Cox models vs. machine learning for survival prediction: Do traditional approaches still hold their ground?

R Rosalba Miceli (3Fondazione IRCCS Istituto Nazionale dei Tumori, Unit of Biostatistics for Clinical Research, Department of Data Science, Milan, Italy) G Gabriele Tine' (Biostatistics for Clinical Research, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy) D Dario Callegaro (Sarcoma Service, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy) S Sandro Pasquali (Molecular Pharmacology, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milano, Italy) S Salvatore Provenzano (Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy) J Jay Wunder (Department of Surgical Oncology, Princess Margaret Cancer Centre and Department of Surgery, Mount Sinai Hospital, Toronto, ON, Canada) P Peter Charles Ferguson (Mt Sinai Hospital, Toronto, ON, Canada) A Anthony Griffin (School of Polymer Science and Engineering) D Dirk C. Strauss (The Royal Marsden NHS Foundation Trust, London, United Kingdom) A Andrew J Hayes (The Royal Marsden NHS Foundation Trust, London, United Kingdom) S Sylvie Bonvalot D Dimitri Tzanis T Toufik Bouhadiba (Institut Curie, Milan, Italy) P Paolo G Casali (Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy) A Alessandro Gronchi (Fahima Dossa, MD, PhD, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA; Chandrajit P. Raut, MD, Department of Surgery, Mass General Brigham, Harvard Medical School, Boston, MA; Andrew J. Wagner, MD, PhD, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA; Robin L. Jones, MD, Sarcoma Unit, The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London, United Kingdom; Rebecca A. Gladdy, MD, PhD, Department of Surgical Oncology, Mount Sinai Hospital and Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada; Abha A. Gupta, MD, Division of Medical Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada; Kenneth Cardona, MD, Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA; David E. Gyorki, MD, Division of Cancer Surgery, Peter MacCallum Cancer Centre, and Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Au...)

Abstract

e13647 Background: Sarculator, a Cox model-based nomogram, has been widely used for survival predictions in patients with extremity soft tissue sarcomas (eSTS), demonstrating user-friendliness and reliability. With growing interest in machine learning (ML), this study investigates whether, given the Sarculator prognostic variables, these more complex approaches offer meaningful improvements. Methods: Data from 3,748 patients with eSTS from four international cohorts were used, including the Sarculator’s development cohort (1,452 patients, Milan, Italy) and the three original external validation cohorts (Toronto, Canada; Villejuif, France; London, UK). Predictions were compared in terms of discrimination (C-index, the higher the better), and calibration (plots; 5- and 10-year Brier score, the lower the better. Four ML models — Extreme Gradient Boosting (XGBoost), Model-Based Boosting (MBoost), Random Survival Forests (RSF), and Optimal Survival Trees (OST)—were benchmarked against Sarculator, all including the same Sarculator covariates. A hybrid SuperLearner, which combined predictions from the Sarculator Cox model and the best-performing ML model, was also evaluated. Results: Sarculator Cox model consistently performed well across the four cohorts (C-index: 0.698–0.775) with reliable calibration and low Brier scores. ML models, particularly XGBoost, demonstrated slightly better calibration but poorer generalizability in external cohorts. MBoost and RSF exhibited calibration-discrimination trade-offs, while OST underperformed compared to all the other models. The SuperLearner, integrating predictions from the Cox and XGBoost models, marginally improved calibration but provided limited additional value compared to the Cox model. Conclusions: Sarculator’s robust performance across development and validation cohorts highlights that traditional Cox models remain clinically valuable. The added complexity of ML approaches does not necessarily result in superior prediction accuracy. Importantly, Cox models retain their interpretability, essential for clinical application, whereas ML models required complex tools for explanation. In the context of clinical-based variables, clinicians might be more likely to prioritize models offering simplicity and reliability over less interpretable, marginally improved alternatives. Model performance across development and validation cohorts. Metric Cox model XGBoost MBoost RSF OST SuperLearner C-index (Development) 0.767 0.806 0.792 0.765 0.755 0.781 C-index (Mean, Validation) 0.745 0.726 0.727 0.667 0.693 0.746 5y Brier Score (Development) 0.478 0.478 0.475 0.523 0.491 0.475 5y Brier Score (Mean, Validation) 0.476 0.434 0.560 0.476 0.464 0.467 10y Brier Score (Development) 0.503 0.497 0.489 0.561 0.519 0.500 10y Brier Score (Mean, Validation) 0.480 0.450 0.510 0.457 0.470 0.470

Article Details

Volume / Issue Vol. 43, Issue 16_suppl
Published June 01, 2025
ISSN 0732-183X
Publisher Lippincott Williams & Wilkins

Journal Info

Journal of Clinical Oncology

Lippincott Williams & Wilkins

ISSN: 0732-183X Health Sciences

Authors (15)

R

Rosalba Miceli

3Fondazione IRCCS Istituto Nazionale dei Tumori, Unit of Biostatistics for Clinical Research, Department of Data Science, Milan, Italy

G

Gabriele Tine'

Biostatistics for Clinical Research, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

D

Dario Callegaro

Sarcoma Service, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

S

Sandro Pasquali

Molecular Pharmacology, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milano, Italy

S

Salvatore Provenzano

Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

J

Jay Wunder

Department of Surgical Oncology, Princess Margaret Cancer Centre and Department of Surgery, Mount Sinai Hospital, Toronto, ON, Canada

P

Peter Charles Ferguson

Mt Sinai Hospital, Toronto, ON, Canada

A

Anthony Griffin

School of Polymer Science and Engineering

D

Dirk C. Strauss

The Royal Marsden NHS Foundation Trust, London, United Kingdom

A

Andrew J Hayes

The Royal Marsden NHS Foundation Trust, London, United Kingdom

S

Sylvie Bonvalot

D

Dimitri Tzanis

T

Toufik Bouhadiba

Institut Curie, Milan, Italy

P

Paolo G Casali

Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milan, Italy

A

Alessandro Gronchi

Fahima Dossa, MD, PhD, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, CA; Chandrajit P. Raut, MD, Department of Surgery, Mass General Brigham, Harvard Medical School, Boston, MA; Andrew J. Wagner, MD, PhD, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA; Robin L. Jones, MD, Sarcoma Unit, The Royal Marsden NHS Foundation Trust and Institute of Cancer Research, London, United Kingdom; Rebecca A. Gladdy, MD, PhD, Department of Surgical Oncology, Mount Sinai Hospital and Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada; Abha A. Gupta, MD, Division of Medical Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada; Kenneth Cardona, MD, Division of Surgical Oncology, Department of Surgery, Winship Cancer Institute, Emory University, Atlanta, GA; David E. Gyorki, MD, Division of Cancer Surgery, Peter MacCallum Cancer Centre, and Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Au...