minimally invasive sentinel lymph node dissection and those undergoing a full lymphadenectomy. DESIGN: Retrospective review. SETTING: Teaching hospital. PATIENTS: All patients undergoing a minimally invasive procedure for endometrial cancer that included nodal evaluation. INTERVENTIONS: Patients who underwent a sentinel lymph node biopsy were compared with those who underwent a full lymphadenectomy at the time of minimally invasive surgery by either laparoscopic or robot-assisted surgery. MEASUREMENTS AND MAIN RESULTS: A total of 241 minimally invasive surgery procedures for endometrial cancer were performed during the 20-month study period. Nodal dissection was indicated and performed in 156 (65%) of these patients, with 93 undergoing a sentinel lymph node biopsy and 63 a full lymphadenectomy. There was no difference between the sentinel group and the lymphadenectomy group with respect to age, estimated blood loss (p = .23), use of a preoperative enhanced recovery after surgery program (p = .82), or body mass index (34.0 kg/m2 vs 33.7 kg/m2; p = .87). The use of full lymphadenectomy was very dependent on the surgeon (p <.001). There was no difference in narcotic use in milligram intravenous equivalents of morphine in surgery (20.9 vs 22.2; p = .37), recovery (4.6 vs 4.9; p = .73), or total dose (25.4 vs 27.0; p = .33). The surgical procedure was longer with lymphadenectomy (185.2 minutes vs 214.2 minutes; p <.001) and the relative risk of discharge from recovery was lower (0.71; 95% confidence interval, 0.51-0.97; p = .03). The hospital stay was longer with lymphadenectomy (16.3 hours vs 25.5 hours; p <.001) and same-day discharge less frequent (48.5% vs 13.8%; p <.001). A multivariate analysis confirmed that sentinel node biopsy was associated with an increased relative risk of discharge of 1.68 (95% confidence interval 1.11-2.53; p = .01) CONCLUSION: Total narcotic requirements are similar between sentinel node biopsy and lymphadenectomy. However, sentinel node biopsy is associated with a shorter surgical time, recovery time, and hospital stay.

Outcomes of Minimally Invasive versus Open Radical Hysterectomy for Early Stage Cervical Cancer Incorporating 2018 FIGO Staging.

STUDY OBJECTIVE: To compare outcomes after minimally invasive surgery (MIS) vs open radical hysterectomy for early stage cervical cancer incorporating 2018 Federation of Gynecology and Obstetrics (FIGO) staging. DESIGN: A retrospective analysis. SETTING: A single teaching hospital. PATIENTS: Patients after radical hysterectomy for stage IA1 with lymphovascular invasion, IA2, or IB1 squamous, adenosquamous, or adenocarcinoma of the cervix between 2007 and 2018, mirroring the Laparoscopic Approach to Cervical Cancer trial criteria. INTERVENTIONS: The use of MIS surgery for performing radical hysterectomy. MEASUREMENTS AND MAIN RESULTS: The outcomes were compared between patients undergoing MIS vs open approaches. A total of 126 patients met the inclusion criteria. The approach was open in 44 patients (35%) and MIS in 82 patients (65%); 49% were laparoscopic and 51% were robotic. Distribution based on the 2009 FIGO staging showed 1 stage IA1 with lymphovascular invasion, 15 stage IA2, and 110 stage IB1 patients. Although not statistically significant, the 3-year disease-free survival (DFS) was higher in the open compared to the MIS group (95% vs 87%; p = .17), and the overall survival was higher in the open compared to the MIS group (97% vs 92%; p = .25). Fourteen patients whose disease recurred were Stage IB1 by FIGO 2009 staging; 11/14 were reclassified to a higher stage by 2018 FIGO staging (5/5 open, 6/9 MIS). Adjuvant therapy was recommended for all these patients based on the Sedlis criteria (10/14) or other risk factors (4/14). Despite this, only 1/9 of MIS patients whose disease recurred received adjuvant therapy compared with 3/5 patients whose disease recurred in the open group (p = .05). CONCLUSION: In a cohort of patients similar to that of the Laparoscopic Approach to Cervical Cancer trial, 2018 FIGO staging may be useful to refine indications for MIS radical hysterectomy in early stage cervical cancer. However, disparate outcomes between MIS and open approaches may be explained by differences in compliance with National Comprehensive Cancer Network guidelines for adjuvant therapy.

Pre-emptive Non-narcotic Pain Medication before Minimally Invasive Surgery in Gynecologic Oncology.

STUDY OBJECTIVE: To review the impact of enhanced recovery after surgery (ERAS) after minimally invasive surgery (MIS) with respect to perioperative narcotics, time in the recovery room, and total time in hospital. DESIGN: Retrospective cohort. SETTING: Teaching hospital. PATIENTS: All patients having MIS in the division of gynecologic oncology during a 20-month period. INTERVENTION: MIS cases were compared before and after the implementation of an ERAS protocol that incorporated orally administered acetaminophen, gabapentin, and celecoxib. MEASUREMENT AND MAIN RESULTS: A total of 800 MIS cases were performed during the period (77% laparoscopy, 18% robotic, 5% mini-lap). Of these, 449 cases were treated without and 351 with the ERAS protocol. There were no significant differences between the groups with respect to age, BMI, surgery type, smoking, surgical indication, blood loss, or diagnosis. Total narcotic use in milligram intravenous equivalents of morphine (mg IV Eq) was significantly less in the ERAS patients (28.5-mg IV Eq vs 23.6-mg IV Eq; p <.001). There was a trend toward less narcotics in recovery (4.8-mg IV Eq vs 4.1-mg IV Eq; p = .08). Postoperative recovery room time was not different between the groups (129 minutes vs 131 minutes; p = .66). ERAS was associated with a higher rate of same day discharge (38.5% vs 49.0%; p = .003) and a shorter length of hospital stay (22.9 hours vs 18.5 hours; p = .008), with a hazard ratio for discharge of 0.82 (0.71-0.94). However, the same day discharge rate varied widely between treating physicians (20% to 56%). CONCLUSIONS: Implementation of an ERAS protocol for MIS appears to reduce total perioperative narcotic use but does not reduce recovery room time. There was a reduction in total hospital time, but this may be dependent on practice patterns of individual physicians.

Re-evaluating "Success" as It Pertains to Surgical Trials.

The objective of this article is to review the difficulties with the design and interpretation of surgical clinical trials. Few surgical procedures are evaluated in a randomized fashion. There are a number of factors that make the design of surgical trials diffiuclt, and many surgical questions cannot be answered with a clinical trial. Issues with standardization of the surgical procedure, variability of surgical skills, and changes in surgical expertise over time further complicate the design and implementation of surgical trials. Statistical methods for surgical trials often require a noninferiorty design and are more complicated to interpret than the more common superiority trial. Even when properly conducted, both superiority and noninferiority trials are often misinterpreted. Because of the relatively high success rate in surgery, trials require large numbers of patients and noninferiority trials are often inconclusive with respect to the primary outcome. Surgical trials are often misinterpreted or over interpreted, and there can be confusion in how the findings of these trials should be incorportated into clinical practice. The interpretation of the results of a surgical trial often differ significantly from the primary and secondary outcomes that were specified in the trial design.

Anti-cancer therapy and clinical trial considerations for gynecologic oncology patients during the COVID-19 pandemic crisis.

OBJECTIVES: The COVID-19 pandemic has consumed considerable resources and has impacted the delivery of cancer care. Patients with cancer may have factors which place them at high risk for COVID 19 morbidity or mortality. Highly immunosuppressive chemotherapy regimens and possible exposure to COVID-19 during treatment may put patients at additional risk. The Society of Gynecologic Oncology convened an expert panel to address recommendations for best practices during this crisis to minimize risk to patients from deviations in cancer care and from COVID-19 morbidity. METHODS: An expert panel convened to develop initial consensus guidelines regarding anti-neoplastic therapy during the COVID-19 pandemic with respect to gynecologic cancer care and clinical trials. RESULTS: COVID-19 poses special risks to patients who are older, have medical co-morbidities, and cancer. In addition, this pandemic will likely strain resources, making delivery of cancer care or conduct of clinical trials unpredictable. Recommendations are to limit visits and contact with health care facilities by using telemedicine when appropriate, and choosing regimens which require less frequent visits and which are less immunosuppressive. Deviations will occur in clinical trials as a result of limited resources, and it is important to understand regulatory obligations to trial sponsors as well as to the IRB to ensure that clinical trial and patient safety oversight are maintained. CONCLUSIONS: The ongoing crisis will strain resources needed to deliver cancer care. When alterations to the delivery of care are mandated, efforts should be taken to minimize risks and maximize safety while approximating standard practice.

European society of medical oncology (ESMO) 2019 meeting report features practice changing data in gynecologic malignancies.

Multiple practice changing studies were presented at the 2019 ESMO Congress in Barcelona, Spain. The ovarian cancer studies presented at the Presidential session will likely refine and redefine the initial treatment of ovarian cancer. Other compelling trial data in ovarian, uterine and cervical cancer were also unveiled. The key oral abstracts from this meeting are summarized in this meeting report.

Safety and Efficacy of Nivolumab Monotherapy in Recurrent or Metastatic Cervical, Vaginal, or Vulvar Carcinoma: Results From the Phase I/II CheckMate 358 Trial.

PURPOSE: Nivolumab was assessed in patients with virus-associated tumors in the phase I/II CheckMate 358 trial (ClinicalTrials.gov identifier: NCT02488759). We report on patients with recurrent/metastatic cervical, vaginal, or vulvar cancers. PATIENTS AND METHODS: Patients received nivolumab 240 mg every 2 weeks. Although patients with unknown human papillomavirus status were enrolled, patients known to have human papillomavirus-negative tumors were ineligible. The primary end point was objective response rate. Duration of response (DOR), progression-free survival, and overall survival were secondary end points. Safety and patient-reported outcomes were exploratory end points. RESULTS: Twenty-four patients (cervical, n = 19; vaginal/vulvar, n = 5) were enrolled. Most patients had received prior systemic therapy for metastatic disease (cervical, 78.9%; vaginal/vulvar, 80.0%). Objective response rates were 26.3% (95% CI, 9.1 to 51.2) for cervical cancer and 20.0% (95% CI, 0.5 to 71.6) for vaginal/vulvar cancers. At a median follow-up of 19.2 months, median DOR was not reached (range, 23.3 to 29.5+ months; + indicates a censored observation) in the five responding patients in the cervical cohort; the DOR was 5.0 months in the single responding patient in the vaginal/vulvar cohort. Median overall survival was 21.9 months (95% CI, 15.1 months to not reached) among patients with cervical cancer. Any-grade treatment-related adverse events were reported in 12 of 19 patients (63.2%) in the cervical cohort and all five patients in the vaginal/vulvar cohort; there were no treatment-related deaths. In the cervical cohort, nivolumab treatment generally resulted in stabilization of patient-reported outcomes associated with health status and health-related quality of life. CONCLUSION: The efficacy of nivolumab in patients with recurrent/metastatic cervical and vaginal or vulvar cancers is promising and warrants additional investigation. No new safety signals were identified with nivolumab treatment in this population.

Workplace Harassment and Discrimination in Gynecology: Results of the AAGL Member Survey.

STUDY OBJECTIVE: To characterize workplace and sexual harassment and discrimination among physicians in gynecology. DESIGN: A beta-tested Internet survey was distributed by e-mail using the REDCap platform. All responses were anonymous. SETTING: The survey was distributed to the 7026 physician members of an international gynecologic society (AAGL), including faculty and trainees. PATIENTS: Not applicable. INTERVENTIONS: The survey was distributed on 3 occasions between July and September 2018. The survey contained questions on demographics, attitudes, experiences, and sequelae regarding harassment and discrimination in the workplace. Frequency distributions and nonparametric tests were performed to determine the percentages and types of harassment and discrimination among respondents. MEASUREMENTS AND MAIN RESULTS: A total of 907 physicians responded, including 603 US physicians and 304 non-US physicians; 59% identified as female and 40% as male, and 20% were trainees. Females were more likely than males to think the #MeToo movement was "justified and overdue" (p < .05), independent of age or trainee status. More females than males reported experiencing workplace discrimination (67% vs 39%; p < .001); gender-based discrimination was the most common basis for both. Females indicated decreased self-confidence and lower salary; males indicated fewer employment opportunities and lower patient volume. Harassment was reported by more females than males (53% vs 17%; p < .001), including sexual harassment (39% vs 11%, p <.05). Most experienced loss of self-confidence, felt the offender was in a position of power, and did not report the incident, often due to fear of reprisal. Multiple respondents experienced workplace-related sexual assault. CONCLUSION: Workplace harassment and discrimination are commonly experienced by female and male gynecologists and are usually related to a power differential. Improvements must be made in the workplace environment to achieve equity and a safe workplace free of harassment and discrimination.