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Surgical Outcomes After Neoadjuvant Chemo-Immunotherapy for Stage III NSCLC: A Systematic Review and Meta-Analysis
by
, , , , and
Claudia Bardoni
1,*,†, 
Matteo Chiari
1,†,
Luca Bertolaccini
1
,
Cristina Diotti
1,
Alessia De Fabiani
1,
Giuseppe Nicolosi
1,
Antonio Mazzella
1
,
Monica Casiraghi
1,2 and
Lorenzo Spaggiari
1,2 1
Department of Thoracic Surgery, European Institute of Oncology (IEO) IRCCS, 20141 Milan, Italy
2
Department of Oncology and Hemato-Oncology, University of Milan, 20141 Milan, Italy
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Cancers 2025, 17(9), 1426; https://doi.org/10.3390/cancers17091426
Submission received: 17 March 2025
/
Revised: 15 April 2025
/
Accepted: 18 April 2025
/
Published: 24 April 2025
(This article belongs to the Special Issue Immunotherapy with Checkpoint Inhibitors for Non-small Cell Lung Cancer)
Simple Summary
Lung cancer is a leading cause of cancer-related deaths worldwide, and many patients are diagnosed at an advanced stage, where treatment is more complex. A promising strategy to improve outcomes involves giving patients a combination of chemotherapy and immune-based therapy before surgery to shrink the tumor and strengthen the body’s ability to fight the disease. This approach, however, has raised questions about whether it could delay surgery or increase the risk of complications. In this study, we reviewed and combined data from multiple clinical reports to evaluate how safe and effective surgery is after this treatment. We found that almost all patients could proceed with surgery, which was generally performed on time and with results similar to those seen in patients who did not receive immune-based therapy beforehand. Most operations were completed without major complications, and less invasive surgical techniques remained feasible in many cases. These findings suggest that this new approach does not compromise surgical safety and may offer significant benefits. By helping to ensure that surgery remains effective and timely, this combined treatment strategy may lead to better long-term outcomes for people with lung cancer.
Abstract
Background. To comprehensively assess surgical safety, we conducted a meta-analysis on neoadjuvant chemo-immunotherapy for NSCLC. Methods. This systematic review and meta-analysis followed PRISMA guidelines (PROSPERO: CRD42023470682). A literature search and data extraction were performed independently by two reviewers. Primary outcomes included surgical feasibility and safety. Pooled prevalence proportions with 95% confidence intervals (CIs) were calculated. A random-effects model was applied if heterogeneity was significant (I2 ≥ 50% or p ≥ 0.10). Sensitivity analysis assessed robustness and publication bias was examined using funnel plots and Egger’s test (p < 0.05 significant). Results. Fifteen studies were included, analyzing different immune checkpoint inhibitors with 2–3 cycles of neoadjuvant therapy. Surgery occurred 10–45 days post-treatment. The pooled surgical resection rate was 98.96% (95% CI: 98.93–98.98, I2 = 0%). The conversion to thoracotomy rate was 16.49% (95% CI: 12.95–20.03, I2 = 89.74%). Minimally invasive surgery was performed in 53.62% (95% CI: 49.53–57.72, I2 = 95.92%). The median surgical delay was 28.53 days (95% CI: 23.66–33.41, I2 = 0%). Surgical time averaged 165.27 min (95% CI: 112.32–218.22, I2 = 0%), with mean blood loss of 182.0 mL (95% CI: 134.0–230.0, I2 = 0%). Conclusions. Surgical intervention following neoadjuvant chemo-immunotherapy for NSCLC is feasible and safe, with a high resection rate (98.96%). Variability in minimally invasive surgery and conversion rates suggests differences in surgical approaches, while surgical time, blood loss, and delay showed consistency. These findings highlight the need for a multidisciplinary approach to optimize patient outcomes.
