In an analysis of data from the PORTEC-1, -2, and -3 trials reported in The Lancet Oncology, Wakkerman et al found that older age was associated with more aggressive tumor features and poorer outcomes in patients with endometrial cancer.
Study Details
The analysis included data from 1,801 patients enrolled in the three trials, including 714 with intermediate-risk disease from PORTEC-1 (randomly assigned to receive adjuvant external-beam radiotherapy [EBRT] or no adjuvant therapy), 427 with high-intermediate risk disease from PORTEC-2 (randomly assigned to receive EBRT or vaginal brachytherapy), and 666 with high-risk disease from PORTEC-3 (randomly assigned to receive chemoradiation or EBRT). Multivariate competing risk analyses were performed to determine the independent prognostic value of age. A deep learning causal inference model—AutoCI—was used to analyze age as a potential causal prognostic variable.
Key Findings
Estimated median follow-up was 12.3 years for PORTEC-1, 10.5 years for PORTEC-2, and 6.1 years for PORTEC-3.
Older patients had a higher frequency of deep myometrial invasion (53.6%, 68.5%, and 75.3% for ages < 60, 60–70, and > 70 years, respectively), serous tumor histology (6.0%, 7.6%, and 6.9%), and p53-abnormal tumors (6.8%, 16.0%, and 14.5%).
Both overall recurrence and endometrial cancer–specific death significantly increased with age, with the largest differences observed between the group aged < 60 years vs other age groups.
In the multivariate competing risk analyses corrected for cancer stage, histotype and grade, lymphovascular space invasion, molecular class, and adjuvant treatment, age was an independent risk factor for overall recurrence (hazard ratio [HR] = 1.02 per year, 95% confidence interval [CI] = 1.01–1.04, P = .0012) and endometrial cancer–specific death (HR = 1.03 per year, 95% CI = 1.01–1.05, P = .0012), as well as for locoregional recurrence (HR = 1.02 per year, 95% CI = 1.00–1.05, P = .030) and vaginal recurrence (HR = 1.05 per year, 95% CI = 1.01–1.08, P = .0059).
As stated by the investigators, “These results were supported by AutoCI analyses, which identified age as a significant causal variable alongside all established clinicopathological and molecular risk factors for overall recurrence, endometrial cancer–specific death, and all other oncological outcomes.”
The investigators concluded: “This study showed that advanced age was associated with more aggressive tumor features in women with endometrial cancer and was independently and causally related to worse oncological outcomes. Therefore, our findings suggest that older women with endometrial cancer should not be excluded from diagnostic assessments, molecular testing, and adjuvant therapy based on their age alone.”
Nanda Horeweg, PhD, of the Department of Radiation Oncology, Leiden University Medical Center, Leiden, Netherlands, is the corresponding author for The Lancet Oncology article.
Disclosure: For full disclosures of the study authors, visit thelancet.com.
