by Deileta Kamhunga
Post-surgical circulating tumor DNA detection is predictive of poor recurrence-free survival in stage I endometrial cancer patients, according to a recent retrospective analysis.
Endometrial cancer (EC) is the most common gynecologic malignancy of the female reproductive tract. Circulating tumor DNA (ctDNA), a blood-based biomarker, predicts disease outcomes and detects molecular relapse ahead of radiological imaging across various malignancies. However, its prognostic value in EC is unknown.
A multi-center retrospective analysis of clinical data published in Gynecologic Oncology evaluated the postoperative ctDNA levels in stage I EC patients and assessed their association with patient outcome, risk groups, and p53 and mismatch repair (MMR) status.
Patient Characteristics
The study included 101 patients with stage I uterine malignancies (88% EC). Post-surgical plasma samples were tested for ctDNA. The median age was 67 years, and ctDNA was monitored for a median of 6.8 months. The median follow-up for clinical outcomes was 5.7 months post-surgery.
Post-Surgical ctDNA Status Emerges as a Significant Prognostic Marker
At the first postoperative time point, ctDNA-positive patients had significantly worse recurrence-free survival (RFS) (hazard ratio (HR): 6.2, p=0.0006) compared to ctDNA-negative patients. A recurrence rate of 58% was noted in ctDNA-positive patients, compared to 6% in ctDNA-negative patients. Patients who were ctDNA-positive longitudinally also had significantly worse RFS (HR: 15.5, p<0.0001) than patients who were serially ctDNA-negative. The recurrence rate was 52% vs. 0% in longitudinally ctDNA-positive vs. serially negative patients, respectively.
Additionally, patients who were ctDNA-positive post-adjuvant therapy showed significantly reduced RFS (p<0.0001) compared to ctDNA-negative patients, with a recurrence rate of 100% vs. 8%, respectively. Univariate analyses showed that ctDNA status was the only significant predictor of patient outcome at the first time point (HR: 14.5, p=0.001) and remained significant in multivariate analyses after accounting for other factors, such as age, risk groups, MMR, and p53 status (adjusted HR: 18.9, p=0.001).
ctDNA-Negativity Confers Favorable Outcomes Regardless of MMR or p53 Status
MMR-deficient and MMR-proficient patients who were ctDNA-positive had significantly worse RFS than their ctDNA-negative counterparts. MMR-deficient patients who were ctDNA-positive had worse RFS than MMR-proficient ctDNA-positive patients. Moreover, MMR-proficient patients demonstrated higher ctDNA detection than MMR-deficient patients, although the latter had higher ctDNA levels.
The median ctDNA levels were significantly higher in patients with altered p53 status than in patients with wild-type p53 status at the first time point, while the longitudinal ctDNA detection rate was 30% vs. 19%, respectively. Patients who were ctDNA-positive had significantly worse RFS than ctDNA-negative patients, regardless of their p53 status. Patients who were ctDNA-negative had favorable outcomes, irrespective of MMR or p53 status.
Differential ctDNA Detection Rates Noted Across Risk Groups
A significantly lower ctDNA detection rate was observed in low-risk patients than in sarcoma patients at the first time point. Patients with high-risk EC and sarcoma showed a significantly higher longitudinal ctDNA detection rate than patients with high-intermediate-risk EC. High-risk ctDNA-positive patients demonstrated significantly reduced RFS compared to their ctDNA-negative counterparts. Similarly, ctDNA-positive patients in the low-/high-intermediate-risk cohort had significantly worse RFS than their ctDNA-negative counterparts. None of the ctDNA-negative patients had disease recurrence, regardless of risk groups.
Source:
Recio, F. O., Scalise, C. B., Loar, P., Lumish, M., Berman, T., Peddada, A., Kalashnikova, E., Rivero-Hinojosa, S., Beisch, T., Nicosia, B., Farmer, T. D., Dutta, P., Malhotra, M., ElNaggar, A. C., Liu, M. C., Vaccarello, L., & Holloway, R. W. (2024). Post-surgical ctDNA-based molecular residual disease detection in patients with stage I uterine malignancies. Gynecologic Oncology, 182, 63–69. https://doi.org/10.1016/j.ygyno.2023.12.025
