Prognostic value of radiologically enlarged lymph nodes in patients with metastatic colorectal cancer: Subgroup findings of the randomized, open-label FIRE-3/AIO KRK0306 trial

Abstract Purpose To determine the prognostic impact of radiologically enlarged lymph nodes ≥ 10 mm on the survival of patients with metastatic colorectal cancer. Materials and methods The prospective, randomized, open-label FIRE-3/AIO KRK0306 trial evaluated the first-line therapy of patients with KRAS exon 2 wild-type metastatic colorectal cancer with fluorouracil, folinic acid and irinotecan plus either cetuximab or bevacizumab. In the RAS wild-type population (n = 400), adequately evaluable baseline computed tomographies (n = 339) were reviewed for enlarged regional and distant lymph nodes. Their prognostic relevance was retrospectively analyzed in uni- and multivariable Cox proportional hazard regressions. Results Median overall survival was 21.7 months in patients with enlarged lymph nodes and 33.2 months in patients without (hazard rate ratio [HR] = 1.61, 95% confidence interval [CI], 1.23–2.09; P   0.001). This was confirmed in multivariable analysis (HR = 1.37, 95% CI, 1.02–1.83; P  = 0.036). Progression-free survival of patients with enlarged lymph nodes showed a consistent but insignificant trend (9.9 vs. 11.1 months; HR = 1.23, 95% CI, 0.98–1.54; P  = 0.072). Enlarged lymph nodes were also associated with BRAF-mutations ( P  = 0.004). Conclusion The presence of radiologically enlarged lymph nodes in baseline staging has a negative prognostic value beyond established and potential prognostic parameters.