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.

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.

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.

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

OBJECTIVE: To investigate the survival of patients with lymph node positive endometrial carcinoma by type of surgical lymph node assessment. METHODS: 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. RESULTS: 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%, p<0.001) and more likely to receive radiation therapy alone (19.8% vs 5.4%, p<0.001) compared with patients who had systematic lymphadenectomy. There was no difference in overall survival between patients who had sentinel lymph node biopsy alone and systematic lymphadenectomy (p=0.27 from log rank test), and 3 year overall survival rates were 82.2% and 79.4%, respectively (p>0.05). 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). CONCLUSIONS: Performance of sentinel lymph node biopsy alone was not associated with an adverse impact on survival in patients with lymph node positive endometrial cancer.

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

OBJECTIVE: 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. RESULTS: 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). CONCLUSIONS: 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.

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

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSION: Adjuvant chemotherapy (with or without radiotherapy) is associated with a survival benefit for uterine serous carcinoma confined to the endometrium.

Surgical and oncologic outcomes of minimally invasive surgery for stage I high-grade endometrial cancer.

OBJECTIVE: To evaluate the prevalence and outcomes of minimally invasive surgery for stage I high grade endometrial cancer. We hypothesized that route of surgery is not associated with survival. MATERIALS: Patients diagnosed between 2010 and 2014, with stage I grade 3 endometrioid, serous, clear cell and carcinosarcoma endometrial carcinoma, who underwent hysterectomy with lymphadenectomy were drawn from the National Cancer Database. Patients converted to open surgery were excluded. Overall survival was assessed with Kaplan-Meier curves and compared with the log-rank test. A Cox model was constructed to control for confounders. RESULTS: A total of 12852 patients were identified. The rate of minimally invasive surgery was 62.2%. An increase in the use between 2010 and 2014 was noted (p < 0.001). Open surgery was associated with longer hospital stay (median 3 vs 1 day, p < 0.001), higher 30-day unplanned re-admission rate (4.5% vs 2.4%, p < 0.001) and 30-day mortality (0.6% vs 0.3%, p = 0.008). There was no difference in overall survival between patients who had open or minimally invasive surgery, p = 0.22; 3-yr overall survival rates were 83.7% and 84.4% respectively. After controlling for patient age, tumor histology, substage, type of insurance, type of reporting facility, receipt of radiation therapy and chemotherapy, extent of lymphadenectomy, the presence of comorbidities and personal history of another tumor, minimally invasive surgery was not associated with a worse survival (hazard ratio: 1.06, 95% confidence interval: 0.97, 1.15). CONCLUSIONS: Minimally invasive surgery for patients with stage I high grade endometrial cancer, was associated with superior short-term outcomes with no difference in overall survival noted.

Low rate of intraperitoneal port placement in ovarian cancer patients, a population-based assessment.

INTRODUCTION: The National Comprehensive Cancer Network (NCCN) guidelines recommend intraperitoneal chemotherapy in optimally debulked stage III ovarian cancer patients. The objective of this investigation was to determine the rate of intraperitoneal port placement in patients undergoing surgery for ovarian cancer in a national database maintained by the American College of Surgeons. METHOD: We identified ovarian cancer patients in the National Surgical Quality Improvement Program database from 2006 to 2012. Demographics, comorbidities, operative outcomes, and postoperative complications were abstracted. Descriptive analyses were conducted using Wilcoxon rank-sum and Chi square tests, and multivariate regression models were used to analyze pre-operative and post-operative variables associated with intraperitoneal port placement. RESULTS: We identified 2659 ovarian cancer patients who underwent primary surgical management. Of these patients, only 128 (4.8%) had an intraperitoneal port placed at the time of surgery. In multivariable analyses, intraperitoneal ports were associated with body mass index ≤25, disseminated cancer, later portion of the study period (2009-2012), and operative time >200 min. Intraperitoneal port placement was not associated with any difference in surgical site infection, wound disruption, major postoperative complication, readmission within 30 days, or death within 30 days. DISCUSSION: Recent investigation of practice at NCCN institutions between 2003 and 2012 found only 35% of eligible ovarian cancer patients received intraperitoneal chemotherapy. Using intraperitoneal port placement as a surrogate for intraperitoneal chemotherapy administration, our investigation suggests an even lower rate (4.8%) nationally.