The role of surgery in locally advanced non-small cell lung cancer (NSCLC) is continuously evolving with the introduction of effective neoadjuvant systemic treatments. Beyond tumor reduction, treatment response may influence surgical decision-making by improving resectability and allowing parenchymal-sparing approaches while maintaining oncological principles.
The authors present the case of a 75-year-old male with a right lower lobe squamous cell carcinoma, which was incidentally diagnosed during hospitalization for diffuse myalgias. The patient was a former smoker with good functional status and preserved pulmonary function. Initial staging demonstrated an 11 cm right lower lobe tumor with high metabolic activity on positron emission tomography-computed tomography (PET-CT) (maximum standardized uptake value [SUVmax] 14), without mediastinal lymph node involvement or distant metastases. A magnetic resonance imaging (MRI) scan of the brain was negative. A bronchoscopic biopsy confirmed squamous cell carcinoma with high programmed death-ligand 1 (PD-L1) expression, classified as cT4N0M0.
Due to the tumor size and anatomical relationships, particularly the proximity to the diaphragm and concerns regarding adequate surgical margins, the initial surgical strategy considered was a right bilobectomy including the middle lobe.
The patient received three cycles of neoadjuvant chemoimmunotherapy with platinum-based chemotherapy, paclitaxel, and pembrolizumab. Restaging CT demonstrated a major radiological response, with significant tumor regression and improved anatomical relationships. The suspected diaphragmatic involvement became less suggestive of direct invasion and more compatible with treatment-related fibrosis and adhesions. This response modified the surgical plan, allowing a parenchymal-sparing approach.
A robot-assisted right lower lobectomy was therefore performed, which preserved the middle lobe and avoided an extended bilobectomy. Systematic hilar and mediastinal lymph node dissection was completed, including stations 2R, 4R, 7, 10R, and 11. Intraoperatively, dense inflammatory adhesions related to neoadjuvant therapy were encountered, which required meticulous stepwise dissection. No macroscopic diaphragmatic invasion was identified, and no diaphragmatic resection was required.
The final pathological examination demonstrated a complete pathological response, with no viable residual tumor cells and no lymph node metastases, corresponding to ypT0N0. The surgical margins were free of disease.
This case highlights the concept of downstaging-driven surgical strategy in locally advanced NSCLC. Neoadjuvant therapy should not be considered only as a means of tumor reduction, but also as a tool that may redefine surgical planning. In selected patients, a major pathological response can allow avoidance of extended resections, preserving functional lung parenchyma while maintaining complete oncological resection principles.
References
- Forde PM, Spicer J, Lu S, Provencio M, Mitsudomi T, Awad MM, et al. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med. 2022;386(21):1973-1985.
- Hellmann MD, Chaft JE, William WN Jr, Rusch V, Pisters KMW, Kalhor N, et al. Pathological response after neoadjuvant chemotherapy in resectable non-small-cell lung cancers: proposal for the use of major pathological response as a surrogate endpoint. Lancet Oncol. 2014;15(1):e42-e50.
- Fang W, Yang Y, Ma Y, et al. Perioperative Toripalimab Plus Chemotherapy for Resectable Stage III Non-Small-Cell Lung Cancer: The Neotorch Randomized Clinical Trial. JAMA Surg. 2024;159(9):1030-1040.
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