Dimitrios Nasioudis

Background: Outcomes for advanced or recurrent endometrial cancer (EC) remain poor, with historically limited systemic options beyond platinum-based chemotherapy. EC is uniquely immunotherapy-amenable among solid tumors: it harbors the highest prevalence of mismatch repair deficiency (dMMR) and microsatellite instability-high (MSI-H) status of any cancer, and its molecular classification into four major molecular subtypes defines a spectrum of tumor mutational burden, neoantigen load, and immune infiltration that predicts the response to checkpoint blockade. Current Landscape: Over the past several years, multiple programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors have received regulatory approval in EC, spanning monotherapy in dMMR/MSI-H disease, combination with carboplatin–paclitaxel in the first-line advanced setting, and combination with anti-angiogenic therapy in biomarker-unselected recurrent disease, fundamentally altering the standard of care. Scope and Objectives: This narrative review synthesizes the molecular rationale for checkpoint inhibition in EC, including the biological basis of its molecular subtypes and their immune microenvironments, and provides a focused overview of the trial evidence supporting each major checkpoint inhibitor class, including PD-1 inhibitors, PD-L1 inhibitors, cytotoxic T-lymphocyte-associated protein 4 inhibitors, and emerging targets. We further review the landscape of ongoing trials addressing unresolved questions, including chemotherapy-free regimens in dMMR disease, maintenance intensification for mismatch repair-proficient (pMMR) disease, neoadjuvant and fertility-sparing approaches, and novel combinations. This review aims to provide a comprehensive, up-to-date synthesis of this rapidly evolving field and to identify challenges and opportunities that will shape the next phase of immunotherapy in EC.

Cervical cancer is the third most common gynecologic malignancy in the United States. Traditionally, a radical hysterectomy with bilateral salpingo-oophorectomy with lymph node assessment had been the standard of care; however, there has been a recent shift towards less radical surgery with the establishment of the oncologic safety of conization (as fertility preserving surgery), and simple hysterectomy for certain subgroups of patients with early-stage disease. In addition, uptake in the utilization of sentinel lymph node mapping, compared to systematic lymphadenectomy, has translated to improved perioperative outcomes. While laparotomy is the preferred mode of surgery for patients with cervical cancer, emerging data suggest that protective maneuvers may not compromise oncologist outcomes and multiple clinical trials are evaluating the oncologic safety of minimally invasive surgery. In this present review, we summarize recent advances in surgical management in patients with cervical cancer.