The Role of Surgery in Small-Cell Lung Cancer in the Chemoimmunotherapy Era
- 1Department of Thoracic Surgery, Fondazione IRCCS San Gerardo dei Tintori, 20900 Monza, Italy
- 2Department of Oncology and Hemato-Oncology, University of Milan, Via Festa del Perdono 7, 20122 Milan, Italy
Abstract
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.
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BibTeX
@article{petrella2026role,
title = {{The Role of Surgery in Small-Cell Lung Cancer in the Chemoimmunotherapy Era}},
author = {Francesco Petrella and Andrea Cara and Enrico Mario Cassina and Jessica Dell’Agosto and Lidia Libretti and Emanuele Pirondini and Federico Raveglia and Antonio Tuoro},
journal = {Cancers},
year = {2026},
month = oct,
doi = {10.3390/cancers18213484},
url = {https://www.mdpi.com/2072-6694/18/21/3484},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The Role of Surgery in Small-Cell Lung Cancer in the Chemoimmunotherapy Era
AU - Francesco Petrella
AU - Andrea Cara
AU - Enrico Mario Cassina
AU - Jessica Dell’Agosto
AU - Lidia Libretti
AU - Emanuele Pirondini
AU - Federico Raveglia
AU - Antonio Tuoro
PY - 2026
DA - 2026/10/29
JO - Cancers
DO - 10.3390/cancers18213484
UR - https://www.mdpi.com/2072-6694/18/21/3484
AB - 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.
SN - 2072-6694
ER -