Monitoring intravesical bacillus Calmette-Guerin treatment of superficial bladder carcinoma by postoperative urinary cytology

We studied 51 patients with superficial bladder carcinoma who had been treated with transurethral resection of all gross tumor followed by intravesical bacillus Calmette-Guerin weekly for 6 weeks. Within 72 hours of either the first or second quarterly cystoscopic surveillance examination after bacillus Calmette-Guerin therapy, a conventional cytology study was obtained. Of these patients 8 (15.7 per cent) had positive, 9 (17.6 per cent) suspicious and 34 (66.7 per cent) negative postoperative cytology studies. Subsequent tumor recurrence was defined as a positive biopsy or visible papillary tumors on cystoscopic examination. All 8 patients with a positive postoperative cytology study had tumor recurrence at a median interval of 4 months. Of the 9 patients with a suspicious study 7 (77.8 per cent) had recurrent tumor at a median interval of 7 months and 2 (22.2 per cent) had no evidence of disease at 16 and 19 months, respectively. Of the 34 patients with a negative postoperative cytology study 13 (38.2 per cent) had tumor recurrence after a median interval of 4 months and 21 (67.8 per cent) had no evidence of disease after a median of 25 months. The tumor recurrence rate in patients with a positive or suspicious postoperative cytology study was significantly greater than that of patients with a negative study (p equals 0.001, Fisher's exact test). Postoperative cytology appears to be a significant prognostic indicator following transurethral resection and intravesical bacillus Calmette-Guerin treatment of superficial bladder carcinoma.     

Correlation of cytology and cystoscopy.

A total of 152 patients had cytology and cystoscopy performed for either initial or recurrent bladder tumors and postoperative control examinations. Positive cytology was found in 97 per cent of patients with pathologically proved bladder tumors. However, 23 per cent of the patients with negative cytology had positive cystoscopic and pathologically proved findings. Without cystoscopic examination a significant number of recurrent tumors may be missed because of a negative cytology.     

Can transabdominal ultrasonography of the bladder replace cystoscopy in the followup of superficial bladder tumors?

Transabdominal ultrasonography of the bladder was performed on 100 patients 3 to 9 months after endoscopic resection of stage Pa or Pl transitional cell carcinoma of the bladder. In 81 patients there was a close correlation between the results of suprapubic ultrasonography and cystoscopy. In 19 patients the ultrasonography results were incorrect: 4 had false positive and 15 had false negative findings. Specificity for the diagnosis of recurrence was 90 per cent and sensitivity was 74 per cent. Transabdominal ultrasonography combined with cytology studies should be part of the diagnostic approach for recurrent superficial bladder tumors. When performed before cystoscopy these studies should reduce greatly without eliminating the frequency of this investigation.     

Bacillus Calmette-Guerin for superficial transitional cell carcinoma of the bladder

Pasteur strain bacillus Calmette-Guerin was used to treat superficial transitional cell carcinoma of the bladder in 28 patients. Patients selected for treatment had an incomplete resection, positive selected site biopsies and/or post-resection positive cytology findings. Complete response required negative histology and cytology findings at cystoscopic followup 4 to 8 weeks after completion of treatment. Of the patients 20 (71 per cent) demonstrated a complete response, including all 6 with carcinoma in situ. Results converted to negative in 16 of 17 patients with positive urine cytology findings and 4 with positive prostatic urethral biopsies. Of the responders 8 had received prior treatment with thiotepa. The treatment regimen of 120 mg. Pasteur strain bacillus Calmette-Guerin weekly for 6 weeks was well tolerated. It was necessary to limit the number of treatments to 5 because of local irritative effects in only 3 patients. No chronic bladder disability has been noted during followup of 3 to 30 months. This experience supports the efficacy of bacillus Calmette-Guerin as a cost-effective, well tolerated treatment modality for patients with superficial transitional cell carcinoma of the bladder.     

Flow cytometry as a predictor of response and progression in patients with superficial bladder cancer treated with bacillus Calmette-Guerin

Simultaneous bladder wash flow cytometry, voided urinary cytology and cystoscopic examinations were performed at 3-month intervals during a median of 18 months (range 5.5 to 50 months) in 65 patients receiving intravesical bacillus Calmette-Guerin treatment for superficial bladder cancer. Of the 65 patients treated 36 (56 per cent) had a complete response, 12 (18 per cent) had no response and 17 (26 per cent) had progression. Results of examinations at 6 months suggested that a negative bladder wash flow cytometry (29 of 36 patients, r equals 0.73, p less than 10(-7) is a strong predictor of response to bacillus Calmette-Guerin, comparable with cytological (r equals 0.60, p less than 10(-7) or cystoscopic (r equals 0.38, p less than 0.005) examinations alone or combined with cytology (r equals 0.74, p less than 10(-7)). At 6 months a positive bladder wash flow cytometry (r equals 0.44, p less than 0.0005) is as strong a predictor of disease progression as a positive cystoscopic examination (r equals 0.43, p less than 0.0005). The combination of bladder wash flow cytometry and voided urinary cytology is not superior to positive bladder wash flow cytometry alone. Median estimated interval to progression for these patients treated with bacillus Calmette-Guerin was 38 months. In the subgroup with positive bladder wash flow cytometry at 6 months the median interval to progression was 30 months. With a negative bladder wash flow cytometry at 6 months the probability of survival free of progression at 30 months was 85 per cent (p less than 0.01). Thus, negative bladder wash flow cytometry at 6 months is a strong predictor of response to bacillus Calmette-Guerin and also survival free of progression.     

Results of 6 weekly intravesical bacillus Calmette-Guerin instillations on the treatment of superficial bladder tumors

We evaluated 104 patients with superficial bladder tumors for response to intravesical bacillus Calmett-Guerin therapy. Patients received 6 weekly intravesical bacillus Calmette-Guerin instillations and they were followed for response every 3 months with urinary cytology, cystoscopy and bladder biopsy. Patients were considered treatment failures if either the cytology studies or biopsies were positive for tumor. Of 65 patients who failed the initial treatment course 57 were given an additional 6-week course of therapy. One 6-week course of bacillus Calmette-Guerin was successful in 20 of 55 patients (36 per cent) treated for prophylaxis, 12 of 32 (37 per cent) treated for carcinoma in situ and 7 of 17 (41 per cent) treated for residual tumor. The response rate for the total patient population treated with 1, 6-week course was 37.5 per cent (39 of 104). A second 6-week course was successful in 19 of 29 patients (65 per cent) treated for prophylaxis, 11 of 18 (71 per cent) treated for carcinoma in situ and 4 of 10 (40 per cent) treated for residual tumor. The response rate for all patients receiving a second course of bacillus Calmette-Guerin was 59.6 per cent (34 of 57). Of 6 patients who refused another 6-week course of bacillus Calmette-Guerin 4 had additional recurrences and 3 of these 4 suffered invasive disease. The over-all therapeutic response rate for patients treated with either 6 or 12 weeks of therapy was 70 per cent. These results suggest that 6 weeks of intravesical bacillus Calmette-Guerin do not provide optimal therapy for superficial bladder tumors. The data further suggest that more intensive regimens may increase therapeutic efficacy.     

Further study of fibrinogen degradation products in bladder cancer detection

A new, rapid immunoassay kit for assaying fibrinogen degradation products (FDP) was studied in 56 patients with cancer of the bladder and in 48 control patients. The specificity of the kit was demonstrated with a small number of false positive results. In bladder cancer patients with low-stage, small superficial tumors, FDP was positive in 32.2 per cent. The combination of urinary cytologic examination with FDP increased the accuracy of the positive results to 80 per cent. The rapid FDP test supplements the urinary cytology in the follow-up and detection of early bladder cancer.     

Positive urinary cytology after tumor resection: an indicator for concomitant carcinoma in situ

Concomitant urothelial atypia (grade II atypia or carcinoma in situ) is predictive of new tumor growth after transurethral tumor resection. Concomitant urothelial atypia can be demonstrated by pre-selected site mucosal biopsies. However, a number of patients have new tumors despite normal pre-selected site biopsies. To investigate whether urinary cytology is a better indicator for concomitant urothelial atypia than pre-selected site biopsies, we studied in bladder tumor patients the correlation between the findings of pre-selected site biopsies (8 per patient) at tumor resection and urinary cytology (2 per patient) after successful resection. Concomitant urothelial atypia was demonstrated by biopsies in 52 per cent of the patients, of whom 60 per cent had grade II atypia and 40 per cent had carcinoma in situ. All patients with concomitant carcinoma in situ in biopsies had positive cytology findings. Of the patients with concomitant grade II atypia in biopsies 15 per cent had negative cytology studies. In 48 per cent of the patients no urothelial atypia in pre-selected site biopsies was demonstrable. However, cytology was positive, that is neoplastic cells were present, in 64 per cent of these specimens (19 patients). Of the 19 patients 16 currently have had demonstrable urothelial atypia in pre-selected site mucosal biopsies at a later occasion. We conclude that urinary cytology seems to be a better indicator for the presence of concomitant urothelial atypia than pre-selected site mucosal biopsies and, therefore, it can be used as a screening procedure for patients without demonstrable concomitant carcinoma in situ at tumor resection.     

Superficial bladder cancer treated with bacillus Calmette-Guerin: a multivariate analysis of factors affecting tumor progression

A multivariate analysis was performed on data from 221 patients with superficial bladder tumors (papilloma in 30, grade II to III stage Ta in 51, grade II to III stage Tis in 111 and grade II to III stage T1 in 29) who were treated with intravesical bacillus Calmette-Guerin and followed for a minimum of 24 months or until progression. The purpose of this analysis was to identify prognostic variables predictive of tumor progression defined as muscle invasion, metastasis or endoscopically uncontrolled superficial bladder carcinoma involving the bladder and/or prostatic urethra. Variables examined before bacillus Calmette-Guerin, and at 3 and 6 months after bacillus Calmette-Guerin included age, sex, race, purified protein derivative reaction, duration of disease, tumor category, tumor grade, multifocality, results of cytology, flow cytometry, cystoscopy, biopsy, prior chemotherapy and bacillus Calmette-Guerin treatment regimen. Significant variables (Cox regression analysis, p less than 0.07) for tumor progression were before bacillus Calmette-Guerin--stage T1 tumors and duration of disease less than 1 year, at 3 months after bacillus Calmette-Guerin--stage T1 tumor, duration of disease less than 1 year, positive cytology studies and multifocality, and at 6 months after bacillus Calmette-Guerin--stage T1 tumor, positive cytology and positive biopsy other than stage T1 tumors. Prognostic risk groups were best defined at 6 months after bacillus Calmette-Guerin, the probability of tumor progression thereafter being at 1, 3 and 5 years, respectively, as follows: for risk group 1 (T1 tumor)--71, 100 and 100 per cent, for risk group 2 (positive biopsy other than T1 plus positive cytology)--25, 79 and 100 per cent, for risk group 3 (either positive biopsy other than stage T1 or positive cytology studies)--18, 40 and greater than 81 per cent, and for risk group 4 (negative biopsy and negative cytology studies)--2, 11 and 26 per cent, respectively. Evaluation of patients with superficial bladder carcinoma at 6 months after intravesical bacillus Calmette-Guerin therapy identifies the probability of tumor progression. Patients at high risk for tumor progression require alternative treatment strategies, whereas low risk patients can be observed for further therapy if necessary.     

The influence of lower urinary tract infection on the recurrence rate of superficial transitional cell carcinoma of the bladder

We studied retrospectively 78 patients with recurrent superficial bladder tumors in an effort to determine whether transitional tumor cells implant and grow preferentially in patients who have undergone endoscopic resection of stage T1 bladder tumors in the presence of an inflamed urothelium. Of the patients 32 (group 1) had an undetected lower urinary tract infection at the time transurethral resection was performed and 46 (group 2) were free of infection. All patients had intravesical chemotherapy by thiotepa (triethylenethiophosphoramide) and were treated with appropriate antibiotics as soon as the urinary tract infection was recognized from 24 to 48 hours postoperatively. Of the patients in group 1, 37.5 per cent had tumor recurrence in less than 6 months and 15.6 per cent in less than 3 months, compared to 30.4 and 6.5 per cent, respectively, in group 2. Although the tumor recurrence rates 3 and 6 months postoperatively were higher among the group 1 patients (with urinary tract infection) the difference between the 2 groups was not significant. Because the patients were treated by intravesical chemotherapy, and antibiotics in those with urinary tract infection, our study does not allow a definite conclusion regarding the contribution of urinary tract infection on the recurrence rate of superficial bladder tumors.     

Recurrences during the chemoprophylactic treatment of superficial tumors of the bladder

A total of 88 patients who underwent resection for superficial stages Ta and T1 bladder tumors received chemoprophylactic treatment to prevent recurrence postoperatively. The first 44 patients were given doxorubicin at monthly intervals and the second 44 received doxorubicin plus mitomycin C alternately, with the first 6 instillations at weekly intervals and the rest monthly beginning 1 month after resection. Recurrences during treatment were assessed as an index of drug resistance. Tumor developed while the patients were undergoing treatment (9 to 10 months) in 15.9 per cent (7 of 44) of group 1 patients, 18.1 per cent (8 of 44) of group 2 patients and 17.0 per cent (15 of 88) of the total patients studied. At the initial post-treatment cystoscopy 12 to 16 months later 2 more patients in group 1 and none in group 2 had recognizable tumors. Treatment was continued in patients with recurrences. A total of 41 recurrences in 435 months of followup was recorded, for a rate of 9.42 recurrences per 100 patient-months. No worsening of the histological grading was noted but 2 patients with initial stage T1 disease had subsequent carcinoma in situ.     

Management of superficial transitional cell carcinoma in the intramural ureter: what to do?

PURPOSE: We analyze the evolution of superficial transitional cell carcinoma in the intramural distal ureter treated with transurethral resection. MATERIALS AND METHODS: A total of 19 patients underwent transurethral resection of the intramural distal ureter with a mean followup of 57 months. All cases were diagnosed as superficial transitional cell carcinoma and all but 2 had a history of bladder tumor. Upper urinary tract followup consisted of excretory urography every 6 months and ureterorenoscopy in cases with a doubtful diagnosis or positive cytology. RESULTS: Pathological examination revealed stage Ta disease in 42%, T1 in 31.5% and Tx in 26.3% of intramural tumors. Upper urinary tract recurrence was noted in 8 patients (42.1%), including 5 (62.5%) with involvement of the distal ureter. Nontumoral stenosis of the distal ureter in 3 cases was treated endoscopically. An endoscopic procedure resolved 75% of recurrences. A high surgical risk patient who did not undergo open surgery died of recurrence. CONCLUSIONS: Superficial transitional cell carcinoma of the intramural ureter is uncommon in the setting of multiple bladder tumors and recurrent bladder carcinoma. There was a 42.1% rate of ipsilateral recurrence and endoscopic treatment allowed us to preserve 89.5% of the involved renal units. Closer followup of the urinary tract must be performed since these tumors have a higher incidence of upper urinary tract recurrence.     

Conservative management of muscle-infiltrating bladder cancer: prospective experience

Between May 1979 and July 1983, 217 consecutive patients with documented primary bladder tumors invading muscle were evaluated to determine the fate of patients with conservatively treated muscle-infiltrating bladder cancer. The disease was re-staged by urine cytology, bimanual examination with the patient under anesthesia and transurethral biopsy or resection. Of the 217 patients 172 underwent total or partial cystectomy and 45 (21 per cent, 37 with stage T2, 7 with stage T3a and 1 with stage T4 disease) did not because re-staging showed no residual tumor (stage T0) in 20, carcinoma in situ in 17, stage T1 tumor in 4 and local stage T2 cancer in 4. The median followup was 5.1 years (range 3 to 7 years). Of the 45 patients 30 (65 per cent) are free of tumor or have required transurethral resection and intravesical therapy for recurrent tumors but cystectomy has not been necessary. Of the 15 failures 11 underwent cystectomy 9 to 30 months after re-staging (7 are alive and 4 died of disease) and 4 are alive with metastatic disease (2 with negative bladder biopsies). Re-staging in the 4 patients who died showed stage T0 disease in 2, carcinoma in situ in 1 and stage T2 tumor in 1. The over-all survival rate was 82 per cent (37 of 45) and it was 67 per cent (30 of 45) for patients with a functioning bladder. The data suggest that endoscopic re-staging may identify a subset of patients with limited muscle-infiltrating bladder tumors that can be managed conservatively without immediate cystectomy.     

Stage T1, grade 3 transitional cell carcinoma of the bladder: an unfavorable tumor?

Transurethral resection only was performed in 172 patients with initial stage Ta, T1 transitional cell carcinoma of the bladder. Additional treatment during the course of disease was given to 9 patients with carcinoma in situ and to 8 patients with tumor progression. The mean followup was 106 months. The 10-year survival rates were 95 per cent for patients with stage Ta, grade 1 disease, 89 per cent for stage Ta, grade 2, 84 per cent for stage Ta, grade 3, 78 per cent for stage T1, grade 2 and 50 per cent for stage T1, grade 3. The percentage of first tumor recurrence at the same site increased with tumor grade (stage T1, grade 3 was 74 per cent). The recurrence rate in stage T1, grade 3 tumors (4.08) differed significantly from the other groups of superficial tumors. The tumor progression rate for stage T1, grade 3 tumors (32.5 per cent) was significantly higher as well. The characteristics of stage T1, grade 3 tumors with and without progression were different in regard to multiplicity, recurrence rate, mean interval to recurrence and type of tumor invasion. Of the 13 patients who died of progressive neoplastic disease 11 presented initially with stage T1, grade 3 tumors. When these results are considered it is obvious that a patient with a stage T1, grade 3 tumor deserves additional therapy, such as chemotherapy, immunotherapy or phototherapy.     

Evaluating the need for transurethral bladder biopsy at first follow up after intravesical BCG therapy for superficial bladder cancer: Preliminary data

IntroductionPatients with high-risk superficial transitional cell carcinoma (TCC) of the bladder have a lifelong risk of progression and require particular attention. Intravesical Bacillus Calmette-Guerin (BCG) is recommended as a first-choice adjuvant treatment to reduce the risk of progression of high-grade tumors and carcinoma in situ (CIS).ObjectivesTo evaluate the need for routine transurethral bladder biopsy from the site of previously resected tumor three months following intravesical BCG therapy, even if the urine cytology and cystoscopy were both negative.Subjects and methodsA prospective study was carried out on 45 patients of both genders presenting with superficial bladder cancer. All patients received a six-week course of intravesical BCG. The mean age of the patients was 59 (range 33–80) years. Three months following resection, urine cytology was negative in all patients. Cystoscopy was then performed and although it was negative for any suspicious lesions, a routine biopsy from the previous resection site was taken.ResultsThe indication for BCG instillation was T1G1 in 20 patients (44%), T1G2 in 12 patients (27%) and TaG2 in eight patients (18%). Three patients (7%) had a positive bladder biopsy for malignancy at follow-up despite the negative cystoscopy and cytology. There were no statistically significant differences between patients with positive and those with negative biopsies with regard to the stage and grade of the tumor before resection or the number of resected lesions. The original pathology of the three positive patients was T1G1 (two patients) and T1G2 (one patient). The pathology after BCG treatment was the same as before instillation, T1G1 (two patients) and T1G2 (one patient).ConclusionUntil more studies on larger numbers of patients are done, a routine biopsy from the site of previously resected tumor at the time of check cystoscopy may improve the detection of tumor recurrence.     

Implications of peritoneal washing cytology in patients with potentially resectable pancreatic cancer

BACKGROUND: The aim of this study was to assess the implications of positive peritoneal washing cytology for management of patients with potentially resectable pancreatic cancer.METHODS: Cytological examination of peritoneal washings was performed in 134 patients who underwent surgical resection for pancreatic adenocarcinoma. The clinicopathological findings and the relationship between cytology results (including cytomorphology) and survival were investigated.RESULTS: One hundred and fourteen patients (85 per cent) had negative cytology results (group 1). Excluding one patient with atypical cells, positive cytology results were obtained in 19 patients (14 per cent): 16 patients without macroscopic peritoneal metastases (group 2) and three patients with minimal macroscopic peritoneal metastases (group 3). The patients in group 2 had significantly larger (P < 0.001) and more advanced (P = 0.022) tumours than those in group 1. However, there were no significant differences in postoperative cumulative survival rates between groups 1 and 2 (P = 0.347). Two patients in group 2 are long-term survivors (40 and 58 months). In cytomorphological analyses, the presence of clusters with ragged edges and isolated carcinoma cells can be considered to indicate a high risk of peritoneal recurrence.CONCLUSION: Positive cytology does not directly predict peritoneal carcinomatosis and, while associated with advanced disease, does not contraindicate radical surgery.     

Monoclonal antibody 486 P 3/12: a valuable bladder carcinoma marker for immunocytology

Monoclonal antibodies directed against tumor-associated antigens of bladder carcinoma were used to identify tumor cells in bladder washout specimens of 40 patients with bladder carcinoma (group 1), 41 with no bladder disease or with urinary tract infections (group 2), 41 who received long-term mitomycin C instillation therapy after excision of the tumors (group 3) and 39 who received no prophylaxis after excision of the tumors (group 4). In all groups the same bladder washout specimen was used for standard urinary cytological and immunocytological tests. True positive results were obtained in 90 per cent of the patients in group 1 according to our immunocytological criteria and in 43 per cent according to standard cytology studies. No urine specimens in group 2 (controls) were immunocytologically positive, while 16 of 41 in group 3 and 17 of 39 in group 4 were positive immunocytologically but only 4 and 5, respectively, were positive according to standard cytology studies. Further followup of these patients will show whether cells positive for monoclonal antibody 486 P 3/12 will permit early detection of recurrent bladder cancer and whether one can identify patients who require prophylaxis after removal of the superficial bladder tumors.     

The management of superficial bladder tumors and carcinoma in situ with intravesical bacillus Calmette-Guerin

A phase II study was performed to assess the role of bacillus Calmette-Guerin as a prophylaxis against recurrent stages O and A bladder tumors, and in the treatment of existing superficial bladder tumors and carcinoma in situ. Tice strain bacillus Calmette-Guerin (1 vial, 2 to 8 times 10(8) organisms in 60 cc saline) was instilled intravesically without cutaneous inoculation. Instillations were given weekly for 6 weeks and then monthly or until recurrence in 22 patients with a history of recurrent tumors, while 22 with existing stages O and A transitional cell carcinoma, and 19 with carcinoma in situ were treated weekly for 8 weeks and then monthly for 12 months or until failure. Complications included cystitis in 88 per cent of the patients (severe in 20 per cent), fever in 15 per cent, a flu-like syndrome in 13 per cent, edema and pruritus in 1.5 per cent, and ureteral stenosis in 1.5 per cent. Twelve patients (19 per cent) did not complete the study owing to toxicity. Of the patients in the prophylaxis group 67 per cent have had no tumor recurrence 10 to 26 months (mean 15 months) after therapy. Of the patients with existing tumors 36 per cent had complete regression following bacillus Calmette-Guerin therapy and 23 per cent had a partial response. Among the patients with carcinoma in situ 13 (68 per cent) had reversal to normal urothelium and 3 (16 per cent) had marked improvement. None of the patients had recurrence at 11 to 20 months. Intravesical Tice strain bacillus Calmette-Guerin is effective as a prophylaxis against recurrent superficial bladder tumors and in the treatment of carcinoma in situ.     

Telomerase activity in urine after transurethral resection of superficial bladder cancer and early recurrence

BACKGROUND: To explore the relationship between telomerase activity in urine after transurethral resection (TUR) of superficial bladder cancer and early intravesical recurrence. METHODS: Urine samples were obtained from 42 patients with superficial bladder cancers prior to TUR and on the postoperative day 1 and day 6. These patients were followed-up prospectively by cystoscopy at 3 and 6 months after TUR in combination with urinary cytology and telomerase activity. Telomerase activity in the urine was assessed by the telomeric repeat amplification protocol assay. RESULTS: Urinary telomerase activity prior to TUR was positive in 24 (57%) of the 42 patients. On the postoperative day 1 and day 6, positive urinary telomerase activity was seen in 13 (31%) and nine (21%) patients, respectively. Postoperative urinary telomerase activity on either day 1 or day 6 was significantly associated with pre-operative urinary telomerase activity status (P = 0.0024). Fifteen patients showed intravesical tumor recurrence at 3 months cystoscopic check-up and an additional nine had recurred at the 6 months check-up. Recurrence rate within 6 months in patients with pre-operative positive urinary telomerase activity was similar to that in those with negative activity (58.3 vs 58.8%). However, recurrence rate at 3 months for patients with positive activity was higher than that of those with negative activity (50 vs 17.7%), in 23 patients treated only by TUR. CONCLUSIONS: Presence of cells positive for telomerase activity in urine after TUR of superficial bladder cancer indicates persistently existing cancer cells in the urine. It is, however, not a sole predictor of the early intravesical recurrence.     

Urinary level of nuclear matrix protein 22 in the diagnosis of bladder cancer: experience with 130 patients with biopsy confirmed tumor

PURPOSE: We prospectively evaluated the value of nuclear matrix protein 22 (NMP22dagger) and cytology in the diagnosis of bladder cancer. MATERIALS AND METHODS: We analyzed NMP22 in voided urine from 235 patients before cystoscopy. Of the patients 130 had transitional cell carcinoma of the bladder and subsequently underwent surgery. In a subset of 200 patients bladder washout samples for cytology were collected during cystoscopy. The cutoff for NMP22 was 10.0 units per ml. For cytology only high grade atypia was considered positive. RESULTS: Histology showed 77 superficial (pTa, pTis) and 53 invasive (pT1 or greater) tumors. Sensitivity of NMP22 was 51% and specificity was 83%. NMP22 sensitivity was 36% for superficial tumors and 73% for invasive transitional cell carcinoma. Overall sensitivity of cytology was 52% and specificity was 89%. Cytology sensitivity was 38% for superficial tumors and 83% for invasive transitional cell carcinoma. NMP22 sensitivity for grades 1, 2 and 3 tumors was 30%, 56% and 68%, respectively. Cytology sensitivity for grades 1, 2 and 3 tumors was 30%, 50% and 91%, respectively. Combined NMP22 and cytology had a sensitivity of 70%. CONCLUSIONS: NMP22 has sensitivity and specificity similar to those of cytology from bladder washout samples. Particularly in low stage and low grade tumors both tests show the same disappointing sensitivity. Because of a false-negative rate of 49%, NMP22 cannot replace cystoscopy in clinical practice, as the danger of missing NMP22 negative tumors is too high to rely on its results in an individual patient.