# OTSurv: A Novel Multiple Instance Learning Framework for Survival Prediction with Heterogeneity-aware Optimal Transport

arXiv: https://arxiv.org/abs/2506.20741 · HTML: https://mlsanity.com/paper/2506.20741/

## Key facts

- Cited by 8 papers in the map (data through 14 Oct 2026).
- Builds on 19 of its 37 references that are in the map.
- First posted on arXiv 25 Jun 2025.

## Builds on (most cited first, 19 of 19)

- [Attention-based Deep Multiple Instance Learning](https://mlsanity.com/paper/1802.04712/) (2018)
- [Temporal Ensembling for Semi-Supervised Learning](https://mlsanity.com/paper/1610.02242/) (2016)
- [Data Efficient and Weakly Supervised Computational Pathology on Whole Slide Images](https://mlsanity.com/paper/2004.09666/) (2020)
- [Scaling Vision Transformers to Gigapixel Images via Hierarchical Self-Supervised Learning](https://mlsanity.com/paper/2206.02647/) (2022)
- [DTFD-MIL: Double-Tier Feature Distillation Multiple Instance Learning for Histopathology Whole Slide Image Classification](https://mlsanity.com/paper/2203.12081/) (2022)
- [Whole Slide Images based Cancer Survival Prediction using Attention Guided Deep Multiple Instance Learning Networks](https://mlsanity.com/paper/2009.11169/) (2020)
- [Patch-based Convolutional Neural Network for Whole Slide Tissue Image Classification](https://mlsanity.com/paper/1504.07947/) (2015)
- [Optimal Entropy-Transport problems and a new Hellinger-Kantorovich distance between positive measures](https://mlsanity.com/paper/1508.07941/) (2015)
- [Interventional Bag Multi-Instance Learning On Whole-Slide Pathological Images](https://mlsanity.com/paper/2303.06873/) (2023)
- [Morphological Prototyping for Unsupervised Slide Representation Learning in Computational Pathology](https://mlsanity.com/paper/2405.11643/) (2024)
- [Multiple Instance Learning Framework with Masked Hard Instance Mining for Whole Slide Image Classification](https://mlsanity.com/paper/2307.15254/) (2023)
- [Task-specific Fine-tuning via Variational Information Bottleneck for Weakly-supervised Pathology Whole Slide Image Classification](https://mlsanity.com/paper/2303.08446/) (2023)
- [Multimodal Prototyping for cancer survival prediction](https://mlsanity.com/paper/2407.00224/) (2024)
- [Rethinking Semi-Supervised Medical Image Segmentation: A Variance-Reduction Perspective](https://mlsanity.com/paper/2302.01735/) (2023)
- [Mine yOur owN Anatomy: Revisiting Medical Image Segmentation with Extremely Limited Labels](https://mlsanity.com/paper/2209.13476/) (2022)
- [Scalable Optimal Transport Methods in Machine Learning: A Contemporary Survey](https://mlsanity.com/paper/2305.05080/) (2023)
- [PathBench: A comprehensive comparison benchmark for pathology foundation models towards precision oncology](https://mlsanity.com/paper/2505.20202/) (2025)
- [P2OT: Progressive Partial Optimal Transport for Deep Imbalanced Clustering](https://mlsanity.com/paper/2401.09266/) (2024)
- [HMIL: Hierarchical Multi-Instance Learning for Fine-Grained Whole Slide Image Classification](https://mlsanity.com/paper/2411.07660/) (2024)

## Built on by (most cited first, 8 of 8)

- [Supervise Less, See More: Training-free Nuclear Instance Segmentation with Prototype-Guided Prompting](https://mlsanity.com/paper/2511.19953/) (2025)
- [Together, Then Apart: Balancing Alignment and Distinctiveness for Multimodal Survival Analysis](https://mlsanity.com/paper/2511.18089/) (2025)
- [Spatially-Aware Mixture of Experts with Log-Logistic Survival Modeling for Whole-Slide Images](https://mlsanity.com/paper/2511.06266/) (2025)
- [Reflection Pretraining Enables Token-Level Self-Correction in Biological Sequence Models](https://mlsanity.com/paper/2512.20954/) (2025)
- [Bayesian Integration of Nonlinear Incomplete Clinical Data](https://mlsanity.com/paper/2602.01924/) (2026)
- [Region-Graph Optimal Transport Routing for Mixture-of-Experts Whole-Slide Image Classification](https://mlsanity.com/paper/2604.07298/) (2026)
- [Hystar: Hypernetwork-driven Style-adaptive Retrieval via Dynamic SVD Modulation](https://mlsanity.com/paper/2605.10009/) (2026)
- [Semantic-Anchored Evidential Fusion for Domain-Robust Whole-Slide Survival Analysis](https://mlsanity.com/paper/2606.19966/) (2026)

## Abstract (arXiv)

Survival prediction using whole slide images (WSIs) can be formulated as a multiple instance learning (MIL) problem. However, existing MIL methods often fail to explicitly capture pathological heterogeneity within WSIs, both globally -- through long-tailed morphological distributions, and locally through -- tile-level prediction uncertainty. Optimal transport (OT) provides a principled way of modeling such heterogeneity by incorporating marginal distribution constraints. Building on this insight, we propose OTSurv, a novel MIL framework from an optimal transport perspective. Specifically, OTSurv formulates survival predictions as a heterogeneity-aware OT problem with two constraints: (1) global long-tail constraint that models prior morphological distributions to avert both mode collapse and excessive uniformity by regulating transport mass allocation, and (2) local uncertainty-aware constraint that prioritizes high-confidence patches while suppressing noise by progressively raising the total transport mass. We then recast the initial OT problem, augmented by these constraints, into an unbalanced OT formulation that can be solved with an efficient, hardware-friendly matrix scaling algorithm. Empirically, OTSurv sets new state-of-the-art results across six popular benchmarks, achieving an absolute 3.6% improvement in average C-index. In addition, OTSurv achieves statistical significance in log-rank tests and offers high interpretability, making it a powerful tool for survival prediction in digital pathology. Our codes are available at https://github.com/Y-Research-SBU/OTSurv.