The addition of metastasis-directed radiotherapy (MDRT) to immunotherapy in patients with advanced urothelial carcinoma (aUC) has shown promising results. We report the real-world data from the ARON-2 study (NCT05290038) on the impact of conventional (CRT) or stereotactic body radiotherapy (SBRT) on the outcome of aUC patients receiving pembrolizumab after platinum-based-chemotherapy. Medical records of 837 patients were reviewed from 60 institutions in 20 countries. Two hundred and sixty-two patients (31%) received radiotherapy (cohort A), of whom 193 (23%) received CRT and 69 (8%) received SBRT. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). Univariate and multivariate analyses were used to explore the association of variables of interest with OS and PFS. With a median follow-up of 22.7 months, the median OS was 10.2 months, 6.8 months and 16.0 months in no RT, CRT and SBRT subgroups (p = 0.005), with an 1y-OS rates of 47%, 34% and 61%, respectively (p < 0.001). The 1y-OS rate in the SBRT subgroup were significantly higher for both lower (63%) and upper tract UC (68%), for pure urothelial histology (63%) and variant histologies (58%), and for patients with bone (40%) and lymph-node metastases (61%). Median PFS was 4.8 months, 9.6 months and 5.8 months in the CRT, SBRT and no RT subgroups, respectively (p = 0.060). The 1y-PFS rate was significantly higher (48%) in the SBRT population and was confirmed in all patient subsets. The difference in terms of ORR was in favour of SBRT. Our real-world analysis showed that the use of SBRT/pembrolizumab combination may play a role in a subset of aUC patients to increase disease control and possibly overall survival.

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

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

Centre for Cancer Translational and Clinical Research Institute Newcastle University Newcastle Upon Tyne UK

Clinical Oncology Sociedad de Oncología y Hematología del Cesar Valledupar Colombia

Department of Health Sciences Section of Clinical Pharmacology and Oncology University of Florence Florence Italy

Department of Medical Oncology Azienda Ospedaliera Universitaria Maggiore Della Carità Novara Italy

Department of Medical Oncology Institut d'Investigació Biomèdica Sant Pau Hospital de La Santa Creu 1 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 Urology Saitama Medical Center Saitama Medical University Saitama Japan

Department of Urology University Hospital Bonn Bonn Germany

Division of Medical Oncology Markey Cancer Center University of Kentucky Lexington KY 40536 0293 USA

Division of Medical Oncology National Cancer Centre Singapore Singapore Singapore

Division of Oncology Department of Oncology and Hematology University Hospital of Modena Modena Italy

Genitourinary Medical Oncology Department Fondazione IRCCS Istituto Nazionale Dei Tumori Milan Italy

Interdisciplinary Department of Medicine University of Bari Aldo Moro Bari Italy

Latin American Cooperative Oncology Group LACOG Porto Alegre Brazil

Medical Oncology Department University Hospital La Paz Madrid Spain

Medical Oncology IRCCS Azienda Ospedaliero Universitaria Di Bologna Bologna Italy

Medical Oncology Unit Azienda Ospedaliera Ospedali Riuniti Marche Nord Pesaro Italy

Medical Oncology Unit Azienda Ospedaliero Universitaria Consorziale Policlinico Di Bari Piazza Giulio Cesare 11 70124 Bari Italy

Medical Oncology Unit Hospital Israelita Albert Einstein São Paulo SP Brazil

Medical Oncology Unit Macerata Hospital Macerata Italy

Medical Oncology Unit Ospedale A Murri Fermo Italy

Medical Oncology Unit Presidio Ospedaliero Pugliese Ciaccio Azienda Ospedaliera Universitaria Renato Dulbecco Catanzaro Italy

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

Oncology and Hematology Department Hospital Sírio Libanês Brasília Federal District Brazil

Oncology Institute of Vojvodina Faculty of Medicine University Novi Sad Novi Sad Serbia

Oncology Unit Santa Maria Delle Croci Hospital Department Oncology and Haematology AUSL Romagna Ravenna Italy

Radiation Oncology Unit Hospital Israelita Albert Einstein São Paulo SP Brazil

Radiation Oncology Unit Macerata Hospital Macerata Italy

Territorial Oncology Operative Complex Unit Casa Della Salute di Aprilia ASL Latina Latina Italy

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