Shariat Shahrokh F, Karakiewicz Pierre I, Ashfaq Raheela, Lerner Seth P, Palapattu Ganesh S, Cote Richard J, Sagalowsky Arthur I, Lotan Yair
Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9110, USA.
Cancer. 2008 Jan 15;112(2):315-25. doi: 10.1002/cncr.23162.
Tested was whether the assessment of 5 established bladder cancer biomarkers (p53, pRB, p21, p27, and cyclin E1) could improve the ability to predict disease recurrence and cancer-specific survival after radical cystectomy in patients with pTa-3N0M0 urothelial carcinoma of the bladder (UCB).
The study comprised 191 patients with pTa-3N0M0 UCB treated with radical cystectomy and bilateral lymphadenectomy (median follow-up, 3.1 years). Biomarker expression was assayed on serial tissue microarray slides using quantitative immunohistochemistry using advanced cell imaging and color detection software. Predictive accuracy was quantified using the concordance index and 200-bootstrap resamples were used to reduce overfit bias. Bootstrap-adjusted predictive accuracy estimates were compared using the Mantel-Haenszel test.
UCB recurred in 36 (18.8%) patients and 30 (15.7%) died of bladder cancer; 157 (82.2%) patients had altered expression of at least 1 biomarker. In univariate analyses the number of altered biomarkers had the highest predictive accuracy for both disease recurrence (76.8%, P< .001) and cancer-specific mortality (78.3%, P< .001). Addition of the number of altered biomarkers increased the predictive accuracy of nomograms based on the TNM staging system for disease recurrence and cancer-specific mortality by 10.9% (83.4% vs 72.5%, P< .001) and 8.6% (86.9% vs 78.3, P< .001), respectively.
Assessment of the number of altered biomarkers in the cystectomy specimen improves the prediction of bladder cancer recurrence and survival in patients with pTa-3N0M0 disease. Prospective evaluation of alteration in these biomarkers can help identify patients who would benefit from adjuvant treatment after radical cystectomy.
本研究旨在检测5种已确立的膀胱癌生物标志物（p53、pRB、p21、p27和细胞周期蛋白E1）的评估是否能够提高预测Ta-3N0M0期膀胱尿路上皮癌（UCB）患者根治性膀胱切除术后疾病复发及癌症特异性生存的能力。
本研究纳入了191例接受根治性膀胱切除术及双侧淋巴结清扫术的Ta-3N0M0期UCB患者（中位随访时间为3.1年）。使用先进的细胞成像和颜色检测软件，通过定量免疫组织化学在连续组织微阵列玻片上检测生物标志物表达。使用一致性指数对预测准确性进行量化，并采用200次自抽样重采样以减少过度拟合偏差。使用Mantel-Haenszel检验比较自抽样调整后的预测准确性估计值。
36例（18.8%）患者出现UCB复发，30例（15.7%）死于膀胱癌；157例（82.2%）患者至少有1种生物标志物表达改变。在单变量分析中，生物标志物改变的数量对疾病复发（76.8%，P<0.001）和癌症特异性死亡率（78.3%，P<0.001）具有最高的预测准确性。基于TNM分期系统的列线图对疾病复发和癌症特异性死亡率的预测准确性，分别通过增加生物标志物改变的数量提高了10.9%（83.4%对72.5%，P<0.001）和8.6%（86.9%对78.3，P<0.001）。
对根治性膀胱切除标本中生物标志物改变数量的评估可改善Ta-3N0M0期疾病患者膀胱癌复发和生存的预测。对这些生物标志物改变进行前瞻性评估有助于识别根治性膀胱切除术后将从辅助治疗中获益的患者。
