Preoperative serum interleukin-6 and severe postoperative complications after colorectal cancer resection

Abstract Purpose To evaluate whether preoperative serum interleukin-6 (IL-6) is associated with severe postoperative complications after colorectal cancer resection. Methods This retrospective analysis included 474 patients undergoing curative-intent colorectal cancer resection at Oulu University Hospital between 2010 and 2020. Preoperative serum IL-6 was measured using the Olink Target 96 Immuno-Oncology panel and analysed as a continuous normalized protein expression (NPX) variable. The primary outcome was 90-day Clavien–Dindo classification (CD) grade IV–V complications. Secondary outcomes included overall, surgical, and non-surgical complications. Multivariable models were adjusted for age, sex, American Society of Anesthesiologists (ASA) class, Charlson Comorbidity Index, surgical approach, and tumor location. Bootstrap-based stability assessment was performed using 2000 resamples. Results Median preoperative IL-6 was 3.62 NPX. CD grade IV–V complications occurred in 28 patients (5.9%) and non-surgical complications in 134 patients (28.3%). After adjustment, higher IL-6 remained associated with CD grade IV–V complications (adjusted OR per 1-NPX increase 1.59, 95% CI 1.17–2.19) and non-surgical complications (adjusted OR 1.24, 95% CI 1.01–1.53). In exploratory incremental performance analysis, IL-6 alone showed discrimination comparable to the clinical model, with optimism-corrected AUCs of 0.780 and 0.750, respectively, and adding IL-6 to clinical variables increased the optimism-corrected AUC to 0.795, whereas the Brier score did not improve. Conclusion Higher preoperative IL-6 remained associated after adjustment with severe and non-surgical complications, but its incremental prognostic value was limited. IL-6 should be considered an exploratory marker of baseline vulnerability requiring direct evaluation in relation to frailty and external validation.