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Neo-adjuvant chemotherapy for metastatic endometrial cancer : study finds benefit

This is a very important study because it offers legitimate hope to advanced endometrial cancer patients.  Usually, endometrial cancer is not advanced and very curable, but advanced disease is a different story. Endometrial cancer often spreads to lymph nodes, but it can also spread to the liver and inside the abdominal cavity where the intestines are found.  These areas can often be reached for surgical removal.  Sometimes even lung metastases can also be removed.  But the point is, a combined aggressive surgery and chemotherapy approach can lead to very good outcomes.  At the Gynecologic Oncology Institute, we approach cancer on an individual basis, including minimally invasive robotic surgery, even for advanced disease.  This is an approach we have often used and this research supports it.

“Women with metastatic endometrial cancer treated with primary debulking surgery (PDS) have an increased risk of early death, but also have a more favorable long-term prognosis, according to a cohort study published in JAMA Network Open.

Conversely, the study also showed that women treated with neoadjuvant chemotherapy (NACT) may experience superior short-term survival, especially if they eventually undergo surgery.

“These results suggest that, like its benefits in ovarian cancer, NACT may potentially lower perioperative morbidity and serve as an important treatment option in women with metastatic endometrial cancer,” the study authors write.

In this study, the National Cancer Database was used to evaluate women 70 years of age or younger with stage IV endometrial cancer and minimal comorbidity (comorbidity score = 0). The researchers performed an intent-to-treat (ITT) analysis, as well as a protocol analysis, which included women treated with both chemotherapy and surgery in both sequences.

Of 4,890 women identified with stage IV endometrial cancer, NACT was used to treat a total of 952 (19.5%). Remarkably, NACT consumption increased from 106 of 661 women (16.0%; 95% CI, 13.2% -18.8%) in 2010 to 224 of 938 women (23.9%; 95% CI, 21 , 2% -26.6%) in 2015 (P <) .001).

In the multivariate analysis, the use of NACT was associated with the last year of diagnosis (risk ratio) [RR]1.42; 95% CI, 1.21-1.79 for 2015 versus 2010), stage IVB disease (RR 1.31; 95% CI 1.03-1.67 for stage IVB versus IVA) and serous histology (RR 1, 38; 95% CI 1.13-1.69) for serous vs. endometrioid histology). In addition, in a cohort with a balanced propensity score, a time-varying correlation with survival was found using NACT.

In the ITT analysis, NACT was associated with reduced mortality in the first 3 months after diagnosis (hazard ratio) [HR] after 2 months 0.81; 95% CI, 0.66-0.99). Furthermore, the survival curves crossed after 4 months and the NACT treatment was associated with an increased mortality (HR after 6 months 1.23; 95% CI 1.09-1.39).

In the protocol analysis, the use of NACT in the first 8 months after diagnosis was correlated with reduced mortality (HR after 6 months 0.79; 95% CI 0.63-0.98). After 9 months the survival curves crossed and the NACT maintenance was again associated with increased mortality (HR after 12 months 1.22; 95% CI 1.04-1.43).

“To the best of our knowledge, there is so far little data on the use of NACT for the early detection of chemotherapy-resistant diseases and the resulting patient outcomes. Hypothetically, information about initial treatment response may influence surgical intervention decisions, prior enrollment in clinical trials, palliative care referrals, and goals of nursing discussions that have favorable outcomes for quality of life in end-stage disease. The authors wrote. “More data to examine the predictive value of response rates to NACT and the benefits of NACT in patients suspected of unresectable disease at diagnosis is certainly needed.”

Importantly, one possible limitation of the current study is that the decision to have chemotherapy versus primary surgery depends on both the patient and the clinician and is based on a variety of factors that are not fully determined from medical records or observational data can be. Although the National Cancer Database includes women from a number of hospitals, the data may not be representative of the entire population.

Reference:

Tobias CJ, Chen L., Melamed A. et al. Association of neoadjuvant chemotherapy with overall survival in women with metastatic endometrial cancer. JAMA network open. doi: 10.1001 / jamanetworkopen.2020.28612

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Dr Steve Vasilev MD
“I help and guide women to defeat gynecologic cancers and advanced pelvic conditions such as endometriosis, using a unique combination of minimally invasive robotic surgery, precision medicine therapies and complementary holistic natural support towards thriving in survivorship." Dr. Vasilev is the only physician quadruple board certified in Ob-Gyn, Gynecologic Oncology and Integrative & Holistic Medicine in the United States. He is an accomplished advanced robotic surgeon and serves as Medical Director of Integrative Medicine and Integrative Gynecologic Oncology at Providence Saint John's Health Center, Professor at John Wayne Cancer Institute in Santa Monica, California and is Clinical Professor at Loma Linda University School of Medicine. He is former faculty and professor at UC Irvine, UCLA, USC and City of Hope. He is an active member of multiple medical societies and has been nationally listed in "Best Doctors" for 18 years.

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