Surrogate endpoints for overall survival in early colorectal cancer from the clinician's perspective

The administration of adjuvant chemotherapy after resection of stage III colon cancer to prolong disease-free survival (DFS) and increase overall survival (OS) has been clinical standard since the early 1990s. Recently, 3-year DFS was recognized as surrogate endpoint for OS based on a meta-analysis of trials utilizing 5-fluorouracil as only active chemotherapy component. The standard of care in adjuvant therapy, however, has moved on to modern combination regimens including oxaliplatin, and novel targeted agents such as angiogenesis inhibitors and antibodies against epidermal growth factor receptor are currently undergoing rigorous testing in phase III adjuvant trials. For the practicing clinician, the use of surrogate endpoints to appreciate the efficacy of a specific adjuvant therapy contains various challenges, in particular, in discussions with patients. It is questionable whether 3-year DFS can still be considered an appropriate predictor of OS in complex clinical scenarios with continuous change in treatment standards in the adjuvant and palliative situation. Thus, the practicing oncologist needs to be aware of the limitations in the definition of surrogate endpoints in the adjuvant setting.