History Of Superficial Bladder Cancer Research Articles

Isolated Ovarian Metastasis in a Woman with Prior History of Superficial Bladder Cancer

Isolated Ovarian Metastasis in a Woman with Prior History of Superficial Bladder Cancer

Perforation during TUR of bladder tumours influences the natural history of superficial bladder cancer

Bladder perforation is the second most common complication during transurethral resection of bladder tumours. It is unknown whether perforation affects the natural history of the tumour through cell seeding. The aim of this study was to study the impact of perforation on the oncologic outcomes of bladder carcinoma. Between 2003 and 2007, 926 consecutive patients underwent transurethral resection of bladder tumours at our institution; 327 cases were staged ≥ pT2 and were treated immediately with cystectomy and/or multimodal therapy and therefore excluded from the study. An additional 34 cases without urothelial carcinoma were excluded. Of the remaining 565 patients with non-muscle invasive bladder cancer, 457 (80.8 %) were male and 108 (19.2 %) were female with a mean age of 69.5 years in men and 67.3 years in women. Thirty-seven patients (6.5 %) experienced bladder perforation at the time of tumour resection. This group of patients (Group 1) was compared to the remaining 528 patients (Group 2) who did not experience a bladder perforation. Patients with bladder wall perforation experienced a shorter disease-free survival in both univariate (p = 0.003) and multivariate analyses (p = 0.006). In addition, subsequent recurrences revealed stage progression of recurrent disease (p = 0.05) and trended to a higher number of cystectomies in the perforated group of patients (p = 0.06). Nevertheless, perforation did not appear to influence overall survival (p = 0.127) or cancer-specific survival (p = 0.141). The results indicate that bladder perforation during resection of superficial bladder tumours is burdened by a shortened disease-free survival and T-stage progression.

National Practice Patterns for Immediate Postoperative Instillation of Chemotherapy in Nonmuscle Invasive Bladder Cancer

We assessed the use of intravesical postoperative chemotherapy among United States urologists in patients with nonmuscle invasive bladder cancer. A national sample of United States based urologists (259) retrospectively assessed their practice patterns involving intravesical postoperative chemotherapy after transurethral resection in patients with nonmuscle invasive bladder cancer. These urologists reviewed the medical records of their last 4 patients with nonmuscle invasive bladder cancer, and completed a case report form for specific demographic, pathological and treatment information. Selection criteria included the pathological and patient factors of histologically confirmed diagnosis of nonmuscle invasive bladder cancer-transitional cell carcinoma, completion of initial treatment plan with ongoing observation, candidate for or recipient of intravesical therapy, and no ongoing initial intravesical induction therapy. Overall the participation rate among those sampled was 61%. Of the 1,010 eligible patients with nonmuscle invasive bladder cancer 59.6% received instillation therapy during the initial treatment, of whom 28.4% (16.9% of patients overall) received intravesical postoperative chemotherapy. Primary, low risk patients most often received intravesical postoperative chemotherapy and 90.4% of the time patients received immediate instillation within 12 hours of surgery. However, of the urologists surveyed 66% never used intravesical postoperative chemotherapy, 17% used intravesical postoperative chemotherapy half (50%) of the time and only 2% used intravesical postoperative chemotherapy all (100%) of the time. Wide variation in the use of intravesical postoperative chemotherapy exists among urologists in the United States. The reason for the great diversity in the use of intravesical postoperative chemotherapy is speculative. However, physician awareness, physician bias, recurrence risk, and local pharmacy and hospital practice factors are all likely contributing factors.

Multi-target fluorescence in situ hybridization for prediction of recurrent superficial bladder cancer

Objective To evaluate validity of fluorescence in situ hybridization (FISH) in predicting tumor recurrence in patients with history of superficial bladder cancer. Methods FISH was performed on 20 normal subjects and 43 patients with negative cystoscopy and urinary cytology at the time of FISH assay. The threshold was established based on the assay of normal subjects, and the correlation between FISH and tumor recurrence was analyzed based on the assay of patients. Results After a median follow-up of 24 months,22 patients developed tumor recurrence,including 19 cases (86% ) of abnormal assay and 3 cases (14% ) of normal assay. Twenty-nine patients didn' t suffer from tumor recurrence, including 16 cases (55% ) of abnormal assay,and 13 cases (45% ) of normal assay. Recurrent tumors were developed in 54% of the patients with abnormal assay compared with 19% of the patients with normal assay (P<0.05). Conclusion FISH may be a available tool for predicting tumor recurrence. Key words: Urinary bladder neoplasm; Fluorescence; In situ hybridization; Prognosis

Bladder Conservation Treatment in the Elderly Population

To report the long-term results of bladder conservation strategies in elderly patients with muscle-invasive bladder cancer and evaluate the different factors affecting locoregional control and patient survival. We reviewed the records of 39 elderly patients aged 70 or older, treated with curative intent with radiotherapy, with or without chemotherapy after transurethral resection of bladder for T2-T4aN0 carcinoma of the bladder. Twenty-seven men and 12 women were identified with a median age of 78 (range 70-87). Sixteen of the patients had a previous history of superficial bladder cancer. Twenty-five patients had T2 lesions, 13 patients had T3 lesions, and 1 patient had T4a lesion. The majority of patients were unsuitable for surgery because of medical reasons (67%), whereas the others refused radical cystectomy (33%). Patients were treated with radical radiation therapy with or without chemotherapy. At a median follow-up time of 35.5 months for patients at risk, the 5-year overall survival is 28.9% for all stages, 31.9% for T2 lesions, and 26.8% for T3-T4a lesions. Significant prognostic factors for overall survival on univariate analysis were performance status and age. Five-year cause-specific survival is 37.5% for all stages, 41.5% for T2 lesions, and 34.7% for T3-T4a lesions. No significant prognostic factors for cause-specific survival were indentified on univariate analysis. Toxicity was acceptable. Younger age and good performance status were favorable prognostic factors for overall survival. Bladder conservation strategies achieved satisfactory results and were well-tolerated in this elderly population with invasive bladder cancer.

ENDOUROLOGY Bilateral laparoscopic nephroureterectomy with open cystoprostatectomy for simultaneous upper urinary tract carcinoma

Synchronous bilateral urothelial tumors of the upper urinary tract are extremely rare and their treatment constitutes a real challenge for urologists. Whereas low grade superficial tumors can be treated using endoscopic procedures, in the case of high grade, invasive or large volume tumors bilateral radical nephroureterectomy with cystectomy is considered the standard of care. The authors present the case of large volume high grade tumors of the renal pelvices in a patient with a history of superficial bladder cancer treated by one-stage bilateral laparoscopic nephroureterectomy and open cystoprostatectomy. The aim of the study is not only to present the operative technique but also to show that the combined procedure is safe, effective and no more invasive than the operation exclusively performed laparoscopically.

Superficial bladder cancer: part 1. Update on etiology, classification and natural history

Superficial ‘nonmuscle-invasive’ bladder tumors represent a heterogeneous group of cancers, which include those that are papillary in nature and limited to the mucosa (Ta), high grade, flat and confined to the epithelium (Tis) and those that invade the submucosa or lamina propria (T1). The natural history of these bladder cancers is that of disease recurrence and progression to higher grade and stage. Furthermore, recurrence and progression rates of superficial bladder cancer vary according to several tumor characteristics. The goal in the treatment of superficial bladder cancer is twofold: reducing tumor recurrence and the subsequent need for additional therapies, such as cystoscopy, transurethral resections, intravesical therapy and the morbidity associated with these treatments; and preventing tumor progression and the subsequent need for more aggressive therapy, such as radical cystectomy. The administration of intravesical chemotherapy and immunotherapy has become an important component in accomplishing these goals. This update is the first part of two articles reviewing important contemporary concepts in the etiology, classification and natural history of superficial bladder cancer, while part II of the series will review and highlight important aspects in management of superficial bladder cancer.

Retrospective study of locally advanced bladder cancer in elderly patients

18523 Background: Bladder cancer is one of the most frequent tumors in elderly patients (pts). However, guidelines have not been established yet in this age group. Methods: We analyzed retrospectively pts aged 75 years or more, with muscle invasive or metastatic bladder cancer treated between January 2000 and June 2005, in three institutions in Lyon-France: Léon Bérard Center, Saint Luc Saint Joseph Hospital and Protestant Infirmary. Results: Data from 126 pts (81% male) were available: median age was 80 years (75–94). 99 pts had disease confined to the bladder, 19 confirmed metastatic cancer and 8 at least T2aM0 disease. 42% of pts had a history of superficial bladder cancer; 96% an urothelial carcinoma, 19% an associated in situ carcinoma. Of note, 33% of male pts had a concomitant prostate cancer. Median Performance Status, American Society of Anesthesia score and Charlson Comorbidity index were 1, 2 and 2.14 respectively. Cardiovascular comorbidities were the most common (42.8%). 87% of pts were taking medications; median number of drug intake was 4. We focused on pts with muscle invasive, non metastatic bladder cancer: 55 of 99 pts underwent surgery; 48 of them had external urinary diversion. Postoperative complications occurred in 34% of pts: evisceration (15%), sepsis, hemorrhage, acute cardiac failure, acute renal failure, pulmonary embolism (3.7% each), bowel obstruction and acute arterial thrombosis of lower limbs (1.8% each), and 2 immediate postoperative deaths. 16 pts received radiotherapy with a curative intent, 6 of them had chemoradiation. Mean irradiation dose and duration were respectively 56.4 Gy and 6.5 weeks. Toxicity occurred in 5 pts: 2 discontinuations for intolerance, 1 acute cardiac failure, 1 grade 3 thrombopenia, and 1 toxic death (intestinal perforation). The last 28 pts received palliative care. After a median follow up of 14 months, 33 operated pts and 3 pts treated by radiotherapy were still alive in complete remission. Disease free survival and median survival were 11.5 and 42 months in the surgical group respectively and 12 and 12 months in the radiotherapy group respectively. Conclusions: Treatment of locally advanced bladder cancer in the elderly carries significant morbidity and mortality. Oncogeriatric assessment benefit for individual management must be studied. No significant financial relationships to disclose.

Comparison of NMP22 BladderChek Test and Urine Cytology for the Detection of Recurrent Bladder Cancer

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. 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. 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. 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.

Cyclophosphamide is contraindicated in patients with a history of transitional cell carcinoma

Cyclophosphamide is a urotoxic agent that increases the incidence of malignant neoplasms of the urinary tract. The aim of this study was to evaluate the long-term impact of cyclophosphamide on patients with a history of superficial bladder cancer. Between July 1986 and January 1988, 58 consecutive patients with primary superficial transitional cell carcinoma of the bladder were included in this study. All patients had a transurethral R0 resection. Then 6 weekly intravesical instillations of 120 mg bacillus Calmette-Guérin (BCG) were performed. Until June 1987, 22 consecutive patients (group A) received an additional intravenous application of 700 mg/m(2) cyclophosphamide prior to the BCG immunotherapy, while from July 1987 36 patients were treated without cyclophosphamide. Survival was calculated using the Kaplan-Meier method and comparison of survival using the log rank test. Tumor staging, grading, and size were equally distributed in both groups. No significant difference could be observed regarding the 10-year overall survival rate (group A: 59%, group B: 58%), the 10-year tumor-specific survival rate (89 vs 94%), and the 10-year progression-free survival rate (85 vs 97%). There was a statistically significant deterioration of the 10-year recurrence-free survival rate in the cyclophosphamide group (44 vs 70%, log rank test: p < 0.05). Whereas there were no recurrences in the upper urinary tract among the patients of group B, 2 of the 22 patients from group A developed cancer of the renal pelvis. In patients with a history of superficial bladder cancer, a single dose of cyclophosphamide poses a significantly increased risk of tumor recurrence in the lower and in the upper urinary tract as well.

Prognosis of muscle-invasive bladder cancer: difference between primary and progressive tumours and implications for therapy.

To evaluate the difference in prognosis between progressive and primary muscle-invasive bladder cancer. From 1986 to 2000, 74 patients with progressive muscle-invasive bladder cancer were identified. Eighty-nine patients with primary muscle-invasive bladder cancer were frequency matched for stage to these patients with progressive disease. Baseline data including patient and tumour characteristics were collected at the time of diagnosis of the muscle-invasive tumour. Duration of survival was defined as time from muscle-invasive bladder cancer diagnosis until disease-specific death. Kaplan-Meier curves were drawn to determine the difference in prognosis between the two study groups. To adjust for potential residual confounding due to differences in treatment, 4 subgroups (T2/3, T4, N+ and M+) were constructed according to the TNM classification. In order to see whether age and gender had any effect on outcome, the four stage groups, age and gender were entered in a Cox's proportional hazard regression model. The 3-year bladder cancer-specific survival was 67% in the primary group and 37% in the progressive group (log rank p=0.0015). Kaplan-Meier curves comparing the different stage groups showed a better prognosis for the patients with primary, i.e. pT2/3 or N+, tumours at baseline. Cox regression analysis demonstrated that age and gender had no influence on bladder cancer-specific survival. Patients with muscle-invasive bladder cancer and a history of superficial bladder cancer have a worse prognosis than patients with primary muscle-invasive bladder cancer.

Treated natural history of superficial bladder cancer.

The present study was conducted to examine the natural history of superficial bladder cancer. One hundred and forty-four patients with superficial bladder cancer who had been treated with transurethral resection of bladder tumor (TURBt) alone were analyzed. The non-recurrence rate was 64.8% at 36 months and 61.2% at 60 months after TURBt. When the non-recurrence rate after TURBt was analyzed by background variables, the rate differed significantly between the solitary tumor group and the multiple tumor group. The tumor recurrence hazard curves for the entire population had one high peak before 500 days and another slight peak around 1500 days after TURBt. These results will provide basic information useful when evaluating new regimens of intravesical instillation therapy for prophylaxis of superficial bladder cancer after our complete TURBt in the Nara Uro-Oncology Research Group.

RECURRENCE AND PROGRESSION OF STAGE T1, GRADE 3 TRANSITIONAL CELL CARCINOMA OF THE BLADDER FOLLOWING INTRAVESICAL IMMUNOTHERAPY WITH BACILLUS CALMETTE-GUERIN

We prospectively examined the incidence of recurrence and progression in patients with stage pT1, grade 3 carcinoma of the bladder following complete transurethral resection of the bladder tumor and adjuvant immunotherapy with bacillus Calmette-Guerin (BCG). Between July 1987 and March 1999, 123 patients presenting to our clinic with superficial urothelial carcinoma (stage pT1, grades 1 to 3) received adjuvant intravesical immunotherapy with BCG after histologically confirmed complete transurethral tumor resection. Disease was stage pT1, grade 3 in 44 patients (36%). Median followup was 28 months (mean 43, range 5 to 141). Of the patients 36 (82%) with bladder preservation remained tumor-free during followup after 1 or 2 cycles of BCG. Superficial tumor recurred in 5 patients (11%) and muscle invasive progression was noted in 7 (16%). Radical cystectomy was performed in 4 cases (9%). Of the patients 5 (11%) died of cancer. Tumor-free survival for all patients was 89% (39 of 44). Adjuvant immunotherapy with BCG after complete transurethral resection of bladder tumor represents a highly effective primary treatment of stage pT1, grade 3 carcinoma of the bladder. Immediate radical cystectomy does not appear necessary.

Urinary NMP22TM and Karyometry in the Diagnosis and Follow-Up of Patients with Superficial Bladder Cancer

Objective: To study the value of two outpatient urine tests with regard to the diagnosis and recurrence of bladder tumors. Methods: Fifty patients with a history of superficial bladder cancer were evaluated with urinary NMP22^TM levels (cutoff level 10 U/ml), bladder wash karyometry (low versus intermediate and high risk) and cystoscopy. All patients were followed for 1 year. Results: Diagnostic negative and positive predictive values (NPV and PPV) of the tests were, respectively: NMP22 91.2 and 56.3%, and karyometry 80 and 33.3%. Prognostic NPV and PPV with regard to a subsequent recurrence were, respectively: NMP22 77.8 and 27.3%, and karyometry 82.6 and 50%. Conclusion: The diagnostic value of NMP22 is good. Since the 3 false-negative results were in low-stage and low-grade lesions, this test could be used as a prescreening for cystoscopy. The NPV of these tests with regard to tumor recurrence is around 80%, but only karyometry has a significant PPV. Change in the follow-up policy on the basis of these tests remains difficult. In patients with neobladders NMP22 appears to be of little use, because of the high urinary NMP22 levels in the absence of malignancy.

Pharmacokinetics of Intravesical Doxorubicin in Superficial Bladder Cancer Patients

The urine and plasma pharmacokinetics of intravesical doxorubicin were studied in 8 patients with a history of superficial bladder cancer. Patients received 6 weekly treatments of 40mg. doxorubicin in 20ml. physiological saline. Doxorubicin was detectable (0.2ng./ml. or more) in plasma from 6 of 8 patients during the initial treatment. The maximal concentrations ranged from 0.5 to 4.5ng./ml. (mean 1.4). Doxorubicin was not detected in plasma from 7 of 8 patients during treatment 2 and not detected in any patient during treatment 4. The doxorubicin concentrations in urine decreased to approximately 50% at 5 minutes after dosing due to dilution by post-catheterization residual urine, and decreased by a further 6-fold by the end of the 2-hour treatment due to urine production. The recovery of doxorubicin at the end of treatment averaged 88.3%, with an additional recovery of 3.7% during the subsequent 4 hours. Urinary pH (range 5.5 to 8.5) did not affect the stability nor the systemic absorption of doxorubicin. In conclusion, we found that for intravesical doxorubicin therapy there was insignificant systemic exposure to doxorubicin, the highest systemic absorption from the bladder occurred shortly after surgery, there was high target site (bladder tissue) specificity, insignificant metabolism and/or degradation of doxorubicin, and dilution of urinary doxorubicin concentrations and, therefore, decreased tumor exposure to the drug due to residual urine and urine production.

Intravesical therapy in superficial bladder cancer

Objective. To identify the appropriate characteristics of superficial bladder cancer that allow the physician to predict tumor behavior. Methods. We analyzed 1,745 patients with primary superficial bladder cancer with regard to disease and patient characteristics. Results. With the characteristics we found, the population can be described and prognostic factors can be found. Moreover, with the use of these factors, it appears to be possible to predict tumor behavior on a group level. Prediction on an individual level, however, remains far from ideal. Conclusions. Three treatment options can be chosen: follow-up after initial transurethral resection, additional instillations with intravesical chemotherapy, or instillations with bacillus Calmette-Guerin (BCG). In case instillations are indicated, most (but not all) superficial bladder cancer trials show superiority of BCG over intravesical chemotherapy, although at the cost of more side effects. However, with intravesical BCG, it seems possible to influence the natural history of superficial bladder cancer, which means that we can delay progression and improve survival.

Prognostic factors in superficial bladder cancer.

A large body of evidence suggests that intravesical prophylaxis using bacillus Calmette-Guérin can favorably alter the natural history of superficial bladder cancer. The search for prognostic factors impacting the clinical alternative between conservative and radical treatment has been the subject of numerous efforts and remains a major objective in improving the carcinological results and the quality of life patients with superficial bladder cancer. In this regard, information is available on three levels: clinicopathological parameters, quantitative analysis, and biological markers. Recent advances in as well as the limitations and pitfalls of the use of three kinds of information in prognostication are reviewed. The proper use of prognostic factors will modify our attitude toward superficial bladder cancer in the near future.

Seminal vesicle involvement by in situ and invasive transitional cell carcinoma of the bladder.

We report six cases of seminal vesicle involvement by transitional cell carcinoma of the bladder among 187 consecutive cystoprostatectomy specimens. Two of these six cases showed mucosal spread without stromal invasion (type A); the remaining four cases presented a direct extension (type B) from muscle-invasive carcinomas of the bladder. Type A involvement of the seminal vesicle was associated with a long history of superficial bladder cancer with similar mucosal spread to the prostatic ducts, acini, and ejaculatory ducts. One type A case showed extensive pagetoid spread of transitional cell carcinoma to the urethral meatus and collecting ducts of the kidney. Because the clinical significance of mucosal spread or direct invasion of seminal vesicles is not clear, pathologists and urologists need to be aware of these phenomena. More cases should be analyzed to determine further clinicopathologic implications.

Influence of Blood Group Type on the Natural History of Superficial Bladder Cancer

The blood group was correlated with the grade and stage at diagnosis, and with the subsequent clinical course in 494 patients with bladder cancer treated at our institution from 1977 to 1986 who were followed for a mean of 5.5 years (range 2 to 9 years). The distribution of blood groups was similar to that reported for the general population and to that of 100 consecutive patients with urolithiasis used as controls, and the distribution was not different among patients with superficial cancer (stages O and A) than in those with advanced disease (stage B or higher). However, among patients with superficial disease high grade (III or IV) lesions were more frequent in those with blood group O (36 per cent) than in those with other blood groups (13 to 18 per cent) (p less than 0.001). In addition, in patients with superficial cancer of all grades progression to advanced disease was significantly greater among those with blood group O (37 per cent) than in those with other groups (12 to 16 per cent) (p less than 0.05). More importantly, in patients with low grade (I or II) superficial cancer development of advanced disease was significantly more frequent among those with blood group O (24 per cent) than in those with other blood groups (0 to 7 per cent) (p less than 0.004). Our findings suggest that individual genetic factors influence the natural history of superficial bladder cancer. The molecular basis of this phenomenon remains to be elucidated.

449 - Influence of Blood Group Type in the Natural History of Superficial Bladder Cancer

449 - Influence of Blood Group Type in the Natural History of Superficial Bladder Cancer