Journal: Journal of internal medicine
This review article analyzes the evolving role of immune checkpoint inhibitors (ICIs) in the perioperative setting (neoadjuvant, adjuvant, and combined strategies) across a broad spectrum of tumor types, including melanoma and non-melanoma skin cancers, non-small cell lung cancer, triple-negative breast cancer, esophageal/gastroesophageal junction cancer, renal cell carcinoma, urothelial carcinoma, head and neck squamous cell carcinoma, colorectal cancer, gynecologic malignancies, and hepatocellular carcinoma.
Key points:
• Neoadjuvant immunotherapy
- • Biologically attractive because the immune system encounters intact tumor and nodal disease.
- • Consistently improves event-free survival and pathologic response rates across multiple tumor types.
- • Landmark signals include:
- • NSCLC: trials such as CheckMate 816 showing improved event-free survival and higher pathologic response.
- • TNBC: trials such as KEYNOTE-522 demonstrating enhanced pathologic complete response and event-free survival.
- • Melanoma: emerging data suggesting neoadjuvant or perioperative strategies may outperform adjuvant-only approaches.
- • Pathologic complete response (pCR) and major pathologic response (MPR) are highlighted as strong surrogate endpoints that correlate with long-term outcomes.
• Adjuvant immunotherapy
- • Provides recurrence-free survival benefit in several cancers.
- • Overall survival advantages are less consistent and often immature, raising concerns about overtreating patients who may already be cured with surgery alone.
- • The risk–benefit balance is less clear when long-term OS data are lacking.
• Clinical challenges
- • Lack of validated predictive biomarkers for most tumor types, limiting patient selection.
- • Immune-related adverse events occur in up to roughly 30% of patients, with potential long-term consequences.
- • High financial cost of prolonged perioperative ICI use.
- • Many indications are based on trials with limited OS follow-up, complicating assessment of true curative impact.
• Future directions
- • Development and validation of biomarkers (e.g., response or resistance signatures) to refine selection and duration of therapy.
- • Adaptive, response-guided trial designs (e.g., escalation/de-escalation based on pathologic or radiologic response).
- • Systematic assessment of long-term toxicity and survivorship issues in cured or near-cured patients.
The authors conclude that perioperative immunotherapy is substantially changing curative-intent cancer management, with neoadjuvant approaches appearing particularly promising. However, better patient selection, optimized sequencing of neoadjuvant and adjuvant components, and improved safety and cost-effectiveness strategies are needed before these regimens can be fully and appropriately integrated into standard practice.