Alkhateeb Sultan S, Neill Mischel, Bar-Moshe Sas, Rhijn Bas Van, Kakiashvili David M, Fleshner Neil, Jewett Michael, Petein Michel, Schulman Claude, Hanna Sally, Bostrom Peter J, Roumeguere Thierry, Shariat Shahrokh F, Rorive Sandrine, Zlotta Alexandre R
Department of Surgical Oncology, Princess Margaret Hospital, University Health Network, Toronto, Canada.
Urol Ann. 2011 Sep;3(3):119-26. doi: 10.4103/0974-7796.84954.
To evaluate the long-term prognostic value of the combination of the EORTC risk calculator and proapoptotic, antiapoptotic, proliferation, and invasiveness molecular markers in predicting the outcome of intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC) treated with intravesical Bacille Calmette-Guérin (BCG) therapy.
This study included 42 patients accrued prospectively presenting with intermediate- to high-risk NMIBC (high-grade T1 tumors or multiple rapidly recurrent tumors refractory to intravesical chemotherapy) treated with transurethral resection (TUR) and BCG. TUR samples were analyzed for the molecular markers p53, p21 waf1/cip, Bcl-2, CyclinD1, and metallothionein 9 (MMP9) using immunohistochemistry. Frequency of positivity, measured as a percentage, was assessed alone or in combination with EORTC risk calculator, for interaction with outcome in terms of recurrence and progression using univariate analysis and Kaplan-Meier survival curves.
Median follow-up was 88 months (mean, 99; range, 14-212 months). The overall recurrence rate was 61.9% and progression rate was 21.4%. In univariate analysis, CyclinD1 and EORTC risk groups were significantly associated with recurrence (P value 0.03 and 0.02, respectively), although none of the markers showed a correlation to progression. In combining EORTC risk groups to markers expression status, high-risk group associated with positive MMP9, Bcl-2, CyclinD1, or p21 was significantly correlated to tumor recurrence (log rank P values <0.001, 0.03, 0.02, and 0.006, respectively) and when associated with positive MMP9 or p21, it was significantly correlated to progression (log rank P values 0.01 and 0.04, respectively).
Molecular markers have a long-term prognostic value when combined with EORTC scoring system and they may be used to improve the predictive accuracy of currently existing scoring system. Larger series are needed to confirm these findings.
评估欧洲癌症研究与治疗组织（EORTC）风险计算器与促凋亡、抗凋亡、增殖和侵袭分子标志物联合应用，在预测接受膀胱内卡介苗（BCG）治疗的中高危非肌层浸润性膀胱癌（NMIBC）预后方面的长期价值。
本研究前瞻性纳入了42例中高危NMIBC患者（高级别T1肿瘤或对膀胱内化疗耐药的多发快速复发肿瘤），接受经尿道切除术（TUR）及BCG治疗。采用免疫组化法分析TUR样本中的分子标志物p53、p21 waf1/cip、Bcl-2、细胞周期蛋白D1（CyclinD1）和基质金属蛋白酶9（MMP9）。以百分比衡量的阳性频率，单独评估或与EORTC风险计算器联合评估，通过单因素分析和Kaplan-Meier生存曲线，分析其与复发和进展结局的相关性。
中位随访时间为88个月（平均99个月；范围14 - 212个月）。总复发率为61.9%，进展率为21.4%。在单因素分析中，CyclinD1和EORTC风险组与复发显著相关（P值分别为0.03和0.02），尽管没有标志物与进展相关。将EORTC风险组与标志物表达状态相结合时，与MMP9、Bcl-2、CyclinD1或p21阳性相关的高危组与肿瘤复发显著相关（对数秩P值分别<0.001、0.03、0.02和0.006），与MMP9或p21阳性相关时，与进展显著相关（对数秩P值分别为0.01和0.04）。
分子标志物与EORTC评分系统联合应用具有长期预后价值，可用于提高现有评分系统的预测准确性。需要更大规模的系列研究来证实这些发现。
