The Segment Anything Model (SAM) has demonstrated strong generalizability across a variety of segmentation tasks. However, SAM often struggles in situations where the target to be segmented is ambiguous. This poses a problem in medical imaging, where accurate delineation of targets such as tumors is vital, but even expert radiologists can disagree on the appropriate boundary for a target. Addressing this, we propose SARFA (Segment Anything with Radiomic Feature Alignment), a novel framework for improved medical image segmentation. Via probabilistic prompting, SARFA generates a diverse set of plausible masks for each input image and optimizes them with a radiomics-driven training objective based on Fréchet Radiomic Distance (FRD) and Direct Preference Optimization (DPO). By minimizing the FRD between masked predicted and ground truth regions within each image, SARFA encourages segmentation outputs whose anatomical and textural characteristics align with clinically meaningful ground truth representations, without relying solely on pixel-level overlap. Evaluated on computed tomography (CT) and magnetic resonance imaging (MRI) benchmarks, SARFA outperforms existing ambiguous segmentation methods, demonstrating the effectiveness of radiomic feature alignment and DPO-style candidate mask ranking as a training objective. Our code is available at https://github.com/tbwa233/SARFA.

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