[Combination therapy of transurethral resection (TUR) and radiotherapy in advanced bladder cancer].
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The value of DNA image cytometry in the differential diagnosis of 106 T1G3 urothelial carcinomas of the bladder and the long-term prognosis (recurrence-free interval, survival) of the patients was tested in comparison with Ta/T1G1 (n=30) and Ta/T1G2 carcinoma (n=54). Monolayer smears were prepared from three 50-microm-thick sections by a cell separation technique and were stained according to Feulgen. The DNA content of 250 epithelial cells, chosen at random, was determined using a TV-image analysis system CM-1 (Hund, Wetzlar, Germany). The DNA content of 30 lymphocytes served as an internal standard for the normal diploid value in every individual case. Different DNA cytometric parameters and the mean nuclear area were calculated. In comparison with G1- and G2-cases, the mean values of all DNA cytometric variables were markedly increased in the group of T1G3 cases, most obviously for the 5cEE, the mean ploidy and the ploidy imbalance (0.0006 > or = p > or = 0.0001). However, a remarkable overlay of the data distribution had to be considered. An aneuploid DNA stemline ploidy was highly characteristic for T1G3 urothelial carcinoma (sensitivity: 92%), but not sufficiently specific (57%). However, if increased values for the mean ploidy, the 2cDI, the 5cEE or the 9cEE (specificity: 86%-89%) were present additionally, the diagnosis of a T1G3 urothelial carcinoma could be made cytometrically. Follow-up data for survival (recurrence) analysis was available for 90 (82) patients of the T1G3 group. Using the median value as threshold, significant differences in survival were found for the mean ploidy only (p=0.0353). The length of the recurrence-free interval was significantly different for the entropy (p=0.0205), the 2cDI (p=0.0309) and the mean ploidy (p=0.0442). In conclusion, DNA single cell cytometry represents a highly relevant tool in the objective identification of T1G3 urothelial carcinoma of the bladder, with a sufficient sensitivity and specificity. Further, this method enables prediction of tumor recurrence if suitable variables are chosen. The long-term survival of patients with T1G3 urothelial carcinoma can be estimated by DNA cytometry only in a limited manner, possibly due to the fact that the causes of death in the mostly elderly patients will be independent from the limited tumor disease.
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The interference of Transurethral Resection (TUR) with CT staging of bladder cancer is discussed in reaction to a recent publication.
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210 patients with surface cancer of the bladder were divided into three groups. 67 patients of group 1 underwent transurethral resection of the bladder (TRB) followed by preventive intravesical chemotherapy. 91 patients of group 2 received preventive intravesical BCG after TRB. 61 control patients (group 3) had TRB only. Recurrences emerged in 15 (16.5%), 12 (62.7%) and 45 (73.8%) group 2, 1 and 3 patients, respectively. The preventive chemotherapy was effective only in patients with primary tumor (the recurrence rate 42.3%), the relapses being less responsive to it (the recurrence rate 75.6%).
PURPOSE: We determined the role, if any, of 1 and 5 instillations of intravesical mitomycin C in the treatment of newly diagnosed superficial bladder cancer. MATERIALS AND METHODS: A multicenter randomized clinical trial was done involving 502 patients with newly diagnosed superficial bladder cancer. After complete transurethral resection patients with newly diagnosed superficial bladder cancer. After complete resection patients were randomized into 1 of 3 treatment arms: no further treatment, 1 instillation of mitomycin C at resection and 1 instillation at resection and at 3-month intervals for 1 year (total 5 instillations). The dose of mitomycin C used was 40 mg./40 ml. water. End points were interval to first superficial recurrence, recurrence rate (defined as the number of positive cystoscopies per year) and progression-free interval rate (progression defined as the development of muscle invasive or metastatic disease, or death from bladder cancer). RESULTS: After median followup of 7 years 1 and 5 instillations of mitomycin C resulted in decreased recurrence rates and increased recurrence-free interval. The benefit of mitomycin C was observed in patients at low, medium and high risk for subsequent recurrence. There was suggestive but not conclusive evidence that 5 instillations of mitomycin C offered a slight advantage over 1 instillation. CONCLUSIONS: Our analysis confirms the positive benefit of mitomycin C to decrease the number of subsequent recurrences and increase the recurrence-free interval.
This study was undertaken to evaluate the risk of haematogenous dissemination of epithelial cells induced by endoscopic resection and/or cystoprostatectomy for transitional cell carcinoma of the bladder. Thirty-three patients were studied. Thirty-one had different stages and grades of bladder cancer and two patients had benign bladder conditions. Twenty-five cancer patients required transurethral resection of their bladder tumour. Of those, 20 had superficial disease (pTaG1-G2: n = 19; pT1G2: n = 1) and five had muscle invasive tumours (pT2G3: n = 2; pT3aG3: n = 1; pT4G3: n = 2). Five patients underwent radical cystoprostatectomy for muscle invasive cancers (pT2G3: n = 3; pT3bG3: n = 1; pT4G3: n = 1) and one man received chemotherapy for metastatic disease. Venous blood (10 ml) was obtained from the antecubital fossa in each patient, before and 1-2 h after completion of surgery, and prior to treatment in the metastatic patient. An indirect immunocytochemical technique was used to detect circulating epithelial cells after centrifugation on Ficoll gradient and fixation of mononuclear cells on slides, using a monoclonal antibody directed against three cytokeratins: CK8, CK18 and CK19. Circulating epithelial cells were detected only in the patient with metastatic disease. None of the other patients had evidence of epithelial circulating cells before or after surgery. The results suggest that irrespective of disease stage and grade, neither endoscopic nor open bladder surgery leads to detectable dissemination of urothelial cells in the peripheral circulation. These procedures are therefore unlikely to increase the risk of progression and metastasis in transitional cell carcinoma of the bladder.
Patients with superficial transitional cell carcinoma of the bladder were entered in a randomized clinical trial to compare the efficacies of transurethral resection alone or followed by bladder instillation of doxorubicin hydrochloride or ethoglucid (Epodyl) for 1 year. Results showed that adjuvant chemotherapy with the selected drugs prolonged the mean interval between recurrences. Mild systemic toxicity and chemical cystitis were observed in 3 and 3 per cent, respectively, of the patients given ethoglucid, and in 5 and 4 per cent, respectively, of those taking doxorubicin.
Fifty-four patients mean aged 58.5 years (28 women and 26 men) undergo transurethral resection for superficial bladder carcinoma. Postoperatively 20 mg mitomycin is administered by instillation into the bladder for 8 weeks. Preoperative assessment includes: complete blood count, urea, creatinine, isotope nephrography, ultrasonography, excretory urography and CT scan of pelvis. Multifocal lesions are diagnosed in 22 patients (40.7%). In 36 cases (66.7%) it is a matter of solitary papillomas. The distribution of lesions is as follows: left bladder wall--12 patients (22.2%), right bladder wall--13 (24.07 per cent), trigone--18 (33.3%), and anterior bladder wall--11 (20.03 per cent). Postoperative check-ups: cytological assessment of urine and regular endoscopic study at 3-6 months. Recurrence rate amounts to 42.5% for the maximum follow-up period.
The recurrence preventing effect of Etretinate on 174 superficial bladder tumors was examined by a randomized study using the envelope method. After transurethral resection of the bladder tumor, the tumor-free patients were divided into two groups, one administered one 10 mg capsule of Etretinate once a day, and the other group untreated (control group). As a rule, the patients were examined for recurrence every 3 months. There were 9 drop outs (9.6%) in the Etretinate group, and 8 (10%) in the control group. Therefore, 85 subjects in the Etretinate group and 72 patients in the control group were analyzed for statistics. The recurrence rate during the observation period of over 2 years was 38% in the control group and 18% in the Etretinate group, the number of relapsing cases in the latter group tending to be decreased (P less than 0.1). The cumulative recurrence inhibition rate for cases observed over one year tested by the Kaplan Meier method tended to be higher in the Etretinate group compared to the control group (P less than 0.1). Etretinate administration had a high recurrence inhibitory effect (P less than 0.05) in the cases of relapse, multiple tumors, and tumors less than 1 cm. Side effects of Etretinate administration were seen in 21 cases (22.3%). The major symptoms were dry lips, cheilitis, stomatitis, dermal desquamation, etc., and drug use was discontinued in 7 cases (7.4%). The symptoms all disappeared after drug administration was discontinued.
AIM: Reports specifically addressing transitional cell carcinoma (TCC) of the ureteral orifice are scarce. This paper presents our experiences of such tumors, including the characteristics of the disease and the incidence of subsequent upper urinary tract recurrence. METHODS: This study included 572 new cases of TCC of the urinary bladder diagnosed in our institute during a period of 5 years. Thirty-one (5.4%) patients had superficial tumors involving ureteral orifices. All 31 patients underwent transurethral resection of the bladder tumors, including the involved ureteral orifices. After the surgery, patients received regular follow up with cystourethroscopy, urine cytology and periodic intravenous pyelography (IVP). Ureterorenoscopy was performed in cases of suspicious IVP or urine cytology findings. RESULTS: Thirty-one patients with superficial tumors involving the ureteral orifice were followed up for 5-8 years or until death. The pathological stage was Ta in 16 cases and T1 in 15 cases. Bladder tumor recurrence was noted in three (18.8%) of the pTa patients and in seven (46.7%) of the pT1 patients. Subsequent upper urinary tract tumors developed in four (12.9%) patients between 33 and 67 months (mean: 33.5) after the first transurethral resection. All four cases of upper tract recurrence had pT1 primary bladder tumor, which recurred for 1-3 times (mean 1.8) before upper tract recurrence. None of these patients had ureteral stenting after bladder tumor resection. Three of four patients with upper tract recurrence had single lower ureteral tumor, while the remaining one patient had multiple tumors. Patients with subsequent upper urinary tract tumors underwent nephroureterectomy and bladder cuff excision. One died of the disease; the other three cases were free of the disease after the therapy. CONCLUSIONS: Patients with primary superficial bladder transitional cell carcinoma involving the ureteral orifice have a higher risk of developing subsequent upper urinary tract tumors, particularly for pT1 primary bladder tumors. Frequent and close follow up is recommended.
Our objective was to assess the efficacy and safety of a selective bladder-preserving approach by transurethral resection and sequential chemoradiotherapy in patients with muscle-invasive bladder cancer. From 1989 through 1997, 40 patients with biopsy-confirmed bladder cancer, clinical stages T2-4NxM0, were treated with induction by aggressive transurethral resection (TUR) and three cycles of methotrexate, cisplatin, and vinblastine (MCV) chemotherapy. Tumor response was evaluated by cystoscopy and biopsy. In complete responders, the treatment was continued by radiotherapy (60 Gy to the bladder and 50 Gy to pelvic lymph nodes). Radical cystectomy was recommended to patients with residual tumor. Clinical complete response rate to TUR and MCV chemotherapy was 70%. The 4-year actuarial overall survival rate for the whole series was 80.5%. Among 36 patients who completed chemotherapy and radiotherapy, the 4-year actuarial survival was 84%, with 82.6% surviving with their bladders intact. Freedom from local failure in complete responders to TUR-chemotherapy was 84%. Multivariate analysis revealed that the extent of initial TUR and status after TUR-chemotherapy were independent prognostic factors associated with survival and disease-free survival. This study confirms that the combination of aggressive TUR and sequential chemoradiotherapy with bladder preservation is an alternative treatment option to primary cystectomy for selected patients with invasive bladder carcinoma.
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A 45-year-old male was admitted to our hospital with a complaint of asymptomatic macroscopic hematuria. At cystoscopy a multi-lobulated, dark red tumor, the size of a rice grain, was found on the right lateral wall. He also had a 5 X 4 mm purplish skin tumor on the left leg. Double contrast cystogram also showed the shape of the tumor on the right lateral wall of bladder. Based on the aforementioned findings, we diagnosed this case as hemangioma of the urinary bladder associated with the same lesion on the left leg. The bladder tumor was resected transurethrally and the skin lesion was also excised. Pathological diagnoses were cavernous hemangioma of bladder and angiokeratoma of skin, respectively. Including our case we found 62 cases of hemangioma of the urinary bladder in the Japanese literature. Only 5 of them were associated with the hemangiomas of other regions of the body.
Thirty-nine patients with locally advanced transitional cell carcinoma of the bladder received presurgical combination chemotherapy in an effort to improve survival, reduce local tumor recurrence and distant failure, and enhance surgical resectability and potentially salvage the bladder. One to six cycles (median 2.8) of M-VAC (methotrexate, vinblastine, doxorubicin, cisplatin), CMV (cisplatin, methotrexate, vinblastine), or VP16 CDDP (etoposide, cisplatin) were administered after initial diagnosis and clinical staging of the bladder cancer and transurethral resection of the tumor. Clinical staging was repeated before each cycle of chemotherapy. Transurethral resection and systemic neoadjuvant chemotherapy clinically downstaged 31 of 39 patients (79%). Subsequently, 26 patients underwent radical cystectomy and 13 patients received bladder salvage (6 received a partial surgical resection and 7 observation). At 41 months' median follow-up, 4-year overall survival was 63 +/- 17%, cancer-specific survival was 71 +/- 19%, local recurrence-free survival was 66 +/- 22%, and metastasis-free survival was 73 +/- 16%. Patients with a complete clinical and pathologic response had far better survival than those without a complete response; for pathologic stage, survival was 100% vs. 45% for those with residual tumor (p = 0.003). Local recurrence (Ta or TiS) occurred in 46% of those with their bladder salvaged and still in situ. These data suggest that with neoadjuvant chemotherapy bladder salvage seems feasible in selected patients, although they appear to be at higher risk for tumor recurrence. Accurate selection of the group of patients most likely to benefit is difficult and may not be possible in a predictable manner with currently available selection methods.
The anthracycline derivatives Adriamycin and 4-epirubicin are used to prevent recurrent tumors after transurethral resection of superficial bladder tumors. Both drugs are instilled intravesically. The present report describes the results of two multicenter, prospective, randomized phase III studies carried out by the EORTC GU Group. In protocol 30,790, after a mean follow-up period of 26.6 months, the recurrence rate for 165 patients treated with Adriamycin was 0.29 and the tumor rate was 0.74. For 156 patients treated with Epodyl, the recurrence rate was 0.29 and the tumor rate was 0.57. This difference was not statistically significant. For 70 patients who received transurethral resection alone, the recurrence rate was 0.65 and the tumor rate, 2.04. In protocol 30,763, patients with good prognostic factors were treated with one single instillation of 4-epirubicin versus sterile water. After a mean follow-up period of 16 months, in 190 patients treated with 4-epirubicin the recurrence rate was 0.20 and the tumor rate was 0.35; in 196 patients treated with sterile water, the recurrence rate was 0.37 and the tumor rate was 0.65 (P = 0.0001). Adriamycin and 4-epirubicin were efficacious, and severe side effects were not encountered. The superiority of Adriamycin over Epodyl could not be proven.