Leyh-Bannurah Sami-Ramzi, Abou-Haidar Hiba, Dell'Oglio Paolo, Schiffmann Jonas, Tian Zhe, Heinzer Hans, Huland Hartwig, Graefen Markus, Budäus Lars, Karakiewicz Pierre I
Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Center, Montreal, QC, Canada.
Martini-Clinic, Prostate Cancer Center Hamburg-Eppendorf, Hamburg, Germany.
BJU Int. 2017 May;119(5):692-699. doi: 10.1111/bju.13570. Epub 2016 Aug 5.
To retrospectively assess the rate of high-grade primary Gleason upgrading (HGPGU) to primary Gleason pattern 4 or 5 in a contemporary cohort of patients with D'Amico low-risk prostate cancer including those who fulfilled Prostate Cancer Research International Active Surveillance (PRIAS) criteria, and to develop a tool for HGPGU prediction. HGPGU is a contraindication in most active surveillance (AS) and focal therapy protocols.
In all, 10 616 patients with localised prostate cancer were treated at a high-volume European tertiary care centre from 2010 to 2015 with radical prostatectomy. Analyses were restricted to 1 819 patients with D'Amico low-risk prostate cancer (17.1%) with prostate-specific antigen (PSA) levels of <10.0 ng/mL, cT1c-cT2a and Gleason score ≤6, and were repeated within 772 of the men (7.3%) who fulfilled the PRIAS criteria for AS (PSA level of ≤10 ng/mL, T1c-T2, Gleason score ≤6, PSA density (PSAD) of <0.2 ng/mL , ≤2 positive cores). Uni- and multivariable logistic regression models were fitted, testing predictors of HGPGU. The final logistic regression model was based on the most informative variables.
There was HGPGU in 88 (4.8%) patients with D'Amico low-risk prostate cancer and in 32 (4.1%) of the subgroup who were PRIAS eligible. Multivariable analysis predicting HGPGU for the patients with D'Amico low-risk yielded three independent predictors: age, PSAD, and clinical tumour stage (P = 0.008, P = 0.005 and P = 0.021, respectively). Within the same patients, the model using all vs the most informative variables resulted in area under the curves (AUCs) of 69.2% and 68.3%, respectively. Multivariable analysis of those who were PRIAS eligible, yielded age and number of positive cores as independent predictors of HGPGU (P = 0.002 and P = 0.049, respectively; AUC 64.9%).
The low accuracy (invariably <70%) for HGPGU prediction in both patients with D'Amico low-risk prostate cancer and PRIAS eligibility indicates that these variables have poor predictive ability in contemporary patients. Despite HGPGU being a rare phenomenon, it may have life threatening implications and consequently alternatives such as biomarkers, genetic markers, or imaging modalities at re-biopsy are needed.
回顾性评估当代一组达米科低危前列腺癌患者（包括符合国际前列腺癌研究组织主动监测[PRIAS]标准的患者）中高级别原发性格里森分级升级（HGPGU）至原发性格里森模式4或5的发生率，并开发一种HGPGU预测工具。HGPGU在大多数主动监测（AS）和聚焦治疗方案中是禁忌证。
2010年至2015年，共有10616例局限性前列腺癌患者在一家大型欧洲三级医疗中心接受了根治性前列腺切除术。分析仅限于1819例达米科低危前列腺癌患者（17.1%），其前列腺特异性抗原（PSA）水平<10.0 ng/mL，cT1c - cT2a且格里森评分≤6，并在符合PRIAS主动监测标准（PSA水平≤10 ng/mL，T1c - T2，格里森评分≤6，PSA密度[PSAD]<0.2 ng/mL，≤2个阳性核心）的772例男性患者（7.3%）中重复进行。拟合单变量和多变量逻辑回归模型，测试HGPGU的预测因素。最终的逻辑回归模型基于最具信息量的变量。
1819例达米科低危前列腺癌患者中有88例（4.8%）发生HGPGU，在符合PRIAS标准的亚组中有32例（4.1%）发生HGPGU。对达米科低危患者预测HGPGU的多变量分析产生了三个独立预测因素：年龄、PSAD和临床肿瘤分期（分别为P = 0.008、P = 0.005和P = 0.021）。在同一组患者中，使用所有变量与最具信息量变量的模型的曲线下面积（AUC）分别为69.2%和68.3%。对符合PRIAS标准的患者进行多变量分析，得出年龄和阳性核心数量是HGPGU的独立预测因素（分别为P = 0.002和P = 0.049；AUC为64.9%）。
达米科低危前列腺癌患者和符合PRIAS标准患者中HGPGU预测的低准确性（始终<70%）表明这些变量在当代患者中的预测能力较差。尽管HGPGU是一种罕见现象，但它可能具有危及生命的影响，因此需要诸如重新活检时的生物标志物、基因标志物或成像方式等替代方法。
