The Role of Surgery in Small-Cell Lung Cancer in the Chemoimmunotherapy Era

The modern role of surgery in small-cell lung cancer (SCLC) is best understood as an unresolved question rather than a settled recommendation. Older randomized trials established that surgery has no role in unselected SCLC, but these trials predate PET-CT staging, endosonographic mediastinal staging, and immunotherapy, and therefore cannot answer today’s clinical question in modern, invasively staged, node-negative disease. Current guideline support for resection in cT1–2N0 SCLC rests largely on retrospective, registry-based data (SEER, NCDB) that carry substantial selection bias rather than randomized confirmation. Meanwhile, the nonsurgical comparator has advanced: chemo-radiotherapy plus durvalumab consolidation, validated in the ADRIATIC trial, now defines the modern limited-stage standard against which any surgical strategy must be benchmarked. Molecular subtyping (ASCL1, NEUROD1, POU2F3, inflamed phenotypes; TP53/RB1 co-alteration) and emerging neoadjuvant and perioperative chemo-immunotherapy data introduce plausible, though unproven, avenues for patient selection and treatment sequencing. Surgical tissue also offers a translational platform for studying immune microenvironment, clonal evolution, and treatment resistance. This review argues that surgery for SCLC is neither obsolete nor an established standard in isolation. Its future role requires two distinct lines of prospective investigation: comparisons of upfront surgery with neoadjuvant chemoimmunotherapy followed by resection, which address treatment sequencing, and comparisons of surgery-based multimodality treatment with definitive concurrent chemoradiotherapy followed by durvalumab, which address the incremental value of surgery over contemporary nonsurgical care.