Despite the increasing incidence of endometrial cancer (EC) worldwide and the poor overall survival of patients who recur, no reliable biomarker exists for detecting and monitoring EC recurrence and progression during routine follow-up. Circulating tumor DNA (ctDNA) is a sensitive method for monitoring cancer activity and stratifying patients that are likely to respond to therapy. As a pilot study, we investigated the utility of ctDNA for detecting and monitoring EC recurrence and progression in 13 patients, using targeted next-generation sequencing (tNGS) and personalized ctDNA assays. Using tNGS, at least one somatic mutation at a variant allele frequency (VAF) > 20% was detected in 69% (9/13) of patient tumors. The four patients with no detectable tumor mutations at >20% VAF were whole exome sequenced, with all four harboring mutations in genes not analyzed by tNGS. Analysis of matched and longitudinal plasma DNA revealed earlier detection of EC recurrence and progression and dynamic kinetics of ctDNA levels reflecting treatment response. We also detected acquired high microsatellite instability (MSI-H) in ctDNA from one patient whose primary tumor was MSI stable. Our study suggests that ctDNA analysis could become a useful biomarker for early detection and monitoring of EC recurrence. However, further research is needed to confirm these findings and to explore their potential implications for patient management.

Despite the increasing incidence of endometrial cancer (EC) worldwide and the poor overall survival of patients who recur, no reliable biomarker exists for detecting and monitoring EC recurrence and progression during routine follow-up. Circulating tumor DNA (ctDNA) is a sensitive method for monitoring cancer activity and stratifying patients that are likely to respond to therapy. As a pilot study, we investigated the utility of ctDNA for detecting and monitoring EC recurrence and progression in 13 patients using targeted next-generation sequencing (tNGS) and personalized ctDNA assays. Using tNGS, at least 1 somatic mutation at a variant allele frequency (VAF) >20% was detected in 69% (9/13) of patient tumors. The four patients with no detectable tumor mutations at >20% VAF were whole exome sequenced, with all four harboring mutations in genes not analyzed by tNGS. Analysis of matched and longitudinal plasma DNA revealed earlier detection of EC recurrence and progression and dynamic kinetics of ctDNA levels reflecting treatment response. We also detected acquired high microsatellite instability (MSI-H) in ctDNA from one patient whose primary tumor was MSI stable. Our study suggests that ctDNA analysis, and in particular MSI analysis in ctDNA could become a useful biomarker for early detection and monitoring of EC recurrence and progression.

Objective: Circulating tumour DNA (ctDNA) is emerging as a potential option to detect disease recurrence in many cancer types however, ensuring patient acceptability of changing clinical practice and the introduction of new technology is paramount. This study aimed to explore women’s opinions on the acceptability of ctDNA to monitor for endometrial cancer (EC) recurrence. Methods: Women enrolled on a non-intervention cohort study determining the ability of ctDNA to detect recurrent endometrial cancer were invited to participate in a semi-structured interview. Data was analysed using Template Analysis. Results: Eighteen women were interviewed. Participants represented a mix of cases, including early stage high-risk EC, metastatic disease at diagnosis and EC recurrence, to ensure a wide range of participant experiences were captured. A ctDNA blood test was viewed by participants as more physically and psychologically acceptable than clinical examination to monitor for EC recurrence. In particular, participants expressed overwhelming preference for a blood test rather than pelvic examination. Although participants acknowledged that an abnormal ctDNA result could cause anxiety, they expressed a preference to be informed of their results, even if a recurrence was too small to detect radiologically. Explanations for these opinions were a desire for certainty whether their cancer would recur or not, and knowledge would help them be more aware of symptoms that should be reported to their clinician. Conclusions: ctDNA monitoring to identify EC recurrence appears to be acceptable to patients, and for many, may be preferable to clinical examination.