Under the spotlight: Nature Reviews Disease Primers illuminates the complexities of endometrial cancer & updates on recent advancements, emerging trends and therapeutic opportunities

Dra. Ana Oaknin

Published last week in Nature Reviews Disease Primers, a comprehensive review* focused on endometrial cancer (EC) updates on the epidemiology, pathophysiology, diagnosis and molecular classification of this disease, and emerging developments in the rapidly evolving EC therapeutic landscape.

The authors, including Ana Oaknin, Principal Investigator of VHIO’s Gynecological Malignancies Group, also discuss advancements in cancer management, critical considerations including the quality of life of these patients, and the socioeconomic and racial disparities that affect EC incidence and mortality.

EC ranks sixth as the most commonly occurring cancer in women, with an incidence 417, 336, worldwide in 2020. Both incidence and mortality of this disease are rapidly increasing at global level, with the highest disease burden in North America and Western Europe, which might be attributed to a high prevalence of lifestyle risk factors including obesity, which is associated with around half of EC cases.

As highlighted in the introduction of this timely Primer article*, while 67% of patients present with early-stage disease, which has an 81% 5-year overall survival (OS), the 5-year OS for stage IVA and IVB EC drops to 17% and 15%, respectively. The more precise, effective treatment and management of these patients thus represent an urgent, unmet clinical need.

“While molecularly-driven insights have undoubtedly improved our understanding of the biological complexities of this disease, we must work together to more precisely define the optimal use of molecular classification of disease to better guide surgical staging, the selection of adjuvant therapy, and surveillance scheduling,” said Ana Oaknin, Senior Author of this present article, and Head of the Gynecological Cancer Program, Medical Oncology Department, the Vall d’Hebron University Hospital (HUVH – Vall d’Hebron Barcelona Hospital Campus).

She continued, “Research efforts must continue to identify, describe, hone in on and attack the drivers of endometrial cancers, with particular focus on microbiome machinery and the effect of BMI. As importantly, we need to achieve a deeper understanding of the molecular and immunological actors that govern response and resistance to novel therapies.”

First authored by Vicky Makker, Medical Oncologist at the Gynecological Oncology Service, Memorial Sloan Kettering Cancer Center (MSKCC, New York, USA), this review begins by highlighting the socioeconomic and racial disparities that impact on the incidence and mortality of EC, and explore various associated risk factors including health and lifestyle, as well as genetic considerations. They then go on to discuss the underlying mechanisms and pathophysiology of this disease including precursor lesions, molecular subgroups of EC and associated mutations, as well as the immune landscape and tumor microenvironment.

The what to watch for and ‘where to’ next

The authors then provide a superb update on advances and recommended approaches aimed at the improved diagnosis, screening and disease prevention in EC, covering areas of clinical management including the presentation of disease and diagnostic assessment, preoperative staging using imaging, histological and molecular classification, prognosis by molecular subtype, screening strategies, conservative management based on specific rationale, and adjuvant therapy according to EC risk criteria.

Considering several studies reported in the literature, they then update on chemotherapy and immunotherapy as options for treating recurrent and metastatic disease, and crucially, call for more exclusively dedicated research into the quality of life in patients with EC by proposing possible lines of study.

Finally, in their Outlook, the authors draw on the promise of current studies, summarize progress thus far, and point to novel therapies that could achieve improved outcomes for EC patients such as immune-based treatments as well as targeted agents including PARP inhibitors. In their wrap up of next step directions, they set out their recommendations in order to deliver on the true promise of precision medicine in EC.

“In addition, it is imperative that research funding also supports studies that can better identify, address, and successfully overcome the major existing health disparities in endometrial cancer. We must strive to resolve issues such as the lack of inclusion of under-represented minorities in clinical trials and molecular studies,” concluded Ana Oaknin, who also serves as co-Chair of the Gynecological Cancer InterGroup’s (GCIG) Cervix Cancer Committee.

 

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Reference:

* Makker, V., MacKay, H., Ray-Coquard, I. et al. Endometrial cancer. Nat Rev Dis Primers 7, 88 (2021). https://doi.org/10.1038/s41572-021-00324-8.

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