Treatment options in the advanced and recurrent setting for endometrial cancer: an update.

INTRODUCTION: Uterine cancer is the most common gynecologic malignancy in women and is projected to surpass ovarian cancer as the deadliest gynecologic malignancy in the United States in 2024. Additionally, rates of advanced and high-risk uterine cancer have been on the rise in the United States, demonstrating a need for innovation in treatment options. There have been multiple recent trials investigating the incorporation of novel agents in the treatment of advanced and recurrent endometrial cancer. AREAS COVERED: This article will discuss the current landscape of the treatment of advanced and recurrent endometrial cancer, focusing on recent phase III trials published or presented on with the incorporation of immunotherapy and other novel therapeutics while also reviewing promising phase I and II trials in the field. Clinical trials were identified via clinicaltrials.gov and a PubMed literature search was performed (initially February 2024, updated May 2024). EXPERT OPINION: The treatment field is promising for patients as many of these trials appear to offer progression free and overall survival benefits in a disease with a historically poor prognosis. Molecular profiling of endometrial cancer will be the backbone of treatment paradigms in the future.

Percutaneous interstitial brachytherapy ablation for targeting oligometastatic gynecologic cancers.

INTRODUCTION: Treatment of recurrent oligometastatic gynecologic malignancy may involve targeted surgery, thermal ablation, or CT-guided high-dose-rate interstitial brachytherapy ablation (CT-HDR-IBTA). The purpose of this study was to describe the safety and efficacy of CT-HDR-IBTA for oligometastatic gynecologic malignancies. METHODS: With institutional review board approval (IRB) approval and compliance with the Health Insurance Portability and Accountability Act of 1996 (HIPAA) compliance, we searched our database to assemble a single-arm study cohort of all patients with oligometastatic gynecologic cancers who underwent CT-HDR-IBTA from 2012-2022 with follow-up. The electronic record was reviewed to determine relevant clinicopathological variables including patient demographics, prior treatments, clinical course, local control, and local and distant recurrence with follow-up imaging. RESULTS: The study cohort comprised 37 lesions in 34 patients treated with CT-HDR-IBTA for recurrent oligometastatic uterine (n = 17), cervix (n = 1), or ovarian cancer (n = 16) with an average lesion size of 2.5 cm with an average patient age of 61.4 years. Each lesion was treated with an average radiation dose of 23.8 Gy in 1.8 fractions and a median follow-up time of 24.0 months. The primary efficacy of CT HDR ITBA was 73% with a median progression-free survival of 8.0 months (95% CI 3.6-12.8 months) and with 58% of patients still alive at 43 months with median overall survival not reached. The rate of Grade 1 adverse events was 22% without any Grade 2, 3 or 4 events. CONCLUSIONS: CT HDR IBTA was safe and effective for treating oligometastatic gynecologic cancers in a heavily pretreated cohort.

Recurrent High-Grade Squamous Intraepithelial Lesion After Loop Excision Procedure Versus Loop Procedure With Top Hat.

OBJECTIVE: To evaluate single-pass loop electrosurgical excision procedure (LEEP-SP) versus LEEP with top hat (LEEP-TH) in terms of treatment failure defined as high-grade squamous intraepithelial lesion (HSIL) cytology within 2 years' follow-up. METHODS: This single-institution cohort study used a prospectively collected cervical dysplasia database including all patients who underwent LEEP-SP or LEEP-TH for biopsy-proven cervical intraepithelial neoplasia between 2005 and 2019. RESULTS: Of 340 patients included, 178 underwent LEEP-SP and 162 LEEP-TH. The LEEP-TH patients were more likely to be older (mean age, 40.4 vs 36.5 years; p < .001) and have a positive preprocedure endocervical sampling (68.5% vs 11.8%; p < .001). Positive margins were found in 23 LEEP-SP (12.9%) and in 25 LEEP-TH (15.4%; p = .507). There was no significant difference in depth of excision between LEEP-SP (13.21 ± 23.19 mm) and LEEP-TH (17.37 ± 28.26 mm; p = .138). At 2 years, there was no difference in the rates of HSIL cytology (5.2% vs 6.3%; p = .698), any positive human papillomavirus test, or HSIL cytology (25% vs 15%; p = .284). The 57 patients undergoing repeat excision were more likely to be older (mean age, 40.95 vs 37.52 years; p = .023), have had a LEEP-TH (26.3% vs 73.7%; p < .001), and have initial cytologic HSIL (64.9% vs 35.0%; p < .001). CONCLUSIONS: In this single-institution study, there is no difference in the rate of recurrent HSIL in patients undergoing LEEP-SP versus LEEP-TH. A LEEP-TH may have limited additional benefit over a LEEP-SP in the treatment of cervical HSIL.

The increasing incidence of stage IV cervical cancer in the USA: what factors are related?

OBJECTIVE: Cervical cancer (International Federation of Gynecology and Obstetrics (FIGO)) stage IVA-B (distant stage) is a rare diagnosis with an approximate 5 year survival rate of 17% and with limited treatment options. The objective of this study was to determine the trends in distant stage cervical cancer in the USA and identify possible factors related to these trends. METHODS: Data were obtained from the United States Cancer Statistics program from 2001 to 2018. Rates of cervical cancer screening and vaccination were evaluated using the Behavioral Risk Factor Surveillance System and TeenVaxView. SEER*Stat 8.3.8.9.2 and Joinpoint regression program 4.9.0.0 were used to calculate incidence trends. RESULTS: Over the last 18 years, 29 715 women were diagnosed with distant stage cervical carcinoma. Black women have disproportionately higher rates at 1.55/100 000 versus 0.92/100 000 in White women (p<0.001). When examining the trends over time, there has been an annual increase in distant stage cervical cancer at a rate of 1.3% per year (p<0.001). The largest increase is seen in cervical adenocarcinoma with an average annual percent change of 2.9% (p<0.001). When performing an intersection analysis of race, region and age, White women in the South aged 40-44 have the highest rise in distant cervical cancer at a rate of 4.5% annually (p<0.001). Using the Behavioral Risk Factor Surveillance System and TeenVax data, compared with Black women, we found that White women have a nearly two-fold higher rate of missed or lack of guideline screening, 26.6% vs 13.8%. White teenagers (13-17 years) have the lowest human papillomavirus vaccination rate at 66.1% compared with others at 75.3%. CONCLUSIONS: Black women have a higher incidence of distant stage disease compared with White women. However, White women have a greater annual increase, particularly in adenocarcinomas. Compared with Black women, White women also have lower rates of guideline screening and vaccination.

Trends in Human Papillomavirus-Associated Cancers, Demographic Characteristics, and Vaccinations in the US, 2001-2017.

Importance: Nearly 45 000 human papillomavirus (HPV)-associated cancers are diagnosed annually in the US. The HPV vaccine has been approved since 2006, but information on the association between vaccination and the incidence of HPV-attributable cancers is unclear. Objective: To evaluate the potential association of screening and vaccination on the trends of HPV-associated cancers. Design, Setting, and Participants: A retrospective, population-based cross-sectional study was conducted using data on HPV-associated (oropharyngeal squamous cell carcinoma [SCC], anal/rectal SCC, vulvar SCC, vaginal SCC, cervical carcinoma, and penile SCC) cancers from the US Cancer Statistics Public Use Database, representing 99% of the US population, between January 1, 2001, and December 31, 2017; HPV vaccination and screening data from the Behavioral Risk Factor Surveillance between January 1, 2001, and December 31, 2016; and TeenVaxView between January 1, 2008, and December 31, 2018. National Cancer Database and Behavioral Risk Factor Surveillance were used to correct for hysterectomy. Data analysis was performed from April 1, 2020, to June 30, 2021. Exposures: Patient demographic characteristics, including age, race and ethnicity, sex, region, and vaccination status. Main Outcomes and Measures: The main outcomes examined in this study were diagnoses of any HPV-associated cancer and HPV vaccination status. Results: A total of 657 317 HPV-associated cancers (exact ages not collected by the United States Cancer Statistics); of these, 264 019 (40.2%) developed in men and 393 298 (59.8%) in women; 14 520 individuals (2.2%) were non-Hispanic Asian/Pacific Islander, 74 641 (11.4%) were non-Hispanic Black, 59 841 (9.1%) were Hispanic, and 499 899 were non-Hispanic White (76.1%). More than half (206 075 [52.4%]) of cancers in women were cervical, whereas most (211 421 [80.1%]) cancers in men were oropharyngeal. In female adolescents (aged 13-17 years), the vaccination rate increased from 37.2% to 69.9% from 2008 to 2018 (annual percent change: 6.57% [95% CI, 5.83%-7.32%]). Before vaccination approval, cervical cancer rates in the 20- to 24-year age group were decreasing at 2.29% annually (P = .045); after vaccine approval, this rate has been decreasing at 9.50% (P = .003). In men, annual increases were noted in oropharyngeal (2.71%) and anal/rectal (1.83%) cancers (P < .001); in women, the incidence of oropharyngeal remained stable but anal/rectal cancer increased at 2.83% every year (P < .001). Conclusions and Relevance: In the US, cervical cancer rates have decreased at a population level, especially in younger women. The findings of this study suggest this decrease may be associated with vaccination. Given the increase in oropharyngeal and anal/rectal cancers, particularly in men, it may be important to highlight vaccination uptake in both sexes.