Although the value of adding AI as a surrogate second reader in various scenarios has been investigated, it is unknown whether implementing an AI tool within double reading practice would capture additional subtle cancers missed by both radiologists who independently assessed the mammograms. This paper assesses the effectiveness of two state-of-the-art Artificial Intelligence (AI) models in detecting retrospectively-identified missed cancers within a screening program employing double reading practices. The study also explores the agreement between AI and radiologists in locating the lesions, considering various levels of concordance among the radiologists in locating the lesions. The Globally-aware Multiple Instance Classifier (GMIC) and Global–Local Activation Maps (GLAM) models were fine-tuned for our dataset. We evaluated the sensitivity of both models on missed cancers retrospectively identified by a panel of three radiologists who reviewed prior examinations of 729 cancer cases detected in a screening program with double reading practice. Two of these experts annotated the lesions, and based on their concordance levels, cases were categorized as 'almost perfect,' 'substantial,' 'moderate,' and 'poor.' We employed Similarity or Histogram Intersection (SIM) and Kullback–Leibler Divergence (KLD) metrics to compare saliency maps of malignant cases from the AI model with annotations from radiologists in each category. In total, 24.82% of cancers were labeled as “missed.” The performance of GMIC and GLAM on the missed cancer cases was 82.98% and 79.79%, respectively, while for the true screen-detected cancers, the performances were 89.54% and 87.25%, respectively (p-values for the difference in sensitivity < 0.05). As anticipated, SIM and KLD from saliency maps were best in ‘almost perfect,’ followed by ‘substantial,’ ‘moderate,’ and ‘poor.’ Both GMIC and GLAM (p-values < 0.05) exhibited greater sensitivity at higher concordance. Even in a screening program with independent double reading, adding AI could potentially identify missed cancers. However, the challenging-to-locate lesions for radiologists impose a similar challenge for AI.
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