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Yet, current molecular profiling technologies are still confined to centralized laboratory testing, which escalates testing costs, result turnaround time, and patient anxiety. Crucially, there is also a scarcity of purposeful clinical validation studies to rigorously evaluate emerging liquid biopsy technologies from research settings to facilitate clinical translation. Here, we report liquid biopsy biosensor advancements in achieving rapid, accurate, and decentralized molecular profiling of a clinically accredited prostate cancer (PCa) urinary circulating RNA biomarker panel. This biosensor approach, termed \u2018Accelerated non\u2010inVasive bioAnalyte testing And Reporting\u2019 (AVATAR), integrates accelerated isothermal assay chemistry and wireless mobile operation capabilities onto a portable electrochemical readout platform. AVATAR enables easy operational control and result display with a custom mobile app following liquid biopsy specimen collection. Using independent training (\n                    <jats:italic>n<\/jats:italic>\n                    = 124) and validation (\n                    <jats:italic>n<\/jats:italic>\n                    = 114) PCa clinical urinary specimen cohorts, we showed AVATAR achieved superior PCa risk stratification to current clinical PCa testing with area\u2010under\u2010curve values of 0.88 (95% confidence interval: 0.84\u22120.92) and 0.86 (95% confidence interval: 0.83\u22120.89), respectively within 55\u00a0min of assay time. To further accelerate AVATAR for using PCa liquid biopsies as a surrogate for invasive tissue sampling, we designed a tailored multi\u2010year PCa follow\u2010up study with individual patient liquid biopsy specimens showing strong molecular biomarker correlation with comprehensive transcriptomic sequencing of matched tissue specimens (\n                    <jats:italic>n<\/jats:italic>\n                    = 39). By creating this bespoke biosensor technology clinical translation framework, we demonstrated AVATAR for decentralized PCa liquid biopsy molecular profiling to augment clinical precision cancer management planning.\n                  <\/jats:p>","DOI":"10.1002\/advs.202512126","type":"journal-article","created":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T12:40:55Z","timestamp":1769517655000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Rapid Decentralized Prostate Cancer Risk Stratification by Portable Liquid Biopsy Analysis within a Clinical Biosensor Validation Framework"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2652-1985","authenticated-orcid":false,"given":"Kevin M.","family":"Koo","sequence":"first","affiliation":[{"name":"The University of Queensland Centre for Clinical Research (UQCCR)  Brisbane QLD Australia"},{"name":"XING Applied Research &amp; Assay 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