Outcomes of Radical Hysterectomy for Early-Stage Cervical Carcinoma, with or without Prior Cervical Excision Procedure.

OBJECTIVE: To investigate the impact of a prior cervical excisional procedure on the oncologic outcomes of patients with apparent early-stage cervical carcinoma undergoing radical hysterectomy. METHODS: The National Cancer Database (2004-2015) was accessed, and patients with FIGO 2009 stage IB1 cervical cancer who had a radical hysterectomy with at least 10 lymph nodes (LNs) removed and a known surgical approach were identified. Patients who did and did not undergo a prior cervical excisional procedure (within 3 months of hysterectomy) were selected for further analysis. Overall survival (OS) was evaluated following the generation of Kaplan-Meier curves and compared with the log-rank test. A Cox model was constructed to control a priori-selected confounders. RESULTS: A total of 3159 patients were identified; 37.1% (n = 1171) had a prior excisional procedure. These patients had lower rates of lymphovascular invasion (29.2% vs. 34.9%, p = 0.014), positive LNs (6.7% vs. 12.7%, p < 0.001), and a tumor size >2 cm (25.7% vs. 56%, p < 0.001). Following stratification by tumor size, the performance of an excisional procedure prior to radical hysterectomy was associated with better OS even after controlling for confounders (aHR: 0.45, 95% CI: 0.30, 0.66). The rate of minimally invasive surgery was higher among patients who had a prior excisional procedure (61.5% vs. 53.2%, p < 0.001). For these patients, performance of minimally invasive radical hysterectomy was not associated with worse OS (aHR: 1.37, 95% CI: 0.66, 2.82). CONCLUSIONS: For patients undergoing radical hysterectomy, preoperative cervical excision may be associated with a survival benefit. For patients who had a prior excisional procedure, minimally invasive radical hysterectomy was not associated with worse overall survival.

Role of systematic lymphadenectomy at the time of interval debulking surgery for patients with advanced-stage epithelial ovarian carcinoma who achieved complete gross resection.

OBJECTIVE: To evaluate the role of systematic lymphadenectomy at the time of interval cytoreductive surgery for patients with advanced-stage epithelial ovarian carcinoma who achieved complete gross resection. METHODS: The National Cancer DataBase was accessed, and patients diagnosed between 2010 and 2015 with advanced-stage ovarian carcinoma who underwent interval cytoreductive surgery and achieved complete gross resection were identified. Patients who did not undergo lymphadenectomy and those who underwent systematic lymphadenectomy (defined as at least 20 lymph nodes removed) were selected for further analysis. Median overall survival was compared with the log-rank test and controlled for a priori selected confounders. RESULTS: A total of 1060 patients were identified. Systematic lymphadenectomy was performed for 125 (11.8%) patients with a median of 29 lymph nodes (range 20-72) removed. Rate of lymph node metastasis was 62.4%. Patients who underwent systematic lymphadenectomy had higher rate of unplanned readmission (8.9% vs 1.6%, p<0.001), and median hospital stay (6 vs 4 days, p<0.001). Median overall survival for patients who did and did not undergo systematic lymphadenectomy was 44.2 and 40.4 months, respectively, p=0.40. After controlling for confounders, performance of systematic lymphadenectomy was not associated with better survival (HR=0.98, 95% CI 0.80 to 1.19). CONCLUSION: Systematic lymphadenectomy is rarely performed at the time of interval cytoreductive surgery and not associated with a survival benefit for patients who achieved complete gross resection.

Impact of delayed interval cytoreductive surgery on the survival of patients with advanced stage high-grade epithelial ovarian carcinoma.

OBJECTIVE: Our objective was to use real-world data to investigate the impact of delayed interval cytoreductive surgery on the survival of patients with advanced stage high-grade ovarian carcinoma. METHODS: We accessed the National Cancer Database and identified patients diagnosed between 2004-2015 with advanced stage high-grade ovarian carcinoma who received neoadjuvant chemotherapy and underwent interval cytoreductive surgery. Based on timing between surgery and chemotherapy administration patients were categorized into standard (9-13.0 weeks) and delayed (13.01-26 weeks) interval cytoreductive surgery groups. Overall survival was compared with the log-rank test and a Cox model was constructed to control for a priori selected confounders. RESULTS: We identified a total of 5051 patients; 2389 (47.3%) and 2662 (52.7%) in the standard and delayed interval cytoreductive surgery groups respectively. There was no difference in complete gross resection rates (53.2% vs 54.5%, p=0.51). Patients in the delayed interval cytoreductive surgery group were less likely to undergo complex surgery (39.3% vs 45.6%, p<0.001) and had lower rates of unplanned re-admission (4.1% vs 2.6%, p=0.003). There was no difference in overall survival between the standard and delayed interval cytoreductive surgery groups, p=0.13 (median 34.3 vs 33.9 months) even after controlling for confounders (hazard ratio (HR) 1.04, 95% confidence intervals (CIs): 0.97, 1.12). There was no difference in overall survival between the two groups for patients with no gross residual (p=0.95; median overall survival 40.08 vs 39.8 months) or gross residual disease (p=0.16; median overall survival 32.89 and 32.16 months). CONCLUSION: For patients with advanced stage ovarian cancer delayed interval cytoreductive surgery may not be associated with worse overall survival.

Next generation sequencing reveals a high prevalence of pathogenic mutations in homologous recombination DNA damage repair genes among patients with uterine sarcoma.

OBJECTIVE: Investigate the incidence of homologous recombination DNA damage response (HR-DDR) genomic alterations among patients with uterine sarcoma. METHODS: The American Association for Cancer Research GENIE v13.0 database was accessed and patients with uterine leiomyosarcoma, adenosarcoma, undifferentiated uterine sarcoma, high-grade endometrial stromal sarcoma, low-grade endometrial stromal sarcoma, and endometrial stromal sarcoma not otherwise specified were identified. We determined the incidence of pathogenic alterations in the following genes involved in HR-DDR: ATM, ARID1A, ATRX, BAP1, BARD1, BLM, BRCA2, BRCA1, BRIP1, CHEK2, CHEK1, FANCA, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCL, MRE11, NBN, PALB2, RAD50, RAD51, RAD51B, RAD51C, RAD51D, WRN. Data from the OncoKB database, as provided by cBioPortal, was utilized to determine the presence of pathogenic genomic alterations. RESULTS: A total of 509 patients contributing with 525 samples were identified. Median patient age at sample collection was 56 years while the majority were White (80.7%). The most common histologic subtype was leiomyosarcoma (63.8%) followed by adenosarcoma (12.3%). The overall incidence of HR-DDR genomic alterations was 28.2%. The most commonly altered genes were ATRX (18.2%), BRCA2 (4%), and RAD51B (2.6%). The highest incidence of HR-DDR genomic alterations was observed among patients with leiomyosarcoma (35.4%), adenosarcoma (27%) and undifferentiated uterine sarcoma (30%), while those with low-grade endometrial stromal sarcoma had the lowest (2.9%) incidence. CONCLUSIONS: Approximately 1 in 3 patients with uterine sarcoma harbor a pathogenic alteration in HR-DDR genes. Incidence is high among patients with uterine leiomyosarcoma and adenosarcoma.

A retrospective case series of Mohs micrographic surgery and interdisciplinary management of female genital skin cancers: Local recurrence rates and patient-reported outcomes.

BACKGROUND: Conventional excision of female genital skin cancers has high rates of local recurrence and morbidity. Few publications describe local recurrence rates (LRRs) and patient-reported outcomes (PROs) after Mohs micrographic surgery (MMS) for female genital skin cancers. OBJECTIVE: To evaluate LRRs, PROs, and interdisciplinary care after MMS for female genital skin cancers. METHODS: A retrospective case series was conducted of female genital skin cancers treated with MMS between 2006 and 2021 at an academic center. The primary outcome was local recurrence. Secondary outcomes were PROs and details of interdisciplinary care. RESULTS: Sixty skin cancers in 57 patients were treated with MMS. Common diagnoses included squamous cell cancer (n = 26), basal cell cancer (n = 12), and extramammary Paget disease (n = 11). Three local recurrences were detected with a mean follow-up of 61.1 months (median: 48.8 months). Thirty-one patients completed the PROs survey. Most patients were satisfied with MMS (71.0%, 22/31) and reported no urinary incontinence (93.5%, 29/31). Eight patients were sexually active at follow-up and 75.0% (6/8) experienced no sexual dysfunction. Most cases involved interdisciplinary collaboration 71.7% (43/60). LIMITATIONS: Limitations include the retrospective single-center design, heterogeneous cohort, and lack of preoperative function data. CONCLUSIONS: Incorporating MMS into interdisciplinary teams may help achieve low LRRs and satisfactory function after genital skin cancer surgery.

Facility level variation in the utilization of neoadjuvant chemotherapy is associated with higher surgical morbidity for patients with advanced stage epithelial ovarian carcinoma.

OBJECTIVE: Investigate outcomes for advanced stage epithelial ovarian cancer (EOC) patients based on facility-level utilization of neoadjuvant chemotherapy (NACT). METHODS: Stage III-IV EOC patients diagnosed between 2010 and 2016 were identified in the National Cancer Database. Percentage of patients managed with NACT was calculated for facilities, reporting ≥120 patients. Facilities with lowest and highest quartile of NACT rate comprised the low and high-utilizing groups. Clinico-pathological characteristics were collected, and appropriate statistical analysis performed. RESULTS: High- and low-utilizing facilities managed on average 54.1% and 25.4% of patients with NACT respectively. Patients managed at high-utilizing facilities were significantly more likely to be >65 (p = 0.029), have stage IV disease (p < 0.001) and comorbidities (p < 0.001). Patients managed with primary debulking surgery (PDS) at low-utilizing facilities were significantly more likely to be >65, have stage IV disease, and have comorbidities (all, p < 0.001). Patients undergoing PDS at low-utilizing facilities were significantly less likely to achieve complete gross resection (p < 0.001), and were significantly more likely to experience 90-day mortality (p < 0.001), and unplanned 30-day readmission (p < 0.001). After controlling for age, comorbidities, race, insurance status, stage, grade and histology, high-utilizing facilities trended towards better overall survival (OS) (HR: 0.92, 95% CI: 0.85-0.99). Overall, patients undergoing PDS had better OS compared to those who had NACT (median 42 vs 27 months, p < 0.001). CONCLUSIONS: Despite treating an EOC population with more advanced disease and comorbidities, high-utilizing facilities have lower surgical morbidity and mortality with no detrimental impact on long-term survival. Careful patient selection to minimize the morbidity and mortality associated with PDS is pivotal.

[18F]FluorThanatrace ([18F]FTT) PET Imaging of PARP-Inhibitor Drug-Target Engagement as a Biomarker of Response in Ovarian Cancer, a Pilot Study.

PURPOSE: PARP inhibitors have become the standard-of-care treatment for homologous recombination deficient (HRD) high-grade serous ovarian cancer (HGSOC). However, not all HRD tumors respond to PARPi. Biomarkers to predict response are needed. [18F]FluorThanatrace ([18F]FTT) is a PARPi-analog PET radiotracer that noninvasively measures PARP-1 expression. Herein, we evaluate [18F]FTT as a biomarker to predict response to PARPi in patient-derived xenograft (PDX) models and subjects with HRD HGSOC. EXPERIMENTAL DESIGN: In PDX models, [18F]FTT-PET was performed before and after PARPi (olaparib), ataxia-telangiectasia inhibitor (ATRi), or both (PARPi-ATRi). Changes in [18F]FTT were correlated with tumor volume changes. Subjects were imaged with [18F]FTT-PET at baseline and after ∼1 week of PARPi. Changes in [18F]FTT-PET uptake were compared with changes in tumor size (RECISTv1.1), CA-125, and progression-free survival (PFS). RESULTS: A decrease in [18F]FTT tumor uptake after PARPi correlated with response to PARPi, or PARPi-ATRi treatment in PARPi-resistant PDX models (r = 0.77-0.81). In subjects (n = 11), percent difference in [18F]FTT-PET after ∼7 days of PARPi compared with baseline correlated with best RECIST response (P = 0.01), best CA-125 response (P = 0.033), and PFS (P = 0.027). All subjects with >50% reduction in [18F]FTT uptake had >6-month PFS and >50% reduction in CA-125. Utilizing only baseline [18F]FTT uptake did not predict such responses. CONCLUSIONS: The decline in [18F]FTT uptake shortly after PARPi initiation provides a measure of drug-target engagement and shows promise as a biomarker to guide PARPi therapies in this pilot study. These results support additional preclinical mechanistic and clinical studies in subjects receiving PARPi ± combination therapy. See related commentary by Liu and Zamarin, p. 1384.

Predictive value of 5-Factor modified frailty index in Oncologic and benign hysterectomies.

Background: The 5-factor modified frailty index (mFI-5) has been validated against the original 11-factor modified frailty index in gynecologic surgery, however its utility has not been evaluated between benign versus gynecologic oncology patient populations. Objective: To evaluate the predictive value of the mFI-5 in identifying women at increased risk for major postoperative complications, readmission, or death within 30 days of hysterectomy for benign and oncologic indications. Methods: Patients who underwent hysterectomy between 2015 and 2017 were identified from the NSQIP database and stratified into benign or malignant indications. Demographic and mFI-5 variables were extracted. The mFI-5 was calculated by dividing the sum of all affirmative variables by the total number of input variables in the database. Logistic regression modeling was performed adjusting for confounders. C-statistic with 95% CI was obtained post-regression. Results: 80,293 hysterectomies (59,078 benign and 21,215 oncologic) were identified. The benign group was more likely to have an mFI-5 score of 0 (70 % vs 50 %, p = 0.001) and had shorter operative times (p = 0.001). In the benign group, mFI-5 was a strong predictor of mortality (c = 0.819, CI 0.704-0.933). Within the oncology group, the mFI-5 was a strong predictor of mortality (c = 0.801, CI 0.750-0.851), particularly for uterine and cervical cancers. It was moderately predictive of readmission (c = 0.671, CI 0.656-0.686) and strongly predictive of Clavien-Dindo class III and IV complications (c = 0.732, CI 0.713-0.750). Conclusion: The mFI-5 is a strong predictor of 30-day mortality and serious postoperative complications. These findings have the potential to improve identification of high-risk patients in the preoperative setting.

Addition of External Beam Radiation Therapy to Adjuvant Chemotherapy for Patients With Stage IIIC Uterine Endometrioid Carcinoma: Utilization and Outcomes.

OBJECTIVES: Evaluate whether the addition of external beam radiation (EBRT) to adjuvant chemotherapy with or without vaginal brachytherapy is associated with better survival for patients with stage IIIC endometrioid endometrial carcinoma. MATERIALS AND METHODS: Patients diagnosed between 2010 and 2015 with apparent early-stage endometrioid adenocarcinoma, without a history of another tumor, who underwent hysterectomy with lymphadenectomy and had positive lymph nodes were identified in the National Cancer Database. Those who received adjuvant chemotherapy (defined as receipt of treatment within 6 mo from surgery) and had at least 1 month of follow-up were selected for further analysis. Overall survival was compared between patients who did and did not receive EBRT within 6 months from surgery with the log-rank test. A Cox model was also constructed to control for confounders. RESULTS: A total of 3116 patients were identified; 1458 (46.8%) received chemotherapy without and 1658 (53.2%) with EBRT. Pathologic characteristics (tumor grade, size, endocervical, and lymph-vascular invasion) were comparable between the two groups. Patients who received external beam radiation had better survival compared with those who did not, P =0.001; 5-year overall survival rates were 83.1% and 77.9%, respectively. After controlling for patient age, race, presence of comorbidities, insurance status, tumor size, grade and endocervical invasion, and the presence of lymph-vascular invasion, the addition of EBRT was associated with a survival benefit (HR: 0.75, 95% CI: 0.62, 0.91). CONCLUSIONS: For patients with endometrioid adenocarcinoma metastatic to the lymph nodes, addition of external beam radiation to adjuvant chemotherapy may be associated with a survival benefit.

Oncologic outcomes of surgical para-aortic lymph node staging in patients with advanced cervical carcinoma undergoing chemoradiation.

OBJECTIVES: We aimed to evaluate the utilization and impact of surgical para-aortic lymph node staging on the survival of patients with locally advanced stage cervical carcinoma receiving definitive chemoradiation. METHODS: We identified patients in the National Cancer Database diagnosed between January 2010 and December 2015 with locally advanced (FIGO 2009 stage IB2-IVA) cervical carcinoma who did not undergo hysterectomy, received primary chemoradiation and had at least 1 month of follow-up. Two groups of patients were formed based on the assessment method of para-aortic lymph node status - radiologic assessment only versus surgical lymphadenectomy. Overall survival was compared with the log-rank test after Kaplan-Meier curves were generated. A Cox model was constructed to control for a priori selected confounders. RESULTS: We identified a total of 3540 patients who met the inclusion criteria. Para-aortic staging was performed in 333 (9.4%) patients. These patients were younger (median age 46 vs 52 years, p<0.001), less likely to have co-morbidities (8.7% vs 15.6%, p<0.001), more likely to have private insurance (48.9% vs 37.8%, p<0.001) and receive brachytherapy (76.9% vs 70.9%, p=0.022). The rate of para-aortic lymphadenectomy was comparable between patients with stage IB2-II and III-IVA disease (9.4% for both groups, p=0.98). Patients who underwent para-aortic lymphadenectomy were also more likely to have lymph nodes categorized as positive compared with those who had imaging only (27.3% vs 13.2%, p<0.001). There was no difference in overall survival between patients who underwent radiologic only or surgical para-aortic lymph node assessment (p=0.80 from log-rank test); 4 year overall survival rates were 62.9% and 63%. After controlling for confounders, performance of para-aortic lymphadenectomy was not associated with a survival benefit (HR 1.07, 95% CIs: 0.88 to 1.31). CONCLUSIONS: In a large cohort of patients with locally advanced stage cervical carcinoma, para-aortic lymphadenectomy was rarely performed and not associated with a survival benefit.

Safety of ovarian preservation for premenopausal patients with FIGO stage I grade 2 and 3 endometrioid endometrial adenocarcinoma.

OBJECTIVE: To investigate the utilization and outcomes of ovarian preservation for premenopausal patients with International Federation of Gynecology and Obstetrics (FIGO) stage I grade 2 and 3 endometrioid endometrial carcinoma undergoing hysterectomy. METHODS: The National Cancer Database was accessed; patients aged ≤45 years diagnosed between January 2004 and December 2015 with FIGO stage I grade 2 or 3 endometrioid endometrial carcinoma, who underwent hysterectomy with or without bilateral salpingo-oophorectomy and had at least 1 month of follow-up, were identified. Overall survival was assessed following generation of Kaplan-Meier curves and compared with the log-rank test. A Cox model was constructed to control for a priori selected variables. RESULTS: A total of 2941 patients who met the inclusion criteria were identified; 200 (6.8%) patients did not undergo bilateral salpingo-oophorectomy. Rate of ovarian preservation was comparable between patients with grade 2 (n=163, 6.6%) and grade 3 (n=37, 7.7%) tumors (p=0.38). Patients who did not undergo bilateral salpingo-oophorectomy were younger (median 39 vs 41 years, p<0.001) and less likely to undergo surgical lymph node assessment (52% vs 76.2%, p<0.001). There was no difference in overall survival between patients who did and did not undergo bilateral salpingo-oophorectomy (p=0.94); 5 year overall survival rates were 96.6% and 97%, respectively. After controlling for confounders, including tumor grade, ovarian preservation was not associated with worse overall survival (HR 0.92, 95% CI 0.47 to 1.84). CONCLUSIONS: For patients with grade 2 and 3 FIGO stage I endometrioid carcinoma undergoing hysterectomy, ovarian preservation is rarely performed while no clear detrimental effect on overall survival was found.

Adjuvant chemotherapy for stage I high-intermediate risk endometrial carcinoma with lymph-vascular invasion.

OBJECTIVE: The goal of this study was to evaluate if addition of adjuvant chemotherapy to radiation therapy improves overall survival in patients with high-intermediate risk stage I endometrial carcinoma with lymphovascular invasion. METHODS: Patients diagnosed between January 2010 and December 2015 with FIGO (International Federation of Gynecology and Obstetrics) stage I endometrioid endometrial carcinoma with lymphovascular invasion who underwent hysterectomy with lymphadenectomy and met the GOG-99 criteria for high-intermediate risk were identified in the National Cancer Database. Patients who received adjuvant radiotherapy with or without adjuvant chemotherapy (administered within 6 months of surgery) and had at least 1 month of follow-up were selected for further analysis. Overall survival was compared with the log-rank test following stratification by type of radiation treatment. A Cox model was constructed to control for a priori selected confounders. RESULTS: A total of 2881 patients who met the inclusion criteria were identified; 2417 (83.9%) patients received radiation therapy alone while 464 (16.1%) received chemoradiation. Rate of adjuvant chemotherapy administration was comparable between patients who received vaginal brachytherapy alone (16.2%), and external beam radiation therapy (with or without vaginal brachytherapy) (15.8%), p=0.78. Rate of chemoradiation was higher for patients with grade 3 (28.8%) tumors compared with those with grade 2 (9.9%) and grade 1 (8.3%) tumors, p<0.001. After controlling for confounders for patients receiving external beam radiation, addition of chemotherapy was not associated with improved overall survival (HR 0.90, 95% CI 0.56 to 1.46). For patients receiving vaginal brachytherapy addition of chemotherapy was associated with better overall survival (HR 0.644, 95% CI 0.45 to 0.92). Benefit was limited to patients with grade 3 tumors, p=0.026; 4-year overall survival rate was 81.1% versus 74.9%. CONCLUSIONS: In patients with high-intermediate risk FIGO stage I endometrioid endometrial carcinoma and lymphovascular invasion, addition of chemotherapy to radiation therapy was associated with a survival benefit for patients with grade 3 tumors receiving vaginal brachytherapy.

Delay in adjuvant chemotherapy administration for patients with FIGO stage I epithelial ovarian carcinoma is associated with worse survival; an analysis of the National Cancer Database.

OBJECTIVE: The administration of adjuvant chemotherapy within 42 days from surgery is one of the proposed quality measures for patients with epithelial ovarian cancer (EOC). The aim of the present study was to evaluate the impact of chemotherapy delay in the survival of patients with stage I EOC. METHODS: The National Cancer Database was accessed, and patients diagnosed between 2004 and 2015 with FIGO stage I EOC who received multi-agent chemotherapy were identified. Overall survival (OS) was compared between patients who received chemotherapy <6 weeks and 6-12 weeks from surgery with the log-rank test following generation of Kaplan-Meier curves. Cox model was constructed to control for a priori selected confounders. RESULTS: A total of 8549 patients who received adjuvant chemotherapy at a median 35 days from surgery (interquartile range 19) were identified; 67.7% received adjuvant chemotherapy <6 weeks from surgery while 32.3% experienced a delay. Patients who experienced a delay were more likely to have comorbidities (18.4% vs 14.9%, p < 0.001), and be managed in non-academic facilities (57.1% vs 53.2%, p = 0.001). Patients who experienced a delay had worse OS compared to those who did not, p < 0.001; 5-year OS rates 85.7% and 89.7%, respectively. For patients with high-grade serous tumors, those who experienced a delay had a 5-yr OS of 81.9% compared to 88.6% for those who did not, p < 0.001. After controlling for age, race, presence of comorbidities, insurance status, tumor histology and grade, performance of lymphadenectomy and substage, chemotherapy delay was associated with worse survival (HR: 1.25, 95% CI: 1.10, 1.42). CONCLUSIONS: For patients with early stage EOC administration of adjuvant chemotherapy within 6 weeks from surgery was associated with better overall survival, especially for those with stage IC disease.

Fertility-sparing surgery for patients with stage IC2 or IC3 epithelial ovarian carcinoma: any evidence of safety?

OBJECTIVE: Investigate the overall survival of patients with stage IC2/IC3 epithelial ovarian carcinoma undergoing fertility-sparing surgery. METHODS: Patients aged <45 years diagnosed between January 2004 and December 2015 with epithelial ovarian carcinoma, who underwent surgical staging and had tumor involving the ovarian surface (IC2), malignant ascites or positive cytology (IC3), were identified in the National Cancer Database. The fertility-sparing surgery group included patients who had preservation of the uterus and the contralateral ovary while the radical surgery group included patients who had hysterectomy with bilateral salpingo-oophorectomy. Overall survival was evaluated following generation of Kaplan-Meier curves while a Cox model was constructed to control for tumor grade and performance of lymphadenectomy. A systematic review of the literature was performed and cumulative relapse rate among patients with IC2/IC3 disease who underwent fertility-sparing surgery was calculated. RESULTS: A total of 235 cases were identified; 105 (44.7%) patients underwent fertility-sparing surgery. There was no difference in overall survival between the fertility-sparing and radical surgery groups (p=0.37; 5- year overall survival rates 90.2% and 85%, respectively). After controlling for tumor grade and performance of lymphadenectomy, fertility-sparing surgery was not associated with worse overall survival (HR 1.22, 95% CI 0.56, 2.62). A systematic review identified 151 patients with stage IC2/IC3 disease who underwent fertility-sparing surgery. Cumulative relapse rate was 19.3% (n=29) while 12 (6.7%) deaths were reported. Median time to recurrence was 19 (range 1-128.5) months. Tumor recurrence involved the ovary exclusively in 42% (11/26) of patients, while 15% (4/26) had a lymph node, 35% (9/26) a pelvic/abdominal, and 8% (2/26) a distant tumor relapse. CONCLUSIONS: In a large cohort of patients with stage IC2/IC3 epithelial ovarian carcinoma, fertility-sparing surgery was not associated with worse overall survival. However, based on a literature review, relapse rate is approximately 20%.

Ascites volume at the time of primary debulking and overall survival of patients with advanced epithelial ovarian cancer.

OBJECTIVES: To investigate the impact of malignant ascites volume on the outcomes of patients with advanced epithelial ovarian carcinoma who undergo primary debulking surgery. METHODS: Patients diagnosed with stage III-IV epithelial ovarian carcinoma and bulky intra-abdominal (TIIIC) disease between 2010 and 2015, who underwent primary debulking surgery followed by multi-agent chemotherapy and known status of residual disease, were drawn from the National Cancer Database. Based on available information, the presence and volume of malignant ascites was categorized as absent, low (<980 mL), and high (>980 mL) volume. Median overall survival was determined from Kaplan-Meier curves and compared with the log rank test. A multivariate Cox model was constructed to control for confounders. RESULTS: 2493 patients were identified; 31.9% (n=795) had no ascites, 40.2% (n=1001) had low, and 28% (n=697) had high volume malignant ascites. Rate of complete gross resection was higher for patients with no ascites (65.9%) compared with those with low (35.6%) and high (23%) volume ascites (p<0.001). After controlling for stage, histology, grade, age, and comorbidities, compared with those with no ascites, patients with low (odds ratio (OR) 3.49, 95% confidence intervals (CI) 2.89 to 4.26) and high (OR 6.40, 95% CI 5.07 to 8.06) volume ascites were more likely to have gross residual disease. For patients who achieved complete gross resection after controlling for confounders compared with patients with no ascites, those with low (hazard ratio (HR) 1.37, 95% CI 1.09 to 1.72) and high volume ascites (HR 1.94, 95% CI 1.47 to 2.55) had worse overall survival. Similarly, patients with low volume ascites had better survival compared with those with high volume ascites (HR 0.71 95% CI 0.54 to 0.93). CONCLUSIONS: The presence and volume of malignant ascites at the time of primary debulking surgery was associated with the likelihood of achieving a complete gross resection and worse overall survival.

Outcomes of comprehensive lymphadenectomy for patients with advanced stage ovarian carcinoma and rare histologic sub-types.

OBJECTIVE: To investigate the prognostic significance of comprehensive lymphadenectomy at the time of primary debulking surgery for patients with rare histologic sub-types of epithelial ovarian carcinoma and clinically advanced stage disease who underwent complete gross resection. METHODS: The National Cancer Database was accessed and patients diagnosed between January 2010 and December 2015 with stage III-IV clear cell, endometrioid, mucinous, and low-grade serous carcinoma who underwent primary debulking surgery and achieved complete gross resection were identified. Patients who did not undergo lymphadenectomy and those who underwent comprehensive lymphadenectomy (defined as at least 20 lymph nodes removed) were selected for further analysis. Overall survival was compared with the log-rank test and a Cox model was constructed to control for confounders. RESULTS: A total of 381 patients were identified; 133 (34.9%) patients underwent comprehensive lymphadenectomy while 248 (65.1%) patients did not. There were no differences between the two groups in terms of patient race, age, presence of co-morbidities, type of treatment facility, disease stage, histology, and extent of intra-abdominal disease (p>0.05). There was no difference in overall survival between patients who did and did not undergo comprehensive lymphadenectomy (p=0.42); median overall survival was 51.48 and 47.38 months, respectively. After controlling for patient age, race, insurance status, presence of co-morbidities, intra-abdominal tumor spread, stage and histology, performance of systematic lymphadenectomy was not associated with better survival (HR 0.96, 95% CI 0.69 to 1.35). CONCLUSION: Comprehensive lymphadenectomy is not associated with a survival benefit for patients with rare histologic sub-types of epithelial ovarian carcinoma and advanced stage disease who underwent primary debulking surgery and complete gross resection.

Role of lymphadenectomy for apparent early stage uterine sarcoma; a comprehensive analysis of the National Cancer Database.

OBJECTIVE: Investigate the role of lymphadenectomy for patients with apparent stage I uterine sarcoma. METHODS: The National Cancer Database was accessed and patients without a history of another tumor diagnosed between 2004 and 2015 with an apparent early stage leiomyosarcoma, adenosarcoma, low-grade endometrial stromal and high-grade endometrial stromal/undifferentiated sarcoma who underwent hysterectomy with or without lymphadenectomy were identified. Overall survival was assessed after stratification by histology with the log-rank test while Cox models were constructed to control for confounders. RESULTS: A total of 6412 patients with apparent early stage uterine sarcoma who underwent hysterectomy were identified; 2820 (44%) underwent lymphadenectomy. Rate of lymph node metastasis was 3.4% (42/1250) for patients with leiomyosarcoma, 2.3% (19/826) for those with adenosarcoma, 4.5% (21/463) for patients with low-grade endometrial stromal sarcoma and 7.9% (22/280) for those with high-grade endometrial stromal/undifferentiated sarcoma, p < 0.001. After controlling for confounders lymphadenectomy was not associated with better survival for patients with adenosarcoma (HR: 0.92, 95% CI: 0.73, 1.17), or low-grade endometrial stromal sarcoma (HR: 1.17, 95% CI: 0.73, 1.87). Patients with leiomyosarcoma who underwent lymphadenectomy had worse survival (HR: 1.15, 95% CI: 1.03, 1.28). Patients with high-grade endometrial stromal/undifferentiated sarcoma who underwent lymphadenectomy had better survival (HR: 0.66, 95% CI: 0.48, 0.89). CONCLUSIONS: Incidence of lymph node metastasis in apparent early stage uterine sarcoma is rare while the performance of lymphadenectomy was not associated with a clear survival benefit for all histologic subtypes except high-grade endometrial stromal/undifferentiated sarcoma.

Minimally invasive hysterectomy for stage IA cervical carcinoma: a survival analysis of the National Cancer Database.

OBJECTIVE: To evaluate the outcomes of minimally invasive surgery for patients with stage IA cervical carcinoma undergoing hysterectomy. METHODS: Patients with pathological stage IA (IA1, IA2, IA not otherwise specified) squamous, adenocarcinoma, adenosquamous carcinoma of the cervix, no history of another tumor, who underwent radical or simple hysterectomy with known mode of surgery, diagnosed between 2010 and 2015 with at least 1 month of follow-up, were drawn from the National Cancer Database. Comparisons of demographic and clinicopathologic characteristics were made with the χ2 test. The impact of minimally invasive surgery (robotic-assisted or traditional laparoscopic) on overall survival was assessed with the log-rank test following generation of Kaplan-Meier curves. A Cox model was constructed to control for confounders. RESULTS: A total of 1930 patients were identified; the majority (73.3%, 1414 patients) had stage IA1 disease, while 458 (23.7%) patients had stage IA2, and 58 (3%) patients had stage IA not otherwise specified. In the present cohort, 685 patients (35.5%) had open, 438 patients (22.7%) had laparoscopic, and 807 patients (41.8%) had robotic-assisted laparoscopic hysterectomy. Patients who had an open approach were more likely to undergo lymphadenectomy (58.1% vs 52.7%, p=0.021) and have radical hysterectomy (42% vs 32.4%, p<0.001). Patients who had minimally invasive surgery had a shorter hospital stay (median 1 vs 3 days, p<0.001). There was no difference in overall survival between patients who had open and minimally invasive hysterectomy (p=0.87); 4-year overall survival rates were 97.7% and 98.6%, respectively. There was no difference in overall survival between the open and minimally invasive surgery groups for patients who had simple (p=0.61; 4-year overall survival rates 97.6% and 98.7%, respectively) or radical hysterectomy (p=0.70; 4-year overall survival rates 97.8% and 98.4%, respectively). After controlling for patient age, tumor histology, and presence of lymphovascular invasion, minimally invasive hysterectomy was not associated with worse survival (HR 0.94, 95% CI 0.49 to 1.81). In a sensitivity analysis, based on 3048 patients with clinical stage IA after controlling for confounders, minimally invasive surgery was not associated with worse survival than laparotomy (HR 1.06, 95% CI 0.65 to 1.72). CONCLUSIONS: In a large cohort of patients with stage IA cervical carcinoma, performance of minimally invasive hysterectomy was not associated with a detrimental effect on overall survival.

Role of adjuvant radiation therapy after radical hysterectomy in patients with stage IB cervical carcinoma and intermediate risk factors.

OBJECTIVE: To investigate the outcomes of observation-alone versus adjuvant radiotherapy for patients with lymph node negative FIGO 2018 stage IB cervical carcinoma following radical hysterectomy with negative prognostic factors. METHODS: The National Cancer Database was accessed and patients with no history of another tumor, diagnosed with intermediate risk (defined as tumor size 2-4 cm with lymph-vascular invasion or tumor size >4 cm) pathological stage IB squamous, adenosquamous carcinoma or adenocarcinoma of the cervix between January 2010 and December 2015 who underwent radical hysterectomy with lymphadenectomy and had negative tumor margins were identified. Overall survival was assessed following generation of Kaplan-Meier curves and compared with the log-rank test. A Cox model was constructed to control for a priori selected confounders known to be associated with overall survival. RESULTS: A total of 765 patients were identified and adjuvant external beam radiotherapy was administered to 378 patients (49.4%). There was no difference in overall survival between patients who did and did not receive adjuvant radiotherapy, P=0.44: 4-year overall survival rates were 88.4% and 87.1% respectively. After controlling for patient age, histology, and surgical approach, the administration of adjuvant radiotherapy was not associated with better survival (HR 0.86, 95% CI 0.54 to 1.38). For patients who received adjuvant radiotherapy, there was no survival difference between those who did (n=219) and did not (n=159) receive concurrent chemotherapy, P=0.36: 4-year overall survival rates were 89.8% and 86.3%, respectively. CONCLUSION: In a large cohort of patients with lymph node negative, margin negative, stage IB cervical carcinoma, with negative prognostic factors, the administration of adjuvant external beam radiation therapy was not associated with a survival benefit compared with observation alone.

Oncologic outcomes of minimally invasive versus open radical hysterectomy for early stage cervical carcinoma and tumor size <2 cm: a systematic review and meta-analysis.

OBJECTIVE: To investigate the oncologic outcomes of patients with early-stage cervical carcinoma and tumor size <2 cm who underwent open or minimally invasive radical hysterectomy. METHODS: The Pubmed/Medline, Embase, and Web-of-Science databases were queried from inception to January 2021 (PROSPERO CRD 42020207971). Observational studies reporting progression-free survival and/or overall survival for patients who had open or minimally invasive radical hysterectomy for early-stage cervical carcinoma and tumor size <2 cm were selected. Level of statistical heterogeneity was evaluated with the I2 statistic. A random-effects model was used to compare progression and overall survival between the two groups and HR with 95% confidence intervals were calculated with the Der Simonian and Laird approach. Risk of bias and quality of included studies was assessed with the Newcastle-Ottawa scale. RESULTS: A total of 10 studies that met the inclusion criteria were included encompassing 4935 patients. Of these, 2394 (48.5%) patients had minimally invasive and 2541 (51.5%) patients had open radical hysterectomy; respectively. Patients who underwent minimally invasive hysterectomy had worse progression-free survival than those who had open surgery (HR 1.68, 95% CI 1.20, 2.36, I2 26%). Based on five studies, patients who had minimally invasive (n=1808) hysterectomy had a trend towards worse overall survival than those who had open surgery (n=1853) (HR 1.64, 95% CI 1.00 to 2.68, I2 15%). CONCLUSION: Based on a systematic review of the literature and meta-analysis of studies that control for confounders, for patients with cervical cancer and tumor size <2 cm, minimally invasive radical hysterectomy was associated with worse progression-free survival than laparotomy.