Early metastatic spread and clonal expansion of individual mutations result in a heterogeneous tumour landscape in metastatic urothelial cancer (mUC). Substantial molecular heterogeneity of common drug targets, such as membranous NECTIN4, FGFR3 mutations, PDL1 or immune phenotypes, has been documented between primary and metastatic tumours. However, translational and clinical studies frequently do not account for such heterogeneity and often investigate primary tumour samples that might not be representative in patients with mUC. We propose this as a potential factor for why many biomarkers for mUC have failed to be integrated into clinical practice. Fresh pre-treatment metastatic biopsies enable the capturing of prevailing tumour biology in real time. The characterization of metastatic tumour samples can improve response prediction to immunotherapy, the anti-NECTIN4 antibody–drug conjugate enfortumab vedotin and the FGFR inhibitor erdafitinib. Routine metastatic biopsy can thus improve the precision of identifying driver druggable alterations, thus improving treatment selection for patients with mUC.
In the USA, Black men are approximately twice as likely to be diagnosed with and to die of prostate cancer than white men. In the UK, despite Black men having vastly different ancestral contexts and health-care systems from Black men in the USA, the lifetime risk of being diagnosed with prostate cancer is two-to-three times higher among Black British men than among white British men and Black British men are twice as likely to die of prostate cancer as white British men. Examination of racial disparities in prostate cancer in the USA and UK highlights systemic, socio-economic and sociocultural factors that might contribute to these differences. Variation by ancestry could affect incidence and tumour genomics. Disparities in incidence might also be affected by screening guidelines and access to and uptake of screening. Disparities in treatment access, continuity of care and outcomes could contribute to survival differences. In both localized and metastatic settings, equal access could diminish the observed disparities in both the USA and the UK. An understanding of behavioural medicine, especially an appreciation of cultural beliefs about illness and treatment, could inform and improve the ways in which health systems can engage with and deliver care to patients in minoritized groups affected by prostate cancer. Methods of promoting equity include targeting systemic barriers including systemic racism, proportional recruitment of patients into clinical trials, diversifying the health-care workforce and facilitating care informed by cultural humility. Actively engaging patients and communities in research and intervention might enable the translation of research into increasingly equitable care for patients with prostate cancer in the UK, the USA and globally.
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