Primary cytoreductive surgery compared with neoadjuvant chemotherapy in patients with BRCA mutated advanced high grade serous ovarian cancer: 10 year survival analysis.

OBJECTIVES: Given the high response to platinum based chemotherapy in BRCA 1/2 mutated high grade serous ovarian cancers, there is uncertainty about the relative benefits of primary cytoreductive surgery versus neoadjuvant chemotherapy in this population. We aimed to compare the survival outcomes for women with BRCA 1/2 mutated high grade serous ovarian cancers undergoing either primary cytoreductive surgery or neoadjuvant chemotherapy. METHODS: We conducted a retrospective cohort study of all stage III/IV BRCA mutated high grade serous ovarian cancers treated with primary cytoreductive surgery or neoadjuvant chemotherapy at a single tertiary cancer center between 1991 and 2020. Baseline demographics, initial disease burden, surgical complexity, and survival outcomes were examined. RESULTS: Of 314 women with germline or somatic BRCA mutations, 194 (62%) underwent primary cytoreductive surgery and 120 (38%) underwent neoadjuvant chemotherapy followed by interval cytoreductive surgery. Those undergoing primary cytoreductive surgery were younger (median age 53 years (range 47-59) vs 59 years (50-65), p<0.001), but there were no differences in functional status or underlying comorbidities. The initial disease burden was lower (disease score high (40% vs 44%; p<0.001) but surgical complexity was higher (surgical complexity score high (18% vs 3%; p<0.001) in the primary cytoreductive surgery cohort. The rate of optimal or complete cytoreduction was similar in both groups (89% vs 90%; p=0.23) as well as the rate of poly (ADP-ribose) polymerase inhibitor use (62% vs 68%; p=0.3). The 10 year overall survival and recurrence free survival were superior in the primary cytoreductive surgery cohort (overall survival 49% vs 25%, p<0.001 and progression free survival 25% vs 10%, p<0.001). After controlling for confounders, primary cytoreductive surgery remained a significant predictor of improved overall survival (hazard ratio (HR) 0.45; 95% confidence interval (CI) 0.27 to 0.74; p=0.002) and recurrence free survival (HR 0.55; 95% CI 0.37 to 0.80; p=0.002). CONCLUSIONS: Primary cytoreductive surgery was associated with improved survival in women with stage III/IV BRCA mutated high grade serous ovarian cancers compared with neoadjuvant chemotherapy.

Comprehensive molecular assessment of mismatch repair deficiency in Lynch associated ovarian cancers using next generation sequencing panel.

OBJECTIVES: Abnormalities in mismatch repair have been described in ovarian cancer, but few studies have examined the causes of mismatch repair deficiency (MMRd). To address this, we completed targeted mutational and methylation sequencing on MMRd ovarian cancer cases. The objective of this study was to explore the molecular mechanism of MMRd using our targeted next generation sequencing panel. METHODS: Newly diagnosed non-serous/mucinous ovarian cancers (n=215) were prospectively recruited from three cancer centers in Ontario, Canada, between 2015 and 2018. Tumors were reflexively assessed for mismatch repair protein by immunohistochemistry. Matched tumor-normal MMRd cases were analyzed on a custom next generation sequencing panel to identify germline and somatic mutations, copy number variants, rearrangements, and promoter methylation in mismatch repair and associated genes. RESULTS: Of 215 cases, 28 (13%) were MMRd. The MMRd cohort had a median age of 52.3 years (range 33.6-62.2), with mostly stage I (50%) and grade 1 or 2 endometrioid histotype (57%). Of the 28 cases, 22 were available for molecular analysis, and Lynch syndrome was detected in 50% of MMRd cases (11/22; seven ovarian cancer and four synchronous ovarian and endometrial cancer: seven MSH6, two MLH1, one PMS2, and one MSH2). An explanation for the observed mismatch repair phenotype was available for 22/22 deficient cases, including 12 MLH1/PMS2 deficient (nine somatic methylation, one bi-allelic somatic deletion, and two pathogenic germline variant), one PMS2 deficient (one pathogenic germline variant), seven MSH6 deficient (seven pathogenic germline variant), and two MSH2/MSH6 deficient (one pathogenic germline variant and one bi-allelic somatic mutation). Concordance between clinical germline testing and panel sequencing results was 100%. CONCLUSIONS: Use of our custom next generation sequencing panel allowed for the streamlined assessment of hereditary and somatic causes of MMRd in ovarian cancers.

Cost impact analysis of enhanced recovery after minimally invasive gynecologic oncology surgery.

OBJECTIVE: The implementation of a peri-operative care program based on enhanced recovery after surgery principles for minimally invasive gynecologic oncology surgery led to an improvement in same day discharge from 29% to 75% at our center. This study aimed to determine the program's economic impact. METHODS: Our initial enhanced recovery quality improvement program enrolled consecutive patients undergoing minimally invasive hysterectomy at a single center during a 12-month period and compared them to a pre-intervention cohort. The primary outcome was overall costs. The secondary outcomes were surgical and post-operative visit costs. The surgical visit costs included pre-operative and operating room, post-operative stay, pharmacy, and interventions costs. The 30-day post-operative visit costs included clinic and emergency room, and readmission costs. The costs for every visit were collected from the case-cost department and expressed in 2020 Canadian dollars (CAD). RESULTS: A total of 96 and 101 patients were included in the pre- and post-intervention groups, respectively. The median total cost per patient for post-intervention was $7252 compared with $8381 pre-intervention (p=0.02), resulting in a $1129 cost reduction per patient. The total cost for the program implementation was $134 per patient for a total cost of $13 106. The median post-operative stay cost was $816 post-intervention compared with $1278 pre-intervention (p<0.05). Statistically significant savings for the post-intervention group were also found for operative visit, operating room costs, and pharmacy (p<0.05). On multivariate analysis, surgical approach was the only factor associated with operating room costs, whereas both surgical approach and group (pre- vs post-intervention) impacted the total and post-operative stay costs (p<0.05). CONCLUSION: In addition to increasing the same day discharge rate after minimally invasive gynecologic oncology surgery, an enhanced recovery-based peri-operative care program led to significant reductions in cost.

Safety of fertility sparing management in invasive mucinous ovarian carcinoma.

BACKGROUND: The aim of the study was to evaluate the safety of fertility-sparing surgery in invasive mucinous ovarian carcinomas (MOC). METHODS: Retrospective review was performed of MOCs diagnosed between 1999 and 2019 at two tertiary cancer centers. Pathology was reviewed to rule out metastasis from gastrointestinal tract. The demographics and survival outcomes were compared between women who underwent fertility-sparing surgery and those who underwent radical surgery (at least hysterectomy, bilateral salpingo-oophorectomy +/- staging). Cox proportional hazard models were constructed to evaluate the effect of fertility sparing surgery on survival. RESULTS: Of 134 with stage I disease, 42 (31%) underwent fertility-sparing surgery with unilateral salpingo-oophorectomy. Compared to women who underwent radical surgery, these women were younger with low grade, early-stage disease. Two patients (5%) in the fertility-sparing cohort experienced a recurrence and 1 of these 2 patients died due to disease progression. There was no difference in either OS or RFS between those that underwent fertility-sparing surgery and radical surgery. In a multivariable analysis adjusting for age and use of adjuvant chemotherapy, fertility-sparing surgery was not significantly associated with OS (HR 0.18; 95% CI 0.01-2.78) or RFS (HR 0.19; 95% CI 0.03-1.45). There were 4 patients (9%) with documented full-term delivery with median interval to conception of 11 months. CONCLUSIONS: Fertility-sparing surgery in stage I MOC is not associated with worse outcomes compared to radical surgery and is reasonable to offer to those with early stage disease who wish to retain fertility.

Impact of lymphadenectomy and intra-operative tumor rupture on survival in early-stage mucinous ovarian cancers.

OBJECTIVE: Mucinous ovarian carcinoma is a rare subtype of epithelial ovarian cancer with scarce literature guiding its management. We aimed to investigate the optimal surgical management of clinical stage I mucinous ovarian carcinoma by examining the prognostic significance of lymphadenectomy and intra-operative rupture on patient survival. METHODS: We conducted a retrospective cohort study of all pathology-reviewed invasive mucinous ovarian carcinomas diagnosed between 1999 and 2019 at two tertiary care cancer centers. Baseline demographics, surgical management details, and outcomes were collected. Five-year overall survival, recurrence-free survival, and the association of lymphadenectomy and intra-operative rupture on survival were examined. RESULTS: Of 170 women with mucinous ovarian carcinoma, 149 (88%) had clinical stage I disease. Forty-eight (32%; n=149) patients had a pelvic and/or para-aortic lymphadenectomy, but only 1 patient with grade 2 disease was upstaged due to positive pelvic lymph nodes. Intra-operative tumor rupture was documented in 52 cases (35%). On multivariable analysis, after adjusting for age, final stage, and use of adjuvant chemotherapy, there was no significant association between intra-operative rupture with overall survival (HR 2.2 (0.6-8.0); p=0.3) or recurrence-free survival (HR 1.3 (0.5-3.3); p=0.6), or lymphadenectomy with overall survival (HR 0.9 (0.3-2.8); p=0.9) or recurrence-free survival (HR 1.2 (0.5-3.0); p=0.7). Advanced stage was the only factor that was significantly associated with survival. CONCLUSIONS: In clinical stage I mucinous ovarian carcinoma, systematic lymphadenectomy has low utility, as very few patients are upstaged and recurrence typically occurs in the peritoneum. Furthermore, intra-operative rupture does not appear to independently confer a worse survival, and therefore these women may not benefit from adjuvant treatment based on rupture alone.

Oncologic Outcomes of Surgically Treated Cervical Cancer with No Residual Disease on Hysterectomy Specimen: A 4C (Canadian Cervical Cancer Collaborative) Working Group Study.

Minimally invasive surgery for the treatment of macroscopic cervical cancer leads to worse oncologic outcomes than with open surgery. Preoperative conization may mitigate the risk of surgical approach. Our objective was to describe the oncologic outcomes in cases of cervical cancer initially treated with conization, and subsequently found to have no residual cervical cancer after hysterectomy performed via open and minimally invasive approaches. This was a retrospective cohort study of surgically treated cervical cancer at 11 Canadian institutions from 2007 to 2017. Cases initially treated with cervical conization and subsequent hysterectomy, with no residual disease on hysterectomy specimen were included. They were subdivided according to minimally invasive (laparoscopic/robotic (MIS) or laparoscopically assisted vaginal/vaginal hysterectomy (LVH)), or abdominal (AH). Recurrence free survival (RFS) and overall survival (OS) were estimated using Kaplan-Meier analysis. Chi-square and log-rank tests were used to compare between cohorts. Within the total cohort, 238/1696 (14%) had no residual disease on hysterectomy specimen (122 MIS, 103 AH, and 13 VLH). The majority of cases in the cohort were FIGO 2018 stage IB1 (43.7%) and underwent a radical hysterectomy (81.9%). There was no statistical difference between stage, histology, and radical vs simple hysterectomy between the abdominal and minimally invasive groups. There were no significant differences in RFS (5-year: MIS/LVH 97.7%, AH 95.8%, p = 0.23) or OS (5-year: MIS/VLH 98.9%, AH 97.4%, p = 0.10), although event-rates were low. There were only two recurrences. In this large study including only patients with no residual cervical cancer on hysterectomy specimen, no significant differences in survival were seen by surgical approach. This may be due to the small number of events or due to no actual difference between the groups. Further studies are warranted.

Mismatch-repair deficiency, microsatellite instability, and lynch syndrome in ovarian cancer: A systematic review and meta-analysis.

OBJECTIVE: Investigating for mismatch repair protein deficiency (MMRd), microsatellite instability (MSI), and Lynch syndrome (LS) is widely accepted in endometrial cancer, but knowledge is limited on its value in epithelial ovarian cancer (EOC). The primary objective was to evaluate the prevalence of mismatch repair protein deficiency (MMRd), microsatellite instability (MSI)-high, and Lynch syndrome (LS) in epithelial ovarian cancer (EOC), as well as the diagnostic accuracy of LS screening tests. The secondary objective was to determine the prevalence of MMRd, MSI-high, and LS in synchronous ovarian endometrial cancer and in histological subtypes. METHODS: We systematically searched the MEDLINE, Epub Ahead of Print, MEDLINE In-Process and Other Non-Indexed Citations, Cochrane Central Register of Controlled Trials, and Embase databases. We included studies analysing MMR, MSI, and/or LS by sequencing. RESULTS: A total of 55 studies were included. The prevalence of MMRd, MSI-high, and LS in EOC was 6% (95% confidence interval (CI) 5-8%), 13% (95% CI 12-15%), and 2% (95% CI 1-3%) respectively. Hypermethylation was present in 76% of patients with MLH1 deficiency (95% CI 64-84%). The MMRd prevalence was highest in endometrioid (12%) followed by non-serous non-mucinous (9%) and lowest in serous (1%) histological subtypes. MSI-high prevalence was highest in endometrioid (12%) and non-serous non-mucinous (12%) and lowest in serous (9%) histological subtypes. Synchronous and endometrioid EOC had the highest prevalence of LS pathogenic variants at 7% and 3% respectively, with serous having lowest prevalence (1%). Synchronous ovarian and endometrial cancers had highest rates of MMRd (28%) and MSI-high (28%). Sensitivity was highest for IHC (91.1%) and IHC with MSI (92.8%), while specificity was highest for IHC with methylation (92.3%). CONCLUSION: MMRd and germline LS testing should be considered for non-serous non-mucinous EOC, particularly for endometrioid. PRECIS: The rates of mismatch repair deficiency, microsatellite instability high, and mismatch repair germline mutations are highest in endometrioid subtype and non-serous non-mucinous ovarian cancer. The rates are lowest in serous histologic subtype.

Acceptability of bariatric surgery in people with endometrial cancer and atypical hyperplasia: A qualitative study.

OBJECTIVE: In young individuals with obesity, infertility, and endometrial cancer, significant, sustained weight loss through bariatric surgery may result in a durable oncologic and reproductive response. However, it is not known whether bariatric surgery is acceptable to this patient population. We performed a qualitative study to understand the acceptability of bariatric surgery in young individuals with obesity and endometrial cancer or atypical hyperplasia. STUDY DESIGN: All participants were of reproductive age with body mass index [BMI] ≥ 35 and grade 1 endometrial cancer or atypical hyperplasia. Semi-structured interviews were used to explore participant perception of their weight, fertility, and the possibility of bariatric surgery as part of the treatment strategy for their endometrial cancer/atypical hyperplasia. Thematic saturation was reached after 14 interviews. RESULTS: Fourteen participants with a median age of 34 years (range 27-38) and BMI of 42 (33-64) were interviewed. Participants were reluctant to accept bariatric surgery as a treatment option due to 1) lack of knowledge about the procedure, 2) stigma attached to bariatric surgery, and 3) fear of the risks associated with bariatric surgery. Their perception towards their weight, fertility, and cancer diagnosis was characterized by concepts of 'helplessness', 'isolation', 'frustration', and 'guilt'. We observed a significant gap in participant understanding of the complex interplay between their cancer, infertility, and obesity. CONCLUSIONS: More support and resources are required, with patient-oriented counseling focused on the implication of their weight on their cancer diagnosis and fertility, before presenting bariatric surgery as a treatment option.

The impact of interval between primary cytoreductive surgery with bowel resection and initiation of adjuvant chemotherapy on survival of women with advanced ovarian cancer: a multicenter cohort study.

OBJECTIVE: Our aim was to determine if the time interval between bowel resection and initiation of adjuvant chemotherapy impacts survival in advanced ovarian cancers. METHODS: This was a retrospective cohort study using data from two cancer centers, Princess Margaret Cancer Centre in Toronto, Ontario, Canada and Samsung Comprehensive Cancer Center in Seoul, South Korea. Patients with International Federation of Gynecology and Obstetrics (FIGO) stage III or IV ovarian cancer that underwent large bowel resection during primary cytoreductive surgery (PCS) were included. RESULTS: Ninety-one women were eligible of which the majority (90.1%) were diagnosed with high-grade serous cancer. The median interval from PCS to chemotherapy for all patients was 21 days (7-86 days). Patients were stratified into 3 groups: 1) Interval ≤14 days, 32 (35.2%) patients; 2) Interval between 15-28 days, 27 (29.6%) patients; and 3) Interval between 29-90 days, 32 (35.2%) patients. Surgical procedures and postoperative outcomes were similar between groups. Multivariate analysis indicated that PCS to chemotherapy interval of 2-4 weeks, younger age, and completion of 4 or more adjuvant chemotherapy cycles were independent prognostic factors of favorable overall survival. CONCLUSION: Initiation of adjuvant chemotherapy between 2 to 4 weeks after PCS with bowel resection may improve survival outcomes in women with advanced ovarian cancer by maximizing the benefit of PCS plus adjuvant chemotherapy.

Implementation of a standardized voiding protocol after minimally invasive surgery: A quality improvement initiative.

OBJECTIVES: To assess the effects of the implementation of a standardized voiding protocol in patients undergoing minimally invasive hysterectomy at a single cancer center in terms of the urinary tract infection (UTI) rate, time to first void, and overnight stays secondary to urinary retention. METHODS: We enrolled 102 consecutive patients undergoing minimally invasive hysterectomy at a single cancer center during a 12-month period. A pre-intervention cohort of 100 consecutive patients was identified for comparison. A multidisciplinary team developed and implemented a standardized voiding protocol using quality improvement methodology. We compared the demographics, time to first void, rate of urinary retention, and UTI rates between the pre- and post-intervention cohorts. RESULTS: Our intervention led to a significant reduction in the time to first void (289 min vs. 566 min; P < 0.001), rate of urinary retention (2% vs. 10%; P = 0.015), and postoperative UTI (4% vs. 8%; P = 0.249). There was a similar rate of patients going home with a Foley catheter (9% vs. 11%; P = 0.850). CONCLUSIONS: Implementation of a standardized voiding protocol was associated with a reduction in rate of UTI, time to first void, and overnight stays secondary to urinary retention.

Management of Isolated Fever in Labour Compared with Clinical Chorioamnionitis in a Quaternary Centre.

OBJECTIVES: To investigate treatment patterns of women with isolated fever in labour and evaluate if variables in the sepsis in obstetrics score (SOS) or fetal tachycardia are associated with treatment differences. Our secondary objective was to compare women with isolated fever in labour with women with clinical chorioamnionitis to identify any clinicodemographic differences. METHODS: A retrospective cohort study of 473 patients at BC Women's Hospital who presented with isolated fever in labour between January 2011 and April 2016 compared with a dataset of 1135 women with clinical chorioamnionitis from 2011 to 2016 in the same institution. RESULTS: In our cohort of isolated fever in labour, antibiotics were given 74.2 % of the time, and the majority received cefazolin and metronidazole (80.9%, of those who received antibiotics). Higher maternal temperature and heart rate at time of first fever and fetal tachycardia were associated with more antibiotic use. Slightly higher maternal temperature was associated with use of a saline bolus and blood cultures. The proportion of women with a SOS greater than 5 increased 4.5-fold from time of first fever to time of maximum SOS. There were fewer cesarean deliveries in the isolated fever in labour group compared with the clinical chorioamnionitis group (22.4% vs. 54.0%; P < 0.0001). CONCLUSIONS: Slightly higher maternal temperature was associated with increased treatment, including antibiotic use, saline bolus administration, and blood cultures. As evidenced by the higher proportion of women with an SOS over 5, women with isolated fever in labour may have a propensity to deteriorate clinically.

Enhanced recovery after minimally invasive gynecologic oncology surgery to improve same day discharge: a quality improvement project.

OBJECTIVES: Same day discharge after minimally invasive hysterectomy has been shown to be safe and feasible. We designed and implemented a quality improvement perioperative program based on early recovery after surgery principles to improve the rate of same day discharge from 30% to 75% after minimally invasive gynecologic oncology surgery over a 12 month period. METHODS: We enrolled 102 consecutive patients undergoing minimally invasive hysterectomy at a single cancer center during a 12 month period. A pre-intervention cohort of 100 consecutive patients was identified for comparison of clinicodemographic variables and perioperative outcomes. A multidisciplinary team developed a comprehensive perioperative care program and followed quality improvement methodology. Patients were followed up for 30 days after discharge. A statistical process chart was used to monitor the effects of our interventions, and a multivariate analysis was conducted to determine factors associated with same day discharge. RESULTS: Same day discharge rate increased from 29% to 75% after implementation (p<0.001). The post-intervention cohort was significantly younger (59 vs 62 years; p=0.038) and had shorter operative times (180 vs 211 min; p<0.001) but the two groups were similar in body mass index, comorbidity, stage, and intraoperative complications. There was no difference in 30 day perioperative complications, readmissions, reoperations, emergency department visits, or mortality. Overnight admissions were secondary to nausea and vomiting (16%), complications of pre-existing comorbidities (12%), and urinary retention (8%). On multivariate analysis, longer surgery, timing of surgery, and narcotic use on the ward were significantly associated with overnight admission. Overall, 89% of patients rated their experience as 'very good' or 'excellent', and 87% felt that their length of stay was adequate. CONCLUSIONS: Following implementation of a perioperative quality improvement program targeted towards minimally invasive gynecologic oncology surgery, our intervention significantly improved same day discharge rates while maintaining a low 30 day perioperative complication rate and excellent patient experience.

Brief family history questionnaire to screen for Lynch syndrome in women with newly diagnosed non-serous, non-mucinous ovarian cancers.

OBJECTIVES: While ovarian cancer is the third most common Lynch syndrome-associated cancer in women, there is no established screening strategy to identify Lynch syndrome in this population. The objective of this study was to assess whether the 4-item brief Family History Questionnaire can be used as a screening tool to identify women with ovarian cancer at risk of Lynch syndrome. METHODS: In this prospective cohort study, participants with newly diagnosed non-serous, non-mucinous ovarian cancer completed the brief Family History Questionnaire, extended Family History Questionnaire, and had tumors assessed with immunohistochemistry for mismatch repair proteins, MLH1 methylation, and microsatellite instability testing. All underwent universal germline testing for Lynch syndrome. Performance characteristics were compared between the brief Family History Questionnaire, extended Family History Questionnaire, immunohistochemistry±MLH1 methylation, and microsatellite instability testing. RESULTS: Of 215 participants, 169 (79%) were evaluable with both the brief Family History Questionnaire and germline mutation status; 12 of these 169 were confirmed to have Lynch syndrome (7%). 10 of 12 patients (83%) with Lynch syndrome were correctly identified by the brief Family History Questionnaire, compared with 6 of 11 (55%) by the extended Family History Questionnaire, 11 of 13 (85%) by immunohistochemistry±MLH1 methylation, and 9 of 11 (82%) by microsatellite instability testing. The sensitivity, specificity, positive predictive values, and negative predictive values of the brief Family History Questionnaire were 83%, 65%, 15%, and 98%, respectively. A combined approach with immunohistochemistry and the brief Family History Questionnaire correctly identified all 12 patients with Lynch syndrome. The brief Family History Questionnaire was more sensitive than the extended Family History Questionnaire and took <10 min for each patient to complete. CONCLUSIONS: The brief Family History Questionnaire alone or combined with immunohistochemistry may serve as an adequate screening strategy, especially in centers without access to universal tumor testing.

Efficacy and toxicity of intraperitoneal chemotherapy as compared to intravenous chemotherapy in the treatment of patients with advanced ovarian cancer.

OBJECTIVE: To assess the efficacy and toxicity of intraperitoneal (IP) chemotherapy compared to intravenous (IV) chemotherapy. METHODS: Toxicity profiles, recurrence patterns, and long-term survival outcomes of 271 women with Stage IIIC or IV high-grade serous ovarian cancer (HGSC) treated with primary cytoreductive surgery followed by adjuvant IP or IV chemotherapy during 2001-2015 were reviewed. RESULTS: Women who received IP chemotherapy (n = 91) were more likely to have undergone aggressive and longer surgery with no residual disease compared to the IV arm (n = 180). Chemotherapy-related toxicities were comparable between the two groups. Extraperitoneal recurrences were more common in the IP arm compared to the IV arm. Five-year progression-free survival was 19% versus 18% (P = 0.63) and overall survival was 73% versus 44% (P < 0.01) in the IP versus IV arms, respectively. After adjustment for significant clinicopathologic factors in a multivariable model, use of IP was no longer a statistically significant predictor of overall survival. CONCLUSION: IP chemotherapy in advanced HGSC has not been widely adopted due to concerns about toxicity and inconvenience. Use of IP chemotherapy was associated with comparable safety profile and efficacy to IV chemotherapy in women with Stage IIIC/IV HGSC. Recurrences were more likely to be extraperitoneal with IP treatment.

Secondary cytoreductive surgery for recurrent low-grade serous ovarian carcinoma: A systematic review and meta-analysis.

OBJECTIVES: Low-grade serous ovarian cancer (LGSC) is a relatively chemo-resistant disease with limited effective treatment options for patients with recurrence. Secondary cytoreductive surgery (SCS) is commonly offered at recurrence, although any benefit this has on survival is not fully determined. This review evaluates the impact of SCS, including residual disease, on progression-free survival (PFS) and overall survival (OS) in recurrent LGSC. METHODS: A comprehensive search of Medline ALL, Embase Classic + Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Web of Science was conducted to obtain studies evaluating optimal or complete SCS versus suboptimal SCS and the amount of residual disease in recurrent LGSC. Meta-analysis was performed and PFS and OS outcomes were calculated. RESULTS: 1Of 5296 studies screened, 350 progressed to full-text review, with 9 ultimately selected for inclusion in the systematic review. Two studies met criteria for meta-analysis of PFS and of OS. The presence of visible residual disease at the conclusion of SCS negatively impacted PFS (HR = 3.51, 95% CI = 1.72-7.14), whereas SCS with no residual disease significantly improved OS (HR = 0.4, 95% CI = 0.23-0.7) in patients with recurrent LGSC. Diffuse and extensive disease distribution was inversely linked to survival. In addition, SCS as an initial treatment for recurrent LGSC was associated with superior survival in comparison to chemotherapy. A short platinum-free interval was not associated with worse survival in this cohort. CONCLUSIONS: Complete SCS, and to a lesser extent optimal SCS, are associated with improved PFS and OS in patients with recurrent LGSC. SCS may be a better initial treatment strategy than systemic chemotherapy for recurrent disease. Patients with recurrent LGSC should be evaluated for the role of SCS based on disease distribution and functional status, irrespective of the platinum-free interval. Prospective studies are needed to further study the role of SCS in patients with recurrent LGSC.

Implementation of a restrictive opioid prescription protocol after minimally invasive gynecologic oncology surgery.

OBJECTIVES: Opioids are routinely prescribed after minimally invasive gynecologic oncology surgery, with minimal data to inform the ideal dose. The aim of this study was to evaluate the impact of a restrictive opioid prescription protocol on the median morphine milligram equivalents prescribed and pain control in patients undergoing minimally invasive surgery. METHODS: A restrictive opioid prescription protocol was implemented from January through December 2020 at a single tertiary cancer center in Ontario, Canada. Consecutive patients undergoing minimally invasive hysterectomy for suspected malignancy were included. Simultaneously, we implemented use of multimodal analgesia, patient and provider education, pre-printed standardized prescriptions, and tracking of opioid prescriptions. Total median morphine milligram equivalents prescribed were compared between pre- and post-intervention cohorts. Patients were surveyed regarding opioid use and pain control at 30 days post-surgery. RESULTS: A total of 101 women in the post-intervention cohort were compared with 92 consecutive pre-intervention controls. Following protocol implementation, median morphine milligram equivalents prescribed decreased from 50 (range 9-100) to 25 (range 8-75) (p<0.001). In the post-intervention cohort, 75% (76/101) used 10 median morphine milligram equivalents or less and 55 patients (54%) used 0 median morphine milligram equivalent. There was no additional increase in opioid refill requests after implementation of our strategy. Overall, patients reported a median pain score of 3/10 at 30 days post-surgery; the highest pain scores and most of the pain occurred in the first week after surgery. CONCLUSIONS: Implementation of a restrictive opioid prescription protocol led to a significant reduction in opioid use after minimally invasive gynecologic oncology surgery, with over 50% of patients requiring no opioids postoperatively.

The correlation between BRCA status and surgical cytoreduction in high-grade serous ovarian carcinoma.

OBJECTIVE: BRCA-associated ovarian cancers are biologically unique; it is unclear if this translates to favorable outcomes at the time of primary cytoreduction (PCS). The aim of this study was to compare the amount of residual disease after PCS in BRCA mutated (BRCAm) and wild-type (BRCAwt) high-grade serous ovarian cancers (HGSC), and to assess whether BRCA status was an independent predictor of complete cytoreduction. METHODS: We conducted a retrospective analysis of patients with stage III/IV HGSC with known germline and somatic BRCA status, treated with PCS from 2000 to 2017. We compared the complete, optimal and suboptimal cytoreduction rates between the BRCAm and BRCAwt cohorts and built a predictive model to assess whether BRCA status was predictive of complete cytoreduction. RESULTS: Of 303 treated with PCS, 120 were germline/somatic BRCAm (40%) and 183 were BRCAwt (60%). BRCAm women tended to be younger, but there were no differences between the two groups in preoperative CA-125, disease burden, surgical complexity, length of surgery, or perioperative complications. BRCAm group had a higher rate of complete cytoreduction to no residual disease (0 mm) [72% vs. 48%] (p < 0.001). In a multivariate model, after accounting for age, length of surgery, CA-125 level, stage, disease burden and surgical complexity, BRCAm status was predictive of 0 mm residual disease with odds ratio of 5.3 (95% CI 2.45-11.5; p < 0.001). CONCLUSIONS: BRCAm status is predictive of complete cytoreduction at the time of PCS. Despite similar disease burden and surgical efforts, one is more likely to achieve complete resection in BRCAm HGSC.

Factors associated with an increased risk of recurrence in patients diagnosed with high-grade endometrial cancer undergoing minimally invasive surgery: A study of the society of gynecologic oncology of Canada (GOC) community of practice (CoP).

BACKGROUND: Minimally invasive surgery (MIS) is a standard surgical approach for comprehensive surgical staging in women with endometrial cancer. As rates and complexity of MIS are steadily increasing, it is important to identify potential risk factors which may be associated with this approach. This study evaluates the impact of local factors on the risk of disease recurrence. METHODS: A retrospective cohort study was conducted of patients diagnosed with high grade endometrial cancer (HGEC) who underwent MIS between 2012 and 2016 at eight Canadian centers. Data was collected from medical records. The 75th percentile was calculated for estimated uterine volume and weight. All recurrences were categorized into two groups; intra-abdominal vs. extra-abdominal. To search for significant covariates associated with recurrence-free survival a Cox proportional hazard model was performed. RESULTS: A total of 758 patients were included in the study. Intra-uterine manipulator was used in 497 (35.8%) of patients. Vaginal lacerations were documented in 9.1%. Median follow-up was 30.5 months (interquartile range 20-47). There were 157 who had disease recurrence (20.71%), including 92 (12.14%) intra-abdominal and 60 (7.92%) extra-abdominal only recurrences. In univariate analysis myometrial invasion, LVI, stage, uterine volume and weight > 75th percentile and chemotherapy were associated with increased risk of intra-abdominal recurrence. In multivariable analysis only stage, and specimen weight > 75th percentile (OR 2.207, CI 1.123-4.337) remained significant. Uterine volume, and weight were not associated with increased risk of extra-abdominal recurrences. CONCLUSION: For patients diagnosed with HGEC undergoing MIS, extracting a large uterus is associated with a significantly increased risk for intra-abdominal recurrence.

Sentinel lymph node biopsy in high-grade endometrial cancer: a systematic review and meta-analysis of performance characteristics.

OBJECTIVE: A sentinel lymph node biopsy is widely accepted as the standard of care for surgical staging in low-grade endometrial cancer, but its value in high-grade endometrial cancer remains controversial. The aim of this systematic review and meta-analysis was to evaluate the performance characteristics of sentinel lymph node biopsy in patients with endometrial cancer with high-grade histology (registered in the International Prospective Register of Systematic Reviews with identifying number CRD42020160280). DATA SOURCES: We systematically searched the MEDLINE, Epub Ahead of Print, MEDLINE In-Process & Other Non-Indexed Citations, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Embase databases all through the OvidSP platform. The search was performed between January 1, 2000, and January 26, 2021. ClinicalTrials.gov was searched to identify ongoing registered clinical trials. STUDY ELIGIBILITY CRITERIA: We included prospective cohort studies in which sentinel lymph node biopsy were evaluated in clinical stage I patients with high-grade endometrial cancer (grade 3 endometrioid, serous, clear cell, carcinosarcoma, mixed, undifferentiated or dedifferentiated, and high-grade not otherwise specified) with a cervical injection of indocyanine green for sentinel lymph node detection and at least a bilateral pelvic lymphadenectomy as a reference standard. If the data were not reported specifically for patients with high-grade histology, the authors were contacted for aggregate data. METHODS: We pooled the detection rates and measures of diagnostic accuracy using a generalized linear mixed-effects model with a logit and assessed the risk of bias using the Quality Assessment of Diagnostic Accuracy Studies 2 tool. RESULTS: We identified 16 eligible studies of which the authors for 9 of the studies provided data on 429 patients with high-grade endometrial cancer specifically. The study-level median age was 66 years (range, 44-82.5 years) and the study-level median body mass index was 28.6 kg/m2 (range, 19.4-43.7 kg/m2). The pooled detection rates were 91% per patient (95% confidence interval, 85%-95%; I2=59%) and 64% bilaterally (95% confidence interval, 53%-73%; I2=69%). The overall node positivity rate was 26% (95% confidence interval, 19%-34%; I2=44%). Of the 87 patients with positive node results, a sentinel lymph node biopsy correctly identified 80, yielding a pooled sensitivity of 92% per patient (95% confidence interval, 84%-96%; I2=0%), a false negative rate of 8% (95% confidence interval, 4%-16%; I2=0%), and a negative predictive value of 97% (95% confidence interval, 95%-99%; I2=0%). CONCLUSION: Sentinel lymph node biopsy accurately detect lymph node metastases in patients with high-grade endometrial cancer with a false negative rate comparable with that observed in low-grade endometrial cancer, melanoma, vulvar cancer, and breast cancer. These findings suggest that sentinel lymph node biopsy can replace complete lymphadenectomies as the standard of care for surgical staging in patients with high-grade endometrial cancer.