Role of dynamic ctDNA monitoring in cervical and anal epidermoid carcinomas under curative chemoradiation

Circulating tumor DNA (ctDNA) is a promising biomarker to predict recurrence in solid tumors such as colorectal and breast cancer. Defining complete response after chemoradiation remains challenging, as post-treatment inflammatory and tissue changes limit clinical and imaging evaluation.

The authors conducted a prospective longitudinal study of patients with localized cervical and anal cancer treated with curative-intent chemoradiation with the aim of evaluating the role of ctDNA as a predictor of recurrence. Blood specimens were collected at D1, D29, immediately post-treatment, 8-weeks, 24-weeks, and every 6-months up to 5-years. ctDNA testing (Signatera™) was provided by Natera as an in-kind donation. The primary endpoint was correlation between 8-week ctDNA and recurrence.

28 patients were evaluable. Ten recurrences occurred, all in patients with positive ctDNA after chemoradiation and before radiologic progression. The median interval between ctDNA positivity and radiologic progression was 3.0-months (range 0.5-21.3). All patients with radiologic complete response at 6 months had negative 8-week ctDNA. Among those without complete response, 8-week ctDNA identified most who later progressed (6/8), while all without complete response who did not progress had negative ctDNA. Eight-week ctDNA positivity was strongly associated with inferior progression-free survival: median 6.7-months in ctDNA-positive versus not reached in ctDNA-negative patients (HR = 40.09, p = 0.001).

Among patients with cervical and anal cancer, ctDNA monitoring after definitive chemoradiation identifies individuals without complete response and predicts recurrence. ctDNA positivity at 8-weeks identifies a very high-risk group for whom treatment intensification trials are warranted.