Zhulin Liu, Yin Zhu, Wanda Bi, Zhaojie Han, Xiangju Xing, Conghua Lu, Ying Liu, Zhenzhou Yang, Yang Xia, Li Li
In this selected surgical cohort, pCR was more frequent after NIC than NC and showed different EFS associations across treatment groups in exploratory analyses. Both examined NIC pCR specimens were immune-hot, but these mIF observations are hypothesis-generating and cannot establish a mechanism. These findings require prospective validation.
BACKGROUND: Neoadjuvant immunochemotherapy achieves higher pathological complete response (pCR) rates than chemotherapy alone in limited-stage small cell lung cancer (LS-SCLC), but whether pCR carries similar prognostic information across treatment modalities is uncertain.
PATIENTS AND METHODS: This multicenter retrospective cohort study included 85 patients with stage I-III LS-SCLC who underwent radical resection after neoadjuvant immunochemotherapy (NIC, n = 28) or chemotherapy (NC, n = 57). pCR rates were compared between regimens, and treatment-stratified associations of pCR with event-free survival (EFS) and overall survival (OS) were assessed. Treatment-by-pCR interactions were examined using Firth-penalized Cox models. Seven-plex multiplex immunofluorescence (mIF) in nine purposively selected specimens and two public transcriptomic cohorts provided exploratory immune context.
RESULTS: The pCR rate was 35.7% for NIC and 14.0% for NC (P = 0.022). At a median NIC follow-up of 21.1 months, pCR was associated with longer EFS (NR vs 20.3 months, P = 0.007). No corresponding association was detected in the NC group (18.0 vs 19.8 months, P = 0.892). The treatment-by-pCR interaction was significant (Firth-penalized Cox, P = 0.004), indicating that the association between pCR and EFS differed between treatment groups. In the descriptive mIF analysis, both selected NIC pCR specimens showed an immune-hot phenotype, characterized by the highest CD8 + T cell infiltration among the specimens examined and lower PD-1 exhaustion than the NIC non-pCR specimens. Higher antitumor immune scores were associated with longer OS in GSE60052.
CONCLUSIONS: In this selected surgical cohort, pCR was more frequent after NIC than NC and showed different EFS associations across treatment groups in exploratory analyses. Both examined NIC pCR specimens were immune-hot, but these mIF observations are hypothesis-generating and cannot establish a mechanism. These findings require prospective validation.