Association of pathological response with long-term survival outcomes after neoadjuvant immunotherapy: A meta-analysis

Background Complete pathological response (pCR) and major pathological response (MPR) have been proven to have a close association with improved event-free survival (EFS) and overall survival (OS) for patients accepting chemotherapy or chemoradiotherapy. However, further study focusing on neoadjuvant immunotherapy is limited. Here we provided an updated and comprehensive evaluation of the association between pathological response and long-term survival outcomes at patient level and trial level for neoadjuvant immunotherapy. Methods We systematically searched and assessed studies in PubMed, Embase, the Cochrane Library and relevant conference abstracts from inception to June 1, 2023. Studies reported EFS/OS results by pCR/MPR status were eligible. Results Forty-three studies comprising a total of 4100 patients were eligible for the analysis, which included 39 studies for the patient-level analysis and 5 randomized controlled trials for the trial-level analysis. Our results highlighted that pCR was associated with improved EFS (HR, 0.48 [95 % CI, 0.39–0.60]) and OS (HR, 0.55 [95 % CI, 0.41–0.74]). The magnitude of HRs by MPR status were similar to the results by pCR status (EFS HR, 0.31 [95 % CI, 0.18–0.53]) and OS HR, 0.43 [95 % CI, 0.19–0.96]). However, no association between pCR and EFS at trial level was found (P = 0.8, R2 = 0). Conclusion Our meta-analysis demonstrates a strong association between pathological response and long-term survival outcomes at patient level across studies applying neoadjuvant immunotherapy in most solid tumors but we fail to validate the relationship at trial level. Therefore, an accepted surrogate endpoint applied to both patient and trial levels are waited for further search.