Continuing immune checkpoint inhibitors after pseudoprogression improves survival in lung cancer patients: a systematic review and meta-analysis.

Background: Pseudoprogression (PsP) in lung cancer patients receiving immune checkpoint inhibitors (ICIs) complicates treatment decisions. This study evaluated the prognostic impact of continuing versus discontinuing ICI post-PsP and developed tools for PsP identification via an individual patient data (IPD) pooled analysis. Methods: This IPD pooled analysis included 40 PsP cases (4 institutional cases + 36 literature-derived cases, who were categorized into continued-ICI and interrupted-ICI groups. Prognoses were compared using Fisher's exact test (12-month survival) and Kaplan-Meier/log-rank tests (median overall survival). A chest computed tomography (CT) pattern diagram and proposed diagnostic-therapeutic framework were developed. Results: The median time to PsP onset was 8 weeks. Initially, 87.5% of cases were misclassified as progressive disease (PD) by Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1), whereas Immune-Related Response Evaluation Criteria in Solid Tumors (iRECIST) corrected such misclassifications. Continued ICI treatment was associated with significantly longer median overall survival (16.6 vs. 7.4 months, P<0.01) and a higher 12-month survival rate (66.7% vs. 40.0%, P<0.01). To improve clinical recognition, we developed a chest CT pattern diagram delineating characteristic PsP imaging features. Additionally, a proposed diagnostic-therapeutic framework was developed to guide management, but it remains hypothesis-generating and requires validation. Conclusions: Continuing ICIs post-PsP improves outcomes in lung cancer patients. iRECIST facilitates the accurate diagnosis of PsP, while chest CT pattern diagrams and a diagnostic-therapeutic framework contribute to optimizing the management of immunotherapy. Prospective trials are warranted to validate this framework.