Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas 10065, USA.
J Urol. 2010 Jan;183(1):68-75. doi: 10.1016/j.juro.2009.08.115.
We tested whether the combination of 4 established cell cycle regulators (p53, pRB, p21 and p27) could improve the ability to predict clinical outcomes in a large multi-institutional collaboration of patients with pT3-4N0 or pTany Npositive urothelial carcinoma of the bladder. We also assessed whether the combination of molecular markers is superior to any individual biomarker.
The study comprised 692 patients with pT3-4N0 or pTany Npositive urothelial carcinoma of the bladder treated with radical cystectomy and bilateral lymphadenectomy (median followup 5.3 years). Scoring was performed using advanced cell imaging and color detection software. The base model incorporated patient age, gender, stage, grade, lymphovascular invasion, number of lymph nodes removed, number of positive lymph nodes, concomitant carcinoma in situ and adjuvant chemotherapy.
Individual molecular markers did not improve the predictive accuracy for disease recurrence and cancer specific mortality. Combination of all 4 molecular markers into number of altered molecular markers resulted in significantly higher predictive accuracy than any single biomarker (p <0.001). Moreover addition of number of altered molecular markers to the base model significantly improved the predictive accuracy for disease recurrence (3.9%, p <0.001) and cancer specific mortality (4.3%, p <0.001). Addition of number of altered molecular markers retained statistical significance for improving the prediction of clinical outcomes in the subgroup of patients with pT3N0 (280), pT4N0 (83) and pTany Npositive (329) disease (p <0.001).
While the status of individual molecular markers does not add sufficient value to outcome prediction in patients with advanced urothelial carcinoma of the bladder, combinations of molecular markers may improve molecular staging, prognostication and possibly prediction of response to therapy.
我们检测了 4 种已确立的细胞周期调控因子（p53、pRB、p21 和 p27）联合应用是否可以提高在包含 692 名患者的大型多机构合作中预测临床结局的能力，这些患者患有 pT3-4N0 或 pTanyN+膀胱癌。我们还评估了分子标志物的联合应用是否优于任何单一生物标志物。
该研究纳入了 692 名接受根治性膀胱切除术和双侧淋巴结清扫术（中位随访 5.3 年）治疗的 pT3-4N0 或 pTanyN+膀胱癌患者。评分使用先进的细胞成像和颜色检测软件进行。基础模型纳入了患者年龄、性别、分期、分级、脉管侵犯、切除的淋巴结数量、阳性淋巴结数量、同时存在原位癌和辅助化疗等因素。
单个分子标志物并未提高疾病复发和癌症特异性死亡率的预测准确性。将这 4 个分子标志物组合为改变的分子标志物数量，可显著提高预测准确性（p＜0.001）。此外，将改变的分子标志物数量添加到基础模型中，可显著提高疾病复发（3.9%，p＜0.001）和癌症特异性死亡率（4.3%，p＜0.001）的预测准确性。改变的分子标志物数量的添加对于预测 pT3N0（280 例）、pT4N0（83 例）和 pTanyN+（329 例）疾病患者的临床结局仍然具有统计学意义（p＜0.001）。
虽然单个分子标志物的状态在晚期膀胱癌患者的预后预测中没有增加足够的价值，但分子标志物的组合可能会改善分子分期、预后，并可能预测对治疗的反应。
