HPV-DNA integration into cellular chromatin is usually a necessary event in the pathogenesis of HPV-related cancer; however, the mechanism of integration has not been clearly defined. Breaks must b...

Since the 2009 FIGO staging update, focused exclusively on the anatomic extent of disease, there have been several advances in the understanding of the pathologic and molecular features of endometrial cancer. In a significant departure from the 2009 FIGO staging system, the 2023 FIGO staging update integrates both histopathological and molecular classification. With the inclusion of non-anatomic pathologic parameters such as histology, tumor grade, lymphovascular space invasion, and molecular subtype, the 2023 FIGO staging update aims to create more clinically relevant substages that improve prognostic value and allows for more individualized treatment paradigms. This review will evaluate the clinical impact of the 2023 FIGO staging update, describe the stage shifts that lead to higher prognostic precision, and illustrate the current state of molecular analysis in clinical practice. Furthermore, this review will explore how incorporating factors such as molecular subtype into endometrial cancer staging can offer valuable insights into the racial disparities seen in morbidity and mortality.

Background: Abdominoperineal resection (APR) has been advocated for persistent or recurrent disease after failure of chemoradiation (CRT) for anal squamous cell cancer (SCC). Treatment with salvage APR can potentially achieve a cure. This study aimed to analyze oncological outcomes for salvage APR in a recent time period at a comprehensive cancer center. Methods: A retrospective review of all patients who underwent APR for biopsy-proven persistent or recurrent anal SCC between 1 January 2007 and 31 December 2020 was performed. Patients with stage IV disease at the time of initial diagnosis and patients with missing data were excluded. Univariate analysis was used with a chi-square test for categorical variables, and non-parametric tests were used for continuous variables. Kaplan–Meier survival analysis was performed to evaluate disease-specific (DSS), post-APR local recurrence-free (RFS), and disease-free survival (DFS). Results: A total of 96 patients were included in the analysis: 39 (41%) with persistent disease and 57 (59%) with recurrent SCC after chemoradiation had been completed. The median follow-up was 22 months (IQR 11–47). Forty-nine patients (51%) underwent extended APR and/or pelvic exenteration. Eight (8%) patients developed local recurrence, 30 (31%) developed local and distant recurrences, and 16 (17%) developed distant recurrences alone. The 3-year DSS, post-APR local recurrence-free survival, and disease-free survival were 53.8% (95% CI 43.5–66.5%), 54.5% (95% CI 44.4–66.8%), and 26.8% (95% CI 18.6–38.7%), respectively. In multivariate logistic regression analysis, positive microscopic margin (OR 10.0, 95% CI 2.16–46.12, p = 0.003), positive nodes in the surgical specimen (OR 9.19, 95% CI 1.99–42.52, p = 0.005), and lymphovascular invasion (OR 2.61 95% CI 1.05–6.51, p = 0.04) were associated with recurrence of disease. Gender, indication for APR (recurrent vs. persistent disease), HIV status, extent of surgery, or type of reconstruction did not influence survival outcomes. Twenty patients had targeted tumor-sequencing data available. Nine patients had PIK3CA mutations, seven of whom experienced a recurrence. Conclusions: Salvage APR for anal SCC after failed CRT was associated with poor disease-specific survival and low recurrence-free survival. Anal SCC patients undergoing salvage APR should be counseled that microscopic positive margins, positive lymph nodes, or the presence of lymphovascular invasion in the APR specimen are prognosticators for disease relapse. Our results accentuate the necessity for additional treatment strategies for the ongoing treatment challenge of persistent or recurrent anal SCC after failed CRT.

In this issue of JAMA Oncology, Leung et al¹ present the first prospective phase 1/2 single-group trial, The Stereotactic Pevlic Adjuvant Radiation Therapy in Cancers of the Uterus (SPARTACUS), of accelerated hypofractionation/stereotactic body radiation therapy (SBRT) for postoperative pelvic radiation in patients with stage I to III uterine cancer. In total, 61 patients were accrued between May 2019 and August 2021 and received 30 Gy in 5 fractions, using either once a week (13 patients) or every other day (48 patients) treatment schedules. The primary end point was physician-reported acute gastrointestinal (GI) tract and genitourinary toxic effects. There are many potential benefits to a shorter radiation treatment schedule, as the authors discuss. The benefits include quicker time of completing systemic therapy in advanced uterine cancer, decreased financial challenges owing to travel, lost wages, and housing that may be needed to facilitate weeks of treatment, and decreased exposure to high-risk hospital settings during the height of the COVID-19 pandemic. The authors found at a median follow-up of 9 months (IQR, 3-15 months) that rates of acute GI tract toxic effects of grade 1 and 2 were 54% and 13%, respectively, and acute genitourinary toxic effects of grade 1 and 2 were 41% and 3%, respectively. Treatment with stereotactic radiation would have been deemed too toxic if more than 20% of patients had grade 3 or higher toxic effects. Identify all potential conflicts of interest that might be relevant to your comment. Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued. Err on the side of full disclosure. If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response. Not all submitted comments are published. Please see our commenting policy for details.