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PubMed1998

Low-dose BCG instillations in the treatment of stage T1 grade 3 bladder tumours: recurrence, progression and success.

The aim of this retrospective study was to evaluate the effects and results of low-dose bacillus Calmette-Guérin (BCG) therapy on a selective high-risk population of stage T1, grade 3 (G3) bladder tumours. Recurrence and progression were also analysed. Thirty-five consecutive patients presenting with T1 G3 tumours were treated with intravesical BCG. All patients underwent complete transurethral tumour resection. A course of BCG 75 mg Pasteur strain was begun 4 weeks after the first resection of the diagnosed tumour and continued for a 6-week period. At the end of treatment, a complete urological evaluation was routinely carried out: urine cytology test, cystoscopy with bladder biopsies randomly performed, and any recurrences were resected. In cases of abnormal cytology and/or recurrence an additional course of BCG was initiated, followed by the same tests. Follow-up examination and cystoscopy or fibroscopy were conducted every 3 months for 1 year, semiannually and annually thereafter. Median follow-up was 45 months (range 10-120); 7 patients (20%) did not respond to BCG instillations. Of these patients, 5 underwent cystectomy and in 2 patients the bladder was left in place in spite of recurrence because of age (+80 years). Twenty-eight patients (80%) responded positively, 24 after one single course of BCG, and 4 patients after two courses. During follow-up, recurrence was observed in 8 cases: stage T1 G3 in 4 patients, T1 CIS (carcinoma in situ) in 2 patients, Ta G2 and Ta G1 in 2 patients. Three of these patients were treated by cystectomy and the remaining patients with transurethral resection alone or combined with additional courses of BCG. Overall, 25 patients (71%) were considered free of tumour occurrence after low-dose BCG therapy. Ten patients underwent cystectomy (29%) or remained in occurrence and 2 patients died of the disease. These results can be closely compared to the results of other trials conducted on stage T1 G3 and BCG treatment, using a different dosage and BCG protocol therapy. BCG is an effective prophylactic and therapeutic agent for T1 G3 carcinoma of the bladder responders. The identification of these responders before beginning instillations still remains a challenge.

Administration, Intravesical↗

PubMed1999

Nephrogenic adenoma: A rare bladder tumor in children.

OBJECTIVE: Nephrogenic adenomas of the urinary bladder are rare benign tumors in children. The purpose of our study was to obtain information about the sex distribution, presenting symptoms, intravesical locations, therapy and recurrence rates in pediatric nephrogenic adenomas. PATIENTS AND METHODS: The records of 3 children with nephrogenic adenoma of the urinary bladder diagnosed between 1990 and 1997 were reviewed to evaluate the initial symptomatology, diagnostic examinations and findings, therapeutic procedures and clinical outcome and recurrence rates. Furthermore our data are compared to the findings of all children reported in the literature. RESULTS: Including the 3 cases reported by us, the data on 18 children with nephrogenic adenoma of the bladder could be analyzed. There was a significant predominance of girls compared to boys (5:1); the medical history in all cases was remarkable for previous bladder surgery 3 months to 7 years prior to tumor diagnosis. Most children presented with unspecific symptoms of gross hematuria, dysuria and bladder instability and in all cases the final diagnosis was established after cystoscopy and histopathologic review of a tumor biopsy specimen. Therapy consisted of transurethral resection in 15 cases, partial cystectomy and open excision in 2 and 1 case, respectively. Tumor recurrence developed in 80% of the children with a latency period of 4 years. CONCLUSIONS: Nephrogenic adenomas represent an epithelial response of the urothelium to chronic inflammation or previous trauma resulting in urothelial metaplasia and the development of papillary lesions. Current treatment of choice consists of transurethral resection and fulguration of the base of the tumor and periodic cystoscopy.

Adenoma↗

PubMed2000

Transurethral resection and sequential chemo-immunoprophylaxis in primary T1G3 bladder cancer.

OBJECTIVES: T1G3 superficial bladder cancer is considered to be at high risk for progression, and in some institutions early cystectomy is advocated. Other authors and personal experience suggest that conservative treatment, such as TURBT followed by intravesical prophylaxis, may be adequate in the majority of cases. The purpose of the present phase II study was to assess the tolerability and efficacy of sequential intravesical administration of a chemotherapeutic agent, epirubicin, followed by BCG, after TURBT. MATERIALS AND METHODS: 81 patients with primary T1G3 superficial bladder cancer, without evidence of Tis or upper tract tumor, underwent TURBT and intravesical prophylaxis with weekly epirubicin 50 mg for 8 weeks followed by weekly BCG Connaught 120 mg for 6 weeks. A control cystoscopy with bladder mapping and/or TUR of suspicious areas was performed at 15-17 weeks. Then patients were followed-up with 3-month urinary cytology and cystoscopy. RESULTS: The sequential chemo-immunoprophylaxis was generally well tolerated. After a mean follow-up of 48 months recurrent tumors were found in 19 patients (23.4%) and progressive disease in 6 cases (7.4%). Of 6 progressions, 4 patients died (5%) of the disease. CONCLUSION: Sequential chemo-immunoprophylaxis with epirubicin followed by BCG is well tolerated and seems to be efficacious in primary T1G3 bladder cancer. The recurrence progression and disease-specific mortality rates were acceptable so that this study seems to confirm previous data which show that TURBT and intravesical prophylaxis are appropriate treatment for the majority T1G3 tumors.

Administration, Intravesical↗

PubMed2001

Incidence of Helicobacter pylori in patients with interstitial cystitis.

OBJECTIVE: Chronic gastritis has compelling similarities to interstitial cystitis (IC). It is characterised by chronic pain in a tubular organ. Histologically, epithelial damage, inflammatory response in the lamina propria and epithelial ulcerations are seen. An infective cause was rarely considered until the emergence of Helicobacter pylori over the past 15 years. We have had experience of patients with bladder pain and irritability reporting improvement with antihistamines. It has also been reported that IC symptoms improved dramatically after treatment for H. pylori infection. Previous studies have determined the incidence of H. pylori antibodies in women with IC but we examined bladder material histologically and performed the Campylobacter-like organism (CLO) test on the biopsy specimens. MATERIALS AND METHODS: A prospective controlled study was performed. Patients with urinary symptoms fulfilling the National Institute of Diabetes and Digestive and Kidney Diseases criteria for IC underwent GA cystoscopy at which the macroscopic appearance of the bladder was noted and biopsies were taken. The biopsy material underwent histological examination and CLO test. Control patients who were undergoing cystoscopy for reasons other than investigation of IC also had biopsy taken and the CLO test was performed on these specimens. RESULTS: Five of 15 patients with symptoms and signs of IC had a positive CLO test. Three of 15 patients of the control group had a positive CLO test. With the 2-sided chi(2) test there was no statistical difference between the 2 groups. CONCLUSION: Our small prospective control study does not support the hypothesis that H. pylori is an important component in the pathogenesis of interstitial cystitis.

Cystitis, Interstitial↗

PubMed2001

The use of valrubicin for the chemoresection of superficial bladder cancer -- a marker lesion study.

OBJECTIVES: To assess the effect and tolerance of a 6-week course of intravesical valrubicin on a tumour intentionally left in the bladder (marker lesion) following incomplete transurethral resection of the bladder (TURBT). PATIENTS AND METHODS: In a prospective phase II study, 40 patients with refractory superficial transitional cell carcinoma (TCC), with or without carcinoma in situ, underwent TURBT at which a tumour <1 cm in diameter was deliberately left in the bladder. They were then treated with six instillations of 800 mg valrubicin at weekly intervals. Patients were assessed three months after the initial TURBT by cystoscopy and biopsy. Patients remaining clear of disease underwent repeat cystoscopies at 3-monthly intervals until recurrence or for up 2 years. RESULTS: 21/39 (54%) of patients were found to be clinically clear of disease upon cystoscopic examination at 3 months. 18/39 (46%) of patients were considered histologically clear of bladder disease. The current estimate of the mean time to recurrence is 248 days. CONCLUSIONS: A 6-week course of intravesical valrubicin has proved effective in ablating a marker tumour left in the bladder after incomplete TURBT and in preventing or delaying recurrence of further tumours in a group of patients with previously treated superficial TCC.

Administration, Intravesical↗

PubMed2000

BTA quantitative assay and NMP22 testing compared with urine cytology in the detection of transitional cell carcinoma of the bladder.

PURPOSE: Both BTA TRAK and NMP22 urine concentrations have shown a sensitivity superior to urine cytology in the detection of bladder cancer. We compared these tumor markers with urine cytology performed on 3 consecutive samples and evaluated by an expert cytopathologist. PATIENTS AND METHODS: The investigations were conducted on 94 patients undergoing a diagnostic cystoscopy for a high suspicion of bladder cancer (group 1) and on 102 patients with previous history of transitional cell carcinoma awaiting a follow-up cystoscopy (group 2). Biopsy specimens were obtained also from tumor negative patients. Immunoassays for BTA TRAK and NMP22 were carried out according to standard methods. The choice of the cut-off was based on the ground of sensitivity and specificity curves intersection. Urine cytology results were expressed as positive, negative and 'dubious'. RESULTS: Overall sensitivity was 56% for NMP22 (cut-off 11 U/ml) and 57% for BTA TRAK (cut-off 60 U/ml). When dubious results were considered as positive cases, urine cytology achieved a sensitivity of 73.3%. Assuming dubious cases as negative results, urine cytology sensitivity resulted 59.3%. When the 2 groups of patients were evaluated separately with different cut-off, there was no significant gain in sensitivity for BTA TRAK and NMP22 over urine cytology. CONCLUSIONS: Urine cytology performed on 3 samples showed the highest sensitivity and specificity. The diagnostic advantage of urine cytology over BTA TRAK and NMP22 was maintained when patients were stratified by tumor grade.

Aged↗

PubMed2004

Urinary basic fibroblast growth factor in bladder cancer patients. Histopathological correlation and clinical potential.

INTRODUCTION: Angiogenesis plays a significant role in the growth and progress of cancer, thus we evaluated the levels of urinary basic fibroblast growth factor (bFGF) in bladder cancer (Ca) patients and investigated any possible correlation between this angiogenic factor with tumor stage and grade. MATERIALS AND METHODS: Urine samples from 41 patients with bladder Ca, 11 patients with history of bladder Ca but negative follow-up cystoscopy, 18 patients with benign prostate hyperplasia (BPH) and 15 normal healthy volunteers were assayed using an enzyme-linked immunosorbent assay for bFGF. Resulting values were normalized against urine creatinine and expressed as pg/g. RESULTS: The median urinary bFGF level of patients with active disease, history of bladder carcinoma and negative follow-up cystoscopy, BPH, and healthy volunteers were 2,717, 1,009, 1,414 and 1,100 pg/g, respectively. There was a statistically significant difference between median bFGF levels of patients with active bladder Ca and those of the other groups (p = 0.000). Eleven patients with invasive bladder Ca had a median bFGF value of 6,880 pg/g that was significantly increased (p = 0.002) compared to the median of 2,312 pg/g of those with superficial tumors (Ta 14, T1 16). Grades 1, 2 and 3 carcinoma were found in 5, 19 and 17 patients which had a median bFGF of 2,717, 1,762 and 3,617 pg/g, respectively, but the difference was not statistically significant (p = 0.13). CONCLUSIONS: Our results confirm the implication of bFGF in the biology of bladder cancer, and demonstrate that urinary bFGF concentration seems to be significantly related to the stage but not to the grade of the disease supporting the proposed mechanisms of release of bFGF. Further studies are required in order to validate the potential clinical applications of bFGF for specific groups of bladder cancer patients.

Adult↗

PubMed2004

First case of lymphangioma of the bladder in an adult.

Lymphangioma is a congenital malformation consisting of a developmental or primary defect of the lymphatic channels. We report the first case of lymphangioma of the bladder in an adult and review the literature. In our case a 49-year-old man presented with irritative voiding symptoms, cystoscopy showed a non-papillary tumor between the two orifices within the trigone, and transurethral resection was performed. Three months after operation the irritative voiding symptoms had improved and cystoscopy showed no residual tumor.

Humans↗

PubMed2006

Treatment of urethral syndrome: a prospective randomized study with Nd:YAG laser.

INTRODUCTION: The urethral syndrome is characterized by irritative disturbances, the urgency-frequency syndrome and/or pain associated with negative urine cultures. Areas of metaplasic tissue in the trigonal-bladder neck region (trigonitis) are sometimes present. We performed a comparative randomized study to assess the efficacy of side- or end-firing neodymium (Nd):YAG laser surgery in destroying metaplasia and relieving symptoms. MATERIALS AND METHODS: Between January 1997 and December 2003, 62 consecutive women with the urethral syndrome and squamous metaplasia of the bladder neck-trigone, who were refractory to drugs, were randomly assigned to treatment with end-firing (group A) or side-firing (group B) Nd:YAG laser. Three, 6 and 12 months after surgery all patients underwent a clinical urological examination and cystoscopy. Surgery was considered successful when patients reported they were satisfied with the outcome or stated on the UDI-6 questionnaire that symptoms were reduced by at least 75%. RESULTS: Group A end-firing laser: patients rapidly improved (2-3 weeks) but symptoms worsened within 3 months. At 6-12 months, symptoms had improved in 19% of the 31 patients and remained unchanged or worsened in 81%. Group B side-firing laser: irritative disturbances worsened in the 7-10 days after therapy but markedly improved within 2-3 months. Symptoms significantly improved in 68% of the 28 patients and remained unchanged or worsened in 32%. Results were significantly better after side-firing laser (p < 0.001) and a trend towards improvements emerged as the joule levels rose. At 3 months, cystoscopy and biopsy showed squamous metaplasia was no longer present in patients whose symptoms had improved. Whitish areas were still present in the bladder neck-trigone in patients whose symptoms had remained unchanged or worsened. These patients were retreated. CONCLUSIONS: In the treatment of the urethral syndrome the few reports on attempts to restore a normal urothelium by means of diathermocoagulation and cryotherapy have been encouraging. Side-firing laser, which produces necrotic coagulation followed by reconstitution of normal functional epithelium, was significantly more successful than end-firing and was associated with a 78% success rate. These results are encouraging in patients who are usually refractory to medical therapy.

Adult↗

PubMed1994

Late urinary bladder metastases after radical resection of prostatic carcinoma.

The case of a 69-year-old man who underwent radical prostatectomy because of carcinoma of the prostate is reported. A preoperative cystoscopy was normal. The histological evaluation of the radical prostatectomy showed an infiltration of the urethral margin. 14 months later, cystoscopy showed papillary metastases of the prostatic carcinoma in the bladder. Immunohistochemistry and flow cytometry for various prognostic factors showed a high malignant potential of this tumor. Preoperative transurethral instrumentation for the treatment of urethral strictures may be responsible for the dissemination of tumor cells into the bladder.

Adenocarcinoma↗

PubMedDate not supplied

Tumor markers in the detection of recurrent transitional cell carcinoma of the bladder: a brief review.

OBJECTIVE: To determine the status of the most promising tumor markers of bladder cancer, including comparison with cytology, technical complexity and utility in patient management. STUDY DESIGN: An extensive literature search was performed, and multiple markers were evaluated. The markers with the greatest potential for use as an adjunct to cytology were reviewed to determine the value of clinical implementation. Markers with a paucity of clinical research and poor results in clinical trials were omitted from review, as were genetic and cytologic prognostic determinants. RESULTS: NMP22, bladder tumor antigen, fibrin/fibrinogen degradation products, telomerase and QUANTICYT image analysis cytometry produced the most favorable and reproducible results. Each test obtained favorable sensitivities in comparison with cytology, especially in the detection of low grade lesions. Many also retrospectively placed patients in high- and low-risk groups based on the test results, allowing increased follow-up time between cystoscopies. However, inability to detect some high grade lesions reduces their utility. CONCLUSION: Continued clinical trials using these and other predictors of bladder cancer will eventually find a test that is suitable, in sensitivity and specificity, for use in urology clinics. Until that time, these tests may be useful in conjunction with cytology to prolong the interval between cystoscopies.

Biomarkers, Tumor↗

PubMed1997

Application of clinical trials to the care of patients with bladder cancer.

Patients with bladder cancer are fortunate because much of the treatment they receive is based on the findings of randomized clinical trials that ensure a sound, scientific basis for the treatment decisions they will agree with their urologist. Patients with Ta or T1 transitional cell carcinoma will be distressed to learn their diagnosis but will be comforted to know that they are most unlikely to die of the disease. They will be well advised to have at least one instillation of intravesical chemotherapy and if they are confirmed to have a good-prognosis tumour, they will probably need only annual follow-up cystoscopies. Other patients will have to accept the inconvenience of more frequent cystoscopies. Should they develop multiple superficial recurrences, more intensive intravesical chemotherapy or BCG is effective. This should probably be repeated at 6-monthly intervals for up to 3 years, although the optimum duration of treatment and the best treatment regimens require further clarification. Patients with muscle invasive bladder cancer do not have a good prognosis and, unfortunately, the addition of systemic chemotherapy does not offer any clear survival advantage at the present time. New, more effective forms of treatment are awaited. The confidence with which bladder cancer patients can be treated is based on the results of collaborative, multicentre trials that have been conducted over the past two decades. The important lesson to be learned, by physician and patient alike, is that randomized clinical trials are worthwhile because the results influence clinical practice and assure best possible care.

Carcinoma in Situ↗

PubMed1992

Bladder wash cytology and flow cytometry for the diagnosis of transitional cell carcinoma of the urinary bladder.

The role of bladder wash (BW) cytology and flow cytometry in the diagnosis of low-grade transitional cell carcinoma (TCC) of the bladder is yet to be demonstrated. We have studied a series of BW specimens by both conventional cytology and flow cytometry: there were 16 BW from patients with histologically proven TCC and 14 BW from patients with clinical suspicion of tumor or under follow-up for previous TCC in which no evidence of tumor was found by cystoscopy and multiple biopsies. As control group, 21 BW were studied from patients undergoing cystoscopy for causes other than TCC. In conclusion, the conventional cytologic study of BW specimens was highly sensitive for grade II-III TCC, but missed most grade I TCC; flow cytometric analysis did not improve significantly the detection rate in low-grade TCC.

Carcinoma, Transitional Cell↗

PubMed2026

Induction and characterization of neoplastic bladder tumors in a transgenic porcine model.

BACKGROUND: Large animal models of bladder cancer are lacking. OBJECTIVE: This study aimed to develop and characterize a transgenic porcine model of bladder cancer (BC) using Oncopigs expressing Cre-inducible KRASG12D and TP53R167H mutations. METHODS: Eleven female Oncopigs underwent tumor induction via three cystoscopic inoculation procedures: Procedure I (N = 3, 1 inoculation/pig), chemical dissolution of the glycosaminoglycan layer with N-Dodecyl-β-d-Maltoside DDM followed by adenoviral Cre-recombinase (AdCre) instillation; Procedure II (N = 4, 3 inoculation/pig), mechanical mucosal denudation followed by AdCre instillation; and Procedure III (N = 4, 3 inoculation/pig), cystoscopy-guided submucosal injection of AdCre. Animals were clinically monitored throughout follow-up (14-28 days). Tumor development was assessed on cystoscopy and ultrasonography, and pathologically, immunohistochemically (IHC), and genomically characterized. RESULTS: All pigs remained clinically healthy. Tumors developed at 59% (16/27) of inoculation sites: nine (33%) were neoplastic and seven (26%) were inflammatory. Procedure I achieved 100% neoplastic tumors and produced both non-muscle invasive (71%) and muscle-invasive (29%) tumors. Procedure II achieved 50% neoplastic tumors, all of which were muscle invasive (100%). Procedure III generated only inflammatory tumors. Histologically, neoplastic tumors were pathologically interpreted as urothelial cell carcinomas with sarcomatoid differentiation, with IHC confirming the presence of both epithelioid and sarcomatoid features with abundant mixed leukocytic infiltrates. Genomic analyses verified Cre-induced alterations alongside other mutations seen in human BC. CONCLUSIONS: We herein demonstrate an efficient and reproducible method for developing autochthonous neoplastic bladder tumors in Oncopigs that resemble human bladder cancer of varying stages. This large animal model facilitates the evaluation of novel surgical and intravesical therapies in BC.

bladder cancer↗

PubMed2006

Primary PEComa of the bladder treated with primary excision and adjuvant interferon-alpha immunotherapy: a case report.

BACKGROUND: Perivascular epithelioid cell tumors (PEComas) are rare mesenchymal neoplasms of uncertain malignant potential, which have in common the co-expression of muscle and melanocytic immunohistochemical markers. CASE PRESENTATION: A 48-year-old man presented with dysuria, passage of urinary sediment and lower abdominal discomfort. A three centimeter mass was identified by cystoscopy in the posterior midline of the bladder. Computerized tomography suggested an enterovesical fistula. The patient underwent laparotomy, partial cystectomy and partial small bowel resection. Pathological examination revealed PEComa of the bladder. The patient underwent adjuvant interferon-alpha immunotherapy. Subsequent follow-up procedures, including cystoscopy and imaging, have not revealed evidence of recurrence. The patient is clinically free of disease 48 months after surgery. CONCLUSION: This case represents the second documented PEComa of bladder and demonstrates that adjuvant therapies, including anti-angiogenic and immunotherapy, may be considered for patients with locally advanced or metastatic genitourinary PEComa.

Chemotherapy, Adjuvant↗

PubMed1993

Combined radiation and chemotherapy for invasive transitional-cell carcinoma of the bladder: a prospective study.

PURPOSE: To improve the results obtained by cystectomy alone and to determine the possibilities of conservative treatment in invasive bladder cancer, we designed a prospective study using a combination of fluorouracil (5-FU) plus cisplatin and concomitant radiation therapy, followed by either cystectomy or additional chemoradiotherapy. PATIENTS AND METHODS: Fifty-four patients with stage T2 to T4 operable untreated invasive bladder cancer were entered onto the study. Treatment was begun in all patients by transurethral resection (TUR) and followed by the 5-FU-cisplatin combination with concomitant bifractionated split-course radiation therapy. A control cystoscopy was performed 6 weeks after completion of the neoadjuvant program. Patients with persistent tumor underwent cystectomy. Complete responders were treated by either additional chemoradiotherapy (group A) or cystectomy (group B). RESULTS: At control cystoscopy, 40 of 54 patients (74%) had a histologically documented complete response. Four responders developed recurrent pelvic disease after a mean follow-up time of 27 +/- 12 months (three in group A and one in group B). Metastatic disease, which developed in 16 patients, occurred more frequently in the nonresponders (71%) than in responders (15%). The disease-free survival rate at 3 years was 62%; it was significantly better in responders (77%) than in nonresponders (23%). There was no difference in survival between groups A and B. CONCLUSION: This neoadjuvant chemoradiotherapy combination, easy to implement and well tolerated even in elderly patients, provides a high complete response rate. It may prove to be effective in inoperable patients and may be proposed as conservative treatment in patients with a complete response to the initial course of chemoradiation.

Adult↗

PubMed2006

Phase I trial of intravesical docetaxel in the management of superficial bladder cancer refractory to standard intravesical therapy.

PURPOSE: Up to 50% of patients treated with intravesical agents for superficial bladder cancer will experience recurrence. Response rates to second-line intravesical therapies range from 20% to 40%. For these high-risk patients, novel agents are necessary to prevent recurrence. Docetaxel is a microtubule depolymerization inhibitor with unique physiochemical properties, making it an excellent candidate for investigation as an intravesical agent. PATIENTS AND METHODS: This phase I trial included patients with recurrent Ta, T1, and Tis transitional cell carcinoma who experienced treatment failure with at least one prior intravesical treatment. Docetaxel was administered as six weekly instillations at a starting dose of 5 mg, with a dose-escalation model used until a maximum tolerated dose (MTD) was achieved. Primary end points were dose-limiting toxicity (DLT) and MTD. Efficacy was evaluated by cystoscopy with biopsy, cytology, and computed tomography imaging. RESULTS: Eighteen patients (100%) completed the trial, and the distribution of stages included six patients with Tis, seven with Ta, and five with T1 disease. No grade 3 or 4 DLTs occurred in 108 infusions, and no patient had systemic absorption of docetaxel. Eight (44%) of 18 patients experienced grade 1 or 2 toxicities, with dysuria being the most common. Ten (56%) of 18 patients had no evidence of disease at their post-treatment cystoscopy and biopsy. None of the patients who experienced relapse had disease progression. CONCLUSION: Intravesical docetaxel exhibited minimal toxicity and no systemic absorption in the first human intravesical clinical trial. This suggests that docetaxel is a safe agent for further evaluation of efficacy in a phase II trial.

Administration, Intravesical↗

PubMed2006

Molecular markers of urothelial cancer and their use in the monitoring of superficial urothelial cancer.

Multiple molecular markers have been described for use in bladder cancer patients. Some of these have been studied more extensively than others, and it is difficult for the clinician to maintain a perspective over the myriad findings that have been made. We have reviewed a selection of markers used for surveillance with an emphasis on clinical utility. The best studied markers and those with the most promising preliminary results were selected. Only studies that included surveillance for recurrence in patients with a history of bladder cancer were considered. Each marker is briefly described and its performance in monitoring bladder cancer patients is summarized. Several promising markers are available, although only four have obtained US Food and Drug Administration approval. The clinical applications that have been studied include replacement or reduction in the number of cystoscopies performed in the surveillance of bladder cancer patients, substitution for or complementary use with urinary cytology in the same setting, predicting disease recurrence and progression, and predicting and monitoring treatment response. None of the markers have been proved sensitive and specific enough to replace cystoscopy. Others, such as nuclear matrix protein 22 (NMP22) and UroVysion, appear to have some utility when used to complement or replace cytology. The other applications have not been adequately studied for any given marker. While multiple molecular markers exist for bladder cancer, their full clinical utility will not be realized until more multicenter prospective trials are conducted to verify their efficacy and safety in the monitoring of patients with superficial bladder cancer.

Biomarkers, Tumor↗