Time-dependent prognostic impact of distant metastatic sites in small cell lung cancer: a comparative analysis of pre- and post-immunotherapy eras.

AIMS: To investigate whether the prognostic impact of distant metastatic sites in extensive-stage small cell lung cancer (ES-SCLC) has changed between the pre-immunotherapy and immunotherapy eras.

MATERIALS AND

METHODS

We analyzed 43,279 metastatic SCLC patients from the SEER database, comparing the pre-immune checkpoint inhibitor (ICI) era (2010-2018) with the ICI era (2019-2022). Overall survival (OS) was assessed using multivariable Cox models. A novel time-dependent area under the curve (AUC) analysis evaluated the dynamic prognostic performance of metastatic sites up to 36 months.

RESULTS

Liver metastasis was the most prevalent site (46.3%) and the strongest independent adverse prognostic factor in both the pre-ICI and ICI eras (Mean AUC: 0.626 vs. 0.621, respectively). Notably, the prognostic impact of brain metastasis was neutralized in the ICI era (mean AUC dropping from 0.507 to 0.482), suggesting improved intracranial control. Bone metastasis showed limited prognostic discrimination without concurrent liver involvement.

CONCLUSIONS

The prognostic landscape of metastatic SCLC has evolved significantly in the immunotherapy era. Liver metastasis persists as the dominant negative factor, whereas the adverse prognostic impact of brain involvement is significantly diminished. These findings underscore the need for organ-specific prognostic stratification in modern SCLC management.