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Validation metrics are a key prerequisite for the reliable tracking of scientific progress and for deciding on the potential clinical translation of methods. While recent initiatives aim to develop comprehensive theoretical frameworks for understanding metric-related pitfalls in image analysis problems, there is a lack of experimental evidence on the concrete effects of common and rare pitfalls on specific applications. We address this gap in the literature in the context of colon cancer screening. Our contribution is twofold. Firstly, we present the winning solution of the Endoscopy computer vision challenge (EndoCV) on colon cancer detection, conducted in conjunction with the IEEE International Symposium on Biomedical Imaging (ISBI) 2022. Secondly, we demonstrate the sensitivity of commonly used metrics to a range of hyperparameters as well as the consequences of poor metric choices. Based on comprehensive validation studies performed with patient data from six clinical centers, we found all commonly applied object detection metrics to be subject to high inter-center variability. Furthermore, our results clearly demonstrate that the adaptation of standard hyperparameters used in the computer vision community does not generally lead to the clinically most plausible results. Finally, we present localization criteria that correspond well to clinical relevance. Our work could be a first step towards reconsidering common validation strategies in automatic colon cancer screening applications.