Immune phenotype and RAS/BRAF status predict outcomes after lung metastasectomy for colorectal cancer.

[PURPOSE] Colorectal cancer (CRC) presents a marked biological heterogeneity, and the lung is a frequent site of metastatic spread. Although pulmonary metastasectomy can lead to a long-term survival, recurrence rates remain high and prognostic markers are lacking. This study evaluated the prognostic value of clinical, molecular, and histopathological features in CRC patients undergoing lung metastasectomy.

[METHODS] A retrospective cohort of CRC patients who underwent pulmonary metastasectomy at Hospital de la Santa Creu i Sant Pau between September 2011 and October 2023 was analyzed. Clinical variables, molecular alterations, and histopathological characteristics were collected. Immune phenotype (IP) and histological growth pattern (HGP) were assessed by pathologists and survival outcomes were estimated using Kaplan-Meier methods.

[RESULTS] 61 patients (median age 67 years) were included. Median overall survival (OS) was 73.1 months, and median recurrence-free survival (RFS) was 17.5 months. Early-stage CRC at diagnosis (stages I-II) was associated with longer RFS (42.7 vs 12.6 months; p = 0.02), whereas elevated preoperative CEA levels predicted shorter RFS (7.1 vs. 21.3 months, p = 0.005) and lung-only metastatic disease was associated with longer OS (80.3 vs 28.6 months; p = 0.01). An immune-desert IP correlated with shorter RFS (4.0 vs. 20.4 months, p = 0.03), and tumors harboring RAS/BRAF mutations had worse lung-specific RFS (14.9 vs. 24.3 months, p = 0.034).

[CONCLUSIONS] An immune-desert phenotype and RAS/BRAF mutations identify CRC patients at higher risk of recurrence after lung metastasectomy, whereas earlier CRC stage and solitary lung metastasis are associated with more favorable outcomes. Integrating clinical, molecular, and immune-histologic features may improve selection for pulmonary metastasectomy in oligometastatic CRC.