2016年8月3日 讯 /生物谷BIOON/ --近日，来自剑桥大学等处的研究人员在国际杂志PLoS Medicine上发表文章表示，诊断为前列腺癌的男性患者应当被准确估计其因前列腺癌死亡的风险以及合适的疗法进行疾病的治疗。
前列腺癌是一种影响男性健康最常见的癌症，当病灶主要集中于前列腺上患者就会被诊断为前列腺癌，同时该疾病进展及死亡的风险存在着非常大的可变性，因此提供一种准确的方法来评估个体因前列腺癌死亡的风险对于制定合理的疗法非常重要，而给患者提供的合适疗法包括从进行手术到定期观察管理，同时还应当给予患者一定的建议和支持。
基于对来自1万多名英国前列腺癌男性患者数据的分析，研究者Gnanapragasam及其同事就开发出了一种新型策略，这种策略中，研究者根据简单通用的临床测量方法，比如前列腺特异抗原（PSA）水平、疾病阶段及肿瘤级别等因素，将患者分为具有因前列腺癌死亡风险不同水平的5个层次；研究人员对两大前列腺癌群体进行单独分析，结果表明，相比当前大多数国家和国际认可的指导方针中的3级危险分层系统而言，这种新型策略就可以更好地预测个体因前列腺癌死亡的风险。
研究者指出，由于本文研究受限于癌症登记记录及相对较短的随访持续时间（中值6.9年），因此未来还需要进行额外独立的群组研究来进一步证实。最后在一篇观点文章中，研究者Sigrid V. Carlsson等人讨论了前列腺癌的精确风险评估对于医生和患者进行决策制定指导的重要性。（生物谷Bioon.com）
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doi:10.1371/journal.pmed.1002063
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Improving Clinical Risk Stratification at Diagnosis in Primary Prostate Cancer: A Prognostic Modelling Study
Vincent J. Gnanapragasam , Artitaya Lophatananon , Karen A. Wright, Kenneth R. Muir, Anna Gavin, David C. Greenberg
Introduction Over 80% of the nearly 1 million men diagnosed with prostate cancer annually worldwide present with localised or locally advanced non-metastatic disease. Risk stratification is the cornerstone for clinical decision making and treatment selection for these men. The most widely applied stratification systems use presenting prostate-specific antigen (PSA) concentration, biopsy Gleason grade, and clinical stage to classify patients as low, intermediate, or high risk. There is, however, significant heterogeneity in outcomes within these standard groupings. The International Society of Urological Pathology (ISUP) has recently adopted a prognosis-based pathological classification that has yet to be included within a risk stratification system. Here we developed and tested a new stratification system based on the number of individual risk factors and incorporating the new ISUP prognostic score. Methods and Findings Diagnostic clinicopathological data from 10,139 men with non-metastatic prostate cancer were available for this study from the Public Health England National Cancer Registration Service Eastern Office. This cohort was divided into a training set (n = 6,026; 1,557 total deaths, with 462 from prostate cancer) and a testing set (n = 4,113; 1,053 total deaths, with 327 from prostate cancer). The median follow-up was 6.9 y, and the primary outcome measure was prostate-cancer-specific mortality (PCSM). An external validation cohort (n = 1,706) was also used. Patients were first categorised as low, intermediate, or high risk using the current three-stratum stratification system endorsed by the National Institute for Health and Care Excellence (NICE) guidelines. The variables used to define the groups (PSA concentration, Gleason grading, and clinical stage) were then used to sub-stratify within each risk category by testing the individual and then combined number of risk factors. In addition, we incorporated the new ISUP prognostic score as a discriminator. Using this approach, a new five-stratum risk stratification system was produced, and its prognostic power was compared against the current system, with PCSM as the outcome. The results were analysed using a Cox hazards model, the log-rank test, Kaplan-Meier curves, competing-risks regression, and concordance indices. In the training set, the new risk stratification system identified distinct subgroups with different risks of PCSM in pair-wise comparison (p < 0.0001). Specifically, the new classification identified a very low-risk group (Group 1), a subgroup of intermediate-risk cancers with a low PCSM risk (Group 2, hazard ratio [HR] 1.62 [95% CI 0.96–2.75]), and a subgroup of intermediate-risk cancers with an increased PCSM risk (Group 3, HR 3.35 [95% CI 2.04–5.49]) (p < 0.0001). High-risk cancers were also sub-classified by the new system into subgroups with lower and higher PCSM risk: Group 4 (HR 5.03 [95% CI 3.25–7.80]) and Group 5 (HR 17.28 [95% CI 11.2–26.67]) (p < 0.0001), respectively. These results were recapitulated in the testing set and remained robust after inclusion of competing risks. In comparison to the current risk stratification system, the new system demonstrated improved prognostic performance, with a concordance index of 0.75 (95% CI 0.72–0.77) versus 0.69 (95% CI 0.66–0.71) (p < 0.0001). In an external cohort, the new system achieved a concordance index of 0.79 (95% CI 0.75–0.84) for predicting PCSM versus 0.66 (95% CI 0.63–0.69) (p < 0.0001) for the current NICE risk stratification system. The main limitations of the study were that it was registry based and that follow-up was relatively short. Conclusions A novel and simple five-stratum risk stratification system outperforms the standard three-stratum risk stratification system in predicting the risk of PCSM at diagnosis in men with primary non-metastatic prostate cancer, even when accounting for competing risks. This model also allows delineation of new clinically relevant subgroups of men who might potentially receive more appropriate therapy for their disease. Future research will seek to validate our results in external datasets and will explore the value of including additional variables in the system in order in improve prognostic performance.
