Prophylactic cranial irradiation together with molecular subtyping in surgically resected small-cell lung cancer: a inverse-probability-of-treatment weighted cohort study

Prophylactic cranial irradiation (PCI) remains a contentious therapeutic approach in small-cell lung cancer (SCLC) despite its established efficacy in reducing brain metastases. The debate persists particularly in the context of modern imaging techniques like brain MRI. This retrospective study examined the survival outcomes associated with PCI in surgically resected SCLC patients who underwent pre-PCI brain MRI at a Chinese cancer center. A total of 309 patients were initially screened, with 110 meeting inclusion criteria after applying rigorous exclusion criteria based on a decade-long dataset. Among them, 77 patients underwent molecular subtyping based on immunohistochemistry (IHC). Clinical and pathological features, along with survival outcomes, were compared between the PCI and observation groups. Among the final cohort, 58 patients received PCI while 52 were in the observation group. The PCI group exhibited significantly prolonged overall survival compared to the observation group (HR = 0.368, 95% CI 0.154–0.882, P = 0.0249) after adjusting for baseline imbalances using inverse probability of treatment weighting Subgroup analyses indicated notable survival benefits in male patients, those ≤ 65 years old, and individuals with pathological N0 disease. Compared to subtypes P (5.2%) and Y (11.7%), molecular subtyping indicates a higher prevalence of subtypes A (42.8%) and N (40.3%). Neuroendocrine subtypes (A and N) tend to have poorer prognoses and could obtained overall survival benefits from PCI. (HR = 0.276, 95% CI 0.091–0.839, P = 0.015). This study supporting the use of PCI in surgically resected SCLC patients with pre-PCI brain MRI evaluation, demonstrating a significant survival advantage. Molecular subtyping through IHC may help identify SCLC patients who can benefit from PCI.