PDF(Pubmed)
Abstract：
Accurate prostate cancer (PCa) patient diagnosis and risk assessment are key to ensure the best outcome. Currently, low- and favorable intermediate-risk PCa patients may be offered AS due to the indolent nature of the disease. Nonetheless, deciding between active surveillance and curative-intent treatment remains an intricate task, as a subset of these patients may eventually progress, enduring poorer prognosis. Herein, we sought to construct risk calculators based on cancer biomarkers, enabling more accurate discrimination among patients which may benefit from active interventions.Ki67 immunoscore, GSTP1 and KLF8 promoter methylation levels (me) were assessed in PCa tissues. Study endpoints included overall and biochemical recurrence-free (BCR) survival. Combination with relevant clinicopathological parameters allowed for construction of graphical calculating tools (nomograms).Higher Ki67 index correlated with worse BCR-free survival, whereas higher KLF8me levels were associated with improved overall survival, especially in patients with lower-grade tumors. GSTP1me levels had no prognostic value. Among prognostic models tested, a BCR-risk calculator - ProstARK (including Ki67 and clinicopathologic parameters) - disclosed 79.17% specificity, 66.67% sensitivity, 55% positive predictive value, 86% negative predictive value, and 75.76% accuracy. Similar results were found using an independent PCa biopsy cohort, validating its prognostication ability.Combining clinicopathologic features and Ki67 index into a risk calculator enables easy and accurate implementation of a novel PCa prognostication tool. This nomogram may be useful for a more accurate selection of patients for active surveillance protocols. Nonetheless, validation in a larger, multicentric, set of diagnostic PCa biopsies is mandatory for further confirmation of these results.
摘要：
准确的前列腺癌（PCa）患者诊断和风险评估是确保最佳结果的关键。目前,由于疾病的惰性性质，低和有利的中危PCa患者可能会接受AS治疗。尽管如此，在积极监测和治愈性治疗之间做出决定仍然是一项复杂的任务，这些患者的一部分最终可能会进展，预后较差。在这里，我们试图构建基于癌症生物标志物的风险计算器，能够在患者之间进行更准确的区分，这可能会从积极的干预措施中受益。Ki67免疫核心,在PCa组织中评估GSTP1和KLF8启动子甲基化水平(me)。研究终点包括总体和无生化复发(BCR)存活。结合相关临床病理参数，可以构建图形计算工具（列线图）。较高的Ki67指数与较差的无BCR生存率相关，而较高的KLF8me水平与总生存率的提高有关，尤其是低度肿瘤患者。GSTP1me水平无预后价值。在测试的预后模型中，BCR风险计算器-ProstARK（包括Ki67和临床病理参数）-揭示了79.17％的特异性，灵敏度66.67%，55%的阳性预测值，86%阴性预测值，准确率为75.76%。使用独立的PCa活检队列发现了类似的结果，验证其预测能力。将临床病理特征和Ki67指数结合到风险计算器中，可以轻松准确地实施新型PCa预测工具。此列线图可用于更准确地选择主动监测方案的患者。尽管如此，在一个更大的验证，多中心,为了进一步确认这些结果,必须进行一组诊断性PCa活检.
