Photodynamic Diagnosis in Non-Muscle-Invasive Bladder Cancer

ObjectiveThis paper reviews the development and clinical validation of photodynamic diagnosis (PDD) of bladder cancer.MethodsThe authors reviewed the literature on the development of PDD, in particular the evidence for the clinical efficacy of hexaminolevulinate PDD in the diagnosis of bladder cancer.ResultsAfter initial work on ultraviolet cystoscopy following oral tetracycline, the focus of PDD research shifted to the use of synthetic porphyrins. First, the prodrug delta-aminolevulinic acid (ALA) was shown to cause a transient but significant accumulation of protoporphyrin IX (PpIX) in malignant or premalignant bladder tissue. Excitation by blue light leads to PpIX fluorescence (red), which distinguishes tumour from normal tissue (blue). Hexaminolevulinate (HAL, Hexvix), an ester of ALA, was then developed and has greater bioavailability and stability than the parent compound. It has been approved for clinical use in the diagnosis of bladder cancer. Clinical studies have shown that HAL PDD detects tumours, including carcinoma in situ (CIS), that are missed by conventional white-light cystoscopy.ConclusionsHAL PDD is a valuable aid to the detection of bladder tumours, including CIS.     

Results of Transurethral Resection Plus Adjuvant Intravesical Chemotherapy for Superficial Bladder Cancer

Background : We analyzed the results of conservative therapy for superficial bladder cancer to determine the risk factors for recurrence and progression.
Methods : Between May 1984 and February 1997, 111 patients with primary superficial bladder cancer were treated by a transurethral resection with or without intravesical instillation of chemotherapy, or for patients with concomitant carcinoma in situ (CIS), bacillus Calmette-Guerin. We examined the relationship between tumor stage, grade, incidence of concomitant CIS and recurrence-free survival according to pathologic findings and the drugs instilled.
Results : The incidence of concomitant CIS in pTI, grade 3 tumors was significantly higher than that in pTa, grade 1 tumors (42% vs. 3%, P= 0.006). The 5-year recurrence-free survival rate of all patients was 73%. There was no significant difference in recurrence-free survival and pathologic stage, tumor grade, presence of concomitant CIS, or drugs used for instillation. However, the recurrence-free survival in patients with 5 tumors was significantly lower than in patients with less than 5 tumors. Of the 111 patients, only 3 patients demonstrated disease progression and underwent a radical cystectomy, while 1 patient with a pTI b, grade 3 tumor developed a tumor in the ureter. No patient died of bladder cancer.
Conclusion : Our results indicate that the prognosis of superficial bladder cancer patients with a high-stage, high-grade (pTI, grade 3) tumor is favorable when treated by a transurethral resection and intravesical instillation. Bacillus Calmette-Guerin therapy is useful to prevent the recurrence of tumors with concomitant CIS.     

Up-Front Intravesical Chemotherapy for Low Stage, Low Grade Recurrent Bladder Cancer

Purpose

We evaluated the ablative and prophylactic potential of short schedule, up-front topical chemotherapy on low stage and grade recurrent bladder tumors.

Materials and Methods

The study design consisted of 4 weekly instillations followed by transurethral resection during week 5. Mitomycin C was administered initially and mitoxantrone was administered following the same schedule if disease recurred during followup.

Results

After up-front mitomycin C, 29 of 42 patients (69 percent) has a complete response with no need for transurethral resection, whereas residual disease was resected in the remaining 13 (31 percent). Disease recurred during followup in 22 of the 42 patients (52.4 percent), who were then treated with up-front mitoxantrone with a complete response in 14 (63.7 percent). Residual disease was resected in 8 patients (36.3 percent) with progression to grade 3 in 2.

Conclusions

Short schedule intravesical chemotherapy can completely ablate small volume recurrent superficial bladder cancer in a relevant number of patients but it is not adequate prophylaxis.     

TUR-BT术后吡柔比星即刻膀胱灌注预防非肌层浸润性膀胱癌复发的疗效观察

目的观察经尿道膀胱肿瘤切除术(TUR-BT)后吡柔比星(THP)即刻膀胱灌注预防非肌层浸润性膀胱癌(NMIBC)复发的临床疗效。方法回顾性分析2000~2009年收治的301例非肌层浸润性膀胱癌行经尿道膀胱肿瘤切除术患者,随机分为治疗组(184例)和对照组(117例),治疗组术后24小时内行即刻膀胱灌注,对照组术后未行24小时内即刻膀胱灌注,随访比较两组患者的复发情况。结果患者术后24小时内行即刻膀胱灌注与肿瘤复发风险相关(HR=2.564,P0.0001),但与肿瘤进展风险无关,治疗组和对照组无复发生存时间有显著的统计学差异(P0.0001)。结论经尿道膀胱肿瘤切除术后24小时内行吡柔比星即刻膀胱灌注是预防非肌层浸润性膀胱癌复发有效的治疗方法。     

The Treatment of Non–Muscle-Invasive Bladder Cancer with Intravesical Chemotherapy and Immunotherapy

ObjectivesTo determine the efficacy, best indications, and regimens of intravesical adjuvant instillations in case of non–muscle-invasive bladder tumours.MethodsThe authors analyse the most significant articles of the literature to draw recommendations.ResultsThe three main factors that appear to determine a patient's ultimate prognosis are tumour size at presentation, the grade, and the prior recurrence rate per year. Bacillus Calmette-Guérin (BCG) has a beneficial effect in preventing progression, especially in patients with pT1G3 disease and carcinoma in situ. It seems to be important to improve the results achieved so that at least maintenance, whatever it is, may occur. The effectiveness of mitomycin C with relation to progression may, in fact, be diluted because of its lack of effective usage. The recommendation seems to indicate one single early mitomycin C postoperative instillation in patients with superficial low- and intermediate-risk tumours.ConclusionsMitomycin C and BCG are effective agents in both preventing recurrence and progression. It is customary to use mitomycin C in the perceived less aggressive lesions and BCG for patients at higher risk.     

Intravesical Chemotherapy and BCG for the Treatment of Bladder Cancer: Evidence and Opinion

ObjectivesReview the chemotherapeutic and immunotherapeutic options for post-resection intravesical treatment of low-risk, intermediate-risk, and high-risk non-muscle-invasive bladder cancer (bCA).Design, Setting, and ParticipantsThe authors conducted a review of the literature on chemotherapy and immunotherapy regimens used to reduce the risk of cancer recurrence and progression after transurethral resection of the bladder (TURB).Results and LimitationsThe choice of post-TURB regimen for intravesical treatment of non-muscle-invasive bCA depends on the risk category of the tumour: Chemotherapy is the treatment of choice for low-risk superficial bladder carcinoma; intermediate-risk disease can be treated with either chemotherapy or immunotherapy with bacillus Calmette-Guérin (BCG); and BCG is now the treatment of choice for high-risk tumours. In all cases, the overall aim of treatment is to prevent recurrence and delay disease progression. There is debate over the optimal treatment regimens, and the options may include sequential treatment with chemotherapy and BCG.ConclusionsIntravesical chemotherapy and BCG are both effective post-TURB treatments for non-muscle-invasive bCA, and the choice of regimen depends on the risk category of the tumour. There may also be a role for sequential instillations of chemotherapy and BCG.     

Experience with Sequential Intravesical Gemcitabine and Docetaxel as Salvage Therapy for Non-Muscle Invasive Bladder Cancer

Patients with high-grade muscle invasive bladder cancer (NMIBC) receive intravesical therapy with bacillus Calmette-Guérin (BCG) as the well-established standard-of-care. However, even with prompt induction of intravesical therapy, approximately 40 % of patients will recur within 2 years. For patients who fail BCG, options include radical cystectomy, repeat BCG therapy, or alternative intravesical salvage therapy. In this review, we will discuss the most recent published evidence on salvage intravesical therapy with an emphasis on a more in-depth report of our therapeutic strategy with sequential gemcitabine and docetaxel intravesical therapy for this treatment-refractory population. In addition, we will provide practical advice on our approach to this challenging patient population including the use of operative staging to aid early identification of treatment failures.     

荧光原位杂交在非肌层浸润行膀胱尿路上皮癌术后随访中的应用

目的:研究多色荧光原位杂交探针(FISH)在非肌层浸润性膀胱尿路上皮癌术后监洲的应用价值,并与尿细胞学检查相比较.方法:应用FISH和尿细胞学检查分析215例非肌层浸润性膀胱尿路上皮癌术后随访尿沉渣标本.FISH探针是用随机引物法标记3、7、17号染色体着丝粒及9p21区带.比较分析两种检查结果.结果:215例中有58例患者病理证实膀胱尿路上皮癌复发.FISH对膀胱尿路上皮癌诊断高于尿脱落细胞学检查(71.4%和26.2 %),并有统计学差异(P<0.05),特异性分别为90%和95%,无统计学差异;阳性预测值分别是95.5%和95.7%,阴性预测值分别为52.9%和34.5%.结论:FISH检查可以作为非肌层浸润性尿路上皮癌术后随访的手段,并且敏感性高于尿细胞学检查.     

密集膀胱灌注对抑制非肌层浸润性膀胱肿瘤术后复发的随机对照研究

目的：观察短期密集疗程膀胱腔内蒽环类药物灌注化疗对抑制非肌层浸润性膀胱肿瘤（nonmuscle invasive bladder cancer,NMIBC）经尿道电切术（TUR）后复发的效果。方法：我院自2006年1月～2008年12月对221例NMIBC患者行TUR术,经随机分为两组,密集疗程组术后执行表柔比星（epirubicin,EPI）40mg／40ml每周1次,连续8次的腔内灌注方案;常规化疗组则在连续8次的密集灌注化疗后续行40mg／40ml每月1次,连续10次的灌注方案。记录患者每3个月1次膀胱镜检查情况至术后24个月或肿瘤复发。结果：共有141例获得完整资料。24个月随访期中;45例（31．9％）肿瘤复发。其中常规化疗组22例（30．1％）,密集化疗组23例（33．2Vo）（p-0．64）。复发时间常规化疗组为（8．73±5．23）个月,密集化疗组为（8．74±4．42）个月（P=0．38）。15例（10．6％）复发肿瘤进展,其中常规化疗组7例（9．6％）,密集疗程组8例（11．8％）（P=0．675）。对141例患者的肿瘤大小,单发多发,初发复发,肿瘤病理类型,以及临床分期方面进行分层研究,密集疗程组与常规化疗组的无肿瘤复发率差异均无统计学意义。结论：TUR术后短期密集葸环类药物膀胱腔内灌注化疗可以获得与常规灌注化疗方案相同的降低NMIBC复发的效果。     

Neoadjuvant Chemotherapy for Invasive Bladder Cancer

Neoadjuvant cisplatin-based combination chemotherapy is an established standard for resectable muscle-invasive bladder cancer, a disease with a pattern of predominantly distant and early recurrences. Pathologic complete remission appears to be an intermediate surrogate for survival when employing combination chemotherapy. Moreover, baseline host and tumor tissue studies may enable the discovery of biomarkers predictive of activity. The neoadjuvant setting also provides a window of opportunity to evaluate novel biologic agents or rational combinations of biologic agents to obtain a signal of biologic activity. The residual tumor after neoadjuvant therapy may be exploited to study the mechanism of action and resistance. Cisplatin-ineligible patients warrant the evaluation of tolerable neoadjuvant regimens. Given that bladder cancer is characterized by initial localized presentation in the vast majority of cases, the paradigm of neoadjuvant therapy may expedite the development of novel systemic agents.     

经尿道膀胱电切术后吡柔比星灌注治疗表浅性膀胱癌临床分析

目的总结膀胱肿瘤电切术（transurethral resection of bladder tumor,TURBt）加吡柔比星（tetrahydnopyrany adriamyrin,THP）灌注治疗表浅性膀胱癌的疗效。方法48例表浅性膀胱癌患者,均行TURBt,术毕用THP40mg＋注射用水40ml行灌注化疗30min,术后每周化疗1次,共8次,然后改为每个月1次,持续1年。结果均顺利完成手术,术中未出现膀胱穿孔、膀胱出血等并发症。48例患者平均随访2.1（0.5~3）年,术后1年内6例在非原来位置复发（12.5%）,再次行TURBt加THP灌注,随访1年无复发。结论TURBt加THP膀胱灌注疗效确切,可降低复发率,是治疗表浅膀胱癌的有效方法。