Utilization of sentinel lymph node biopsy in the early ovarian cancer surgery.

OBJECTIVE: Sentinel lymph node (SLN) biopsy has been incorporated into surgical care for many malignancies; however, the utility has not been examined in ovarian cancer. This study examined population-level trends, characteristics, and outcomes related to SLN biopsy in early stage ovarian cancer. METHODS: This is a retrospective cohort study querying the National Cancer Institute's Surveillance, Epidemiology, and End Result Program from 2003-2018. The study population consisted of 11,512 women with stage I ovarian cancer who had adnexectomy-based surgical staging including lymph node evaluation. Exposure allocation was based on SLN biopsy use. Main outcomes measured were (i) trends and characteristics associated with SLN biopsy use, assessed by multivariable logistic regression model, and (ii) overall survival assessed with inverse provability of treatment weighting propensity score. RESULTS: SLN biopsy was performed in less than 1% of study population. In a multivariable analysis, recent surgery (2011-2018 versus 2003-2010, odds ratio [OR] 1.64, 95% confidence interval [CI] 1.03-2.59), smaller tumor size (< 10 versus ≥ 10 cm, OR 3.07, 95% CI 1.20-7.84), and East registry area (OR 2.74, 95% CI 1.73-4.36) remained independent characteristics for SLN biopsy use. In a propensity score weighted model, 5-year overall survival rate was 90.5% for the SLN biopsy-incorporated group and 88.6% for the lymphadenectomy group (hazard ratio 0.96, 95% CI 0.53-1.73). CONCLUSION: SLN biopsy was rarely performed for early ovarian cancer surgery during the study period with insufficient evidence to interpret the survival effect. SLN biopsy in early ovarian cancer appears to be in early development phase, warranting further study and careful evaluation to assess feasibility and oncologic outcome.

Secondary ovarian cancer after external beam radiotherapy for nonovarian pelvic malignancy.

OBJECTIVE: To examine characteristics and survival of patients who developed secondary ovarian cancer after external beam radiotherapy (EBRT) for a prior nonovarian pelvic malignancy. METHODS: This is a population-based retrospective cohort study, querying the Surveillance, Epidemiology, and End Result program from 1975 to 2016. 167,269 women who received EBRT for 7 malignancies (anus, rectum, bladder, cervix, uterus, vulva, or vagina) were examined to identify subsequent secondary ovarian cancer diagnosis after EBRT. Then, within the ovarian cancer cohort (n = 147,618), characteristics and survival of patients with secondary ovarian cancer after EBRT were compared to those with ovarian cancer who did not receive prior EBRT. RESULTS: Following EBRT for a pelvic malignancy, 215 (1.3 per 1000) patients developed secondary ovarian cancer. Among those, the most frequent prior malignancy was cervical cancer (45.6%), followed by rectal cancer (20.9%). The median time from prior EBRT to secondary ovarian cancer was 8.8 years (interquartile range, 2.8-14.5). In multivariable analysis, patients with secondary ovarian cancer after EBRT were more likely to be older, and have a recent year of diagnosis, but less likely to have early-disease compared to ovarian cancer patients without prior EBRT (all, P < 0.05). In weighted model, patients with secondary ovarian cancer after EBRT had decreased overall survival compared to those with ovarian cancer without prior EBRT (5-year rates, 19.6% versus 39.9%, hazard ratio 1.62, 95% confidence interval 1.43-1.85). Similar association was observed in ages <70, ≥70, White, non-White, early-disease, and advanced-disease in sensitivity analyses. CONCLUSION: Radiotherapy-related secondary ovarian cancer may be associated with decreased overall survival.

Utilization and Outcomes of Sentinel Lymph Node Biopsy for Early Endometrial Cancer.

OBJECTIVE: To examine trends, characteristics, and oncologic outcomes of sentinel lymph node biopsy for early endometrial cancer. METHODS: This observational study queried the National Cancer Institute's Surveillance, Epidemiology, and End Results Program by examining 83,139 women with endometrial cancer who underwent primary hysterectomy with nodal evaluation for T1 disease from 2003 to 2018. Primary outcome measures were the temporal trends in utilization of sentinel lymph node biopsy and patient characteristics associated with sentinel lymph node biopsy use, assessed by multivariable binary logistic regression models. Secondary outcome measure was endometrial cancer-specific mortality associated with sentinel lymph node biopsy, assessed by propensity score inverse probability of treatment weighting. RESULTS: The utilization of sentinel lymph node biopsy increased from 0.2 to 29.7% from 2005 to 2018 (P<.001). The uptake was higher for women with endometrioid (0.3-31.6% between 2005 and 2018) compared with nonendometrioid (0.6-21.0% between 2006 and 2018) histologic subtypes (both P<.001). In a multivariable analysis, more recent year surgery, endometrioid histology, well-differentiated tumors, T1a disease, and smaller tumor size were independently associated with sentinel lymph node biopsy use (P<.05). Performance of sentinel lymph node biopsy was not associated with increased endometrial cancer-specific mortality compared with lymphadenectomy for endometrioid tumors (subdistribution hazard ratio [HR] 0.96, 95% CI 0.82-1.13) or nonendometrioid tumors (subdistribution HR 0.85, 95% CI 0.69-1.04). For low-risk endometrial cancer, the increase in sentinel lymph node biopsy resulted in a 15.3 percentage-point (1.4-fold) increase in surgical nodal evaluation by 2018 (expected vs observed rates, 37.8 vs 53.1%). CONCLUSION: The landscape of surgical nodal evaluation is shifting from lymphadenectomy to sentinel lymph node biopsy for early endometrial cancer in the United States, with no indication of a negative effect on cancer-specific survival.

Uptake in sentinel lymph node biopsy for endometrial cancer with T3 classification.

OBJECTIVE: The current clinical practice guidelines for endometrial cancer specify sentinel lymph node (SLN) biopsy to be performed in apparent uterine-confined disease. However, a recent population-based analysis found that the utilization of SLN biopsy is increasing in extra-uterine disease such as T2 classification. The objective of this study was to examine trends and outcomes related to SLN biopsy for endometrial cancer with T3 classification, another extra-uterine disease. METHODS: A population-based retrospective cohort study was conducted to examine 7004 women with T3 endometrial cancer who underwent primary surgery between 2010 and 2018, identified in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Trends and characteristics related to SLN biopsy were assessed by multinomial regression analysis, and inverse probability of treatment weighting propensity score was used to assess overall survival related to SLN biopsy. RESULTS: Nodal evaluation type included lymphadenectomy (n = 5276, 75.3%), SLN biopsy (n = 287, 4.1%), and none (n = 1441, 20.6%). The utilization of SLN biopsy increased from 0.4% to 12.9% between 2010 and 2018 (P < 0.001) that this association remained independent in multivariable analysis (adjusted-odds ratio compared to 2010-2012, 2.63 [95% confidence interval 1.57-4.42] for 2013-2015 and 10.1 [95% confidence interval 6.30-16.2] for 2016-2018). When compared to the lymphadenectomy group, the SLN biopsy group was less likely to have T3b disease (adjusted-odds ratio 0.69, 95% confidence interval 0.51-0.94) but had similar postoperative chemotherapy and radiotherapy (both, P > 0.05). In a weighted model, the 3-year overall survival rate was 66.3% for the SLN biopsy group and 64.7% for the lymphadenectomy group (hazard ratio 0.85, 95% confidence interval 0.69-1.05). Similar association was observed in subcohorts for young, old, endometrioid, non-endometrioid, T3a, T3b, and N0 cases. CONCLUSION: Utilization of SLN biopsy in T3 endometrial cancer is increasing in the United States.

Population incidence and characteristics of secondary breast cancer after uterine cancer: a competing risk analysis.

PURPOSE: To examine incidence and characteristics of women who developed secondary breast cancer after uterine cancer. METHODS: This is a population-based retrospective cohort study utilizing the National Cancer Institute's Surveillance, Epidemiology, and End Result Program from 1973 to 2013. Women with uterine cancer who did not have synchronous or a history of breast cancer were followed after their uterine cancer diagnosis (N = 236,561). A time-dependent competing risk analysis was performed to examine cumulative incidences and clinico-pathological characteristics of those who subsequently developed breast cancer. RESULTS: There were 7110 (3.0%) women who developed secondary breast cancers after uterine cancer with 5-, 10-, and 20-year cumulative incidence rates of 1.5, 2.8, and 4.7%, respectively. The increase in the rate of secondary breast cancer was particularly high in the first 3 years after a uterine cancer diagnosis (annual percent change [APC] 4.9), followed by 3-7 years (APC 1.6) after diagnosis (P < 0.001). The median time to develop secondary breast cancer was 6.4 years. Older women had significantly shorter time intervals between uterine and breast cancer diagnoses (3.7 years for aged > 71, 5.9 for aged 64-71, 7.6 for aged 56-63, and 9.4 for aged < 56, P < 0.001). In a multivariable analysis, older age, White race, married status, endometrioid, serous, and mixed histology types, and early-stage tumors remained as independent factors of developing secondary breast cancer (all, P < 0.05). CONCLUSION: Tumor factors with endometrioid and serous histology types and early-stage disease were the factors associated with secondary breast cancer after uterine cancer diagnosis. Older women had shorter time to develop secondary breast cancer.

Incorporation of sentinel lymph node biopsy in cervical cancer surgery: Recent U.S. trends.

OBJECTIVE: To examine the trends, characteristics, and outcomes related to sentinel lymph node (SLN) biopsy for cervical cancer surgery. METHODS: This retrospective cohort study queried the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Study population included patients with invasive cervical cancer (squamous cell carcinoma, adenocarcinoma, and adenosquamous carcinoma) who underwent both hysterectomy and lymphadenectomy for T1 classification from 2003 to 2018. Exposure allocation was per surgical nodal evaluation type (SLN biopsy or lymphadenectomy). Main outcome measures were (i) trend of utilization and patient characteristics related to SLN biopsy assessed with multivariable analysis and (ii) overall survival associated with SLN biopsy assessed with propensity score inverse probability of treatment weighting. Sensitivity cohorts included uterine-preserving conservative surgeries. RESULTS: A total of 12,966 patients met the inclusion criteria. Of those, 430 (3.3%) patients underwent SLN biopsy. The utilization of SLN biopsy increased significantly from 0.8% to 15.2% during the study period (P < 0.001). This association remained independent in multivariable analysis: 2011-2014 versus 2003-2010 adjusted-odds ratio 4.87, 95% confidence interval (CI) 3.29-7.23, and 2015-2018 versus 2003-2010 adjusted-odds ratio 20.6, 95%CI 14.6-29.2. In a propensity score weighted model, patients who had SLN biopsy had similar overall survival compared to those without SLN biopsy (3-year rates, 94.8% versus 94.2%, hazard ratio 0.95, 95%CI 0.64-1.41, P = 0.799). In sensitivity analysis, the increase in SLN biopsy was also observed in uterine-preserving surgeries (3.5% to 9.6% for trachelectomy, P = 0.043; and 2.5% to 19.5% in cervical excision, P < 0.001). CONCLUSION: Landscape of surgical nodal evaluation is gradually shifting from lymphadenectomy to SLN biopsy in cervical cancer surgery.

Population-level trends and outcomes of sentinel lymph node biopsy in vulvar cancer surgery in the United States.

OBJECTIVE: To examine population-level trends, characteristics, and outcomes related to nodal assessment for vulvar cancer surgery in the United States. METHODS: This is a retrospective cohort study querying the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. The study population was 5604 women with T1b or T2-smaller(≤4 cm) squamous cell carcinoma of the vulva who underwent primary vulvectomy from 2003 to 2018. The exposure allocation was based on nodal evaluation type: lymphadenectomy (LND; n = 3319, 59.2%), sentinel lymph node (SLN) biopsy (n = 751, 13.4%), or no surgical nodal evaluation (n = 1534, 27.4%). The main outcomes were (i) trends and characteristics related to SLN biopsy assessed by multinomial regression model, and (ii) vulvar cancer-specific survival assessed by competing risk analysis and inverse probability of treatment weighting propensity score. Sensitivity analysis included evaluation of external cohort with T1a disease (n = 1291). RESULTS: The utilization of SLN biopsy increased from 5.7% to 23.3% in 2006-2018, while the proportion of LND decreased from 64.1% to 48.8% in 2010-2018, and these associations remained independent in multivariable analysis (adjusted-P < 0.05). In the propensity score weighted model, 5-year cumulative rate for vulvar cancer-specific mortality was 15.2% (interquartile range 12.1-18.9) for the SLN biopsy group and 16.9% (interquartile range 15.6-18.3) for the LND group (subdistribution-hazard ratio 0.90, 95% confidence interval 0.76-1.06, P = 0.217). The increasing SLN biopsy use was also observed in T1a disease from 1.3% to 7.3% during the study period (P < 0.001). CONCLUSION: The landscape of surgical nodal evaluation is shifting from lymphadenectomy to SLN biopsy in vulvar cancer surgery in the United States. SLN biopsy-incorporated treatment approach was not associated with worse survival compared to LND.

Incorporation of vaginal brachytherapy to external beam radiotherapy in adjuvant therapy for high-risk early-stage cervical cancer: A comparative study.

PURPOSE: To examine trends, characteristics, and outcomes related to addition of vaginal brachytherapy (VBT) to external beam radiotherapy (EBRT) for adjuvant radiotherapy in high-risk early-stage cervical cancer. METHODS AND MATERIALS: This comparative study is a retrospective observational analysis of the National Cancer Institutes' Surveillance, Epidemiology, and End Results Program. Surgically treated women with stage T1-2 cervical cancer who had high-risk factors (nodal metastasis and/or parametrial invasion) and received adjuvant radiotherapy from 2000 to 2018 were examined. Propensity score inverse probability of treatment weighting was used to assess the survival estimates for addition of VBT use. RESULTS: Among 2470 women with high-risk factors receiving EBRT, 760 (30.8%) had additional VBT. During the study period, there was an increasing trend of VBT use from 27.4% to 36.1% (p< 0.001). In a multivariable analysis, year of diagnosis and high-risk tumor factors: parametrial involvement, large tumor size, and use of chemotherapy remained independent characteristics associated with VBT use (all, p< 0.05). In propensity score-weighted models, VBT use with EBRT and EBRT alone had comparable overall survival (5-year rates 73.8% vs. 77.4%, hazard ratio [HR] 1.07, 95% confidence interval [CI] 0.92-1.25). Nonsignificant association was also observed in squamous or nonsquamous tumors, young or old age, low or high nodal ratio, chemotherapy use, and simple or radical hysterectomy (all, p> 0.05). Lastly, the addition of VBT was not associated with cervical cancer-specific survival (subdistribution-HR 1.15, 95% CI 0.94-1.41). CONCLUSIONS: Utilization of VBT with EBRT for adjuvant radiotherapy in high-risk early-stage cervical cancer is increasing in the United States. Addition of VBT was associated with neither overall survival nor cancer-specific survival.

Sentinel lymph node biopsy for stage II endometrial cancer: Recent utilization and outcome in the United States.

OBJECTIVE: To examine trends and outcomes related to sentinel lymph node (SLN) biopsy for stage II endometrial cancer. METHODS: This is a retrospective observational cohort study querying the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. The study population was 6,314 women with T2 endometrial cancer who underwent hysterectomy from 2010-2018. Exposure allocation was based on nodal evaluation type: lymphadenectomy (LND; n=4,915, 77.8%), SLN biopsy (n=340, 5.4%), or no surgical nodal evaluation (n=1,059, 16.8%). The main outcomes were (i) trends and characteristics related to nodal evaluation assessed by multinomial regression, and (ii) overall survival (OS) assessed by an inverse probability of treatment weighting propensity score analysis. A sensitivity analysis was performed to examine concurrent LND in women who underwent SLN biopsy. RESULTS: The utilization of SLN biopsy increased from 1.6% to 16.1%, while the number of LND decreased from 81.5% to 65.7% between 2010-2018 (P<0.05). In multivariable analysis, the utilization of SLN biopsy increased 45% annually (adjusted-odds ratio 1.45, 95% confidence interval [CI] 1.37-1.54, P<0.001). The frequency of SLN biopsy alone exceeded the frequency of SLN biopsy with concurrent LND in 2017 (6.8% versus 3.4%), followed by continued increase in SLN biopsy alone (11.2% versus 4.9%) in 2018. In the weighted model, the 3-year OS rate was 79.9% for the SLN biopsy group and 78.6% for the LND group (hazard ratio 0.98, 95%Cl 0.80-1.20, P=0.831). Similarly, the SLN biopsy alone without concurrent LND had comparable OS compared to the LND group (hazard ratio 0.90, 95%CI 0.59-1.36, P=0.615). CONCLUSION: Utilization of SLN biopsy in stage II endometrial cancer increased significantly over time, and SLN biopsy-incorporated nodal assessment was not associated with worsened short-term survival outcome.

Factors Influencing the Decision for Fresh vs Cryopreserved Microdissection Testicular Sperm Extraction for Non-Obstructive Azoospermia.

OBJECTIVE: To determine reproductive urologists' (RU) practice patterns for microdissection testicular sperm extraction (microTESE) and factors associated with use of fresh vs frozen microTESE for non-obstructive azoospermia. MATERIALS AND METHODS: We electronically surveyed Society for Study of Male Reproduction members with a 21-item questionnaire. Our primary outcomes were to determine RU preference for fresh or frozen microTESE and to understand barriers to performing microTESE. Pearson's chi-square and Fisher's exact tests were used to analyze categorical outcomes and candidate predictor variables. Firth logistic regression was performed to identify the predictors for preferring and performing fresh vs frozen microTESE. RESULTS: A total of 208 surveys were sent with 76 responses. Most (63.0%) primarily perform frozen microTESE for non-obstructive azoospermia, while 37.0% primarily perform fresh. However, in an ideal practice, 59.3% prefer fresh microTESE, 22.2% prefer frozen microTESE, and 18.5% had no preference. MicroTESE is performed most often (61.1%) at surgical centers not affiliated with a fertility practice. The most commonly reported barriers for both fresh and frozen microTESE are cost (42.6%), scheduling (33.3%), and andrologist unavailability (16.7%). There are no statistically significant differences between these barriers and performing fresh vs frozen microTESE. On multivariable analysis, reproductive endocrinology and infertility-based surgical center (OR 22.9; 95% CI 1.1-467.2; P = 0.04) and professional fee $2,500-$4,999 (OR 20.7; 95% CI 1.27-337.9; P = 0.03) are significant predictors of performing fresh microTESE. CONCLUSION: Frozen microTESE is performed more commonly than fresh, despite most RU preferring fresh microTESE in an ideal setting. Both fresh and frozen microTESE have a role in reproductive care. Barriers to performing fresh microTESE include cost, scheduling and andrologist availability.

Clinico-pathological significance of suspicious peritoneal cytology in endometrial cancer.

BACKGROUND AND OBJECTIVES: Suspicious peritoneal cytology refers to the result of peritoneal cytology testing that is insufficient in either quality or quantity for a definitive diagnosis of malignancy. This study examined characteristics and survival outcomes related to suspicious peritoneal cytology in endometrial cancer. METHODS: A population-based retrospective study by querying the National Cancer Institute's Surveillance, Epidemiology, and End Results Program was conducted. A total of 41,229 women with Stage I-III endometrial cancer who had peritoneal cytologic sampling at hysterectomy from 2010 to 2016 were examined. A Cox proportional hazard regression model and a competing risk analysis with Fine-Gray model were fitted to assess survival outcome related to suspicious peritoneal cytology. RESULTS: Suspicious peritoneal cytology was seen in 702 (1.7%) cases. In multivariable models, suspicious peritoneal cytology was associated with increased risk of endometrial cancer mortality (subdistribution-hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.29-2.20, p < 0.001) and all-cause mortality (adjusted-HR: 1.55, 95% CI: 1.27-1.90, p < 0.001) compared with negative peritoneal cytology. Sensitivity analysis demonstrated that suspicious peritoneal cytology had discrete overall survival improvement compared with malignant peritoneal cytology in a propensity score weighting model (HR: 0.85, 95% CI: 0.72-0.99, p = 0.049). CONCLUSION: Our study suggests that suspicious peritoneal cytology may be a prognostic factor for decreased survival in endometrial cancer.

Utilization and outcomes of adjuvant systemic chemotherapy alone in high risk, early stage cervical cancer in the United States.

OBJECTIVE: To examine trends and outcomes related to adjuvant systemic chemotherapy alone for high risk, early stage cervical cancer. METHODS: This retrospective observational study queried the National Cancer Institute's Surveillance, Epidemiology, and End Results Program from 2000 to 2016. Surgically treated women with American Joint Commission on Cancer stages T1-2 cervical cancer who had high risk factors (nodal metastasis and/or parametrial invasion) and received additional therapy were examined. Propensity score inverse probability of treatment weighting was used to assess the survival estimates for systemic chemotherapy versus external beam radiotherapy with chemotherapy. RESULTS: Among 2462 patients with high risk factors, 185 (7.5%) received systemic chemotherapy without external beam radiotherapy, of which the utilization significantly increased over time in multivariable analysis (adjusted odds ratio per 1 year increment 1.06, 95% confidence interval (CI) 1.02 to 1.09). In weighted models, adjuvant chemotherapy and combination therapy (external beam radiotherapy and chemotherapy) had comparable overall survival among patients aged <40 years (hazard ratio (HR) 0.73, 95% CI 0.41 to 1.33), in adenocarcinoma or adenosquamous histologies (HR 0.90, 95% CI 0.62 to 1.32), and in those with nodal metastasis alone without parametrial tumor invasion (HR 1.17, 95% CI 0.84 to 1.62). In contrast, systemic chemotherapy alone was associated with increased all cause mortality compared with combination therapy in patients aged ≥40 years (HR 1.57, 95% CI 1.19 to 2.06), with squamous histology (HR 1.63, 95% CI 1.19 to 2.22), and with parametrial invasion alone (HR 1.87, 95% CI 1.09 to 3.20) or parametrial invasion with nodal metastasis (HR 1.64, 95% CI 1.06 to 2.52). CONCLUSION: Utilization of adjuvant systemic chemotherapy alone for high risk, early stage cervical cancer is increasing in the United States in the recent years. Our study suggests that survival effects of adjuvant systemic chemotherapy may vary based on patient and tumor factors. External beam radiotherapy with chemotherapy remains the standard for high risk, early stage cervical cancer, and use of adjuvant systemic chemotherapy without external beam radiotherapy should be considered with caution.

Association Between Adjuvant Therapy and Survival in Stage II-III Endometrial Cancer: Influence of Malignant Peritoneal Cytology.

OBJECTIVE: The aim of this study was to examine the survival effect of adjuvant therapy in stage II-III endometrial cancer based on peritoneal cytology results. METHODS: The National Cancer Institute's Surveillance, Epidemiology, and End Results Program was retrospectively queried to examine 7467 women with stage II-III endometrial cancer who underwent hysterectomy, and with available peritoneal cytology results, from 2010 to 2016. A Cox proportional hazard regression model was fitted to assess the association between adjuvant therapy and all-cause mortality stratified by peritoneal cytology results. RESULTS: Malignant peritoneal cytology was reported in 1662 (22.3%) women and was associated with non-endometrioid histology, higher tumor stage, and nodal metastasis (p < 0.05). In a propensity score-weighted model, malignant peritoneal cytology was associated with increased all-cause mortality compared with negative peritoneal cytology (hazard ratio 1.35, 95% confidence interval 1.23-1.48). Adjuvant therapy types varied based on histology and peritoneal cytology results. In non-endometrioid histology, the combination of chemotherapy and whole pelvic radiotherapy (WPRT) was associated with improved overall survival compared with chemotherapy or WPRT alone irrespective of the peritoneal cytology results (p < 0.05). The combination of chemotherapy and WPRT was also associated with improved overall survival in women with endometrioid histology and malignant peritoneal cytology (p = 0.026). Women with endometrioid histology and negative peritoneal cytology represented the most common subpopulation (46.5%), and overall survival was similar regardless of which of the three adjuvant therapy modalities was used (p = 0.319). CONCLUSIONS: Malignant peritoneal cytology is prevalent and prognostic in stage II-III endometrial cancer. This study found that the surgeon's choice and benefit of adjuvant therapy for women with stage II-III endometrial cancer differed depending on the status of peritoneal cytology.

Trends in peritoneal cytology evaluation at hysterectomy for endometrial cancer in the United States.

OBJECTIVE: The collection of a peritoneal cytologic sample at the time of surgery for endometrial cancer has traditionally been an important part of surgical staging. In 2009, the International Federation of Gynecology and Obstetrics revised the cancer staging schema for endometrial cancer and removed peritoneal cytology from the staging criteria. The current National Comprehensive Cancer Network guidelines and the International Federation of Gynecology and Obstetrics organization, however, recommend evaluation of peritoneal cytology at the time of hysterectomy. This study examined population-based trends, characteristics, and outcomes of peritoneal cytologic sampling for endometrial cancer surgery following the 2009 staging revision in the United States. METHODS: This is a retrospective observational study querying the Surveillance, Epidemiology, and End Results Program to examine women with stage I-III endometrial cancer who underwent hysterectomy from 2010 to 2017. Trends, characteristics, and survival associated with peritoneal cytologic evaluation at the time of hysterectomy were assessed in multivariable analysis and with propensity score weighting. RESULTS: Among 62,809 women who underwent hysterectomy, 43,873 (69.9%) had peritoneal cytologic evaluation at surgery and 18,936 (30.1%) did not. Utilization of peritoneal cytologic evaluation decreased from 75.5% to 64.9% during the study period (P < 0.001). In multivariable analysis, more recent year of surgery was independently associated with a decreased likelihood of performance of peritoneal cytology (adjusted-odds ratio of peritoneal cytology evaluation in 2017 versus 2010 0.56, 95% confidence interval [CI] 0.52-0.60). Peritoneal cytologic evaluation at the time of hysterectomy was associated with improved all-cause mortality (hazard ratio in the whole cohort 0.94, 95%CI 0.89-0.99; and hazard ratio in endometrioid histology 0.90, 95%CI 0.84-0.97). CONCLUSION: Performance of peritoneal cytologic sampling has gradually decreased following the 2009 staging revision in the United States. Our study suggests that peritoneal cytology evaluation at hysterectomy may be associated with improved survival in certain tumor groups.

Risk of Upper-body Adverse Events in Robot-assisted Total Laparoscopic Hysterectomy for Benign Gynecologic Disease.

STUDY OBJECTIVE: Recent studies suggest that prolonged Trendelenburg positioning during robot-assisted total laparoscopic hysterectomy (RA-TLH) may lead to fluid shifts and pulmonary, airway, head and neck, and cranial complications in the upper body. This study examined the upper-body complications during RA-TLH for benign gynecologic disease. DESIGN: Population-based retrospective study. SETTING: The National Inpatient Sample. PATIENTS: A total of 771 412 women who had total hysterectomy for benign gynecologic disease from October 2008 to September 2015, including 661 284 women who had total abdominal hysterectomy (TAH), 51 544 women who had traditional TLH, and 58 584 women who had RA-TLH. INTERVENTIONS: A multiple-group generalized boosted model to balance the measured baseline covariates across the 3 hysterectomy groups and a generalized estimating equation model to assess the effect size of complication risk (overall and upper-body complications). MEASUREMENTS AND MAIN RESULTS: Women in the RA-TLH group were more likely to be older, white, and have a higher comorbidity index (all, p <.001). The overall rate of upper-body complications was 4.6% across the 3 groups. RA-TLH was not associated with increased risk of upper-body complications compared with traditional TLH (odds ratio [OR] 1.06; 95% confidence interval [CI], 0.90-1.26) or TAH (OR 0.98; 95% CI, 0.87-1.11). In contrast, RA-TLH was associated with decreased risk of overall perioperative complications compared with TAH (12.0% vs 18.6%; OR 0.64; 95% CI, 0.59-0.70; p <.001). RA-TLH and traditional TLH had similar risk of overall perioperative complications (12.0% vs 13.1%; OR 0.91; 95% CI, 0.8-1.02; p = .099). Women who developed upper-body complications had a higher perioperative mortality rate (0.4% vs <0.01%; OR 79.1; 95% CI, 36.0-174). The highest rates of complications (62.5%) were observed in morbidly obese women aged 70-79 with a comorbidity index of ≥4. CONCLUSION: In hysterectomy for benign gynecologic disease, RA-TLH was not associated with an increased risk of upper-body complications compared with TAH or traditional TLH. However, older age and higher comorbidity are key risk factors that increase the risk of upper-body complications which carry a disproportionally high mortality rate.

Proposing the 3-tier staging system for improving prognostication in Stage I uterine leiomyosarcoma.

BACKGROUND AND OBJECTIVES: To examine the utility of a 3-tier schema (≤5 cm, 5.1-10 cm, and > 10 cm) in determining characteristics and survival in Stage I uterine leiomyosarcoma. METHODS: This retrospective observational study queried the National Cancer Institute's Surveillance, Epidemiology, and End Result Program from 1988 to 2016. Surgically treated stage I uterine leiomyosarcomas with known tumor size were examined (N = 2217). Trends, characteristics, and survival were assessed based on tumor size. RESULTS: The most common tumor size was 5.1-10 cm (45.7%) followed by >10 cm (35.0%) and ≤5 cm (19.4%). Tumor size-shift occurred during the study period; the percentage of tumor size >10 cm increased from 12.9% to 44.5% and the groups with smaller tumor sizes decreased (p < .001). In weighted models, 5-year overall survival rates ranged from 49.9% to 71.6% in the 3-tier system and 55.2%-70.6% in the 2-tier system: the absolute difference was larger in the 3-tier system (21.7% vs. 15.4%). In the 3-tier system, all-cause mortality risk of tumor size >10 cm versus ≤5 cm nearly doubled (hazard ratio 1.96, 95% confidence interval 1.78-2.16). CONCLUSION: In the past decades, tumors of stage I uterine leiomyosarcoma have become larger. Our study suggests that a tumor size-based 3-tier staging system may be useful to differentiate survival in stage I uterine leiomyosarcoma.

Utility of the 3-tier grouping system for survival discriminatory ability in stage IIA cervical cancer.

OBJECTIVE: Given the improved survival prediction of a tumor size-based 3-tier grouping system for stage IB cervical cancer under the new staging guidelines, this study examined the survival utility of a tumor size-based 3-tier system for stage T2a cervical cancer. METHODS: This is a population-based retrospective observational study utilizing the Surveillance, Epidemiology, and End Result Program from 1988 to 2016. Women with stage T2a/N0-1-x/M0-x cervical cancer were grouped by tumor size in a 3-tier system: stage T2a (≤2 cm), T2a (2.1-4.0 cm), and T2a (>4 cm). Survival outcome was examined by non-proportional hazard analysis with restricted mean survival time (RMST) at 5 years. RESULTS: Among 2449 cases, the most common group was T2a (>4 cm) (n = 1,392, 56.8%), followed by T2a (2.1-4 cm) (n = 783, 32.0%) and T2a (≤2 cm) (n = 274, 11.2%). The median follow-up was 5.2 years. The proposed 3-tier system clearly discriminated survival outcome between the groups: average overall survival time during 5 years of follow-up, 51.0, 47.2, and 43.8 months for T2a (≤2 cm), T2a (2.1-4 cm), and T2a (>4 cm) group, respectively (P < 0.001). Adjusted between-group difference of average overall survival time in the 3-tier system (8.8 months, 95% confidence interval [CI] 6.2-11.3, P < 0.001) was larger compared to the between-group difference in the historical 2-tier system (5.9 months, 95%CI 4.2-7.6, P < 0.001). Women in the T2a (≤2 cm) group were more likely to have longer average overall survival time during 5 years of follow-up compared to those in the T2a (2.1-4 cm) group (3.6 months, 95%CI 1.1-6.1, P = 0.004). CONCLUSION: Our study suggests that a tumor size-based 3-tier grouping system may be useful for improved prediction of survival in stage IIA cervical cancer.

Significance of Malignant Peritoneal Cytology on Survival of Women with Uterine Sarcoma.

PURPOSE: This study was designed to examine the association between malignant peritoneal cytology and survival of women with uterine sarcoma. METHODS: This retrospective, observational study queried the National Cancer Institute's Surveillance, Epidemiology, and End Result Program. Uterine sarcoma cases diagnosed from 2010 to 2016 with known peritoneal cytology results were examined. Propensity score inverse probability of treatment weighting was fitted to balance the measured covariates. Overall survival (OS) was compared between malignant and negative cytology cases. RESULTS: A total of 1481 uterine sarcomas were examined. Malignant peritoneal cytology was seen in 146 (9.9%) cases. Women who had T3 disease and distant metastases had the highest incidence of malignant peritoneal cytology (43.1%). In multivariable analysis, higher T stage, nodal involvement, distant metastasis, poorer tumor differentiation, and rhabdomyosarcoma/endometrial stromal sarcoma were significantly associated with an increased risk of malignant peritoneal cytology (all, P < 0.05). In the weighted model, malignant peritoneal cytology was associated with a nearly twofold increased risk of all-cause mortality compared with negative peritoneal cytology (3-year OS rate 34.7% versus 60.2%; hazard ratio 2.26; 95% confidence interval 1.88-2.71; P < 0.001). The absolute difference in the 3-year survival rate was particularly large in leiomyosarcoma (3-year OS rate 2.8% versus 51.9%; hazard ratio 2.64; 95% confidence interval 1.94-3.59; P < 0.001). Malignant peritoneal cytology was also associated with an increased all-cause mortality risk in early and advanced stages (both, P < 0.05). CONCLUSIONS: Our study suggests that malignant peritoneal cytology may be a prognostic factor for increased mortality in uterine sarcoma, particularly in uterine leiomyosarcoma.

Possible candidate population for neoadjuvant chemotherapy in women with advanced ovarian cancer.

OBJECTIVE: To examine trends and outcomes related to neoadjuvant chemotherapy (NACT) use for advanced ovarian cancer based on patient and tumor factors. METHODS: This retrospective cohort study queried the National Cancer Institute's Surveillance, Epidemiology, and End Results Program to examine women with stage III-IV high-grade serous ovarian carcinoma from 2010 to 2016. Propensity score inverse probability of treatment weighting was used to assess the age-, cancer stage-, and tumor extent-specific survival estimates related to NACT use. RESULTS: Utilization of NACT has significantly increased in older women (≥65 years; 48.4% relative increase), followed by stage IV disease (35.2% relative increase), and stage III disease (25.0% relative increase) (all, P-trend < 0.05). Women who received NACT had overall survival (OS) similar to those who had primary cytoreductive surgery (PCS) in older women (hazard ratio [HR] 1.07, 95% confidence interval [CI] 0.95-1.20, P = 0.284), stage IV disease (HR 0.96, 95%CI 0.84-1.10, P = 0.564), and more disease extent cases (T3/N1/M1, HR 1.06, 95%CI 0.84-1.32, P = 0.640). Moreover, NACT use was associated with decreased other cause mortality risk compared to PCS in the older women (sub-distribution HR 0.61, 95%CI 0.40-0.94, P = 0.025) and stage IV disease (sub-distribution HR 0.49, 95%CI 0.27-0.90, P = 0.021). In contrast, women who received NACT had decreased OS compared to those who had PCS in the younger group (HR 1.22, 95%CI 1.07-1.38, P = 0.004), stage III disease (HR 1.26, 95%CI 1.13-1.41, P < 0.001), and lesser disease extent cases (T3/N0/M0, HR 1.38, 95%CI 1.20-1.58, P < 0.001). CONCLUSION: Our study suggests that survival effect of NACT for advanced ovarian cancer may differ based on patient and tumor factors. In older women, stage IV disease, and greater disease extent, NACT was associated with similar OS compared to PCS.