Leveraging Pathways for Precision in Endometrial Cancer Management

Please introduce yourself by providing your name, title, organization, and relevant professional experience.

Krishnansu S. Tewari, MD: My name is Dr Krishnansu S. Tewari. I am a full professor with tenure in the Division of Gynecologic Oncology at the University of California, Irvine, where I hold the Philip J. DiSaia, MD Endowed Chair in Gynecologic Oncology. I am very active in the surgical management of women diagnosed with gynecologic malignancies and have helped design clinical trials to test new medicines for patients struggling with advanced cases.

How do you view the role of clinical pathways in ensuring adherence to guidelines in endometrial cancer care? Are there specific areas where pathways help standardize care, or do they allow for personalized treatment options?

Dr Tewari: Clinical pathways for endometrial cancer care are valuable, and with the integration of molecular staging, they help clarify the treatment algorithms for patients with potentially aggressive endometrial cancer.

Endometrial cancer often requires a multidisciplinary approach. How do clinical pathways facilitate collaboration among oncologists, radiologists, surgeons, and other healthcare providers?

Dr Tewari: Because patients with advanced and recurrent endometrial cancer may be best treated with a combination of systemic chemotherapy, immunotherapy, and/or stereotactic radiation therapy, having a multidisciplinary team comprised of a gynecologic oncologist, medical oncologist, radiation oncologist, primary care physician, endocrinologist, pathologist, radiologist, geneticist, and oncology nursing is critical to ensure optimal therapy and support of our patients.

For patients with comorbidities, how does the treatment approach for endometrial cancer vary, and what impact does this have on overall treatment costs? What considerations should payers keep in mind when evaluating these cases?

Dr Tewari: Many patients with endometrial cancer have significant comorbidities including hypertension, diabetes, obesity, and even heart disease. Therefore, surgical management may first require medical comorbidity optimization through PCP/internal medicine/cardiology for hysterectomy via minimally invasive approaches (eg, laparoscopy, robotic-assisted laparoscopy, or vaginal hysterectomy). Alternatively, some patients at very high surgical risk, as well as younger patients who desire fertility preservation, may be candidates for treatment of low-risk endometrial cancer using a hormone-releasing intrauterine device.

With novel therapies such as immunotherapy and targeted agents entering the landscape, how are clinical pathways assessing the value of these treatments for endometrial cancer? What factors do you consider in determining the cost-benefit balance for payers?

Dr Tewari: We have now had 5 phase 3 randomized clinical trials that have demonstrated a statistically significant and clinically meaningful benefit to patients with newly diagnosed advanced endometrial cancer using chemotherapy plus immunotherapy (NRG-GY018, RUBY Part 1, DUO-E, AtEND, and RUBY Part 2). Three of these studies have led to US FDA approvals of 3 different immunotherapies for this disease. Clinical pathways that focus on biomarkers (specifically mismatch repair proficiency & deficiency) can be valuable in guiding patient selection for integration of immunotherapy and controlling cost.

How are biomarkers currently influencing treatment decisions in endometrial cancer? Do clinical pathways account for individual biomarker profiles, and if so, how?

Dr Tewari: Yes, they do. A very powerful biomarker is mismatch repair deficiency. Other biomarkers that are likely to further clarify the role of unique targeted therapies include the tumor mutational burden, p53 (wild type and mutated), HER2 overexpression/amplification, and others currently under investigation.