Ovesen H, Horn T, Steven K
Department of Urology, Herlev Hospital, University of Copenhagen, Denmark.
J Urol. 1997 May;157(5):1655-9.
We assessed the influence of the histological response to intravesical bacillus Calmette-Guerin (BCG) and the prevalence of p53 nuclear accumulation on the clinical behavior of patients with carcinoma in situ.
Of 60 patients with Bergquist grade 3 carcinoma in situ 13 had primary and 47 had secondary carcinoma in situ. Patients received 6 weekly instillations and nonresponders received an additional 6 instillations at 2-week intervals. No maintenance was administered. Median followup was 48 months. The p53 nuclear accumulation was detected by immunohistochemical analysis with antibody PAb 1801.
The complete histological response rate to BCG therapy was 64%, which decreased to 52% at 4 years. BCG was more effective for treatment of primary than secondary carcinoma in situ (complete response rate 85 versus 57%, respectively). The 45% progression rate was related to the initial histological response occurring in 26% of patients with a complete versus 77% with a partial and no response. Consequently, the progression rate was only 8% for primary versus 57% for secondary carcinoma in situ. Of the patients receiving only 1 course of BCG 40% had progression compared to 62% of those who received 2 courses. Patients in whom both courses failed had a progression rate of 89%. Intravesical BCG converted the p53 nuclear immunoreactivity from positive to negative in 73% of the 26 patients expressing reactivity before treatment, of whom 68% also had a complete response. The progression rate was related to the prevalence of p53 nuclear reactivity after but not before treatment (90% of patients with versus 37% without p53 nuclear accumulation had progression). All 3 complete responders with p53 nuclear reactivity after BCG had progression, which suggests that molecular genetic change may precede histological change. Complete responders without p53 nuclear accumulation after BCG treatment experienced the lowest progression rate (21%).
Our results suggest that patients with a persistent complete histological response and without p53 nuclear accumulation after BCG treatment can be followed conservatively. Cystectomy should be considered in all other patients.
我们评估了膀胱内卡介苗（BCG）组织学反应以及p53核积聚发生率对原位癌患者临床行为的影响。
60例伯格奎斯特3级原位癌患者中，13例为原发性原位癌，47例为继发性原位癌。患者接受每周1次共6次的灌注，无反应者每隔2周再接受6次灌注。不进行维持治疗。中位随访时间为48个月。采用抗体PAb 1801通过免疫组织化学分析检测p53核积聚情况。
BCG治疗的完全组织学反应率为64%，4年后降至52%。BCG治疗原发性原位癌比继发性原位癌更有效（完全缓解率分别为85%和57%）。45%的进展率与初始组织学反应有关，在完全缓解的患者中有26%出现进展，部分缓解和无反应的患者中则有77%出现进展。因此，原发性原位癌的进展率仅为8%，而继发性原位癌为57%。仅接受1个疗程BCG治疗的患者中40%出现进展，接受2个疗程治疗的患者中这一比例为62%。两个疗程均失败的患者进展率为89%。在治疗前p53核免疫反应阳性的26例患者中，73%的患者经膀胱内BCG灌注后p53核免疫反应性由阳性转为阴性，其中68%的患者也获得了完全缓解。进展率与治疗后而非治疗前p53核反应性的发生率有关（有p53核积聚的患者中90%出现进展，无p53核积聚的患者中这一比例为37%）。BCG治疗后有p53核反应性的3例完全缓解患者均出现进展，这表明分子遗传学改变可能先于组织学改变。BCG治疗后无p53核积聚的完全缓解患者进展率最低（21%）。
我们的结果表明，BCG治疗后组织学反应持续完全且无p53核积聚的患者可采取保守随访。所有其他患者均应考虑行膀胱切除术。
