Intravesical instillation therapy with bacillus Calmette-Guérin for superficial bladder cancer: Study of the mechanism of bacillus Calmette-Guérin immunotherapy

AIM: In order to clarify the initial step of the mechanism by which bacillus Calmette-Guérin (BCG) exhibits antitumor activity via the immune response induced in the bladder submucosa after intravesical BCG therapy for human bladder cancer, various cytokines secreted in the urine after BCG instillation were measured. METHODS: After transurethral resection of bladder cancer, a 6-week course of BCG instillation was performed. At the first and sixth weeks' dosings, spontaneously excreted urine was collected before and 4, 8, and 24 h after BCG instillation. The urinary cytokines were determined by Sandwich enzyme-linked immunosorbent assay using monoclonal antibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF), tumor necrosis factor (TNF)-alpha, granulocyte colony-stimulating factor (G-CSF), interleukin (IL)-1beta, IL-8, interferon (IFN)-gamma, and IL-12. RESULTS: After the BCG therapy, various cytokines, such as GM-CSF, TNF-alpha, G-CSF, IL-1beta, IL-8, IFN-gamma, and IL-12 were secreted, comprising the immune response cascade. The mean urinary excretions of GM-CSF and TNF-alpha 4 h after the sixth week's instillation were significantly higher than the pre-instillation levels. There were no significant increases in the urinary IFN-gamma or IL-12 levels between 4 and 24 h after the sixth week's instillation. The TNF-alpha level 4 h after the sixth week's instillation had a strong tendency towards the absence of recurrence, with a mean follow-up of 54.1 months. The Kaplan-Meier curve showed the 2, 5, and 10-year recurrence-free survival rates were 72.4%, 65.8%, and 56.4%, respectively. CONCLUSIONS: We suggested that the urinary levels of TNF-alpha might be essential in antitumor activity after BCG therapy and might play an important role in the prevention of bladder tumor recurrence.     

BDI-1-MT治疗膀胱癌及预防其术后复发的临床观察

目的　通过临床应用膀胱腔内灌注抗人膀胱癌免疫毒素 (BDI- 1-MT) ,观察治疗膀胱癌和预防膀胱癌术后复发的效果及毒副反应。方法　对 18例术后和 5例未手术的膀胱癌病人 ,膀胱腔内灌注BDI- 1-MT 1个疗程以上 ,观察疗效、复发情况及毒副反应。结果　术后 18例随访 6～ 2 0个月未见复发 ,未手术 5例随访 6～ 2 1个月 ,其中 3例显效 ,2例有效。所有病例均无明显毒副反应。结论　膀胱腔内灌注BDI- 1-MT治疗膀胱癌和预防膀胱癌术后复发有良好效果 ,是一种值得推广的新方法。     

IL-2联合吡柔比星膀胱灌注预防膀胱癌复发

目的：探讨生物制剂联合化疗药物膀胱灌注预防膀胱癌术后复发的机制。方法：对比研究白细胞介素2（IL－2）和吡柔比星联合膀胱灌注与单用吡柔比星膀胱灌注前后患者血、尿肿瘤坏死因子（TNF）和血IL－2受体的动态变化。结果：联合膀胱灌注组的TNF和IL－2受体水平显著高于吡柔比星组（P＜0．01）。结论：联合灌注组机体的细胞免疫功能得到更好改善,IL－2增加肿瘤细胞对免疫反应的应答,两者间有免疫促进及协同作用。     

Controversial issues and optimal management of stage T1G3 bladder cancer

The management of T1G3 bladder cancer is controversial. Diagnostic methods, such as bladder mapping or second-look transurethral resection are recommended to assess risk. Bacillus Calmette–Guérin intravesical therapy with a maintenance regimen is recommended for solitary T1G3 tumors. The timing of radical cystectomy for these patients is controversial, but early recurrence during intravesical therapy is an indication for radical cystectomy. Multifocal disease, concomitant carcinoma in situ and disease in the prostatic urethra and bladder neck also suggest aggressive disease and cystectomy should be considered in these patients.     

A clinical trial of neoadjuvant hyperthermic intravesical chemotherapy (HIVEC) for treating intermediate and high-risk non-muscle invasive bladder cancer

Purpose: Ths paper reports a pilot/feasibility trial of neoadjuvant hyperthermic intravesical chemotherapy (HIVEC) prior to transurethral resection of bladder tumour (TURBT) for non-muscle invasive bladder cancer (NMIBC). Materials and methods: A pilot/feasibility clinical trial was performed and 15 patients with intermediate to high-risk NMIBC received HIVEC prior to TURBT. HIVEC consisting of eight weekly instillations of intravesical MMC (80?mg in 50?mL) delivered with the novel Combat BRS® system at a temperature of 43?°C for 60?min. Treatment-related adverse effects were measured and patients were followed for 2 years for disease recurrence. Results: A total of 119 HIVEC treatments occurred. Grade 1 adverse events consisted of irritative bladder symptoms (33%), bladder spasms (27%), pain (27%), haematuria (20%) and urinary tract infection (UTI; 14%). Grade 2 adverse events were bladder calcification (7%) and reduced bladder capacity (7%). No grade 3 or higher toxicity was observed. At TURBT, eight patients (53%) were complete responders (pT0) while seven (47%) were partial responders. With a median follow-up of 29 months, the 3-year cumulative incidence of recurrence was 15%. Conclusions: The Combat BRS® system achieved target bladder temperatures and delivered HIVEC with a favourable side-effect profile. Our pilot trial also provides preliminary evidence of treatment efficacy.