Tehran University of Medical Sciences Iranian Journal of Microbiology 2008-3289 18 4 2026 08 04 448 459 Fatemeh Khatami Urology Research Center, Tehran University of Medical Sciences, Tehran, Iran Abdolreza Mohammadi Urology Research Center, Tehran University of Medical Sciences, Tehran, Iran Kayhan Azadmanesh Department of Molecular Virology, Pasteur Institute of Iran, Tehran, Iran Roham Deyhimfar Urology Research Center, Tehran University of Medical Sciences, Tehran, Iran Helia Azodian Ghajar Urology Research Center, Tehran University of Medical Sciences, Tehran, Iran Parsa Nikoofar Department of Urology, Thunder Bay Regional Health Research Institute, Thunder Bay, Ontario, Canada Seyed Mohammad Kazem Aghamir Urology Research Center, Tehran University of Medical Sciences, Tehran, Iran 2026 04 05 2026 07 03 Background and Objectives: Bladder cancer (BCa) is the most prevalent malignancy of the urinary tract and is often diagnosed at a late stage. Recurrence remains a major challenge for current treatment strategies. Over the past decade, the antitumor potential of oncolytic viruses (OVs) has been increasingly recognized, with several studies evaluating their safety and efficacy in BCa treatment. In this systematic review, we present clinical trials and animal studies to comprehensively evaluate the safety and therapeutic efficiency of various OVs in BCa. Materials and Methods: After receiving the PROSPERO registration code, four electronic databases PubMed, Web of Science, Scopus, and Embase, were systematically searched to identify studies evaluating the safety and treatment potential of OVs in BCa. Two reviewers independently conducted the screening process, and data from clinical trials and animal studies were systematically extracted into Excel for subsequent synthesis and reporting. All steps of this systematic review adhered to the guidelines outlined in the Cochrane Handbook for Systematic Reviews of Interventions, upholding high standards of methodological rigor and transparency. Results: The initial search strategy yielded 1,061 records. After removing duplicates, 809 articles were screened for relevance. Following the exclusion of 761 studies, 48 were deemed eligible for data extraction, comprising 17 clinical trials and 29 animal studies. Various oncolytic viruses were investigated, either as monotherapies or in combination with other agents, including Vaccinia virus, Adenovirus, Oncolytic adenovirus ONYX, Coxsackievirus A21 (CVA21), oncolytic CVA21 (V937), attenuated measles virus (MV-NIS virus), recombinant adenovirus (rAd), and a serotype 5 adenovirus engineered to express GM-CSF. All studies reported their most effective doses administered within safe parameters. Conclusion: The common virus was the non-replicative recombinant adenovirus serotype 5 (Ad5), which encodes human interferon alfa-2b (IFNα2b) a cytokine with anti-tumor properties. It is administered via intravesical instillation and has received FDA approval. https://ijm.tums.ac.ir/index.php/ijm/article/view/6122 https://ijm.tums.ac.ir/index.php/ijm/article/download/6122/1905