Association between adjuvant therapy and survival in colorectal cancer patients according to metabolic Warburg-subtypes

Purpose Tumor location and tumor node metastasis (TNM) stage guide treatment decisions in colorectal cancer (CRC) patients. However, patients with the same disease stage do not benefit equally from adjuvant therapy. Hence, there remains an urgent clinical need to identify prognostic and/or predictive biomarker(s) to personalize treatment decisions. In this exploratory study, we investigated whether our previously defined metabolic Warburg-subtypes can predict which CRC patients might derive survival benefit from adjuvant therapy. Methods Information regarding treatment (surgery only: n = 1451; adjuvant radiotherapy: n = 82; or adjuvant chemotherapy: n = 260) and Warburg-subtype (Warburg-low: n = 485, -moderate: n = 641, or –high: n = 667) was available for 1793 CRC patients from the Netherlands Cohort Study (NLCS). Kaplan–Meier curves and Cox regression models were used to investigate survival benefit from adjuvant therapy compared to surgery-only for the different Warburg-subtypes. Results Patients with Warburg-moderate CRC (HR CRC-specific 0.64; 95% CI 0.47–0.86, HR overall 0.61; 95% CI 0.47–0.80), and possibly Warburg-high CRC (HR CRC-specific 0.86; 95% CI 0.65–1.14, HR overall 0.82; 95% CI 0.64–1.05), had survival benefit from adjuvant therapy. No survival benefit was observed for patients with Warburg-low CRC (HR CRC-specific 1.07; 95% CI 0.76–1.52, HR overall 0.95; 95% CI 0.70–1.30). There was a significant interaction between Warburg-subtype and adjuvant therapy for CRC-specific survival ( p = 0.049) and overall survival ( p = 0.035). Conclusion Our results suggest that Warburg-subtypes may predict survival benefit from adjuvant therapy in CRC patients. A survival benefit from adjuvant therapy was observed for patients with Warburg-moderate and possibly Warburg-high CRC, but not for patients with Warburg-low CRC. Future prospective studies are necessary to validate our findings.