Özsoy Mehmet, D'Andrea David, Moschini Marco, Foerster Beat, Abufaraj Mohammad, Mathieu Romain, Briganti Alberto, Karakiewicz Pierre I, Roupret Morgan, Seitz Christian, Czech Anna Katarzyna, Susani Martin, Shariat Shahrokh F
Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna General Hospital, Vienna, Austria; Karl Landsteiner Society, Urology and Andrology, Vienna, Austria.
Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.
Urol Oncol. 2018 Apr;36(4):158.e1-158.e6. doi: 10.1016/j.urolonc.2017.12.003. Epub 2017 Dec 27.
To assess the predictive value of TGP on biochemical recurrence (BCR) and its association with clinicopathological outcomes in a large, multicenter cohort of patients with localized prostate cancer (PCa) treated with radical prostatectomy (RP).
Records of 6,041 patients who were treated with RP between 2000 and 2011 for clinically nonmetastatic PCa were, retrospectively, analyzed from prospectively collected datasets. BCR-free survival rates were assessed using univariable and multivariable cox-regression analyses.
Median patient age was 61 years (interquartile range [IQR]: 57-66) with a median preoperative prostrate specific antigen of 6ng/ml (IQR: 4-9). Overall, 28% of patients had Gleason score (GS) 6, 0.3% GS 6 + TGP, 33% GS 7 (3 + 4), 0.2% GS 7 (3 + 4) + TGP, 22% GS 7 (4 + 3), 0.2% GS 7 (4 + 3) + TGP, 0.1% GS 8 and 0.4% GS 9 or 10. Median follow-up was 45 months (IQR: 31-57). Harboring a TGP was associated with higher rates of positive surgical margins, lymphovascular invasion, extraprostatic extension, and seminal vesicle invasion than their counterparts within the same GS group as well as in the next higher GS group (all P ≤ 0.05). At 5 years post-RP, BCR estimates were 5% for patients with GS 6, 13% for patients with GS 6 + TGP, 6% for patients with GS 7 (3 + 4), 22% for patients with GS 7 (3 + 4) + TGP, 16% for patients with GS 7 (4 + 3), 41% for patients with GS 7 (4 + 3) + TGP, 38% for patients with GS 8 (4 + 4) and 46% for patients with GS 9 or 10. Patients harboring a TGP had higher BCR rates than the patients in the next higher GS group: GS 6 + TGP vs. GS 7 (3 + 4), HR = 1.6, P = 0.02 and GS 7 (3 + 4)+TGP vs. GS 7 (4 + 3), HR = 1.4, P = 0.03. Patients with a TGP in the GS 7 (4 + 3) group had comparable BCR rates as patients with GS = 8 (P = 0.4) and GS 9 to 10 (P = 0.2). On multivariable analysis that adjusted for the effects of preoperative prostrate specific antigen, nodal involvement, positive surgical margin, extraprostatic disease (pT3a), seminal vesicle invasion (pT3b) and different institution, harboring a TGP showed higher risk of developing BCR within the same GS group and comparable risk of developing BCR with the next higher GS group.
Patients with TGP at RP have adverse clinicopathological features when compared to their counterparts in the same and the next higher GS group without TGP. Risk of developing BCR increases with the presence of TGP within the same GS group. This risk seems to be comparable between patients with TGP and their counterparts in the next higher GS group without TGP. Knowledge of TGP in RP specimens is likely to improve risk stratification, patient counseling and follow-up scheduling. Further prospective studies that control significant clinical endpoints such as metastasis and mortality are necessary for more significant predictions.
在接受根治性前列腺切除术(RP)治疗的大量多中心局限性前列腺癌(PCa)患者队列中,评估总基因组图谱(TGP)对生化复发(BCR)的预测价值及其与临床病理结果的关联。
回顾性分析2000年至2011年间因临床非转移性PCa接受RP治疗的6041例患者的记录,这些记录来自前瞻性收集的数据集。使用单变量和多变量cox回归分析评估无BCR生存率。
患者中位年龄为61岁(四分位间距[IQR]:57 - 66),术前前列腺特异性抗原中位值为6ng/ml(IQR:4 - 9)。总体而言,28%的患者Gleason评分(GS)为6,0.3%为GS 6 + TGP,33%为GS 7(3 + 4),0.2%为GS 7(3 + 4)+ TGP,22%为GS 7(4 + 3),0.2%为GS 7(4 + 3)+ TGP,0.1%为GS 8,0.4%为GS 9或10。中位随访时间为45个月(IQR:31 - 57)。与同一GS组以及下一个更高GS组中无TGP的患者相比,存在TGP与手术切缘阳性、淋巴管浸润、前列腺外扩展和精囊浸润的发生率更高相关(所有P≤0.05)。RP术后5年,GS 6患者的BCR估计值为5%,GS 6 + TGP患者为13%,GS 7(3 + 4)患者为6%,GS 7(3 + 4)+ TGP患者为22%,GS 7(4 + 3)患者为16%,GS 7(4 + 3)+ TGP患者为41%,GS 8(4 + 4)患者为38%,GS 9或10患者为46%。存在TGP的患者比下一个更高GS组的患者BCR发生率更高:GS 6 + TGP vs. GS 7(3 + 4),风险比(HR)= 1.6,P = 0.02;GS 7(3 + 4)+ TGP vs. GS 7(4 + 3),HR = 1.4,P = 0.03。GS 7(4 + 3)组中存在TGP的患者与GS = 8(P = 0.4)和GS 9至10(P = 0.2)的患者BCR发生率相当。在对术前前列腺特异性抗原、淋巴结受累、手术切缘阳性、前列腺外疾病(pT3a)、精囊浸润(pT3b)和不同机构的影响进行调整的多变量分析中,存在TGP在同一GS组中显示出发生BCR的风险更高,与下一个更高GS组发生BCR的风险相当。
与同一和下一个更高GS组中无TGP的患者相比,RP时存在TGP的患者具有不良的临床病理特征。在同一GS组中,存在TGP会增加发生BCR的风险。这种风险在存在TGP的患者与下一个更高GS组中无TGP的患者之间似乎相当。了解RP标本中的TGP可能会改善风险分层、患者咨询和随访安排。需要进一步的前瞻性研究来控制转移和死亡率等重要临床终点,以进行更有意义的预测。