Background: Prognostic factors for ambulatory oncology patients have been described, including Eastern Cooperative Oncology Group (ECOG), tumor stage and malnutrition. However, there is no firm evidence on which variables best predict mortality in hospitalized patients receiving active systemic treatment. Our main goal was to develop a predictive model for 90-day mortality upon admission., Methods: Between 2020 and 2022, we prospectively collected data from three sites for cancer patients with hospitalizations. Those with metastatic disease receiving systemic therapy in the 6 months before unplanned admission were eligible to this study. The least absolute shrinkage and selection operator (LASSO) method was used to select the most relevant factors to predict 90-day mortality at admission. A multivariable logistic regression was fitted to create the PROgnostic Score for Hospitalized Cancer Patients (PROMISE) score. The score was developed in a single-center training cohort and externally validated., Findings: Of 1658 hospitalized patients, 1009 met eligibility criteria. Baseline demographics, patient and disease characteristics were similar across cohorts. Lung cancer was the most common tumor type in both cohorts. Factors associated with higher 90-day mortality included worse ECOG, stable/progressive disease, low levels of albumin, increased absolute neutrophil count, and high lactate dehydrogenase. The c-index after bootstrap correction was 0.79 (95% CI, 0.75-0.82) and 0.74 (95% CI, 0.68-0.80) in the training and validation cohorts, respectively. A web tool (https://promise.vhio.net/) was developed to facilitate the clinical deployment of the model., Interpretation: The PROMISE tool demonstrated high performance for identifying metastatic cancer patients who are alive 90 days after an unplanned hospitalization. This will facilitate healthcare providers with rational clinical decisions and care planning after discharge., Funding: Merck S.L.U., Spain., Competing Interests: OM reports writing aid from Merck and Roche, and travel aid from Almirall, Kyowa Kirin, and Recordati. JR reports payment or honoraria for lectures from Merck and LEO Pharma, and travel aid from Adamed and LEO Pharma. DG reports payment or honoraria for lectures from LEO Pharma. RB is currently employed by AstraZeneca. GV reports consulting fees from Reveal Genomics, and payment or honoraria for lectures from MSD, Pierre Fabre, Pfizer, and GSK. SB reports payment or honoraria for lectures from Pfizer, and travel aid from MSD. AH reports grants for research support from Gilead, and payment or honoraria for lectures at the TTCC and THNO congresses. MR reports payment or honoraria for lectures from ROVI. EM reports consulting fees from BMS, MSD, Novartis, Sanofi, Pierre Fabre, Regeneron, Inmunocore, and Roche, payment or honoraria for lectures from BMS, MSD, Novartis, Sanofi, Pierre Fabre, Regeneron, and Inmunocore, and travel aid from MSD and Novartis. AM reports consulting fees from AstraZeneca, BMS, Roche, and MSD, payment or honoraria from AstraZeneca, BMS, Roche, participation as a steering committee member for AstraZeneca, travel aid from AstraZeneca, BMS, and Roche, and participation on the advisory board for AstraZeneca, MSD, and BMS. TM reports grants from MSD, Novocure, QED Therapeutics, Roche, Sanofi-Aventis, Servier, Zymeworks, consulting fees from Ability Pharmaceuticals SL, Arcus Bioscience Inc., AstraZeneca, Basilea Pharma, Baxter, BioLineRX Ltd, Celgene, Eisai, Incyte, Ipsen Bioscience Inc., payment or honoraria from Janssen, Lilly, Esteve, Daïchi, Biontech, Novartis, Jazz Pharmaceuticals, and travel aid from Servier, AstraZeneca, Sanofi, Incyte, Lilly, MSD, and Roche. AO reports consulting fees from AstraZeneca, Clovis Oncology, Corcept Therapeutics, Deciphera Pharmaceuticals, Daiichi Sankyo, Debiopharm International, Eisai, Exelixis, F. Hoffmann-La Roche, Genmab, GSK, ImmunoGen, Itheos, MSD, Mersana Therapeutics, Myriad Genetics, Novocure, OncoXerna Therapeutics Inc., PharmaMar, Regeneron, Sattucklabs, Seagen/Pfizer, Sutro Biopharma, and Zentalis; travel aid from AstraZeneca, PharmaMar, and Roche, and participation on the advisory board for AstraZeneca, Clovis Oncology, Corcept Therapeutics, Deciphera Pharmaceuticals, Daiichi Sankyo, Debiopharm International, Eisai, Exelixis, F. Hoffmann-La Roche, Genmab, GSK, ImmunoGen, Itheos, MSD, Mersana Therapeutics, Myriad Genetics, Novocure, OncoXerna Therapeutics Inc., PharmaMar, Regeneron, Sattucklabs, Seagen/Pfizer, Sutro Biopharma, and Zentalis. CS reports grants from AX'Consulting, AX's Consulting SARL, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Byondis BV, Daiichi Sankyo, Eisai, Exeter Pharma, F. Hoffmann-La Roche Ltd, Genentech, Grupo de Mama Alemán, Galaad, Glaxo, INDITEX, ISSECAM, Innoup, Grupo Internacional de Estudio del Cáncer de Mama (IBCSG), Liriomacrogénicos, MediTech, Consultoría de Estadísticas Médicas, Medseñor, Menarini, Merck Sharp & Dohme, Merus, Milenio, Instituto Holandés del Cáncer (NKI), Novartis, Pfizer, Philips, Pierre Fabre, Pintafarma, Puma, Queen Mary (University of London), Roche Farma, SACE Medhealth SL, Sanofi, Sanofi Aventis, Seagen, Genética de Seattle, Simon Kucher & Partners SL, Solti, Biofarmacéuticos Synthon, and Zymeworks, consulting fees from AstraZeneca, Daiichi Sankyo, Eisai Europe Ltd., Gilead, Novartis, Pharmalex, Pfizer Inc., Philips Health Works, Pierre Fabre, PintPharma, Puma Biotechnology Inc., Roche Farma SA, Seagen International, Solti, Synthon Biopharmaceuticals, and Zymeworks, payment or honoraria for lectures from AstraZeneca, Daiichi Sankyo, Eisai Europe Ltd., Gilead, Novartis, Pharmalex, Pfizer Inc., Philips Health Works, Pierre Fabre, PintPharma, Puma Biotechnology Inc., Roche Farma SA, Seagen International, Solti, Synthon Biopharmaceuticals, Zymeworks, Sociedade Portuguesa de Oncología, travel aid from AstraZeneca, Daiichi Sankyo, Gilead, Lilly, Novartis, Pfizer Inc., Pierre Fabre, PintPharma, Roche Farma SA, Seagen International, Solti, participation on an advisory board for AstraZeneca, Daiichi Sankyo, Gilead, Lilly, Novartis, Pfizer Inc., Pierre Fabre, PintPharma, Roche Farma SA, Seagen, and research funding in the form of third-party medical writing support, furnished by Eleanor Porteous, MSc, of Nucleus Global, an Inizio Company, was provided by F. Hoffmann-La Roche Ltd. EE reports consulting fees from Amgen, Bayer, Cure Teq, AG Hoffmann-La Roche, BMS, Boehringer Ingelheim, Janssen, Lilly, Medscape, Merck Serono, MSD, Novartis, Organon, Pfizer, Pierre Fabre, Repare Therapeutics, RIN Institute, Sanofi, payment or honoraria for lectures from Amgen, Bayer, Cure Teq, AG Hoffmann-La Roche, BMS, Boehringer Ingelheim, Janssen, Lilly, Medscape, Merck Serono, MSD, Novartis, Organon, Pfizer, Pierre Fabre, Repare Therapeutics Inc., RIN Institute Inc., Sanofi, Seagen, Servier and Takeda, travel aid from Amgen, Bayer, Cure Teq, AG Hoffmann-La Roche, BMS, Boehringer Ingelheim, Janssen, Lilly, Medscape, Merck Serono, MSD, Novartis, Organon, Pfizer, Pierre Fabre, Repare Therapeutics Inc., RIN Institute Inc., Sanofi, Seagen, Servier and Takeda, and participation on Advisory Board for Amgen, Bayer, Cure Teq, AG Hoffmann-La Roche, BMS, Boehringer Ingelheim, Janssen, Lilly, Medscape, Merck Serono, MSD, Novartis, Organon, Pfizer, Pierre Fabre, Repare Therapeutics, RIN Institute, Sanofi, Seagen, Servier and Takeda. EF reports consulting fees from AbbVie, Amgen, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Genmab, Gilead, GlaxoSmithKline, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Peptomyc, Pfizer, Regeneron, Sanofi, Takeda, Turning Point, and Daiichi Sankyo; payment or honoraria for lectures from Amgen, AstraZeneca, Bristol Myers Squibb, Daiichi Sankyo, Eli Lilly, F. Hoffmann-La Roche, Genentech, Janssen, Medical Trends, Medscape, Merck Serono, Merck Sharp & Dohme, PeerVoice, Pfizer, Sanofi, Takeda, and Touch Oncology; payment for expert testimony from AstraZeneca, Janssen, and Roche; and is an independent member of the board for Grifols. EG reports grants from Novartis, Roche, Thermo Fisher, AstraZeneca, Taiho, BeiGene, and Janssen; consulting fees from Roche, Ellipses Pharma, Boehringer Ingelheim, Janssen Global Services, Seattle Genetics, Thermo Fisher, MabDiscovery, Anaveon, F-Star Therapeutics, Hengrui, Sanofi, Incyte, Medscape, Pfizer, and Amgen; payment or honoraria for lectures from Merck Sharp & Dohme, Roche, Thermo Fisher, Novartis, and SeaGen; employment for NEXT Oncology; and serves as a principal investigator for Adaptimmune LLC, Affimed GmbH, Amgen SA, Anaveon AG, AstraZeneca AB, Bicycletx Ltd, BioInvent International AB, Biontech SE, Biontech Small Molecules GmbH, Boehringer Ingelheim International GmbH, Catalym GmbH, Cyclacel Biopharmaceuticals, Cytovation AS, Cytomx, F. Hoffmann-La Roche Ltd, F-Star Beta Limited, Genentech Inc, Genmab B.V., Hifibio Therapeutics, Hutchison Medipharma Limited, Icon, Imcheck Therapeutics, Immunocore Ltd, Incyte Corporation, Incyte Europe Sàrl, Janssen-Cilag International NV, Janssen-Cilag SA, Laboratorios Servier SL, Medimmune LLC, Merck & Co., Inc., Merck KGaA, Novartis Farmacéutica S.A., Peptomyc, Pfizer Slu, Relay Therapeutics, Replimmune, Ribon Therapeutics, Ryvu Therapeutics SA, Seattle Genetics Inc., Sotio AS, Sqz Biotechnologies, Symphogen A/S, Taiho Pharma USA Inc., and T-Knife GmbH. JT reports consulting fees from Alentis Therapeutics, AstraZeneca, Aveo Oncology, Boehringer Ingelheim, Cardiff Oncology, CARSgen Therapeutics, Chugai, Daiichi Sankyo, F. Hoffmann-La Roche Ltd, Genentech Inc, hC Bioscience, Ikena Oncology, Immodulon Therapeutics, Inspirna Inc, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Ona Therapeutics, Orion Biotechnology, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Scandion Oncology, Scorpion Therapeutics, Seattle Genetics, Servier, Sotio Biotech, Taiho, Takeda Oncology, and Tolremo Therapeutics; payment or honoraria from Medscape Education, PeerView Institute for Medical Education, and Physicians' Education Resource (PER); and stocks in Oniria Therapeutics, Alentis Therapeutics, Pangaea Oncology, and 1TRIALSP. DP reports grants from Merck; consulting fees from Amgen, Ipsen, and Esteve; payment or honoraria for lectures from Amgen, Novartis, and BMS; and travel aid from Amgen, Merck, Roche, Lilly, Servier, Sanofi, and Ipsen. RD reports grants from Merck, Novartis, Daiichi-Sankyo, GlaxoSmithKline, and AstraZeneca; consulting fees from Roche, Foundation Medicine, and AstraZeneca; payment or honoraria for lectures from Roche, Ipsen, Amgen, Servier, Sanofi, Libbs, Merck Sharp & Dohme, Lilly, AstraZeneca, Janssen, Takeda, Bristol-Myers Squibb, GlaxoSmithKline, and Gilead; and holds stocks in Trialing Health. JC reports consulting fees from Astellas Pharma, AstraZeneca, Bayer, Bristol-Myers Squibb, Exelixis, Ipsen, Johnson & Johnson, MSD Oncology, Novartis (AAA), Pfizer, Sanofi, payment or honoraria for lectures from Astellas Pharma, Bayer, Johnson & Johnson, Sanofi, and support for attending meetings from BMS, Ipsen, Roche, AstraZeneca, and Bayer. Disclosures have been attached in a separate document by each author. More detailed disclosures can be found in the ICMJE forms uploaded. All other authors declare no conflicts of interest., (© 2024 The Author(s).)