Optimizing the clinical assessment of pseudoprogression in patients with solid tumors treated with checkpoint inhibitors: a systematic literature review and meta-analysis of associated features

Pseudoprogression is an atypical response pattern observed during treatment with immune checkpoint inhibitors (CPIs) that can complicate clinical decision-making. It is characterized by initial radiologic progression followed by subsequent tumor regression or stabilization, with confirmation requiring repeat imaging. We aimed to characterize the clinical and imaging features of confirmed pseudoprogression in solid tumors treated with CPIs using pooled study data.

We systematically searched MEDLINE, Embase, and Web of Science through December 2025. Prospective and retrospective cohort studies and randomized trials reporting confirmed pseudoprogression during CPI therapy were eligible. Two independent reviewers performed study selection and data extraction using predefined criteria. Study quality was assessed using the Joanna Briggs Institute checklist. Pooled analyses were conducted with RevMan and Stata. Outcomes included time to initial radiologic progression, magnitude of tumor burden increase, occurrence of new lesions, changes in nontarget lesions, and subsequent objective response.

Thirteen retrospective studies were included; most applied iRECIST criteria. The pooled median time to initial progression was 2.52 months (95% CI, 1.54–3.51). Mean tumor burden increase was 33.0% (95% CI, 22.7–43.3), and new lesions occurred in 35.3% of cases. Tumor burden increases > 100% were rare (3.9%). Despite initial progression, 41.8% subsequently achieved partial response and 6.4% complete response without therapy change. Median time to best response was 2.79 months (95% CI, 0.62–7.20).

Pseudoprogression typically occurs early during CPI therapy and is associated with modest tumor growth. Marked tumor increases are uncommon and may help distinguish true progression. Careful clinical and radiologic assessment remains essential.