The Role of Circulating Tumor DNA in Patients Treated with Adjuvant Immune Checkpoint Inhibitors: Clinical Reality or Distant Horizon?

Purpose of Review Adjuvant immunotherapy has improved outcomes in several cancers, although patient selection and toxicity remain challenges. Circulating tumor DNA (ctDNA) has emerged as a biomarker for minimal residual disease (MRD) detection, although its role in guiding adjuvant immunotherapy remains unproven. The aim of this review was to summarize the current evidence on ctDNA in the adjuvant immunotherapy setting of solid tumors. Recent Findings Data from various tumor types guiding ctDNA-driven treatment escalation or de-escalation in the context of adjuvant immunotherapy remain sparse, limited to small prospective trials, many of which have struggled with enrolment and yielded inconclusive results. Challenges include analytical and clinical validation, as well as the optimal treatment management of either ctDNA positive and negative patients, posing ethical challenges in designing clinical trials. Summary ctDNA has strong prognostic value in detecting MRD but is not validated for guiding adjuvant immunotherapy, and well-designed prospective trials are required to establish its role. Future research should focus on integrated models combining ctDNA with other biomarkers to improve sensitivity and specificity, while balancing cost-effectiveness and clinical feasibility.