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PubMed2006

DNA-based molecular cytology for bladder cancer surveillance.

Surveillance strategies for urothelial cancer (UC) recurrence have historically relied on the diagnostic combination of cystoscopy and conventional urinary cytology. In this review, results of studies evaluating the role of the fluorescence in situ hybridization (FISH) assay in bladder cancer surveillance are critically examined. The published research on FISH compared with conventional cytology and cystoscopy for bladder cancer was identified using a Medline search and was critically analyzed. Sensitivity and specificity data were tabulated and compared. FISH outperformed conventional cytology across all stages and grades in all published reports, and it detected malignancy before the development of lesions visible by cystoscopy. Although overall sensitivity was 48% for cytology and 74% for FISH, its greatest advantage was in the detection of high-grade UC, including carcinoma in situ (CIS). Cumulative data from comparative studies showed the sensitivity of cytology compared with FISH was 19% versus 58% for grade 1, 50% versus 77% for grade 2, and 71% versus 96% for grade 3. Similar findings occurred by stage, where cytology compared with FISH sensitivity was 35% versus 64% for Ta, 66% versus 83% for T1, and 76% versus 94% for muscle-invasive carcinoma. Notably, cytology detected only 67% of CIS versus 100% detection by FISH. Specificity data were comparable. Unlike conventional urinary cytology and cystoscopy, which depend on subjective visible microscopic or macroscopic changes, FISH allows identification of chromosomal abnormalities associated with malignant development before phenotypic expression of those alterations. Use of morphologic cellular changes allows more rapid detection of such alterations, combining the benefits of conventional cytology with molecular diagnostics. It is apparent that we are in the early phases of realizing the potential of molecular diagnostics.

DNA, Neoplasm↗
PubMed2005

Can MRI rule out bladder and rectal invasion in cervical cancer to help select patients for limited EUA?

OBJECTIVES: Although invasion of the bladder or rectum is rare in cervical carcinoma, endoscopic assessment of both organs is part of the standard FIGO clinical staging system, with associated increase in cost and risk of complications. Our objective was to evaluate whether MRI could be used to select patients who did not require invasive staging of the bladder or rectum. METHODS: Two observers, blinded to the results of cystoscopy and endoscopic examination of the rectum, retrospectively reviewed the MR images of 112 patients with cervical carcinoma. A 5-point invasion score was used to determine bladder and rectal invasion (1 = no invasion, 5 = definite invasion). A confidence score of 3 or above was used to identify patients with possible bladder or rectal involvement. The results of cystoscopy and endoscopic examination of the rectum were recorded and correlated with the MR findings. RESULTS: MRI was negative for both bladder and rectal invasion in 94/112 patients. Cystoscopy and endoscopic examination of the rectum were confirmed to be normal in all 94 cases. MRI identified 12 patients with possible rectal invasion, 2 confirmed at endoscopy. MRI identified 14 patients with possible bladder invasion, one confirmed at cystoscopy. Using a low threshold cut-off score of >3 to predict invasion resulted in a 100% negative predictive value (NPV) in detection of bladder and rectal invasion. CONCLUSION: The absence of bladder or rectal invasion can be diagnosed with sufficient confidence using an MRI scoring system to safely obviate the need for invasive cystoscopic or endoscopic staging in the majority of patients with cervical cancer. This could potentially lead to a reduction in staging costs and morbidity.

Adult↗
PubMed1998

Autofluorescence guided biopsy for the early diagnosis of bladder carcinoma.

PURPOSE: We validate the usefulness of laser-induced autofluorescence for the detection of bladder carcinoma. MATERIALS AND METHODS: We obtained and analyzed fluorescence spectra from 75 patients in whom bladder cancer was suspected. Tissue fluorescence was excited by a nitrogen laser using a quartz optical fiber placed in gentle contact with the area of interest. The laser-induced autofluorescence spectrum was recorded using an intensified optical multichannel analyzer system. Spectra were corrected for the spectral response of the optical system, and the ratios of laser-induced autofluorescence intensities (I) at 385 and 455 nm. (I385/I455) were determined. We had previously established this ratio as a diagnostic algorithm. We included only suspicious bladder lesions (erythematous, edematous, raised and so forth) that were difficult to diagnose by cystoscopy as well as areas from which random biopsies were obtained. The fluorescence ratio algorithm was applied to 130 bladder areas. RESULTS: Of the 130 biopsies obtained during routine cystoscopy 107 (82%) were nonmalignant by histological classification. In contrast, because laser-induced autofluorescence effectively guides biopsies towards malignant lesions, only 30 biopsies (72% fewer) would have been obtained from nonmalignant tissue if the fluorescence ratio that identifies 95% of malignant lesions (95th percentile) had been selected as the decision criterion during standard cystoscopy. CONCLUSIONS: By guiding the surgeon to suspicious lesions that are most likely to be malignant, laser-induced autofluorescence substantially decreases the number of biopsies obtained from nonmalignant tissue during cystoscopy to diagnose bladder carcinoma.

Aged↗
PubMed1998

Immunostaining of Lewis X in cells from voided urine, cytopathology and ultrasound for noninvasive detection of bladder tumors.

PURPOSE: We examined the use of immunostaining of the Lewis X antigen in exfoliated cells from voided urine samples, cytopathology and bladder ultrasound for noninvasive detection of bladder tumors as a potential substitute for cystoscopy. MATERIALS AND METHODS: A total of 260 patients were included, of whom 80 were evaluated because of irritative symptoms or hematuria and 180 were examined during followup visits after resection of bladder tumors. Voided urine samples were obtained from each patient for immunocytology and cytopathology. Bladder ultrasound and cystoscopy were performed. Biopsies were obtained whenever a bladder tumor was seen or if carcinoma in situ was suspected. Indirect immunoperoxidase staining was done on cytocentrifuge slides, using the P12 monoclonal antibody against the Lewis X antigen. RESULTS: Cystoscopy and biopsies revealed bladder tumors in 84 patients. Immunocytology of 1 urine sample resulted in a sensitivity of 79.8% and a specificity of 86.4%. The diagnosis of primary carcinoma in situ by immunocytology was correct in 100% of the cases. The examination of 2 consecutive urine samples detected 95.1% of the tumors. False-negative results occurred in a few cases with small, superficial, low grade tumors. Cytopathology and bladder ultrasound resulted in a sensitivity of 47.6 and 66.7%, and a specificity of 97.7 and 97.2%, respectively. The results of immunocytology of 2 urine samples were equivalent to the combination of immunocytology of a single urine sample, cytology and ultrasound. CONCLUSIONS: Immunostaining of the Lewis X antigen is significantly more sensitive than cytopathology for the detection of low grade as well as high grade tumor cells in voided urine. Immunocytological evaluation of 2 consecutive voided urine specimens for the Lewis X antigen is the most sensitive method currently available for noninvasive detection of transitional cell tumors. This assay may replace cystoscopy for detection of bladder cancer.

Humans↗
PubMed1997

The bladder tumor antigen (BTA) test compared to voided urine cytology in the detection of bladder neoplasms.

PURPOSE: Tests to detect recurrent bladder neoplasms are limited and none is consistently accurate. Recent studies suggest that the bladder tumor antigen (BTA) test, an agglutination reaction for basement membrane complexes, is superior to voided urine cytology in clinical practice. We compared BTA and voided urine cytology to bladder washings and cystoscopy, emphasizing diagnostic yield among patients with causes of basement membrane complexes other than bladder cancer. MATERIALS AND METHODS: Random voided urine specimens from 67 patients with a history of bladder neoplasms were collected before cystoscopy and bladder washing. Urine also was obtained from 34 patients with inflammatory bladder conditions including 5 with a history of prostate cancer. Each urine was tested for BTA according to a commercial kit. Positive results were indicated by yellow on a test pad. Blinded to all other results, each urine and each bladder washing were examined microscopically, and a positive test had malignant/suspicious cells. Bladder biopsies were performed when endoscopic lesions were seen. Specimens were grouped into 4 categories: group 1--biopsy proved bladder neoplasm, group 2--history of bladder cancer but not biopsy proved, group 3--history of prostate cancer and group 4--no history of urological cancer. RESULTS: Voided urine cytology was positive in 54% of specimens from patients with biopsy proved bladder neoplasms compared to 29% for BTA. Relative yield for voided urine cytology versus BTA was not changed if all group 2 cases having a positive bladder washing and positive cystoscopy were assumed to have bladder cancer, nor was relative yield altered by subsequent short-term followup. Of voided urine specimens 14% from group 1 patients and 41% from group 2 patients had scant cells. Overall diagnostic yield was superior for bladder washing. False-positive BTA occurred in 7 of 34 patients with no history of urological or prostate cancer. There were no false-positive voided urine cytology interpretations in these groups. CONCLUSIONS: BTA is not superior to voided urine cytology in detecting bladder neoplasms and may be limited by false-positive reactions in patients with other causes of basement membrane complexes in urine. Voided urine samples may be limited by high frequency of hypocellularity. Of 34 patients with a hypocellular urine specimen 4 had biopsy proved bladder cancer. Bladder washing yields best results but requires instrumentation. No test, including cystoscopy, is accurate always.

Antigens, Neoplasm↗
PubMed1992

Treated history of noninvasive grade 1 transitional cell carcinoma. The National Bladder Cancer Group.

A total of 178 patients with grade 1 noninvasive (stage Ta) bladder tumors followed from 1 to 10 years (median 58 months) was prospectively evaluated by cystoscopy, transurethral resection, mucosal biopsies, cytology, size and number of tumors at diagnosis, recurrences, progression in grade and stage, number of negative or positive cystoscopies and death from all causes. Histopathological and cytological studies were confirmed by a Central Pathology Laboratory using the criteria for grade 1 as described previously. Of the patients 122 (68.5%) had a single tumor. Three-quarters of the patients had tumors of less than 2 cm., 95% had mild or no urothelial dysplasia and 1 had positive cytology results. There were 419 recurrent tumors in 109 patients (61%). Patients with multiple tumors were at a significantly greater risk for recurrences (p < 0.001). Size of tumor significantly affected the rate of recurrence in the first 2 years after initial diagnosis in single tumor patients only. Of the multiple tumor patients 90% experienced a recurrence compared to 46% of the single tumor patients. Of the 1,112 cystoscopies performed in 122 single tumor patients 18% were positive, compared to 33% of the 686 cystoscopies performed in 56 multiple tumor patients. A total of 29 patients had a change in grade, 5 having grade 3 and 24 having grade 2 tumors. Progression to stage T1 occurred in 5 patients and to stage T2 or greater in 3. Of the 36 patients who died, 1 died of obstruction due to bladder cancer. Experimental evidence supports the opinion that the cells of stage Ta, grade 1 tumors are different in several ways from normal urothelium. There are little data to support the use of the term papilloma to describe stage Ta, grade 1 tumors without reservation. The data demonstrate that the tumor diathesis being expressed ceases with time and for unknown reasons. Multiple tumor patients with stage Ta, grade 1 disease might be included in chemotherapy trials only with stratification and a control arm of transurethral resection/fulguration alone.

Adult↗
PubMed2002

Current concepts of tumor markers in bladder cancer.

The critical issue in characterizing the usefulness of tumor markers in screening or monitoring for urothelial cancer and in determining prognosis revolves around the question, "What do we need to know?" During surveillance of patients with low-risk disease, highly sensitive markers may detect disease persistence or early recurrence (on the basis of field-effect changes or tumor cell implantation); however, they may not indicate the possibility of progression. If cystoscopy is negative in these instances, is it appropriate to treat? Does earlier treatment actually prevent recurrence or progression? Some investigators have suggested a positive answer to the former question, although lead-time bias may a role. The issue in the latter question may be moot because low-risk disease is by definition unlikely to progress. A corresponding question is whether one should treat the patient if the marker has a low specificity. In such instances, a marker with low specificity may incur more frequent instrumentation and a panoply of additional costs. A marker may have some value in providing earlier diagnosis in low-risk disease if treatments are available to prevent clinical expression and recurrence. A tumor marker would have additional value if it could detect biologic change from low-risk to high-risk disease and permit a corresponding change in treatment. Moreover, if a marker could provide earlier diagnosis in high-risk disease, it might permit identification of those patients likely to progress at earlier and curable stages of disease. To be successful, such markers must have high sensitivity and specificity in diagnosis. It has been suggested that "a simple noninvasive highly sensitive and specific method for detecting bladder cancer would decrease the morbidity associated with current surveillance methods, improve quality of life for patients, and reduce costs by substituting a less expensive test for the more expensive endoscopic procedures" (Dr. M. Soloway, personal communication 2000). In considering this statement, it is tempting to question some of its implications. The term "simple" suggests that point-of-care tests may be the easiest, but tests that are available may be inconsistent and not sufficiently sensitive or specific. The need for a "highly sensitive and specific" test is of critical importance for applicability in the individual, even when such tests are based on the results in large populations. When considering the "morbidity of current methods," it is tempting to question whether cystoscopy is that morbid a procedure. Given the information it provides, it seems improbable that it can be readily replaced. Currently, no markers provide information over and above that provided by cystoscopy and histology- or cytology-based understanding of the biology of the disease especially in considering distinctions between low-risk and high-risk disease. The ability to "improve quality of life" will depend on the use of the predictive value made on the basis of a test's sensitivity and specificity. A false-positive test may lead to anxiety and extensive unnecessary evaluation, whereas a false-negative test may lead to missed diagnosis, delayed treatment, and the possibility of disease progression until accurate diagnosis is obtained. In each case, quality of life is compromised. "Substituting a less expensive test" depends on the benefits of that substitution and the practicality of omitting or delaying standard assessment. Costs depend on the frequency of testing, those incurred by false-positive tests, and those incurred by false-negative tests. Several caveats emerge when taking into account these various considerations. In screening for low-risk disease, the urgency of diagnosis may be less important. High sensitivity is of less importance because the risk of a missed diagnosis has less ominous repercussions. Nevertheless, high specificity is important to avoid unnecessary frequent instrumentations. In considering surveillance for low-risk disease, cytology may be more useful in indicating a change from negative (persistent or recurrent low-risk disease) to positive (high-risk disease) with the consequent need for more aggressive treatment approach. No urinary "screening" markers reliably provide this information. In considering surveillance for high-risk disease, sensitive markers would detect persistence or early recurrence. If such markers are negative, intervals between repeated cystoscopies may be prolonged; however, a high specificity is needed to ensure the validity of a truly negative interpretation. Otherwise, diagnosis may be missed and the risk from progression and the development of incurability increased. Markers for urothelial cancer must be expressed exclusively as a consequence of the presence of cancer cells. The test must be sensitive in detecting disease and must be validated in nonselected populations. It must be sensitive in excluding nondisease, and noncancer conditions must have little influence on its accuracy. There must be little or no interassay or intra-assay variability. Interpretation of an assay for a tumor marker should be all or none, or based on a threshold level. The assays must have sufficient sensitivity and specificity in populations and in the individual to have practical clinical applicability.

Antigens, Neoplasm↗
PubMed2005

[Clinical usefulness of the ImmunoCyt urinary test in the follow-up protocol of patients with urothelial neoplasms].

OBJECTIVES: The overall objective of this study was to carry out a prospective investigation of the usefulness of the IMMUNOCYT commercial kit in the follow-up of patients treated for bladder cancer and to evaluate its utility as a complement to urinary cytology and a possible tool for reducing the number of follow-up cystoscopies required. SUBJECTS AND METHODS: From September 2001 to December 2002, the ImmunoCyt test and urinary cytology were performed in urine simples from a total of 136 patients (115 with a history or suspicion of bladder cancer and 21 patients with other urological pathologies). Urine simples were fixed with an equal volume of 50% alcohol. Urinary cytology and the ImmunoCyt test were interpreted by a cytopathologist unacquainted with the result of the corresponding cytology and bladder biopsy report. Samples were staged and graded using the 1997 TNM classification of the UICC and the 1998 WHO/ISUP classification. Histopathological confirmation of lesions was available for 111 patients (81.6%). RESULTS: The gender distribution was 89% men and 11% women. Mean age was 71.68 years (range 27 to 98 years). Overall sensitivity and specificity were 77.9% and 92.3% for the ImmunoCyt test and 47.9% and 100% for urinary cytology, respectively. The positive (PPV) and negative predictive values (NPV) were 96.4% and 61.7%, respectively, for the ImmunoCyt test and 100% and 36.7% for cytology. In Ta and low-grade carcinomas, the sensitivity of the ImmunoCyt test was 70% (n=20) and 76.4% (n=34) respectively, whereas it was 25% (n=28) and 29.7% (n=37), respectively, for urinary cytology. The differences observed between the sensitivities of the ImmunoCyt test and cytology were statistically significant (X2 p<0.05) overall and for Ta and low-grade carcinomas. The sensitivity and specificity of the combination of both tests were 86.8% and 96.2%, respectively. The sensitivity of the combination of both tests for Ta and low-grade carcinomas was 80% (n=20) and 82.3% (n=34), respectively. The ImmunoCyt test was diagnostic in 36.2% of tumors overall. CONCLUSIONS: In view of the results obtained, we decided to change our follow-up protocol to reduce the number of follow-up cystoscopies by 32.2% in the first 5 years of postoperative follow-up (in a cohort of 140 patients who undergo surgery annually). This benefits patients by reducing the number of urinary infections and iatrogenesis originated by follow-up cystoscopy. In addition, this 32.2% reduction in the number of cystoscopies in 5 years will yield a savings of approximately 35,560 EUR to the health care system in 5 years.

Adult↗
PubMed2005

[Is there a place for randomized biopsies in the follow up of superficial transitional cell carcinoma of the urinary bladder?].

INTRODUCTION: Transitional cell carcinoma of the bladder represents a disease of entire urothelial tract. The follow up is very important to detect any lesion that might represent a progression or a local recurrence. Some authors recommend randomized biopsies as a routine workup, others recommend cystoscopies and urinary cytology as the main part of superficial bladder cancer follow up. PATIENTS AND METHODS: Forty nine patients with superficial bladder cancer were followed up during a ten-year period. Randomized biopsies and urinary cytology were harvested according to the international cancer protocol on bladder cancer. RESULTS: 15 (1%) out of 1.489 randomized biopsies found to be positive to transitional cell carcinoma. Four out (10.5%) of 35 biopsies targeted to suspicious areas were positive to transitional cell carcinoma. 50 (17.4%) out of 288 cystoscopies with urinary cytology found to be positive to transitional cell carcinoma. Sensitivity and Specificity of biopsies (including randomized and targeted) were 31% and 85.2% respectively. Sensitivity and specificity of cystoscopies with urinary cytology were 48% and 86.5% respectively. CONCLUSION: Randomized biopsies did not show to detect more local recurrence or progression when compared to the urinary cytology. Cystoscopies with urinary cytology have good sensitivity and specificity for detection of tumor recurrence during follow up of transitional cell carcinoma.

Adult↗
PubMed2002

A new small-calibre diagnostic flexible cystoscope.

OBJECTIVE: To determine whether flexible cystoscopy with a prototype slim flexible instrument is less uncomfortable than flexible cystoscopy using a standard flexible cystoscope. PATIENTS AND METHODS: In all, 200 men scheduled to undergo flexible cystoscopy for the follow-up of transitional cell carcinoma of the bladder were randomized in equal groups to flexible cystoscopy using the standard instrument or using the prototype slim-scope. Each patient had 11 mL of 2% lignocaine gel instilled intraurethrally 5 min before the procedure. At the end of the procedure the patient was asked to complete a 100-mm non-graphical visual analogue scale to rate how uncomfortable the procedure was. RESULTS: The slim-scope was very significantly less uncomfortable than the conventional instrument (anova P < 0.001). The ease of use and views of the bladder were similar to those obtained with the conventional cystoscope. CONCLUSION: The slim-scope offers a significant benefit in patient comfort, with little loss of image quality or ease of use.

Carcinoma, Transitional Cell↗
PubMed2003

Superficial bladder tumours: analysis of prognostic factors and construction of a predictive index.

OBJECTIVES: To assess the prognostic factors that could be used to predict tumour recurrence and progression, and to construct and validate a predictive index. PATIENTS AND METHODS: Between June 1991 and December 2000, 533 patients (418 men and 115 women; mean age 55.4 years) underwent complete transurethral resection of histologically confirmed pTa and pT1 transitional cell carcinoma of the bladder, after which 377 (test series) were randomized into two subsequent studies, of six groups, to receive adjuvant intravesical sequential bacillus Calmette-Guérin (BCG) and epirubicin, BCG alone, epirubicin (50 or 80 mg), adriamycin 50 mg or no adjuvant therapy. Factors potentially affecting tumour recurrence or progression were assessed using univariate and multivariate analysis, i.e. tumour stage, histological grade, DNA ploidy, history of recurrence, multiplicity, size, tumour configuration, associated carcinoma in situ, recurrence at the first 3-month check cystoscopy and the use of adjuvant therapy. The regression coefficients determined by Cox regression analysis were used to construct a predictive index (PI). The algebraic sum of the regression coefficients of the factors with independent and significant association with disease-free survival for each case represented a proportional hazard score (PHS). The PI was validated in another series of 156 patients (validation series) in whom the same regression coefficients for the same significant factors as the test series were used to categorize it into three risk groups. Kaplan-Meier survival curves were plotted to compare the different risk categories in both test and validation series. RESULTS: The mean (sd, range) follow-up in the test and validation series were 58 (19, 5-96) and 28.3 (14.9, 2-94) months, respectively. In the test series, tumour stage, DNA ploidy, multiplicity, history of recurrence, tumour configuration, cystoscopy result and the type of adjuvant therapy had independent significance for recurrence on multivariate analysis. For progression, the cystoscopy result, DNA ploidy and grade were the only independent and significant predictors. The ranges of PHS for the factors affecting recurrence-free and progression-free survival were 0.0-7.14 and 0.0-5.84, respectively, which were divided equally into three risk categories with significant differences on Kaplan-Meier curves and a log-rank test (P < 0.001). The three categories in the validation series were significantly different from each other and each was comparable with that in the test series. CONCLUSIONS: Tumour stage, DNA ploidy, multiplicity, history of recurrence, tumour configuration and type of adjuvant therapy affected independently the rate of recurrence after resecting superficial bladder tumour. Recurrence at the 3-month cystoscopy, histological grade and DNA ploidy were the only predictors of progression to muscle-invasion. The PI dividing the patients into three risk groups with different treatment and follow-up strategies for recurrence and progression was reproducible in a validation series.

Adult↗
PubMed2003

New diagnostic strategies in the detection and staging of bladder cancer.

PURPOSE OF REVIEW: Bladder cancer is a very frequent disease and represents the second most common genitourinary neoplasm. The most prevalent form of the disease, superficial bladder cancer, can recur in more than 70% of cases, despite correct management. Any way to improve our disease diagnostic and treatment policy is therefore welcome. RECENT FINDINGS: This review covers the following topics: (1). endoscopic tools: standard cystoscopy versus fluorescence cystoscopy and virtual endoscopy; (2). bladder cancer staging: histopathological analysis developments and imaging techniques (positron emission tomography, magnetic resonance imaging, computed tomography); (3). cytology and ancillary procedures (ImmunoCyt and fluorescence in-situ hybridization test, and others); (4). first-generation (bladder tumour antigen, nuclear matrix protein 22, telomerase repeat amplification protocol) and second-generation (loss of heterozygosity, minichromosome maintenance 5, DNA methylation, microsatellite) urine and serum markers. SUMMARY: New diagnostic and therapeutic (endoscopic) tools in superficial bladder cancer should eventually modify our disease management policy. Fluorescence cystoscopy detects carcinoma in situ with a high accuracy, and seems to have a positive impact on reducing residual tumour and recurrence rate. A more specific staining of tissue specimens facilitates histological analysis and helps achieve better staging, especially in T1 diseases. Improving the sensitivity of cytology for low-grade diseases, ancillary procedures to classic cytology such as fluorescence in-situ hybridization and ImmunoCyt tests, may reduce the number of unpleasant cystoscopies in surveillance protocols of selected groups of patients. Second-generation urine markers such as loss of heterozygosity, microsatellite, minichromosome maintenance 5, with a high level of accuracy, show great potential for influencing bladder cancer detection and screening policy.

Diagnostic Techniques, Urological↗
PubMed2004

Bacillus Calmette-Guérin therapy in stage Ta/T1 bladder cancer: prognostic factors for time to recurrence and progression.

OBJECTIVE: To report prognostic factors for time to recurrence and progression after bacillus Calmette-Guérin (BCG) prophylaxis in patients with stage Ta/T1 papillary bladder cancer. PATIENTS AND METHODS: The clinical records were assessed retrospectively for 236 patients with papillary stage Ta/T1 bladder cancer treated with BCG between 1986 and 2000. Patients with known carcinoma in situ were excluded. The median (range) follow-up was 44 (4-155) months. The effect of 13 variables on the time to recurrence and progression was evaluated using multivariate Cox proportional hazard regression and Kaplan-Meier analyses. RESULTS: The recurrence rate was markedly reduced for all grades and stages. Patients with a negative first cystoscopy and maintenance BCG had a significantly longer time to recurrence than those treated with an induction course alone (P < 0.001). Thirty-seven patients (16%) progressed in stage. The result of the first cystoscopy (P < 0.001), tumour grade (P = 0.003) and six or fewer initial instillations (P = 0.002) had prognostic importance for the time to progression. Twenty-eight patients (12%) had a history of an upper tract tumour, which was 3-10 times the expected rate. Age, number of tumours, number of positive cystoscopies, length of tumour history before BCG, BCG strain and treatment year had no influence on time to recurrence and progression. CONCLUSIONS: Maintenance treatment does not seem to be necessary among patients with TaG1-G2 disease after a negative first cystoscopy, as the progression rate was very low. One new finding was that BCG seemed to be equally effective among patients with or with no history of an upper tract tumour. Another new and surprising finding was that patients treated with fewer than six induction instillations, because of very bothersome side-effects, had an increased risk of tumour progression and of local failure.

Adjuvants, Immunologic↗
PubMed2001

NMP 22, BTA stat test and cytology in the diagnosis of bladder cancer: a comparative study.

OBJECTIVE: To evaluate the usefulness of the NMP 22 and BTA stat test in the diagnosis and follow-up of bladder cancer and to compare these tests to cytology and cystoscopy, routine diagnostic methods. METHODS: 150 patients followed up for bladder cancer or symptoms suggestive of bladder cancer underwent cystoscopy after cytology, NMP 22 and BTA stat test using a recently voided urine sample. In suspect cases, TUR and histopathological analysis were performed. RESULTS: Bladder cancer was proven in 76 patients and excluded in 74. For NMP 22 we have used the cutoff value recommended by the manufacturer (10 U/ml) and that obtained by our receiver-operating characteristic curve (6 U/ml). Sensitivity was 84.21% for NMP 22 at the cutoff value of 6 U/ml and 76.32% with 10 U/ml; 72.37% for BTA stat test; 69.74% for cytology, and 100% for cystoscopy. Specificity was 86.49% for NMP 22 at a cutoff value of 6 U/ml and 90.54% at 10 U/ml; 89.19% for the BTA stat test; 93.24% for cytology and 89.19% for cystoscopy. NMP 22 sensitivity for grades 1, 2, and 3 was 68.75, 75.86 and 100%, respectively, at a cutoff value of 6 U/ml, and 50, 68.97 and 96.77%, respectively, at a cutoff level of 10 U/ml; for BTA stat the sensitivity was 56.25% in G1, 62.07% in G2 and 90.32% in G3, and for cytology the sensitivity was 43.75, 62.07 and 90.32%, respectively. The sensitivity of NMP 22 was 68.75% in stage Ta, 84.78% in T1 and 100% in T2-T4 at a cutoff level of 6 U/ml and 50, 80.43 and 92.86%, respectively, at a cutoff level of 10 U/ml; BTA stat sensitivity was 50% in Ta, 73.91% in T1 and 92.86% in T2-T4; and in cytology the results were 37.50, 73.91 and 85.71%, respectively. Using the McNemar test, there was only a significant difference between the sensitivity of NMP 22 at a cutoff level of 6 U/ml and cytology in the overall sample. CONCLUSIONS: The high sensitivity of the NMP 22 and BTA stat test in combination with the data obtained from the parameters used for the evaluation of the test demonstrate their usefulness in the diagnosis and follow-up of bladder cancer. NMP 22 at a cutoff value of 6 U/ml is significantly more sensitive than cytology and consequently a thoroughly valid diagnostic tool in the diagnosis of bladder cancer which may substitute voided urine cytology.

Adult↗
PubMed2003

Eosinophilic cystitis. A rare inflammatory pathology mimicking bladder neoplasms.

PURPOSE: We present a large series of eosinophilic cystitis including 8 cases; 3 of them had tumor-like lesions. MATERIALS AND METHODS: The archives of pathology clinic of Inonu University Medical Faculty were reviewed from 1988 to 2002. The characteristics of patients and their diseases were recorded. Data obtained from 180 cases (172 from the literature and 8 from the present series) was assessed. RESULTS: Seven cases had symptoms such as dysuria, frequency, hematuria, suprapubic pain, and difficulty in voiding. One asymptomatic case with history of bladder carcinoma was diagnosed during routine cystoscopy. The findings were microhematuria in 6 cases, macrohematuria in 2, pyuria in 3, urinary infection in 1, eosinophilia in 1, hyperazotemia in 1, and bladder masses in 3. Cystoscopies detected edematous and erythematous areas in 5 cases and lesions mimicking bladder carcinoma in 3. One case did not take further treatment after cystoscopy and biopsy and completely recovered. Four cases underwent medical therapy with nonsteroidal anti-inflammatory drugs and antihistaminics. They became asymptomatic and control cystoscopies showed no abnormal finding. Two of three patients with mass lesions recovered after steroid therapy following transurethral resection. The lesion in the third recurred and he improved after a second course of steroid therapy. CONCLUSIONS: Eosinophilic cystitis is a rare pathology. Sometimes, it may simulate bladder malignancies. Biopsy is mandatory at diagnosis. Usually, it has a benign course and may be treated with fulguration, analgesics, antihistaminics and steroids, although recurrence is possible.

Adult↗
PubMed1990

The role of abdominal and transrectal ultrasound and cytology in the detection of recurrent bladder tumours.

Transrectal and transabdominal ultrasound combined with cytology were compared with conventional cystoscopy as a mean of detecting recurrences of bladder tumours. One hundred and twenty-five patients underwent combination ultrasound in the outpatient department 1 week before cystoscopy. Combination ultrasound identified 90% of recurrent tumours and tumour identification with the results of ultrasound and cytology combined was 93%. The false positive rate was 2%. The ultrasonographer would have referred 97% of patients with recurrent tumour for cystoscopy. Combination ultrasound and cytology may be a satisfactory alternative to check cystoscopy in certain categories of bladder tumours.

Adult↗
PubMed2006

Recent improvements in the detection and treatment of nonmuscle-invasive bladder cancer.

In total, 70-80% of newly diagnosed bladder cancers are confined to the mucosa and staged as Ta, T1 or carcinoma in situ according to the 2002 tumor, lymph nodes and metastasis classification. The standard treatment for these nonmuscle-invasive bladder cancers is transurethral tumor resection with or without adjuvant intravesical chemotherapy or intravesical immunotherapy and subsequent follow-up. Diagnosis and follow-up of nonmuscle-invasive bladder cancer offers two main problems. First, approximately 10-20% of all tumors are not seen in standard cystoscopy. Additionally, frequently repeated follow-up cystoscopies are bothersome for the patient. As an adjunct to standard cystoscopy, fluorescence-guided cystoscopy has demonstrated significantly higher tumor detection rates and optimized patient treatment in recent Phase III studies. Second, routinely performed urine cytology is characterized by high specificity but low sensitivity. Today, several urine tests are available that may increase diagnostic accuracy and potentially prolong intervals of follow-up cystocopy. Owing to rather high recurrence rates after transurethral tumor resection in most tumors and high progression rates in poorly differentiated tumors, adjuvant intravesical chemotherapy or intravesical immunotherapy has gained widespread use in patients with nonmuscle-invasive bladder cancer. Only a few further immunomodulatory drugs, such as recombinant cytokines, have shown significant clinical effectiveness. Additional approaches, such as photodynamic therapy with different photosensitizers and thermotherapy in combination with intravesical chemotherapy, have been evaluated in Phase III studies.

Biomarkers, Tumor↗
PubMed2000

Practice patterns of Canadian urologists in benign prostatic hyperplasia and prostate cancer. Canadian Prostate Health Council.

PURPOSE: We reviewed the practice patterns of Canadian urologists in benign prostatic hyperplasia (BPH) and prostate cancer, and assessed the changes that occurred between 1995 and 1998. MATERIALS AND METHODS: In 1995 and 1998 questionnaires were mailed to all active members of the Canadian Urological Association who practiced adult urology in Canada. Many questions were similar, allowing for the assessment of changes in practice patterns. RESULTS: A number of changes were observed between 1995 and 1998. Cystoscopy and imaging of the upper urinary tract were used less often to evaluate uncomplicated cases of BPH. However, 39% of respondents continued to perform cystoscopy routinely. Finasteride was no longer administered in men with a smaller prostate. In 1998 before radical prostatectomy 28% of respondents routinely performed a bone scan, 29% cystoscopy and 57% chest x-ray. The number believing that maximal androgen blockade is the most effective hormonal therapy decreased from 90% to 62%, while 24% reported in the 1998 survey that they frequently administered intermittent hormonal therapy. Comparison with an American study from 1995 indicated that American urologists used the American Urological Association symptom score and performed a prostate specific antigen test more frequently than Canadian urologists. However, Canadian urologists performed cystoscopy more frequently. CONCLUSIONS: These surveys provide a useful insight into the variations in clinical practice of Canadian urologists and help to determine whether changes are occurring in regard to the development of practice guidelines. They also indicate the need to develop further guidelines, and ensure that these guidelines are widely promoted and accepted by the urological community.

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