Comparison of ImmunoCyt,UroVysion, and urine cytology in detection of recurrent urothelial carcinoma

BACKGROUND:

ImmunoCyt (uCyt) and UroVysion are ancillary studies that may aid in the detection of urothelial carcinoma in urine specimens. We compared ImmunoCyt and UroVysion to urine cytology in the ability to detect recurrent urothelial carcinoma.

METHODS:

Single voided urine samples were obtained from 100 patients who had a previous history of bladder cancer. All patients underwent cystoscopy immediately after urine sample collection. Forty‐one cystoscopically suspicious lesions were biopsied. Urine samples were divided and processed blindly and independently in 3 different laboratories for ImmunoCyt, UroVysion, and urine cytology (ThinPrep method).

RESULTS:

Of the 41 cystoscopically positive cases, most cystoscopy findings showed multiple tumors that were papillary and less than 1 cm. Biopsies showed many low‐grade tumors (54%). Overall sensitivity of cytology for low‐ and high‐grade urothelial cell carcinoma was 15% and 27%, whereas ImmunoCyt was 62% and 91% and UroVysion was 8% and 18%, respectively. Overall specificity of cytology was 97%, whereas ImmunoCyt was 63% and UroVysion was 90%.

CONCLUSIONS:

ImmunoCyt is more sensitive than either cytology or UroVysion in detecting low‐grade tumors. Both cytology and UroVysion have comparable specificity in cystoscopically negative cases. Whereas ImmunoCyt may improve the cytological detection of recurrent bladder cancer, UroVysion may be used as a confirmatory test for either cytology or ImmunoCyt. Cancer (Cancer Cytopathol) 2009. © 2009 American Cancer Society.     

uCyt+/ImmunoCyt in the detection of recurrent urothelial carcinoma: an update on 1991 analyses

BACKGROUND: The authors provide an update on the clinical value and role of the uCyt+/ImmunoCyt test as a noninvasive tool for the detection of recurrent urothelial carcinoma. METHODS: Between January 2002 and October 2004, 942 patients (mean age, 72.6 yrs; range, 32-87 yrs) were enrolled in this prospective study. These patients mostly had been followed for superficial urothelial carcinoma (UC) confined to the mucosa and lamina propria (pathologic tumor [pT] classification pTa, pT1, and pTis [carcinoma in situ]) for a mean of 15.62 months (range, 4-28 mos). Voided urinary cytology and the uCyt+/ImmunoCyt test for all patients were performed on liquid-based cytology slides. Patients underwent subsequent cystoscopy when cytology or uCyt+/ImmunoCyt results were positive and when they underwent biopsy evaluation of any suspicious lesion. Altogether, 1991 uCyt+/ImmunoCyt analyses were performed. RESULTS: Two hundred ninety-eight patients who had adequate samples available were diagnosed with histologically proven UC. The sensitivity of cytology increased from 8.3% for Grade 1 tumors to 75.3% for Grade 3 tumors; whereas, with the uCyt+/ImmunoCyt, the sensitivity was 79.3% for Grade 1 tumors, 84.1% for Grade 2 tumors, and 92.1% for Grade 3 tumors. For cytology and uCyt+/ImmunoCyt combined, the sensitivity was 79.3% for Grade 1 tumors, 90.9% for Grade 2 tumors, and 98.9% for Grade 3 tumors. CONCLUSIONS: The current data confirmed the clinical usefulness of the uCyt+/ImmunoCyt test in the follow-up of patients with recurrent UC. Used as a noninvasive tool, cytology escorted by uCyt+/ImmunoCyt may reduce the morbidity and cost of follow-up for patients who have a low risk of recurrence while avoiding superfluous cystoscopic examinations. However, additional studies will be necessary to establish and compare the morbidity and cost of each method.     

Evaluation of urine CYFRA 21-1 for the detection of primary and recurrent bladder carcinoma

BACKGROUND: The urinary concentration of soluble cytokeratin 19 fragments, measured by the CYFRA 21-1 assay, may be used for the noninvasive, early detection of bladder carcinoma. METHODS: This prospective study examined urine samples from 325 patients. The authors included 152 patients who presented with hematuria or irritative voiding symptoms (Group 1), 107 patients who were under surveillance after undergoing transurethral resection of bladder carcinoma (Group 2), 46 patients with urinary tract pathology other than bladder carcinoma (Group 3), and 20 healthy participants (Group 4). The urine concentration of CYFRA 21-1 was measured by an immunoradiometric assay. The patients in Groups 1 and 2 underwent cytoscopy and urine cytopathology. Biopsies were obtained if a tumor was seen on cytoscopy or if there was a suspicion of carcinoma in situ (CIS). RESULTS: The optimal cut-off concentration for the detection of primary bladder tumors, 4.9 microg/L, resulted in a sensitivity of 79.3% and a specificity of 88.6%. The optimal threshold for the detection of recurrent bladder tumors (excluding patients who had been treated with intravesical bacillus Calmette-Guerin [BCG]), 4.04 microg/L, resulted in a sensitivity of 76.2% and a specificity of 84.2%. There was no significant advantage for centrifugation of the urine samples or for determination of the creatinine concentration in the urine samples. The CYFRA 21-1 assay of urine samples provided a three-fold greater sensitivity compared with the sensitivity of cytology for detecting Grade 1 transitional cell tumors. CYFRA 21-1 detected 91.9% of Grade 3 tumors, 100% of CIS, and 92.8% of invasive bladder tumors (T2 or higher classification). The CYFRA 21-1 assay detected all tumors that had positive cytology with the exception of only one tumor. Conversely, the assay identified 71% of primary tumors and 65% of recurrent tumors that were missed by cytopathology. Urinary stones, infection, and previous intravesical BCG immunotherapy caused many false positive results. CONCLUSIONS: The urinary CYFRA 21-1 assay is a useful test for the noninvasive detection of bladder carcinoma and for surveillance of patients who were not treated previously with BCG. It may be used in combination with urine cytology and bladder ultrasound. Multi-institutional trials are required to compare the accuracy as well as the cost of this combination of tests with cystoscopy.     

Effect of intravesical Bacillus Calmette-Guérin on detection of a urothelial differentiation antigen in exfoliated cells of carcinoma in situ of the human urinary bladder

Flow cytometry was used to detect and quantify expression of a urothelial differentiation antigen (Om5) and nuclear DNA in exfoliated epithelial cells of the urinary bladder from 15 patients with nonpapillary carcinoma in situ during and after intravesical therapy with Bacillus Calmette-Guérin (BCG). Before BCG treatment exfoliated cells reacting with the mouse monoclonal antibody Om5 were found in 13 cases. Following treatment Om5 positive cells were still present in 9 cases but 4 patients who had had Om5 positive cells prior to BCG therapy no longer had detectable antigen-positive cells after therapy. Thus intravesical BCG therapy can alter detection of a urothelial differentiation antigen in exfoliated bladder epithelial cells. It is not certain whether this antigen or other differentiation antigens measured by flow cytometry will advance our present techniques for assessing effects of therapy on carcinoma in situ and other bladder tumors. However, five of nine patients showing persistence of Om5 positive cells after therapy were found to have recurrent tumor by biopsy and two others had positive cytology (median follow-up, 13 months). None of the four without detectable antigen-positive cells after therapy had clinical evidence of tumor by cystoscopy, biopsy, or cytology (median follow-up, 12 months). It now appears feasible and desirable to initiate clinical investigations of this and other differentiation antigens in combination with DNA by flow cytometry of bladder irrigation specimens.     

The effects of intravesical chemoimmunotherapy with epirubicin and bacillus Calmette-Guérin for prophylaxis of recurrence of superficial bladder cancer: a preliminary report

The effects of intravesical chemoimmunotherapy with epirubicin and bacillus Calmette-Guérin (BCG) for prophylaxis of recurrence of superficial bladder cancer (pTa, pT1) were investigated in 29 patients aged a median of 70 years between January of 1991 and May of 1993. The patients received intravesical instillation of 40 mg epirubicin immediately after transurethral resection (TUR) of the bladder cancer. At 1 week after TUR, 80 mg Tokyo-strain BCG was instilled into the bladder once a week for 6 weeks. Thereafter, the patients were followed by cystoscopy and urinary cytology at 3-month intervals until recurrence was detected. Of the 29 patients, 28 had no evidence of disease over a mean follow-up period of 20 months. The 1 case of recurrence occurred at 3 months after TUR and that patient died of cancer progression. The simple recurrence rate was 3.5% after therapy. According to the person-years method, the number of recurrent tumors per 100 patient-months was 0.17. The cumulative nonrecurrence rate determined for all cases was 96.5% at 30 months. Adverse reactions, including urinary frequency, urgency, and miction pain, among others, were observed in 27 patients (93%). Only 1 patient was withdrawn from the treatment because of severe bladder-irritation symptoms due to the BCG instillation. The intravesical chemoimmunotherapy with epirubicin and BCG seemed to be effective for prophylaxis of recurrence of superficial bladder cancer.Paper presented at the 5th International Conference on Treatment of Urinary Tract Tumors with Adriamycin/Farmorubicin, 24–25 September 1993, Hakone, Japan     

Assessing the Clinical Benefit of UBC Rapid in the Surveillance and Initial Diagnosis of Bladder Cancer

IntroductionSeveral studies have shown that abnormal urine levels of cytokeratins 8 and 18 are associated with bladder cancer. However, the clinical benefit of the UBC (urinary bladder cancer) Rapid assay has remained unclear.Patients and MethodsWe performed the UBC Rapid assay and voided cytology in 336 patients—297 in surveillance for non–muscle-invasive bladder cancer and 39 with newly diagnosed bladder cancer. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated by contingency. We also controlled for the patients with positive UBC Rapid findings but negative cystoscopy findings to prove the former’s ability to provide an anticipatory diagnosis.ResultsWe diagnosed 27 recurrences (9.8%). Overall, the sensitivity of the UBC Rapid assay was better for the higher risk groups and after adding the cytology findings. The only independent predictor of a positive UBC Rapid assay was the tumor size. Of the 81 patients with positive UBC Rapid findings without positive cystoscopy findings, 8 (10%) had developed a recurrence within the first year. Avoiding cystoscopy for the patients with UBC Rapid negative results could avoid 184 cystoscopies (66%) but would result in missing 7 of 13 high-risk recurrences.ConclusionsThe performance of the UBC Rapid assay improved with increasing tumor size. Limiting cystoscopies to patients with UBC Rapid positive results could result in a reduction in surveillance cystoscopies but could result in missing high-risk recurrences. Finally, the UBC Rapid assay was not useful for anticipatory diagnoses.     

Comparison of NMP22 BladderChek test and urine cytology for the detection of recurrent bladder cancer

OBJECTIVE: To assess the clinical performance of the NMP22 BladderChek test, which is a qualitative test, and to compare it with voided urine cytology for the detection of recurrent bladder cancer. We also evaluated whether cystoscopy can be omitted from the surveillance protocol by combining the two tests. METHODS: A total of 131 patients with a history of superficial transitional cell carcinoma of the bladder provided urine samples before a cystoscopic examination. Urine samples were assayed for the presence of NMP22 using the NMP22 BladderChek test and cytology was performed by a cytopathologist. Selected patients underwent a biopsy, with appropriate additional therapy. Results of the two tests were compared with that the results of cystoscopy, which was retained as the gold standard. For positive biopsies, the results of the NMP22 test and cytology were also correlated with the tumor stage and grade. RESULTS: Of the 46 recurrences detected by cystoscopy, the NMP22 test was positive in 39 cases and cytology in 19 cases. The sensitivity of the NMP22 test was 85%, which was significantly greater than that of cytology (41%). In particular, for low-risk tumors it was eight times more sensitive than cytology. The specificities of the NMP22 test and cytology were 77 and 96%, respectively. Combining the two tests increased overall sensitivity to 91%. However, 9% of the tumors were still not detected. CONCLUSION: The NMP22 BladderChek test is an in vitro qualitative test that is easily available and cheap; it can be performed by a urologist in the office and results can be interpreted within 30 min. The NMP22 test is superior to cytology for all grades and stages in the detection of recurrence in patients with a history of superficial bladder cancer. Our study indicates that the NMP22 test can be used as a substitute for urine cytology. The NMP22 test cannot replace cystoscopy, but it can be used as an adjunct to cystoscopy in the surveillance protocol for patients with superficial bladder cancer.     

Bacillus Calmette-Guerin intravesical instillation treatment for carcinoma in situ of the bladder. Gifu BCG Instillation Therapy Research Group

We performed a retrospective long-term study to evaluate the efficacy of intravesical instillation of Tokyo 172 strain Bacillus Calmette-Guerin (BCG) on carcinoma in situ (CIS) of the bladder. Between 1989 and 1998, 42 patients with CIS of bladder underwent intravesical instillation of BCG. In the follow-up period from 6 to 116 months (mean: 37.3 months), the efficacy rate of intravesical BCG instillation for CIS of the bladder was 81.0%. Two patients died from the bladder cancer. The non-recurrence rate in patients with grade 2 carcinoma (19 cases) was not significantly different from that in those with grade 3 carcinoma (23 cases). However, the recurrence rate in patients with secondary CIS (15 cases) was significantly higher than in those with primary CIS (27 cases). The recurrence of CIS was observed in 7 of 42 cases. In 6 of 7 patients, CIS recurred within one year after treatment. Total cystectomy was performed in 10 of 42 patients, and pathological findings of muscle layer invasion were detected in 8 patients. Although side effects occurred in 33 patients (77.5%), no clinically significant side effects were observed. Our results suggest that intravesical BCG therapy may be useful for the treatment of CIS of the bladder.     

Prevention of Recurrence of Superficial Bladder Cancers: Intravesical Instillation of Bacillus Calmette-guerin versus Bacillus Calmette-guerin plus Epirubicin

Purpose The short-term effects of intravesical chemoimmunotherapy with epirubicin and Bacillus Calmette- ‍Guerin (BCG) administered repeatedlly for prophylaxis of recurrence of superficial bladder cancer (pTa, pT1) were ‍investigated in 22 patients with a median of 70 years between March, 1995 and February, 1999, and were compared ‍with those of BCG monotherapy in 50 patients between March, 1995 and February, 1999. ‍Patients and Methods The patients underwent intravesical instillation of Tokyo-strain BCG with or without ‍epirubicin after transurethral resection (TUR) of bladder cancer. For the combined treatment, at 1❛2 weeks after ‍TUR, epirubicin (40 mg) and BCG (80 mg) were instilled into the bladder by turn once a week for 12 weeks. For the ‍BCG alone group, 80 mg instillation were performed with the same schedule. Thereafter, the patients were followed ‍by cystoscopy and urinary cytology every 3 months for up to 3 years after intravesical therapy. ‍Results and Conclusions The simple recurrence rate was 22.7% (5/21) in patients with chemoimmunotherapy ‍and 32.0% (16/50) in BCG-treated patients. Adverse reactions, including increased frequency of urination, urgency ‍and miction pain, were observed in 18 patients (85.7%) undergoing chemoimmunotherapy and 58.0% undergoing ‍BCG monotherapy. One patient receiving chemoimmunotherapy was withdrawn from treatment because of severe ‍bladder-irritation symptoms due to instillation. Intravesical chemoimmunotherapy using epirubicin and BCG was ‍inferior in comparison with BCG monotherapy for prophylaxis of recurrence of superficial bladder cancer.     

Long-term follow-up of intravesical bacillus Calmette-Guérin treatment for superficial transitional-cell carcinoma of the bladder involving the prostatic urethra

BACKGROUND: Intravesical bacillus Calmette-Guérin (BCG) is a treatment option for superficial (5-year follow-up. PATIENTS AND METHODS: Twenty-eight patients with high-risk superficial bladder cancer and prostatic urethral involvement were treated with once-weekly BCG for 6 weeks. Patients with prostatic stromal involvement were excluded. Maintenance was not used before 1995. Currently, we use maintenance BCG after induction. Patients were followed by cystoscopy/cytology and repeat biopsy to detect persistent and/or progressive disease. RESULTS: After 1 or 2 courses of once-weekly BCG for 6 weeks, 64.3% (18 of 28 of patients) exhibited a complete response in the bladder and prostate at their 6-month followup. Of those obtaining a complete response, 55.6% (10 of 18) experienced recurrence. Three recurrences were in the prostate: 1 isolated and 2 associated with multifocal bladder involvement. Twenty-eight percent (8 of 28 patients) underwent cystectomy because of failure of treatment to eradicate superficial disease or disease progression. Disease-specific survival was 89% (25 of 28 patients) at a median follow-up of 7.5 years. CONCLUSION: Our long-term data support the durability of intravesical BCG in select patients with superficial bladder transitional cell carcinoma with prostatic urethral involvement. Follow-up biopsy of the prostatic urethra is mandatory and, if positive, cystectomy is indicated. One third of patients will require cystectomy for persistent or progressive disease; therefore, careful surveillance is critical.     

The study on intravesical instillation of THP in the treatment of in-situ and superficial bladder cancers]

The efficacy and safety of Pirarubicin (THP), administered by intravesical instillation, have been studied in recurrent multiple superficial bladder cancer patients and patients who tested positive by urine cytology but lacked protuberant legions (CIS). The average age and range of the 19 patients (M 15, F4) studied were 63.3 (37-84). Twelve patients had protuberant, multiple cancer and 7 patients had CIS. Sixteen of the cases were recurrent disease. Twenty mg THP, delufed in 40 ml of 5% glucose solution were instilled for 2 hours once or twice a week. Each patients received 8 treatments. One week after the last treatment, the therapeutic result was evaluated on the bases of cystoscopy and urine cytology. Before and after administration, CBC and biochemical blood tests were run. Nine of the 12 patients (75%) with multiple recurrent tumor and all the 7 patients with CIS showed complete response. The total outcome for CR was 84.2% in this study. Intravesical instillation with THP did not cause any serious side effects.     

A comparative clinical trial of UFT medication and intravesical BCG in the recurrence of superficial bladder cancer. Study Group of UFT and BCG adjuvant therapy for bladder cancer

In sixty-four patients who had TUR-bt for superficial bladder cancer, the effect of intravesical BCG and UFT medication were compared. Group A (n = 20) were treated with BCG, group B (n = 22) were treated with UFT and group C (n = 22) were treated with both agents. The patients were followed up for more than 12 months by cystoscopy at a interval of 3 months, urinary cytology and bladder cold cup biopsy, if necessary. Thirteen of the 20 patients in group A and 13 of the 22 patients in group B were free of tumors, compared to 5 of the 22 patients in group C. Although the recurrence-free-rate in each group does not differ significantly, the combination therapy of intravesical BCG and UFT medication seems to decrease the rate of tumor recurrence for superficial bladder cancer. Side effects of BCG and UFT were tolerated well.     

A prospective randomized trial of maintenance versus nonmaintenance intravesical bacillus Calmette-Guérin therapy of superficial bladder cancer

Between August 1981 and July 1984, 93 patients with polychronotopic superficial papillary carcinoma (Ta and/or T1), flat carcinoma in situ (Tis), or concomitant superficial papillary and in situ bladder carcinoma were entered into a prospective randomized trial of maintenance v nonmaintenance intravesical bacillus Calmette-Guérin (BCG) therapy. Forty-six patients who received BCG weekly for 6 weeks were compared with 47 patients receiving the six-weekly doses of BCG plus monthly BCG for 2 years. Both groups were evaluated every 3 months by cytology, cystoscopy, and biopsy. A significant reduction in the number of recurrent tumors per patient-month was demonstrated for both groups (P less than .0001); however, the difference in reduction of tumors between the two groups was not significant. Additionally, patients receiving maintenance and nonmaintenance therapy had similar tumor recurrence and progression rates. These results indicate that monthly maintenance BCG does not prevent, delay, or reduce tumor recurrence or progression observed with the 6-week regimen. Maintenance BCG was associated with increased local toxicity, primarily dysuria, frequency, and urgency. Dosage reduction was required in 22 of 47 patients (46.8%). When the data were subjected to multivariate analysis, the presence or absence of tumor following induction BCG and PPD skin test results were found to be significant variables. Controlling for either the presence or absence of tumor following induction BCG, tumor recurrence and progression rates were not significantly different for the two treatment groups. However, the absence of tumor after induction BCG was associated with a longer disease-free duration (P = .00001) and time to progression (P = .095). Patients with a reactive tuberculin skin test before and after induction BCG had significantly less tumor recurrences than patients with different PPD skin tests results (P = .02). Tumor progression was not related to tuberculin skin testing.     

The prognostic value of cytology and fluorescence in situ hybridization in the follow‐up of nonmuscle‐invasive bladder cancer after intravesical Bacillus Calmette‐Guérin therapy

Molecular markers reliably predicting failure or success of Bacillus Calmette‐Guérin (BCG) in the treatment of nonmuscle‐invasive urothelial bladder cancer (NMIBC) are lacking. The aim of our study was to evaluate the value of cytology and chromosomal aberrations detected by fluorescence in situ hybridization (FISH) in predicting failure to BCG therapy. Sixty‐eight patients with NMIBC were prospectively recruited. Bladder washings collected before and after BCG instillation were analyzed by conventional cytology and by multitarget FISH assay (UroVysion®, Abbott/Vysis, Des Plaines, IL) for aberrations of chromosomes 3, 7, 17 and 9p21. Persistent and recurrent bladder cancers were defined as positive events during follow‐up. Twenty‐six of 68 (38%) NMIBC failed to BCG. Both positive post‐BCG cytology and positive post‐BCG FISH were significantly associated with failure of BCG (hazard ratio (HR)= 5.1 and HR= 5.6, respectively; p < 0.001 each) when compared to those with negative results. In the subgroup of nondefinitive cytology (all except those with unequivocally positive cytology), FISH was superior to cytology as a marker of relapse (HR= 6.2 and 1.4, respectively). Cytology and FISH in post‐BCG bladder washings are highly interrelated and a positive result predicts failure to BCG therapy in patients with NMIBC equally well. FISH is most useful in the diagnostically less certain cytology categories but does not provide additional information in clearly malignant cytology. © 2009 UICC     

Carcinoma in situ of the urinary bladder. Effect of associated neoplastic lesions on clinical course and treatment

Clinical courses of 67 patients with carcinoma in situ (CIS) of the urinary bladder during 14 years from 1971 to 1984 were investigated according to the clinical type of CIS and treatment methods. CIS was classified into four types: the primary group included 18 patients who had neither prior nor simultaneous tumors of the urinary tract; the secondary group included 10 patients who had CIS diagnosed subsequent to the treatment of superficial papillary bladder tumor; the concurrent group included 14 patients who had CIS concomitantly with superficial papillary bladder tumor; and the nonpapillary T1 group included 25 patients who presented with CIS with concomitant nonpapillary T1 tumor. As a rule, the initial treatment was conservative (transurethral resection [TUR] or intravesical chemotherapy) for the primary, secondary, and concurrent CIS groups, whereas treatment was radical (total cystectomy or irradiation) for the nonpapillary T1 group. Five-year survival rates of the primary, secondary, concurrent, and nonpapillary T1 groups were 41%, 100%, 49%, and 68%, respectively. Secondary CIS revealed a rather good prognosis, probably due to the early detection of CIS and early application of intravesical chemotherapy when compared to other groups. Except for patients with nonpapillary T1 tumors, the 5-year rate of malignant progression (invasion or metastasis) and multiple recurrences leading to delayed cystectomy was 81% in 16 patients treated by TUR, whereas it was 39% in 21 patients treated by instillation therapy. It appears likely that intravesical chemotherapy was preferable to other conservative therapies as an initial treatment of CIS. Radical therapy, however, may be the choice for CIS with nonpapillary T1 tumors, ab initio.     

Alternatives to cytology in the management of non-muscle invasive bladder cancer

Opinion statement The natural history of non-muscle invasive bladder cancer is characterized by a high probability of recurrence and in the case of high-grade tumors, progression to muscle invasive cancer. This mandates a follow-up strategy designed to identify recurrences in the bladder early in their evolution in order to facilitate early intervention and ablation. Urine cytol-ogy is considered the gold standard urine biomarker. Although specificity exceeds 90% to 95%, its overall sensitivity ranges from 40% to 60% in expert hands and is both tumor grade and operator dependent. While cytology is an excellent test for detection of high-grade disease, the sensitivity is particularly weak for the detection of low grade tumors. This has spawned an entire field of research of in vitro diagnostic tests and cell-based assays in order to improve the diagnostic accuracy for detection of incident or recurrent disease. To date, the US Food and Drug Administration approved dipstick and immunoassays marketed as point-of-care tests. The point-of-care tests are intended for use as an adjunct to cystoscopy and cytology, and may have a role in the office evaluation of hema-turia patients. Monoclonal antibody-based tests combined with cytology may improve the diagnostic accuracy and are superior to cytology alone. A recently approved cell-based assay, utilizing fluorescent in situ hybridization technology, may help resolve suspicious cytologies, and provide early and additional information about the biology of the bladder urothelium beyond that provided by cytology, a marker of disease relatively late in evolution. Novel promising markers are in various stages of clinical testing, and a panel of biomarkers may serve in the future as a feasible alternative to urine cytology and cystos-copy for the screening, detection, and follow-up of non-muscle invasive bladder cancer.     

Impact of bacillus Calmette–Guérin therapy of upper urinary tract carcinoma in situ: comparison of oncological outcomes with radical nephroureterectomy

The clinical benefits of bacillus Calmette–Guérin (BCG) therapy for the management of upper urinary tract carcinoma in situ (CIS) remain unclear. We aimed to compare the efficacy and safety of BCG therapy for upper urinary tract CIS with those of radical nephroureterectomy (RNU). Of 490 patients with upper urinary tract carcinoma, we retrospectively reviewed the post-treatment course of 58 patients with upper urinary tract CIS who underwent either RNU (RNU group) or BCG therapy (BCG group). Efficacy and safety were compared between the RNU and BCG groups. Inverse probability treatment-weighted (IPTW)-adjusted multivariate Cox regression analysis was performed to identify the influence of BCG therapy on prognosis. The RNU and BCG groups included 20 and 38 patients, respectively. No significant difference was found in patients’ background, including age, sex, and performance status, between the groups. The reason underlying the selection of BCG therapy was bilateral CIS of the upper urinary tract (50%), solitary kidney (26%), unwillingness to undergo RNU (13%), and ineligibility for surgery (11%). The cytology became negative in 30 (79%) out of 38 patients after a 6-week course of BCG therapy, and 17 (57%) out of 30 patients remained negative. BCG-related adverse events (AEs) were observed in 92% of patients. The most common AE was cystitis (76%), followed by fever (50%). No significant differences were found in the progression-free, cancer-specific, and overall survivals between the RNU and BCG groups. IPTW-adjusted multivariate analysis revealed that BCG therapy did not worsen the prognosis of these patients. The limitations of our study were its retrospective design and small sample size. In conclusion, BCG therapy for upper urinary tract CIS might be a useful alternative for patient ineligible for RNU under careful observation for AEs.     

The efficacy of Bacillus Calmette-Guerin instillation therapy of the upper urinary tract for carcinoma in situ

Background. Treatment of carcinoma in situ (CIS) of the upper urinary tract is still difficult. In this study, we assessed the efficacy and safety results of Bacillus Calmette-Guerin (BCG) instillation therapy for CIS of the upper urinary tract. Methods. Thirteen renal units with CIS in eight patients 60–77 years old (median, 68 years) were treated with BCG. BCG (Tokyo 172 strain) was instilled at a dose of 160 mg into each renal unit once a week for 6 consecutive weeks via nephrostomy. The follow-up period ranged from 7 to 63 months (median, 26 months). Results. Of 13 renal units in eight patients, 12 units (92.3%) in eight patients became negative by cytology. Only 1 renal unit showed recurrence. The duration of the response ranged from 7 to 63 months (median, 25 months). Few side effects were observed after BCG instillation. Fever was most frequent (6/8, 75%), followed by symptoms of irritation such as frequency (5/8, 62.5%). Conclusion. BCG instillation therapy is safe and effective for CIS of the upper urinary tract. It can be used as a first-line therapy instead of any surgical option. Received: February 4, 1999 / Accepted: June 21, 1999     

Feasibility of Photodynamic Diagnosis for Challenging TURBt Cases Including Muscle Invasive Bladder Cancer,BCG Failure or 2nd-TUR

Background: Despite widely adopted standard methods for follow-up including cystoscopy plus cytology,recurrence rates of non muscle-invasive bladder cancer (NMIBC) have not improved over the past decades, stillranging from 60% through 70%. Hence, widely acceptable surveillance strategies with excellent sensitivity areneeded. Early recurrence has led to the development of a novel cystoscopy technique utilizing photodynamicdiagnosis (PDD). Although, no studies have evaluated the efficacy of PDD for patients of MIBC, BCG failure or2nd-transurethelial resection (TUR). Materials and Methods: The present study was performed from October2012 through May 2013. IRB approved 25 patients initially underwent a cystoscopy examination of white lightand blue light followed by the resection of tumors identified. Resections were performed from bladder mucosaareas considered suspicious at PDD, along with PDD negative normal bladder mucosa area resected by randombiopsy. Specimens were divided into two groups, PDD positive and negative. Primary endpoints were sensitivityand specificity. Results: A total of 147 specimens extracted from 25 patients were included in the analysis. Some45 out of 92 PDD-positive specimens were confirmed to have bladder cancer, and 51 out of PDD-negative 55specimens were confirmed to be cancer negative. The sensitivity of PDD was 91.8% (45/49) and specificity was52.0% (51/98). The sensitivity:specificity was 89.5% (17/19) : 47.6% (30/63) in 12 2nd-TUR patients, 90.5%(19/21) : 61.1% (11/18) in seven MIBC patients, and 95.0% (19/20) : 48.5% (16/33) in eight failed BCG cases.Conclusions: PDD-TURBT has high sensitivity to diagnose BC even for 2nd-TUR, MIBC or BCG failure cases.     

Quick-staining urinary cytology and bladder wash image analysis with an integrated risk classification: a worthwhile improvement in the follow-up of bladder cancer?

BACKGROUND: With an end toward an increase in patient quality of life, morphologic methods were tested for their combinatory value in expanding the effectiveness of follow-up appointments and finding a more specific supervision of patients with bladder cancer. METHODS: Voided urine and bladder washing specimens were gathered in 223 follow-up sessions of 124 patients with a history of bladder cancer. Hemacolor (Merck, Darmstadt, Germany)-stained cytospin preparations of voided urine specimens were ready for diagnosis within 15 minutes, and results were available shortly before cystoscopy. Feulgen-Schiff-stained cytospin preparations of bladder washings entered the image analysis system. A special software was used to classify the DNA histogram by a risk factor for bladder cancer. RESULTS: Follow-up of patients revealed 83 tumor recurrences. Depending on the grade of the underlying tumor, the sensitivity of quick-staining cytology was 86.4%, 46.2%, or 13.6% for grade 3 to grade 1 TCC, respectively. Cytology and image analysis data demonstrated complementary potency. The combination of methods increased sensitivity to 90.9%, 66.7%, and 31.8%, respectively. Although 24 of 140 image analyses denoted high risk for bladder cancer without simultaneously visible tumor, correct evidence of high risk could be found for 92.2%. CONCLUSIONS: The combinatory use of quick-staining urinary cytology and bladder wash image analysis was demonstrated to be most valuable in diagnosing recurrent bladder cancer and selecting patients needing more intensive follow-up. At a minimum of patients discomfort, the tested combination also seems helpful to surpass diagnostic limits in cystoscopy and cytology caused by therapeutic effects on the bladder epithelium. Cancer (Cancer Cytopathol) Copyright 1999 American Cancer Society.