Recent studies have significantly advanced our understanding of treatment options and outcomes for endometrial cancer (EC), particularly focusing on high-risk and recurrent cases. The ENGOT-en11/GOG-3053/KEYNOTE-B21 trial explored the efficacy of pembrolizumab in patients with mismatch repair-deficient (dMMR) tumors, revealing that this immunotherapy, when combined with adjuvant chemotherapy, improved outcomes in this challenging subgroup (ref: Slomovitz doi.org/10.1200/JCO-24-01887/). In another pivotal study, the COMPASSION-16 trial demonstrated that the addition of cadonilimab to platinum-based chemotherapy significantly enhanced both progression-free survival and overall survival in patients with persistent, recurrent, or metastatic cervical cancer, suggesting a promising new treatment avenue (ref: Wu doi.org/10.1016/S0140-6736(24)02135-4/). Furthermore, a meta-analysis indicated that patients with dMMR advanced endometrial carcinomas derive similar benefits from chemotherapy as those with proficient tumors, challenging previous assumptions about treatment efficacy based on MMR status (ref: Tjokrowidjaja doi.org/10.1093/jncics/). The molecular characteristics of high-risk EC were further elucidated, with a study identifying significant HER2-low and HER2-positive tumor rates in recurrent and metastatic cases, which may influence future targeted therapies (ref: van Dijk doi.org/10.1200/JCO.23.02768/). Additionally, the role of molecular classification in fertility-sparing treatments was highlighted, emphasizing its potential to optimize patient selection and outcomes (ref: Peng doi.org/10.1016/j.ygyno.2024.10.012/).

The intersection of obesity and endometrial cancer has emerged as a critical area of research, with studies revealing obesity's role in driving specific genetic mutations associated with cancer. One study found that obesity is linked to distinct driver mutations in endometrial carcinoma, suggesting that obesity may influence tumor genotype (ref: Tang doi.org/10.1038/s41588-024-01969-3/). Another investigation into obesity-induced extracellular vesicles demonstrated their involvement in the pathogenesis of endometrial cancer, highlighting the therapeutic potential of targeting these pathways with agents like HO-3867 and Metformin (ref: Sakaue doi.org/10.1038/s41388-024-03182-2/). Furthermore, a comparative sequencing study in Kazakhstan revealed a notable prevalence of pathogenic variants in mismatch repair and homology-directed repair genes among endometrial cancer patients, underscoring the genetic diversity and potential for personalized treatment strategies (ref: Zheng doi.org/10.1002/ijc.35215/). Despite the promise of molecular profiling, challenges remain in its implementation, as highlighted by a mixed-methods study that identified barriers to the adoption of molecular classification in clinical practice (ref: Wilson doi.org/10.1002/cncr.35596/).

The epidemiology of endometrial cancer continues to reveal significant disparities and risk factors affecting patient outcomes. A population-based cohort study indicated that cancer diagnosis during pregnancy is associated with increased maternal and neonatal morbidity, emphasizing the need for careful management in this vulnerable population (ref: Kanbergs doi.org/10.1016/j.ajog.2024.10.022/). Additionally, a real-world analysis of clinical trial participation highlighted stark disparities, particularly noting that only 3.8% of endometrial cancer patients participated in clinical trials, with Black patients being disproportionately underrepresented despite facing higher rates of aggressive cancer histologies (ref: Smith doi.org/10.1016/j.ajog.2024.09.103/). These findings underscore the importance of addressing barriers to clinical trial participation and ensuring equitable access to innovative treatments for all demographic groups.

Clinical trials play a crucial role in advancing treatment options for endometrial cancer, yet disparities in participation remain a significant concern. A recent analysis revealed that only 3.8% of endometrial cancer patients participated in clinical drug trials, with notable underrepresentation of Black patients, who often experience more aggressive disease forms (ref: Smith doi.org/10.1016/j.ajog.2024.09.103/). This disparity highlights the need for targeted outreach and strategies to improve enrollment among underrepresented populations. Furthermore, the implementation of molecular classification in early-stage endometrial cancer has been met with challenges, as a mixed-methods study identified barriers to the adoption of recommended molecular profiling practices (ref: Wilson doi.org/10.1002/cncr.35596/). The potential for molecular classification to optimize treatment outcomes, particularly in fertility-sparing contexts, emphasizes the importance of overcoming these barriers to enhance patient care (ref: Peng doi.org/10.1016/j.ygyno.2024.10.012/).

Innovative diagnostic and screening approaches are essential for improving early detection and management of endometrial cancer. However, the current literature does not present specific articles under this theme, indicating a potential gap in research that could benefit from further exploration. Future studies may focus on developing novel screening methodologies or enhancing existing protocols to increase early diagnosis rates and improve patient outcomes.

Obesity has been identified as a significant risk factor for endometrial cancer, with recent studies elucidating its role in tumorigenesis. Research indicates that obesity is implicated in 57% of endometrial cancer cases, and investigations into obesity-induced extracellular vesicles have revealed their contribution to cancer pathogenesis through the secretion of oncogenic proteins (ref: Sakaue doi.org/10.1038/s41388-024-03182-2/). Additionally, a study examining the relationship between obesity and specific driver mutations found that obesity is associated with distinct genetic profiles in endometrial carcinoma, suggesting that obesity may influence tumor behavior and treatment responses (ref: Tang doi.org/10.1038/s41588-024-01969-3/). These findings underscore the importance of addressing obesity as a modifiable risk factor in endometrial cancer prevention and treatment strategies.

Immunotherapy has emerged as a promising treatment modality for endometrial cancer, particularly for patients with high-risk features. The ENGOT-en11/GOG-3053/KEYNOTE-B21 trial demonstrated that pembrolizumab, when combined with adjuvant chemotherapy, significantly improved outcomes in patients with mismatch repair-deficient tumors (ref: Slomovitz doi.org/10.1200/JCO-24-01887/). This finding highlights the potential of immunotherapy to enhance treatment efficacy in a subset of patients who historically have limited options. However, the implementation of molecular classification in clinical practice remains a challenge, as identified in a mixed-methods study that explored barriers to the adoption of recommended profiling practices (ref: Wilson doi.org/10.1002/cncr.35596/). The integration of molecular classification with immunotherapy approaches may optimize patient selection and improve overall treatment outcomes.

Surgical techniques and their outcomes remain a critical focus in the management of endometrial cancer. A randomized controlled trial assessing organized cervical cancer screening demonstrated that targeted invitation letters significantly improved screening uptake among non-adherent women, suggesting that strategic outreach can enhance early detection efforts (ref: Teigné doi.org/10.1016/j.ypmed.2024.108150/). Additionally, the Korean Gynecologic Oncology Group has played a pivotal role in advancing surgical practices through multi-center clinical trials, contributing to the body of knowledge regarding optimal surgical interventions for gynecologic cancers (ref: Min doi.org/10.3390/cancers16193422/). These findings emphasize the importance of continuous improvement in surgical techniques and patient engagement strategies to enhance outcomes in endometrial cancer management.