Continual Model Merging with Test-Time Adaptation for Whole-Slide Image Analysis

Survival analysis on Whole Slide Images (WSIs) is important in computational pathology for prognosis estimation and treatment planning. However, existing survival models are typically trained independently for each cancer cohort, making continual adaptation computationally expensive for gigapixel-scale WSIs. In this study, we propose MergeSurv, a merging-based continual learning framework for WSI survival analysis. A pathology vision-language foundation model is independently fine-tuned on each task, and the learned parameters are sequentially merged into a unified model without storing previous training data. We further investigate two inference strategies: One-for-All (OFA) and Voting-Expert Aggregation (VEA). Experiments on four TCGA cohorts demonstrate that MergeSurv outperforms naive fine-tuning as well as representative regularization-based and rehearsal-based continual learning methods, while effectively reducing catastrophic forgetting. The results suggest that model merging is a promising direction for scalable and privacy-preserving continual learning in computational pathology.

Foundation models are reshaping computational histopathology, yet their value for whole-slide image retrieval relative to strong patch-based and supervised aggregation baselines remains unclear. We benchmarked ten pipelines on 9,387 diagnostic slides spanning 17 organs and 60 diagnoses from The Cancer Genome Atlas (TCGA) using patient-level leave-one-patient-out evaluation. Methods included four pre-trained slide foundation models, a supervised attention-based multiple instance learning (ABMIL) aggregator on patch embeddings, and patch-level retrieval across five sampling densities. Performance varied more across organs and diagnoses than across architectures. Although the slide foundation model TITAN achieved the strongest overall results, its advantage was modest; ABMIL and patch-based methods reached comparable Top-1 and Top-3 accuracy, with no model consistently dominant. Morphologically distinctive entities approached ceiling performance, while rare, heterogeneous, and closely related subtypes remained challenging. Misclassifications aligned with organs exhibiting known inter-observer variability, suggesting an intrinsic ceiling for morphology-only retrieval. Performance was driven primarily by patch-level feature representations, with limited benefit from slide-level aggregation, indicating aggregation may be unnecessary in many settings. These findings argue against a universally optimal architecture and instead support organ-resolved benchmarking, diagnosis-aware or ensemble strategies, stronger feature representations, and multimodal retrieval frameworks. Notably, even the best model achieved only $\approx 68\% \pm 21\%$ retrieval accuracy on TCGA, and some subtypes showed $0\%$ accuracy across all methods, highlighting fundamental limitations of morphology-based representations and the need for substantial progress before reliable clinical deployment.

Deep neural nets achieve remarkable performance when training and test data share the same distribution, but this assumption frequently breaks in real-world deployment, where data undergoes continual distributional shifts. Continual Test-Time Adaptation (CTTA) addresses this challenge by adapting pretrained models to non-stationary target distributions on-the-fly, without access to source data or labeled targets, while mitigating two critical failure modes: catastrophic forgetting of source knowledge and error accumulation from noisy pseudo-labels over extended time horizons. In this comprehensive survey, we formally define the CTTA problem, analyze the diverse continual domain shift patterns that characterize different evaluation protocols, and propose a hierarchical taxonomy that categorizes existing methods into three families: optimization-based strategies (entropy minimization, pseudo-labeling, parameter restoration), parameter-efficient methods (normalization layer adaptation, adaptive parameter selection), and architecture-based approaches (teacher-student frameworks, adapters, visual prompting, masked modeling). We systematically review representative methods within each category and present comparative benchmarks and experimental results across standard evaluation settings. Finally, we discuss the limitations of current approaches and highlight emerging research directions, including the adaptation of foundation models and black-box systems, thereby providing a roadmap for future research in robust continual test-time adaptation.