In cross-modal retrieval tasks, such as image-to-report and report-to-image retrieval, accurately aligning medical images with relevant text reports is essential but challenging due to the inherent ambiguity and variability in medical data. Existing models often struggle to capture the nuanced, multi-level semantic relationships in radiology data, leading to unreliable retrieval results. To address these issues, we propose the Prototype-Enhanced Confidence Modeling (PECM) framework, which introduces multi-level prototypes for each modality to better capture semantic variability and enhance retrieval robustness. PECM employs a dual-stream confidence estimation that leverages prototype similarity distributions and an adaptive weighting mechanism to control the impact of high-uncertainty data on retrieval rankings. Applied to radiology image-report datasets, our method achieves significant improvements in retrieval precision and consistency, effectively handling data ambiguity and advancing reliability in complex clinical scenarios. We report results on multiple different datasets and tasks including fully supervised and zero-shot retrieval obtaining performance gains of up to 10.17%, establishing in new state-of-the-art.