Automated PD-L1 Tumor Proportion Scoring with Uncertainty-Guided Triage in Non-Small Cell Lung Cancer

Kesi Xu, Ayesha Azam, Tanvier Kaur, Monika Kondratowicz, Kinza Asim +5

Programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) informs immunotherapy selection in non-small cell lung cancer. Near the 1% and 50% cutoffs, the score should also indicate when closer review is warranted. We designed a three-stage framework to follow the sequence of TPS assessment. Stage 1 identifies tumor regions and excludes macrophage-rich patches. Stage 2, a dual-branch cell counting network (D2Count-Net), counts PD-L1-positive and PD-L1-negative tumor cells in these regions to calculate TPS. Stage 3, TPS-Guard, an uncertainty-guided triage mechanism, reports model uncertainty as the disagreement among independently trained models, refers the most uncertain slides, and flags scores near the 1% or 50% cutoff when model estimates disagree across that cutoff. Flags state the reason for referral or alert the pathologist to possible scoring errors on auto-reported slides. In a retrospective, single-center study, 154 whole-slide images were scored by three pathologists, and the model and each pathologist were compared in turn with the mean of the other two. On the 114 slides unseen in training, model mean absolute error (MAE) was 6.96 percentage points, within the…