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Objectives: To perform a systematic review and meta-analysis of the literature to understand the variation in the reporting of neuroendocrine staining and determine the influence of reporting neuroendocrine staining at diagnosis on patient outcomes., Methods: Medical databases were searched to identify studies in which adenocarcinoma specimens were stained with any of the following four neuroendocrine markers: chromogranin A (CgA), neuron-specific enolase (NSE), synaptophysin and CD56. The prevalence of neuroendocrine staining and correlation of the prevalence of neuroendocrine staining to patient outcomes were analysed using a random-effects model. All statistical tests were two-sided., Results: Sixty-two studies spanning 7616 patients were analysed. The pooled prevalence for the most common marker, CgA (41%), was similar to that of NSE (39%) and higher than that of synaptophysin (31%). The prevalence of CgA staining was significantly influenced by reporting criteria, where objective thresholds reduced the variation in prevalence to 26%. No correlation was found between CgA prevalence and tumour grade. Patients positive for CgA staining using objective criteria had more rapid biochemical progression (hazard ratio [HR] 1.98, 95% confidence interval [CI] 1.49 to 2.65) and poorer prostate cancer-specific survival (HR 7.03, 95% CI 2.55 to 19.39) compared to negative patients, even among those with low-risk cancers., Conclusion: Discrepancies in the reported prevalence of neuroendocrine cells in adenocarcinoma are driven by the inconsistent scoring criteria. This study unequivocally demonstrates that when neuroendocrine cell staining is assessed with objective criteria it identifies patients with poor clinical outcomes. Future studies are needed to determine the exact quantifiable thresholds for use in reporting neuroendocrine cell staining to identify patients at higher risk of progression., (© 2021 The Authors BJU International © 2021 BJU International.)

The heterogeneity of prostate cancer is evident at clinical, morphological and molecular levels. To aid clinical decision making, a three-tiered system for risk stratification is used to designate low-, intermediate-, and high-risk of disease progression. Intermediate-risk prostate cancers are the most frequently diagnosed, and even with common diagnostic features, can exhibit vastly different clinical progression. Thus, improved risk stratification methods are needed to better predict patient outcomes. Here, we provide an overview of the improvements in diagnosis/prognosis arising from advances in pathology reporting of prostate cancer, which can improve risk stratification, especially for patients with intermediate-risk disease. This review discusses updates to pathology reporting of morphological growth patterns, and proposes the utility of integrating prognostic biomarkers or innovative imaging techniques to enhance clinical decision-making. To complement clinical studies, experimental approaches using patient-derived tumors have highlighted important cellular and morphological features associated with aggressive disease that may impact treatment response. The intersection of urology, pathology and scientific disciplines is required to work towards a common goal of understanding disease pathogenesis, improving the stratification of patients with intermediate-risk disease and subsequently defining optimal treatment strategies using precision-based approaches., (Copyright © 2021. Published by Elsevier B.V.)