An evaluation of the utility of computed tomography in high-risk endometrial cancer surveillance.

OBJECTIVES: Endometrial cancer is a collection of heterogeneous histologies and molecular subtypes with different risk profiles. High-risk endometrial cancer surveillance regimens vary amongst providers. The National Comprehensive Cancer Network (NCCN) recommends symptom and exam-based surveillance for all endometrial cancers after remission, regardless of cancer stage and histology. Our objective was to identify the first method of detection of recurrence in high-risk endometrial cancers and examine disease recurrence and treatment patterns. METHODS: A retrospective review of patients diagnosed with high-risk endometrial cancer between November 2013 and February 2020 was conducted at a large academic institution. High-risk endometrial cancers were classified by histology and pathologic stage and were categorized by primary method of detection. RESULTS: Two hundred and twenty-nine patients were identified with high-risk endometrial cancer, 63 (28 %) of whom had a recurrence. Most recurrences were first detected with routine imaging in 31 patients (49.2 %) and symptom surveillance in 24 patients (38.15 %). Regardless of the detection method, most patients underwent systemic treatment. The average survival after recurrence was 2.0 years in the imaging cohort and 1.6 years in the non-imaging surveillance cohort. CONCLUSIONS: The most common site of recurrence in our cohort of high-risk endometrial cancer was in the lung, and most recurrences were identified with asymptomatic imaging. Though there was no statistically significant difference between the survival of those who underwent imaging surveillance vs. standard of care, there was a trend toward survival that deems further exploration with a larger cohort.

Non-surgical management of advanced ovarian cancer with maintenance PARP inhibitors.

The standard of care for advanced ovarian cancer is cytoreductive surgery followed by a platinum-taxane combination with PARP inhibition as a maintenance strategy. In practice, many advanced ovarian cancer patients are older and are either not candidates for surgery or decline surgical intervention. There are limited data for using PARP inhibitor maintenance in the non-surgical patient population. We describe two cases of patients with advanced-stage ovarian cancer who received platinum-taxane chemotherapy and declined surgical debulking. They were continued on maintenance PARP inhibitors and have no evidence of disease for over four years.

Management of recurrent cervical cancer with peritoneal carcinomatosis with HIPEC.

Cervical cancer is the fourth most common malignancy in women in the world; however, a substantial portion of these malignancies are declining with increasingly sophisticated screening. Unfortunately, recurrent cervical cancer has a dismal prognosis and its management continues to be a growing area of research. While the foundation of treatment remains platinum-based chemotherapies, new techniques such as HIPEC have been evaluated. We present two patients with recurrent cervical adenocarcinoma with peritoneal carcinomatosis who were treated with HIPEC during de-bulking surgery with substantial disease-free survival. One of our patients had 15 months of disease-free survival before developing biliary metastases and the other remains disease free for over 24 months.

Association between Cervical Dysplasia and Adverse Pregnancy Outcomes.

OBJECTIVE: The aim of this study was to determine if cervical dysplasia during pregnancy is associated with pregnancy complications, including preterm delivery and pre-eclampsia. STUDY DESIGN: A retrospective cohort analyses was performed with propensity-score matching to compare complication rates between pregnant women without history of abnormal cervical cancer screening and pregnant women referred for cervical dysplasia assessment to colposcopy clinic. A composite outcome of pregnancy complications included intra-amniotic infection, preterm premature rupture of membranes, pre-eclampsia, preterm delivery, low birth weight, oligohydramnios, and intrauterine fetal demise. Complication rates were compared between women with and without cervical dysplasia using logistic regression models. RESULTS: Overall cohort included 2,814 women, 279 of whom attended colposcopy clinic for cervical dysplasia assessment. Propensity score-matched cohort included 1,459 women, 274 of whom attended colposcopy clinic. Composite complications of pregnancy rates were not significantly different between control and colposcopy groups in both cohorts (25.3% and 29.0%, P = 0.20; 26.5% and 29.3%, P = 0.45). Dysplasia was not associated with composite pregnancy complications in overall and matched cohorts (odds ratio [OR] = 1.09, 95% confidence interval [CI]: 0.77-1.56) and (OR = 1.03, 95% CI: 0.72-1.49). When cervical dysplasia was determined on biopsy or colposcopy, dysplasia was not associated with complications in the overall and matched cohorts. CONCLUSION: Biopsy and/or colposcopy determined cervical dysplasia during pregnancy was not associated with pregnancy complications.

Prognosis and treatment of positive peritoneal cytology in early endometrial cancer: matched cohort analyses from the National Cancer Database.

BACKGROUND: While positive peritoneal cytology is no longer included among the endometrial cancer staging criteria, Federation International de Gynecologie et Obstetrique recommends continued collection of pelvic washings for cytology to produce additional data that may be used to determine the significance of positive cytology for prognosis and treatment of endometrial cancer. OBJECTIVES: The objectives of the study was to validate that positive cytology is a predictor of decreased survival in early endometrial cancer and to test whether adjuvant chemotherapy for positive cytology is associated with increased survival. STUDY DESIGN: We performed an observational retrospective cohort analysis of the 2010-2013 National Cancer Database including women with cytology status and Federation International de Gynecologie et Obstetrique stage IA-II endometrial cancer. Overall cohort and matched cohort survival analyses were performed with and without imputation of missing data. We also performed survival analyses of women with positive cytology grouped by chemotherapy exposure. Multivariable Cox proportional-hazards regressions were performed to adjust for possible confounders. A variety of sensitivity analyses, including robustness of results to possible unmeasured confounding, were reported. RESULTS: A total of 16,851 women including 953 with positive cytology were included. Four-year overall survival was 79.5% (range, 76.2-83.0%) for women with stage I/II with positive cytology vs 92.2% (range, 91.5-92.9%), 83.3% (range, 81.6-84.9%), and 86.8% (range, 85.1-88.5%) for stage IA, IB, and II with negative cytology, respectively (P ≤ .001). Positive cytology was associated with decreased survival (hazard ratio [95% confidence interval], 1.85 [range, 1.54-2.21], P < .001). For women with Federation International de Gynecologie et Obstetrique grade 1/2 endometrioid adenocarcinoma, the hazard of death associated with positive cytology was similar (hazard ratio [95% confidence interval], 1.85 [1.28-2.67], P < .001). Use of adjuvant chemotherapy by women with positive cytology was associated with increased survival (hazard ratio [95% confidence interval], 0.62 [0.40-0.95], P = .03). CONCLUSION: Positive peritoneal cytology was associated with decreased overall survival of women with Federation International de Gynecologie et Obstetrique stage I/II endometrial cancer, including low-grade endometrioid endometrial cancer. Treatment of women with stage I/II endometrial cancer and positive cytology with adjuvant chemotherapy was associated with increased survival.

Delineation of proteolytic and non-proteolytic functions of the membrane-anchored serine protease prostasin.

The membrane-anchored serine proteases prostasin (PRSS8) and matriptase (ST14) initiate a cell surface proteolytic pathway essential for epithelial function. Mice expressing only catalytically inactive prostasin are viable, unlike prostasin null mice, indicating that at least some prostasin functions are non-proteolytic. Here we used knock-in mice expressing catalytically inactive prostasin (Prss8(Ki/Ki)) to show that the physiological and pathological functions of prostasin vary in their dependence on its catalytic activity. Whereas prostasin null mice exhibited partial embryonic and complete perinatal lethality, Prss8(Ki/Ki) mice displayed normal prenatal and postnatal survival. Unexpectedly, catalytically inactive prostasin caused embryonic lethality in mice lacking its cognate inhibitors HAI-1 (SPINT1) or HAI-2 (SPINT2). Proteolytically inactive prostasin, unlike the wild-type protease, was unable to activate matriptase during placentation. Surprisingly, all essential functions of prostasin in embryonic and postnatal development were compensated for by loss of HAI-1, indicating that prostasin is only required for mouse development and overall viability in the presence of this inhibitor. This study expands our knowledge of non-proteolytic functions of membrane-anchored serine proteases and provides unexpected new data on the mechanistic interactions between matriptase and prostasin in the context of epithelial development.