In a National Cancer Database analysis reported in JAMA Network Open, Tobias et al found that receipt of neoadjuvant chemotherapy was associated with improved short-term but not long-term survival vs primary debulking surgery in patients with metastatic endometrial cancer.
As stated by the investigators, “Although primary debulking surgery is often considered the criterion standard for treatment of stage IV endometrial cancer, primary debulking surgery is associated with significant morbidity and poor survival. Neoadjuvant chemotherapy has been proposed as an alternative treatment strategy.”
“The results of this cohort study suggest that women treated with primary debulking surgery are at increased risk of early death but have a more favorable long-term prognosis. In contrast, results suggest that women treated with neoadjuvant chemotherapy, particularly if they ultimately undergo surgery, may have superior survival in the short term.”— Tobias et al
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Study Details
The study involved National Cancer Database data on 4,890 women with stage IV endometrial cancer treated from January 2010 to December 2015. Patients had to be aged ≤ 70 years with minimal comorbidity (comorbidity score = 0). Women were stratified based on receipt of neoadjuvant chemotherapy or primary debulking surgery.
Key Findings
Overall, neoadjuvant chemotherapy was used in 952 women (19.5%), with use increasing from 106 (16.0%) of 661 women in 2010 to 224 (23.9%) of 938 women in 2015 (P < .001).
In multivariate analysis, use of neoadjuvant chemotherapy was associated with more recent year of diagnosis (risk ratio [RR] = 1.42, 95% confidence interval [CI] =1.21–1.79, for 2015 vs 2010), stage IVB vs IVA disease (RR = 1.31, 95% CI = 1.03–1.67), and serous vs endometrioid histology (RR = 1.38, 95% CI = 1.13–1.69).
In a propensity score–balanced cohort, use of neoadjuvant chemotherapy exhibited an association with overall survival that varied over time from diagnosis. In intention-to-treat analysis, neoadjuvant chemotherapy was associated with improved survival vs primary debulking surgery for approximately 3 months (HRs for mortality = 0.56, 95% CI = 0.39–0.80, in month 1 and 0.81, 95% CI = 0.66–0.99 in month 2), with hazard ratios being similar for months 3 and 4; the survival curves crossed after 4 months, and neoadjuvant chemotherapy was associated with worse survival from month 5 onward (HR = 1.17, 95% CI = 1.03–1.33).
Among women who started treatment with surgery, 3,139 (79.7%) ultimately received chemotherapy. Among those who initiated neoadjuvant chemotherapy, 555 (58.3%) underwent surgery. In a per-protocol analysis that included only women who received both chemotherapy and surgery in either sequence, use of neoadjuvant chemotherapy was associated with improved survival for the first 8 months after diagnosis (HR at 6 months = 0.79, 95% CI = 0.63–0.98). The survival curves crossed after 9 months, with neoadjuvant chemotherapy being associated with poorer survival thereafter (HR at 12 months = 1.22, 95% CI = 1.04–1.43).
The investigators concluded, “The results of this cohort study suggest that women treated with primary debulking surgery are at increased risk of early death but have a more favorable long-term prognosis. In contrast, results suggest that women treated with neoadjuvant chemotherapy, particularly if they ultimately undergo surgery, may have superior survival in the short term. Based on these findings, neoadjuvant chemotherapy may be appropriate for select patients with advanced uterine serous carcinoma.”
Jason D. Wright, MD, of the Division of Gynecologic Oncology, Columbia University College of Physicians and Surgeons, is the corresponding author for the JAMA Network Open article.
Disclosure: For full disclosures of the study authors, visit jamanetwork.com.
