Tumor-infiltrating lymphocyte as a prognostic biomarker in stage IV colorectal cancer should take into account the metastatic status and operation modality

Background: Although tumor-infiltrating lymphocytes (TILs) have been understood for years as a favorable prognostic factor for colorectal cancers (CRCs) after complete surgical resection, its prognostic role in metastatic CRC (mCRC) remains poorly defined, and it is largely unknown how this prognostic benefit relates to the metastatic status and operation modality. Materials and methods: After reviewing 2215 consecutive cases of surgically resected CRC, 332 patients newly diagnosed with stage IV CRC and treated at the Sun Yat-Sen University Cancer Center between 2009 and 2014 were included. H&E-stained (HES) slides from surgical specimens were evaluated for the extent of TILs. The primary end point was overall survival (OS). Cox proportional hazards regression was conducted to determine the prognostic significance of TILs. All statistical tests were 2-sided. Results: HES slides from primary tumor samples were evaluable for 302 of the 332 included cases. Among the 302 patients, 105 patients (34.8%) were classified as high TIL, the remaining 197 (65.2%) were defined as low TIL. In the univariate analysis, TILs were significantly associated with better OS (P=0.015). Multivariable analysis confirmed that high TIL strongly predicted better survival (hazard ratio =0.62, 95% CI: 0.44-0.89, P=0.008), independent of other patients' clinicopathological characteristics. Stratified analysis revealed a prognostic benefit of high TIL for patients in the subgroup with non-oligometastatic disease (P=0.002), >= 2 metastatic organs (P=0.006), and non-metastasectomy (P=0.005). By contrast, oligometastatic disease, 1 metastatic organ, or metastasectomy fully abrogated the prognostic effect of TIL. Conclusion: Our findings indicate that the level of TILs can be used to predict the outcome for patients with mCRC; however, the operation modality and the metastatic status of patients should also be taken into account.