Dimitrios Nasioudis

Management of recurrent and persistent malignant ovarian germ cell tumors: a narrative review

Approximately 10% of patients with malignant ovarian germ cell tumors will experience a tumor relapse. Given the rarity of malignant ovarian germ cell tumors, management of these patients is challenging. Secondary cytoreductive surgery can be considered for carefully selected patients with a goal to achieve complete gross or optimal resection. For patients with platinum sensitive disease who have already received platinum-based chemotherapy, standard dose chemotherapy with paclitaxel/ifosfamide/cisplatin or vinblastine/ifosfamide/cisplatin can be considered. High-dose chemotherapy protocols at specialized centers should be explored even for patients with platinum-resistant disease; however, optimal timing is under investigation. A subset of patients with malignant ovarian germ cell tumors harbors potentially actionable genomic alterations. Further research is required to identify novel therapeutic approaches for these patients.

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

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. 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. 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). 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

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. 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. 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). For patients with advanced stage ovarian cancer delayed interval cytoreductive surgery may not be associated with worse overall survival.

Impact of adjuvant chemotherapy on the overall survival of patients with advanced-stage low-grade serous ovarian carcinoma following primary cytoreductive surgery

To investigate the use and outcomes of adjuvant chemotherapy for patients with advanced-stage low-grade serous ovarian carcinoma following primary cytoreductive surgery. Patients diagnosed between 2010 and 2015 with International Federation of Gynecology and Obstetrics stage II-IV low-grade serous ovarian carcinoma who underwent primary debulking surgery with known residual disease status and had at least 1 month of follow-up were identified in the National Cancer Database. Adjuvant chemotherapy was defined as receipt of chemotherapy within 6 months of surgery. Overall survival was evaluated using the Kaplan-Meier method and compared with the log-rank test. A Cox model was constructed to control for a priori-selected confounders. A systematic review of the literature was also performed. In total, 618 patients with stage II-IV low-grade serous ovarian carcinoma who underwent primary cytoreductive surgery were identified; 501 (81.1%) patients received adjuvant chemotherapy, while 117 (18.9%) patients did not. The median follow-up of the present cohort was 47.97 months. There was no difference in overall survival between patients who did and did not receive adjuvant chemotherapy (p=0.78; 4-year overall survival rates were 77.5% and 76.1%, respectively). After controlling for patient age, medical co-morbidities, disease stage, and residual disease status, administration of adjuvant chemotherapy was not associated with better overall survival (HR=0.87, 95% CI 0.55 to 1.38). Based on data from three retrospective studies, omission of adjuvant chemotherapy following cytoreductive surgery was not associated with worse progression-free survival benefit (HR=1.25, 95% CI 0.80 to 1.95) for patients with stage III-V low-grade serous ovarian carcinoma. Adjuvant chemotherapy may not be associated with an overall survival benefit for patients with advanced-stage low-grade serous ovarian carcinoma following primary cytoreductive surgery.

Impact of surgical approach on prevalence of positive peritoneal cytology and lymph-vascular invasion in patients with early-stage endometrial carcinoma: a National Cancer Database study

To investigate the prevalence of positive peritoneal cytology and lymph-vascular invasion by surgical approach among patients with early stage endometrioid endometrial carcinoma undergoing hysterectomy. The National Cancer Database was accessed and patients with FIGO stage I endometrioid endometrial carcinoma (with no history of another tumor diagnosed) who underwent simple hysterectomy (open or minimally invasive) between January 2010 and December 2015 and had available data on the presence of lymph-vascular invasion and/or status of peritoneal cytology were selected for further analysis. The impact of a surgical approach on the odds of lymph-vascular invasion and positive peritoneal cytology was calculated after controlling for tumor grade, size, and depth of myometrial invasion. A total of 74 732 patients who met the inclusion criteria were identified. The rate of minimally invasive hysterectomy was 75.7%. Data on peritoneal cytology status and lymph-vascular invasion were available for 50 185 and 71 641 patients, respectively. A higher proportion of patients who had minimally invasive hysterectomy had positive peritoneal cytology (4.4% vs 2.3%, p<0.001), and presence of lymph-vascular invasion (10.4% vs 9.2%, p<0.001). After controlling for tumor size, tumor grade, and disease substage, the performance of minimally invasive surgery was associated with higher odds of positive peritoneal cytology (OR 2.08, 95% CI 1.83 to 2.37) and presence of lymph-vascular invasion (OR 1.33, 95% CI 1.25 to 1.41). After controlling for confounders there was no difference in survival between open and minimally invasive surgery groups (HR 0.93, 95% CI 0.85 to 1.004). Minimally invasive surgery may be associated with a higher incidence of positive peritoneal cytology and lymph-vascular invasion among patients with early stage endometrioid endometrial cancer. There was no difference in overall survival between patients who had laparotomy or minimally invasive surgery.

The impact of sentinel lymph node sampling versus traditional lymphadenectomy on the survival of patients with stage IIIC endometrial cancer

To investigate the survival of patients with lymph node positive endometrial carcinoma by type of surgical lymph node assessment. Patients diagnosed between January 2012 and December 2015 with endometrial carcinoma and uterine confined disease and nodal metastases on final pathology who underwent minimally invasive hysterectomy were identified in the National Cancer Database. Patients who had sentinel lymph node biopsy alone or underwent systematic lymphadenectomy were selected. Overall survival was evaluated following generation of Kaplan-Meier curves and compared with the log rank test. A Cox model was constructed to evaluate survival after controlling for confounders. A total of 1432 patients were identified: 1323 (92.4%) and 109 (7.6%) underwent systematic lymphadenectomy and sentinel lymph node biopsy only, respectively. The rate of adjuvant treatment was comparable between patients who had sentinel lymph node biopsy alone and systematic lymphadenectomy (83.5% vs 86.6%, p=0.39). However, patients who had sentinel lymph node biopsy were less likely to receive chemotherapy alone (13.6% vs 36.6%, p0.05). After controlling for confounders, there was no difference in survival between the systematic lymphadenectomy and sentinel lymph node biopsy alone groups (hazard ratio 0.82, 95% confidence interval 0.46 to 1.45). Performance of sentinel lymph node biopsy alone was not associated with an adverse impact on survival in patients with lymph node positive endometrial cancer.

Adjuvant treatment for patients with FIGO stage I uterine serous carcinoma confined to the endometrium

The role of adjuvant treatment for early-stage uterine serous carcinoma is not defined. The goal of this study was to investigate the impact of adjuvant treatment on survival of patients with tumors confined to the endometrium. Patients diagnosed with stage I uterine serous carcinoma with no myometrial invasion between January 2004 and December 2015 who underwent hysterectomy with at least 10 lymph nodes removed were identified from the National Cancer Database. Adjuvant treatment patterns defined as receipt of chemotherapy and/or radiotherapy within 6 months from surgery were investigated and overall survival was evaluated using Kaplan-Meier curves, and compared with the log-rank test for patients with at least one month of follow-up. A Cox analysis was performed to control for confounders. A total of 1709 patients were identified; 833 (48.7%) did not receive adjuvant treatment, 348 (20.4%) received both chemotherapy and radiotherapy, 353 (20.7%) received chemotherapy only, and 175 (10.2%) received radiotherapy only. Five-year overall survival rates for patients who did not receive adjuvant treatment (n=736) was 81.9%, compared with 91.3% for those who had chemoradiation (n=293), 85.1% for those who received radiotherapy only (n=143), and 91.0% for those who received chemotherapy only (n=298) (p<0.001). After controlling for age, insurance status, type of treatment facility, tumor size, co-morbidities, and history of another tumor, patients who received adjuvant chemotherapy (HR 0.64, 95% CI 0.42, 0.96), or chemoradiation (HR 0.55, 95% CI 0.35, 0.88) had better survival compared with those who did not receive any adjuvant treatment, while there was no benefit from radiotherapy alone (HR 0.85, 95% CI 0.53, 1.37). There was no survival difference between chemoradiation and chemotherapy only (HR 1.15, 95% CI 0.65, 2.01). Adjuvant chemotherapy (with or without radiotherapy) is associated with a survival benefit for uterine serous carcinoma confined to the endometrium.

Outcomes of minimally invasive surgery for patients with endometrial carcinoma involving the cervix

Most studies evaluating the oncologic safety of minimally invasive surgery for endometrial cancer focus on patients with stage I disease. The aim of this study was to investigate the outcomes of minimally invasive surgery for patients with endometrial carcinoma involving the cervix. Patients diagnosed between January 2010 and December 2015, with clinical stage II endometrial carcinoma, who underwent hysterectomy with lymphadenectomy, were drawn from the National Cancer Database. Inclusion criteria were clinical International Federation of Gynecology and Obstetrics (FIGO 2009) stage II, patients who underwent hysterectomy with lymphadenectomy, and known route of surgery (open or minimally invasive). Patients who received radiation therapy prior to surgery, those who had subtotal/supracervical hysterectomy, or unknown type of hysterectomy were excluded. The exposure of interest was performance of minimally invasive surgery either laparoscopic or robotic-assisted. Overall survival (primary endpoint) was assessed for patients diagnosed between January 2010 and December 2014 following generation of Kaplan-Meier curves and compared with the log-rank test. A Cox model was constructed to control for confounders. A total of 2175 patients were identified and 1282 (58.9%) had minimally invasive surgery. Of these, 339 and 943 patients had laparoscopic or robotic-assisted laparoscopic hysterectomy, respectively. Minimally invasive surgery was converted to open surgery in 74 (5.8%) patients. Those undergoing minimally invasive surgery had shorter hospital stay (median 1 vs 3 days, p<0.001), lower unplanned readmission rate (2.7% vs 4.7%, p=0.014), and 90-day mortality (0.8% vs 1.8%, p=0.05). Patients who had open surgery (n=796) had worse overall survival compared with those who had minimally invasive surgery (n=1048, p=0.003); 3-year overall survival rates were 76.8% and 83.6%, respectively. After controlling for patient age, race, type of insurance, presence of co-morbidities, performance of extensive lymphadenectomy, presence of positive lymph nodes, tumor histology, presence of lymphovascular space invasion, tumor size, and administration of radiotherapy, performance of minimally invasive surgery was not associated with worse survival (HR 0.90, 95% CI 0.73 to 1.11). In this retrospective analysis, minimally invasive surgery in patients with stage II endometrial carcinoma was associated with superior short-term peri-operative outcomes and improved 3-year overall survival.

Premature adoption of adjuvant chemotherapy for locally advanced cervical carcinoma before the OUTBACK trial: cautionary tale on outcomes

The aim of this study was to investigate the use and outcomes of adjuvant chemotherapy for patients with locally advanced cervical carcinoma receiving definitive chemoradiation. The National Cancer Database was accessed, and patients diagnosed between 2004 and 2015 with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB2-IVA disease who underwent definitive chemoradiation were selected. Patients who received radio-sensitizing single agent chemotherapy and those who received adjuvant multi-agent chemotherapy were identified. Overall survival was evaluated following generation of Kaplan-Meier curves while a Cox model was constructed to control for confounders. A total of 9895 patients were identified; 1003 (10.1%) received multi-agent adjuvant chemotherapy. Patients who received adjuvant chemotherapy were less likely to receive brachytherapy (60.9% vs 68.4%, p<0.001). Rate of adjuvant chemotherapy was higher among patients with stage IVA (18.1%) and stage III (11.9%) disease compared with those with stage II (8.4%) and stage IB2 (7.2%) disease (p<0.001). After controlling for confounders, administration of adjuvant chemotherapy was not associated with a survival benefit (hazard ratio 1.09, 95% confidence interval 0.98 to 1.20). Following stratification by disease stage, there was no survival benefit of patients who received adjuvant chemotherapy compared with those who did not; stage IB (p=0.002; 5 year overall survival 59.2% vs 74.9% favoring chemoradiation alone), stage II (p=0.41; 5 year overall survival 63.8% vs 67.6%, respectively), stage III (p=0.52; 5 year overall survival 48% vs 47.8%, respectively), or stage IVA disease (p=0.27; 5 year overall survival 29.5% vs 34.3%, respectively). In the US, approximately 1 in 10 patients with locally advanced cervical carcinoma who underwent definitive chemoradiation also received adjuvant chemotherapy that was not associated with improvement in overall survival.

Lymphadenectomy for early-stage mucinous ovarian carcinoma

There is evidence to suggest that the rate of lymph node metastases in patients with ovarian mucinous tumors is rare. The objective of this study was to investigate the prevalence of regional lymph node metastases among patients with apparent stage IA and IC mucinous ovarian carcinoma. A retrospective cohort study was performed and included patients from the National Cancer Database with apparent stage IA and IC mucinous ovarian tumors who underwent surgery between January 1, 2004 and December 31, 2015. Data collected included demographics, surgical procedures, and pathologic characteristics. The primary outcome was the effect of tumor stage, grade, and size on the risk of lymph node metastases. Categorical and continuous variables were compared using the χ A total of 4379 patients were identified: 3088 and 1213 with stage IA and IC disease, respectively, with an additional 78 patients who were stage I Not Otherwise Specified (NOS). Lymphadenectomy was performed in 70.6% of patients with stage IA and 70.3% of patients with stage IC cancers. Stratifying by grade, 68.4%, 71.3%, and 72.8% of patients with grades 1, 2, and 3 tumors underwent a lymphadenectomy, respectively. Furthermore, lymphadenectomy was performed in 64.9% of patients with tumors 10 cm. Lymph node metastases were identified in 1.2% and 1.6% of patients with stage IA and IC disease, respectively (p=0.063). Additionally, metastases were present in 0.6% of patients with grade 1 tumors, 1.1% of patients with grade 2 tumors, and 5.3% of patients with grade 3 tumors (p10 cm had lymph node metastases (p=0.19). Among patients with mucinous ovarian carcinoma, lymph node metastases are rare. However, metastases are significantly more common in patients with higher grade tumors. These factors may be considered when making decisions regarding the need for lymphadenectomy in early-stage mucinous ovarian tumors.

Fertility sparing surgery for patients with FIGO stage I clear cell ovarian carcinoma: a database analysis and systematic review of the literature

Fertility sparing surgery for patients with early stage ovarian clear cell carcinoma is controversial. We aimed to investigate the impact of fertility sparing surgery on the oncologic outcomes of young patients with stage I ovarian clear cell carcinoma. The National Cancer Database was accessed and patients with pathological stage IA or IC ovarian clear cell carcinoma, aged A total of 57 (35.8%) and 102 (64.2%) patients underwent fertility sparing and radical surgery. There was no difference in overall survival between patients who had fertility sparing and radical surgery (p=0.92); 5 year overall survival rates were 89% and 87.9%, respectively. After controlling for the performance of lymphadenectomy and disease substage, fertility sparing surgery was not associated with worse survival (hazard ratio 0.83, 95% confidence interval 0.30 to 2.32). A systematic review of the literature identified 132 patients with stage I disease who underwent fertility sparing surgery; a total of 20 patients (15.2%) experienced a relapse at a median of 18 months from surgery. In a large cohort of young patients with stage I ovarian clear cell carcinoma, fertility sparing surgery was not associated with worse survival.

Reply to “Is there a promising role of HIPEC in patients with advanced mucinous ovarian cancer?” by lavazzo et al

Ovarian Sertoli-Leydig and granulosa cell tumor: comparison of epidemiology and survival outcomes

To investigate the epidemiology, clinico-pathological characteristics and outcomes of patients diagnosed with malignant ovarian Sertoli-Leydig cell tumors (SLCTs) in comparison to granulosa cell tumors (GCTs). The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database were accessed and patients diagnosed with a malignant SLCT and GCT between 1988 and 2013 were selected. Demographic and clinico-pathological characteristics were compared using the Mann-Whitney and chi-square tests. Overall (OS) and cancer-specific survival (CSS) rates were estimated with the Kaplan-Meier method and compared with the log-rank test. Cox hazard models were constructed to control for confounders. A total of 175 and 1361 patients diagnosed with SLCT and GCT, respectively, were identified. Compared to patients with GCT, those with SLCT were younger (median age 32 vs. 51 years, p  10 cm), SCLTs were associated with a worse cancer-specific mortality compared to GCTs. SLCTs are extremely rare, commonly arise in premenopausal patients. They are associated with a poorer prognosis compared to GCT.

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

Investigate the overall survival of patients with stage IC2/IC3 epithelial ovarian carcinoma undergoing fertility-sparing surgery. Patients aged 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. 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

To investigate the impact of malignant ascites volume on the outcomes of patients with advanced epithelial ovarian carcinoma who undergo primary debulking surgery. 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 ( 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). 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

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. 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. 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). 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.

Oncologic outcomes of uterine preservation for pre-menopausal patients with stage II epithelial ovarian carcinoma

Fertility-sparing surgery is rarely offered for patients with stage II epithelial ovarian carcinoma. The aim of the present study was to evaluate the overall survival of pre-menopausal patients with stage II epithelial ovarian carcinoma who did not undergo hysterectomy. The National Cancer Database was accessed, and patients aged ≤40 years without a history of another tumor diagnosed between 2004 and 2015 with a pathological stage II epithelial ovarian carcinoma, who underwent lymphadenectomy and received multi-agent chemotherapy, were identified. Overall survival was compared with the log-rank test after generation of Kaplan-Meier curves. A Cox model was constructed to control for tumor histology. A total of 185 patients met the inclusion criteria. The rate of uterine preservation was 24.3% (45 patients). Patients who did not undergo hysterectomy were younger (median 32 vs 37 years, p0.05). Median follow-up of the present cohort was 62.3 months (95% CI 53.6 to 71.0) and a total of 22 deaths occurred. There was no difference in overall survival between patients who did and did not undergo hysterectomy (p=0.50; 5-year overall survival rates 87.5% and 91.4%, respectively). After controlling for tumor histology, grade and substage, omission of hysterectomy was not associated with worse survival (HR 0.69, 95% CI 0.22 to 2.12). Uterine preservation was not associated with worse survival in this cohort of pre-menopausal patients with stage II epithelial ovarian carcinoma.

Survival following minimally invasive radical hysterectomy for patients with cervical carcinoma and tumor size ≤2 cm

Role of immunotherapy for lymph node positive vulvar melanoma: utilization and outcomes

To investigate the utilization and outcomes of adjuvant immunotherapy for patients with vulvar melanoma and inguinal lymph node metastases. The National Cancer Database was accessed and patients with vulvar melanoma diagnosed between 2004 and 2015 who did not have distant metastases, underwent inguinal lymphadenectomy, had positive lymph nodes, and at least 1 month of follow-up were identified. Administration of immunotherapy was evaluated and clinicopathological characteristics were compared. Median overall survival was compared with the log-rank test. Stratified analysis based on clinical status of lymph nodes was performed. A Cox model was constructed to evaluate survival after controlling for confounders. A total of 300 patients were identified; the rate of immunotherapy use was 25% (75 patients). Patients who received immunotherapy were younger (median 58 vs 70 years, p<0.001); however, the two groups were comparable in terms of clinical lymph node status, rate of positive tumor margins, presence of tumor ulceration, tumor size, Breslow thickness, and performance of comprehensive lymphadenectomy. There was no overall survival difference between patients who did (median 31.08 months) and did not (median 22.77 months) receive immunotherapy (p=0.18). Following stratification by clinical lymph node status, immunotherapy did not improve overall survival of patients with clinically negative (median 35.35 vs 33.22, p=0.75) or positive lymph nodes (median 23.33 vs 16.99, p=0.64). After controlling for confounders, administration of immunotherapy was not associated with better overall survival (HR 0.81, 95% CI 0.57 to 1.14). In this study approximately one in four patients received adjuvant immunotherapy. Immunotherapy was not associated with improved overall survival.

Utilization and outcomes of sentinel lymph node biopsy in patients with early stage vulvar cancer

A retrospective cohort study comparing survival and perioperative outcomes of patients with early vulvar cancer who underwent sentinel lymph node biopsy versus standard lymphadenectomy METHODS: Patients diagnosed between January 2012 and December 2015 with vulvar squamous cell carcinoma of less than 4 cm in size, with invasion of at least 1 mm, who underwent sentinel lymph node biopsy, lymphadenectomy, or both were identified from the National Cancer Database. Overall survival was evaluated following generation of Kaplan-Meier curves and compared with the log-rank test for patients who had at least 1 month of follow-up. A Cox model was constructed to control for confounders. A total of 1583 patients were identified; 304 patients (19.2%) underwent sentinel lymph node biopsy alone. Sentinel lymph node biopsy utilization increased 13.9% between 2012 and 2015. Patients who underwent sentinel node biopsy alone were less likely to have comorbidities compared with those undergoing lymphadenectomy only or sentinel node biopsy with lymphadenectomy (25.3% vs 32.9% vs 31.9%, p=0.042), had smaller tumors (median 1.6 vs 2.0 vs 2.0 cm, p<0.001), and were less likely to have positive lymph nodes (11% vs 19.6% vs 28.1%, p<0.001). There was no difference in 3 year overall survival between the three groups (86.3% vs 82.1% vs 77.9%, p=0.26). After controlling for age, race, insurance, comorbidities, lymph node metastases, and tumor size, sentinel lymph node biopsy alone was not associated with worse overall survival compared with lymphadenectomy (HR 0.86, 95% CI 0.57 to 1.32). The sentinel node only group had shorter inpatient stays compared with lymphadenectomy only (median 1 vs 2 days, p<0.001) and a lower rate of unplanned readmission (1.7% vs 5.0%, p=0.010). The utilization of sentinel lymph node biopsy is increasing in the management of vulvar cancer and is associated with superior perioperative outcomes without impacting overall survival.

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

To investigate the oncologic outcomes of patients with early-stage cervical carcinoma and tumor size 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 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, I 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

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

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. 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. 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. 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.

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

To evaluate the outcomes of minimally invasive surgery for patients with stage IA cervical carcinoma undergoing hysterectomy. 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 χ 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). 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.

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

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. 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. 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). 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.

Intermediate Risk Cervical Cancer: Radical Surgery +/- Adjuvant Radiotherapy

The objective of the trial is to evaluate if adjuvant (chemo)radiation is associated with a disease-free survival benefit after radical surgery in patients with intermediate risk cervical cancer. The primary endpoint of the study is the disease-free survival from the day of randomisation. A total of 514 patients are required to achieve 80% power on 5% significance level with non-inferiority margin of 5% to test the difference between the ARMs using Cox proportional hazards model. The maximal tolerated margin for non-inferiority in 2-year DFS is 5% (including expected drop-out rate of 10%).