Prognostication is a cornerstone of prostate cancer clinical management. In prostate cancer, imprecise prognostication leads to considerable overtreatment as well as undertreatment, which in turn leads to both avoidable deaths and avoidable side effects. The end goal of this proposal is therefore to develop a new, high-performing prostate cancer prognostic tool that can be implemented in clinical practice and help tailoring the right treatment to the right patient. The ProMort research program is an international, multi-disciplinary project building on extensive prior work, including two case-control studies (ProMort 1 and ProMort 2) within Sweden’s National Prostate Cancer Register. We’ve collected and scanned diagnostic slides from about 1,500 prostate cancer patients who died and 1,500 controls, developed a virtual microscopy system, re-reviewed over 1,000 slides, and established infrastructure for molecular analyses. This proposal aims to use these data to identify and validate novel molecular, histopathological, and clinical prognostic factors, ultimately combining them into a new prognostic tool. ProMort has the following specific aims: 1. To identify molecular factors associated with prostate cancer death in whole-transcriptome RNA profiles, using tumor tissue from diagnostic biopsies of men in ProMort 1 and ProMort 2 2. To identify novel histopathological features associated with prostate cancer death using standard pathological review and artificial intelligence (AI), using scanned images of diagnostic biopsies of men in ProMort 1 and ProMort 2 3. To further develop our recently developed clinical prognostic tool, the Swe-MSKCC nomogram, using molecular and histopathological markers identified in aims 1 and 2, testing potential clinical utility in a new prostate-cancer cohort (ProMort 3)