The Royal Marsden NHS Foundation Trust, London, UK
Institute for Cancer Research, London, UK.
J Med Genet. 2024 Sep 24;61(10):915-926. doi: 10.1136/jmg-2024-109845.
Prostate cancer (PrCa) is a largely heritable and polygenic disease. It is the most common cancer in people with prostates (PwPs) in Europe and the USA, including in PwPs of African descent. In the UK in 2020, 52% of all cancers were diagnosed at stage I or II. The National Health Service (NHS) long-term plan is to increase this to 75% by 2028, to reduce absolute incidence of late-stage disease. In the absence of a UK PrCa screening programme, we should explore how to identify those at increased risk of clinically significant PrCa.Incorporating genomics into the PrCa screening, diagnostic and treatment pathway has huge potential for transforming patient care. Genomics can increase efficiency of PrCa screening by focusing on those with genetic predisposition to cancer-which when combined with risk factors such as age and ethnicity, can be used for risk stratification in risk-based screening (RBS) programmes. The goal of RBS is to facilitate early diagnosis of clinically significant PrCa and reduce overdiagnosis/overtreatment in those unlikely to experience PrCa-related symptoms in their lifetime. Genetic testing can guide PrCa management, by identifying those at risk of lethal PrCa and enabling access to novel targeted therapies.PrCa is curable if diagnosed below stage III when most people do not experience symptoms. RBS using genetic profiling could be key here if we could show better survival outcomes (or reduction in cancer-specific mortality accounting for lead-time bias), in addition to more cost efficiency than age-based screening alone. Furthermore, PrCa outcomes in underserved communities could be optimised if genetic testing was accessible, minimising health disparities.
前列腺癌（PrCa）是一种主要具有遗传性和多基因性的疾病。它是欧洲和美国前列腺患者（PwPs）中最常见的癌症，包括非洲裔的 PwPs。2020 年在英国，52%的癌症在 I 期或 II 期被诊断出。国民保健制度（NHS）的长期计划是到 2028 年将这一比例提高到 75%，以减少晚期疾病的绝对发病率。在英国没有前列腺癌筛查计划的情况下，我们应该探讨如何识别那些患有临床意义重大的前列腺癌风险增加的患者。将基因组学纳入前列腺癌筛查、诊断和治疗途径具有巨大的潜力，可以改变患者的护理方式。基因组学可以通过关注那些具有癌症遗传易感性的患者来提高前列腺癌筛查的效率，当将年龄和种族等危险因素结合起来时，可以用于基于风险的筛查（RBS）计划中的风险分层。RBS 的目标是促进临床意义重大的前列腺癌的早期诊断，并减少那些一生中不太可能经历前列腺癌相关症状的患者的过度诊断/过度治疗。遗传测试可以通过识别那些有致命前列腺癌风险的患者，并使他们能够获得新的靶向治疗，从而指导前列腺癌的管理。如果在大多数人没有症状的 III 期以下诊断出前列腺癌，那么这种癌症是可以治愈的。如果我们能够证明使用遗传特征进行 RBS 除了比单独基于年龄的筛查更具成本效益之外，还能获得更好的生存结果（或减少因导时偏差而导致的癌症特异性死亡率），那么使用遗传特征进行 RBS 可能是关键。此外，如果遗传检测能够普及，那么可以最大限度地减少健康差距，从而优化服务不足社区的前列腺癌治疗效果。
