Roberto Vargas

Importance: Cervical preservation versus removal is commonly debated among urogynecologists performing sacrocolpopexy (SCP), the gold standard reconstructive procedure for prolapse. A randomized controlled trial is unlikely to ever be performed. Objective: The objective was to compare the cost-effectiveness of total (TLH) versus supracervical (SCH) hysterectomy at the time of SCP. Study Design: Markov microsimulation evaluated 5-year outcomes after SCP with TLH or SCH. Route-specific complications included bladder/ureteral injury, cuff dehiscence, port-site hernia, mesh exposure, prolapse recurrence with or without retreatment, and occult uterine cancer. Quality-adjusted life years (QALYs) incorporated recovery, prolapse recurrence, and cancer treatment states with an annual 3% discount rate. Probabilistic sensitivity analysis (PSA, n=10,000) assessed model uncertainty. Results: Median costs were SCP/TLH=$16,117.50, SCP/SCH=$16,078.00 (Δ=$39.50, 0.2%). Median effectiveness was 4.65 QALYs for both. PSA showed TLH was more effective in 15.8%, SCH in 17.3%, with equal effectiveness in 67.0%. Net monetary benefit (NMB) favored SCH by $39.50 (<0.01% of total NMB). Conclusions: While risks vary between TLH and SCH, rare and mostly balanced complications, similar costs, and high efficacy regardless of route explain why both approaches perform equally overall.

Chalif J, et al. J Gynecol Oncol. 2026 ;37:e132. https://doi.org/10.3802/jgo.2026.37.e132

Chambers LM, et al. J Gynecol Oncol. 2026 Jan;37:e69. https://doi.org/10.3802/jgo.2026.37.e69

Supplemental Figures and Tables supporting manuscript.

Endometrial cancer (EC) is the most common type of gynecologic malignancy in the United States, with over 69,120 new cases expected in 2025. The total number of mortalities surpasses that of ovarian cancer. Despite our ability to identify different biological clusters of EC, we have yet to understand the functional impact of key genomic alterations associated with varying prognoses and exploit this knowledge for therapeutic benefits. Our overarching goal is to understand how genomic alterations impact radiotherapy response in EC, and whether manipulation of these signaling pathways could be utilized as a radio-sensitization strategy. Given that TP53-mutated ECs portend the worst prognoses and seem to benefit from escalation of therapy above that of radiotherapy alone, we first focused our attention on understanding the impact of this genomic aberration on radiation response. Using high-throughput in vitro profiling, genomic manipulation, and in vivo studies, we demonstrated that p53 signaling plays a significant role in the radiotherapy response in EC, thus providing a biological rationale for observed clinical trial findings. We also leveraged this same finding to test a therapeutic approach driving p53/p21 signaling using murine double minute-2 (MDM2) inhibitors, subsequently demonstrating synergism with radiation. Thus, MDM2 inhibitors could be considered as a novel radiosensitizing approach for EC.

Endometrial cancer is now the leading cause of gynecologic cancer death in the United States. Recognizing the urgent need to improve outcomes for patients diagnosed with endometrial cancer, the National Cancer Institute Gynecologic Cancer Steering Committee convened a clinical trials planning meeting, Refining the Approach to Endometrial Cancer in the Immunotherapy Era, on January 8 and 9, 2024. Multidisciplinary experts were charged with addressing critical challenges to optimize treatment of endometrial cancer in the new immunotherapy landscape. As part of the clinical trials planning meeting, working groups were assembled to address several important aspects of clinical trial design. Working group 1 focused on translational science and was tasked with reviewing the scientific literature for data on validated discriminants of response to immunotherapy to inform trial concept development by the therapy-focused groups. The working group established that molecular subtyping of endometrial cancer is now the standard approach for classifying endometrial tumors. Molecular subtyping for prognostic and predictive applications should be considered when assessing biomarkers as well as therapeutic targets. Additionally, strategies to improve immune response like incorporation of radiation as well as therapy sequencing considerations should continue to be explored. A major key observation from working group 1 was lack of validated discriminants for immunotherapy response beyond mismatch repair status, and tumor mutational burden and exploration of additional discriminants of response and resistance will be critical with the increasing use of immunotherapy in endometrial cancer.

Advanced-stage endometrial and cervical cancers are associated with poor outcomes despite contemporary advances in surgical techniques and therapeutics. Recent clinical trial results have led to a shift in the treatment paradigm for both malignancies, in which immunotherapy is now incorporated as the standard of care up front for most patients with advanced endometrial and cervical cancers as the standard of care. Impressive response rates have been observed, but unfortunately, a subset of patients do not benefit from immunotherapy, and survival remains poor. Continued preclinical research and clinical trial development are crucial for our understanding of resistance mechanisms to immunotherapy and maximization of therapeutic efficacy. In this setting, syngeneic models are preferred over xenograft models as they allow for the evaluation of the tumor–immune interaction in an immunocompetent host, most closely mimicking the tumor–immune interaction in patients with cancer. Unfortunately, significant disparities exist about syngeneic models in gynecologic malignancy, in which queries from multiple large bioscience companies confirm no commercial availability of endometrial or cervical cancer syngeneic cell lines. Published data exist about the recent development of several endometrial and cervical cancer syngeneic cell lines, warranting further investigation. Closing the disparity gap for preclinical models in endometrial and cervical cancers will support physician scientists, basic and translational researchers, and clinical trialists who are dedicated to improving outcomes for our patients with advanced disease and poor prognosis.