Perioperative immune checkpoint inhibitor therapy across tumors: Insights and shared lessons from a rapidly evolving field

Karl Björkström; Alexios Matikas; Fernanda Costa Svedman; Einar Björgvinsson; Mark Zupancic; Lisa Villabona; Hanna Eriksson; Marcus Skribek; Josefin Fernebro; Magnus Lindskog; Jan-Erik Frödin; Anders Ullén; Simon Ekman; Hildur Helgadottir

doi:10.1111/joim.70073

Perioperative immune checkpoint inhibitor therapy across tumors: Insights and shared lessons from a rapidly evolving field

J Intern Med. 2026 May;299(5):538-569. doi: 10.1111/joim.70073. Epub 2026 Feb 14.

Authors

Karl Björkström^{1

2}, Alexios Matikas^{1

2}, Fernanda Costa Svedman^{1

2}, Einar Björgvinsson^{1

2}, Mark Zupancic^{1

2}, Lisa Villabona^{1

2}, Hanna Eriksson^{1

2}, Marcus Skribek^{1

2}, Josefin Fernebro^{1

2}, Magnus Lindskog^{1

2}, Jan-Erik Frödin^{1

2}, Anders Ullén^{1

2}, Simon Ekman^{1

2}, Hildur Helgadottir^{1

2}

Affiliations

¹ Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
² Theme Cancer, Karolinska University Hospital, Stockholm, Sweden.

PMID: 41690815
DOI: 10.1111/joim.70073

Abstract

The integration of immune checkpoint inhibitors into perioperative management marks a major evolution in curative-intent oncology. This review examines the current evidence for perioperative immunotherapy encompassing neoadjuvant, adjuvant, and combined strategies in melanoma and non-melanoma skin cancers, non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), esophageal and gastroesophageal junction cancer, renal cell carcinoma, urothelial carcinoma, head and neck squamous cell carcinoma, colorectal cancer, gynecological malignancies, and hepatocellular carcinoma. Neoadjuvant immunotherapy demonstrates biological advantages by exposing the immune system to intact tumor antigens, consistently improving event-free survival and pathological response rates across tumor types. Notable successes include CheckMate 816 in NSCLC, KEYNOTE-522 in TNBC, and emerging trials in melanoma that show superior outcomes compared to adjuvant-only approaches. Pathological complete response and major pathological response have emerged as robust surrogate endpoints correlating with long-term survival. In contrast, adjuvant immunotherapy shows more variable results, with demonstrated recurrence-free survival benefits but inconsistent overall survival (OS) advantages-particularly concerning given the risk of overtreatment in patients potentially cured by surgery alone. Critical challenges include the absence of predictive biomarkers in most cancer types, immune-related adverse events occurring in up to 30% of patients, substantial healthcare costs, and insufficient OS follow-up duration in many approved indications. Future priorities include biomarker development, adaptive trial designs incorporating response-guided therapy, and long-term toxicity assessment. Although perioperative immunotherapy is reshaping curative-intent cancer treatment, optimal patient selection, treatment sequencing, and safety optimization remain essential for widespread implementation.

Keywords: adjuvant therapy; immune checkpoint inhibitors; neoadjuvant therapy; neoplasms.

Publication types

Review

MeSH terms

Humans
Immune Checkpoint Inhibitors* / therapeutic use
Immunotherapy* / methods
Neoadjuvant Therapy
Neoplasms* / drug therapy
Neoplasms* / surgery
Neoplasms* / therapy
Perioperative Care* / methods

Substances

Immune Checkpoint Inhibitors