The ARON-2 study (NCT05290038) aimed to assess the real-world efficacy of pembrolizumab in patients recurred or progressed after platinum-based chemotherapy. This retrospective analysis reports the outcomes of urothelial carcinoma (UC) patients with bone metastases (BM). Medical records of patients with documented metastatic UC treated by pembrolizumab as second-line therapy were reviewed from60 institutions in 20 countries. Patients were assessed for Overall Response Rate (ORR), Progression-Free Survival (PFS), and Overall Survival (OS). Univariate and multivariate analyses were used to explore the association of variables of interest with OS and PFS. 881 patients were included; of them, 263 (30%) presented BM. Median follow-up time was 22.7 months. Patients with BM showed both shorter median OS (5.9 months vs 13.1 months, p < 0.001) and PFS (3.5 months, vs 7.3 months, p < 0.001) compared to patients without BM. Patients who received bone targeted agents (BTAs) showed a significantly longer median OS (8.5 months vs 4.6 months, p = 0.003) and PFS (6.1 months vs 3.2 months, p = 0.003), while no survival benefits were observed among patients who received radiation therapy for BM during pembrolizumab treatment compared to those who did not. In multivariate analysis, performance status, concomitant liver metastases, and the lack of use of BTAs were significantly associated with worse OS and PFS. Bone involvement in UC patients treated with pembrolizumab predicts inferior survival. Poor performance status and liver metastases may further worsen outcomes, while the use of BTAs is associated with improved outcomes.

2nd Propaedeutic Department of Internal Medicine School of Medicine ATTIKON University Hospital National and Kapodistrian University of Athens Athens Greece

Biomedical Center Faculty of Medicine in Pilsen Charles University alejSvobody 76 Pilsen Czech Republic

Chair of Oncology Interdisciplinary Department of Medicine University of Bari Aldo Moro Bari Italy

Clinical Oncology Sociedad de Oncología y Hematología del Cesar Valledupar Colombia

Dana Farber Cancer Institute Harvard Medical School Boston MA USA

Department of Clinical Oncology and Radiotherapy University Hospital Hradec Kralove Hradec Kralove Czech Republic

Department of Genitourinary Medical Oncology and Clinical Pharmacology National Institute of Oncology Budapest Hungary

Department of Medical Oncology Bakirköy Dr SadiKonuk Training and Research Hospital Zuhuratbaba District TevfikSaglam St No 11 Bakirkoy Istanbul Turkey

Department of Medical Oncology Centre Hospitalier de Jolimont Haine Saint Paul La Louvière Belgium

Department of Medical Oncology Hospital Ramón y Cajal Madrid Spain

Department of Medical Oncology Institut d'Investigació Biomèdica Sant Pau Hospital de la Santa Creui Sant Pau Barcelona Spain

Department of Medical Oncology King Hussein Cancer Center Amman Jordan

Department of Medical Oncology MD Anderson Cancer Center Madrid Madrid Spain

Department of Oncology and Radiotherapeutics Faculty of Medicine and University Hospital in Pilsen Charles University Pilsen Czech Republic

Department of Oncology San Camillo Forlanini Hospital Rome Italy

Department of Uro Oncology Maria Sklodowska Curie National Research Institute of Oncology Warsaw Poland

Department of Urology Medical University of Innsbruck Anichstrasse 35 6020 Innsbruck Austria

Department of Urology Saitama Medical Center Saitama Medical University Saitama Japan

Dipartimento oncologico usl sud est toscana area senese Località Campostaggia s n c 53036 Poggibonsi Italy

Division of Medical Oncology A O U Consorziale Policlinico di Bari Bari Italy

Klinik fürUrologie Ratzeburger Allee 160 23538 Lübeck Germany

Medical Oncology 1 Unit Department of Oncology Istituto Oncologico Veneto IOV IRCCS 35128 Padua Italy

Medical Oncology IRCCS Azienda Ospedaliero Universitaria di Bologna Via Albertoni 15 Bologna Italy

Medical Oncology Tawam Hospital Al Ain United Arab Emirates

Medicine and Pharmacy Faculty National Institute of Oncology Medical Oncology Unit Mohamed 5 University Rabat Morocco

National Cancer Centre Singapore Singapore Singapore

Oncology Unit Macerata Hospital via Santa Lucia 2 62100 Macerata Italy

Southampton Experimental Cancer Medicine Centre University of Southampton Southampton UK

University of Colorado Anschutz Medical Campus Aurora CO USA

UOC Oncologia A Policlinico Umberto 1 Sapienza University of Rome Rome Italy

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