Precision de-escalation of immunotherapy in extensive-stage small cell lung cancer: a case report on ctDNA-guided management in a long-term survivor.

BACKGROUND: Extensive-stage small cell lung cancer (ES-SCLC), while often initially responsive to therapy, remains a refractory disease characterized by aggressive progression and poor long-term outcomes. Current guidelines recommend continuous treatment until disease progression or unacceptable toxicity, which exposes patients, particularly long-term responders, to prolonged adverse effects and financial burden. Circulating tumor DNA (ctDNA) has emerged as a promising tool in lung cancer management. Notably, a ctDNA-minimal residual disease (MRD)-guided adaptive de-escalation strategy has proven feasible in epidermal growth factor receptor (EGFR)-mutant advanced non-small cell lung cancer (NSCLC). However, the application of such a strategy in the context of immunotherapy for SCLC has not been explored. CASE DESCRIPTION: Here, we present a case of a 64-year-old female diagnosed with ES-SCLC. She initially received four cycles of etoposide plus cisplatin and durvalumab, followed by durvalumab maintenance monotherapy. After nine months of maintenance, we initiated dynamic peripheral blood ctDNA-MRD monitoring every two to three months and all subsequent tests remained negative for ctDNA. Based on the sustained durable partial response (PR), persistent serum tumor markers and ctDNA negativity, treatment was electively discontinued following the 22nd maintenance cycle. As of the last follow-up, the patient had achieved a progression-free survival (PFS) of over 40 months and a treatment-free interval exceeding 17 months. CONCLUSIONS: This case suggests that immune checkpoint inhibitors (ICIs) de-escalation guided by ctDNA-MRD may be a feasible strategy for a selected subset of long-term survivors with ES-SCLC. These findings warrant further validation in prospective clinical trials.