Norming U, Tribukait B, Nyman C R, Nilsson B, Wang N
Department of Urology, South Hospital, Stockholm, Sweden.
J Urol. 1992 Nov;148(5):1420-6; discussion 1426-7. doi: 10.1016/s0022-5347(17)36926-4.
In a prospective series of 71 patients with newly detected grade 3, stages Ta and T1 bladder carcinoma tumor characteristics, including the results of deoxyribonucleic acid (DNA) analysis as well as morphological and DNA characteristics of the grossly normal urothelium, were investigated and related to progression-free survival. The mean duration of followup was 57 months, with a minimum of 24 months. Of the 71 patients 24 underwent primary cystectomy, and 47 were conservatively treated with transurethral resection alone, or followed by instillation therapy or irradiation therapy. Of the cystectomy and conservatively treated patients 2 (8%) and 16 (34%), respectively, died of bladder carcinoma. Among the 47 conservatively treated patients tumor progression could not be predicted by the initial characteristics of tumor stage, papillary or nonpapillary growth, tumor multiplicity, tumor size, existence of 1 or multiple aneuploid cell populations, S phase value, carcinoma in situ and atypia or aneuploidy in the mucosal biopsies. Neither was progression predicted by the recurrence rate during year 1 of observation. However, a change to or persistent mucosal aneuploidy and a change to or persistent morphological abnormality of the mucosa during year 1 of observation were predictive for tumor progression (p = 0.001 and 0.045, respectively). When compared in stepwise regression analysis (Cox's proportional hazard model), DNA aneuploidy in the mucosa at 12 months after diagnosis was a highly significant predictor, whereas morphology added no further prognostic information. Therefore, progression is related to gross chromosomal abnormalities of the mucosa. High risk patients can be identified by evaluation of the grossly normal mucosa, which should be done as part of the initial diagnosis and during followup in conservatively treated patients with stages Ta and T1, grade 3 bladder carcinoma.
在一项针对71例新发现的3级Ta期和T1期膀胱癌患者的前瞻性研究中,对肿瘤特征进行了调查,包括脱氧核糖核酸(DNA)分析结果以及大体正常尿路上皮的形态学和DNA特征,并将其与无进展生存期相关联。随访的平均持续时间为57个月,最短为24个月。71例患者中,24例行原发性膀胱切除术,47例仅接受经尿道切除术保守治疗,或随后接受灌注治疗或放射治疗。在膀胱切除术和保守治疗的患者中,分别有2例(8%)和16例(34%)死于膀胱癌。在47例保守治疗的患者中,肿瘤进展无法通过肿瘤分期、乳头状或非乳头状生长、肿瘤多灶性、肿瘤大小、存在一个或多个非整倍体细胞群、S期值、原位癌以及黏膜活检中的异型性或非整倍性等初始特征来预测。观察第1年的复发率也无法预测进展情况。然而,观察第1年期间黏膜出现非整倍性改变或持续非整倍性以及黏膜出现形态学改变或持续形态学异常可预测肿瘤进展(p分别为0.001和0.045)。在逐步回归分析(Cox比例风险模型)中进行比较时,诊断后12个月时黏膜中的DNA非整倍性是一个高度显著的预测指标,而形态学并未增加进一步的预后信息。因此,进展与黏膜的总体染色体异常有关。对于高危患者,可通过评估大体正常的黏膜来识别,这应作为初始诊断的一部分,并在Ta期和T1期3级膀胱癌保守治疗患者的随访期间进行。