The National Bladder Cancer Group's experience: invasive and metastatic bladder cancer selected reports.

The National Bladder Cancer Group, a multidisciplinary organization that was originally the therapeutic arm of the National Bladder Cancer Project, reported the results of trials using cisplatin with and without cyclophosphamide in patients with advanced bladder cancer. The objective response rate in both arms was 16% of 109 patients with no difference between the arms. Other studies included cisplatin and irradiation for patients who had comorbid conditions that prevented cystectomy (local response--cT2 11/13 patients; cT3 & cT4 2/4 patients). Seventy patients were treated on the same protocol, and 33 were alive 4 years later. Complete response versus local failure produced 57% versus 11% at 4 years. After cessation of funding, the clinicians at the Massachusetts General Hospital agreed to follow a potentially bladder-sparing multimodality protocol, which stipulated that visible tumor be resected following which the patient received methotrexate, vinblastine and cisplatin (MCV), small-volume irradiation, and more cisplatin with midcourse cystectomy if local tumor persisted. Overall survival was 45%. The Radiation Therapy Oncology Group conducted a similar study omitting MCV from one arm. The 5-year survival rate was 38% with no advantage for either arm.

Bladder cancer: race differences in extent of disease at diagnosis.

BACKGROUND: Blacks are less likely than whites to develop bladder cancer; although once diagnosed, blacks experience poorer survival. This study sought to examine multiple biological and behavioral factors and their influence on extent of disease. METHODS: A population-based cohort of black bladder cancer patients and a random sample of frequency-matched white bladder cancer patients, stratified by age, gender, and race were identified through cancer registry systems in metropolitan Atlanta, New Orleans, and the San Francisco/Oakland area. Patients were ages 20-79 years at bladder cancer diagnosis from 1985-1987, and had no previous cancer history. Medical records were reviewed at initial diagnosis. Of the patients selected for study, a total of 77% of patients was interviewed. Grade, stage, and other variables (including age, socioeconomic status, symptom duration, and smoking history) were recorded. Extent of disease was modeled in 497 patients with urothelial carcinoma using logistic regression. RESULTS: Extent of disease at diagnosis was significantly greater in Blacks than in Whites. Older age group, higher tumor grade, larger tumors, and presence of carcinoma in situ were related to greater extent of disease in blacks and in whites. Large disparities between blacks and whites were found for socioeconomic status and source of care. Blacks had greater symptom duration and higher grade. Black women were more likely to have invasive disease than white women; this difference was not seen among men. Blacks in unskilled occupational categories, perhaps reflecting socioeconomic factors, were at much higher risk for muscle invasion than whites. CONCLUSIONS: While specific relationships between variables were noted, an overall pattern defining black and white differences in stage did not emerge. Future studies should examine the basis upon which occupation and life style factors operate by using biochemical and molecular methods to study the genetic factors involved.

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

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

13-cis-retinoic acid in chemoprevention of superficial bladder cancer. The National Bladder Cancer Group.

Animal studies indicate that 13-cis-retinoic acid (CRA) inhibits bladder tumor growth and is effective in treating patients with serious dermatologic disorders. A trial of CRA in patients at high risk for recurrent Ta, T1 tumors was initiated at an experimental dose of 0.5 mg/kg/d in three divided doses, increasing to 1 mg/kg/d at four weeks. Treatment of twenty eligible patients lasted for six months with an additional 24 month follow-up period. One patient was later excluded due to toxicity resulting in an early dose reduction. Eight patients stopped treatment before three months; of these five, had recurrences within three months, one developed pulmonary metastasis, and one developed a T2G3 tumor. Four patients stopped treatment between three and six months; three of them had recurrences before one year and one had no evidence of disease at seven years. Seven patients completed the course; of these three had recurrences within six months, and three more had recurrences at 8, 15, and 45 months, respectively. Toxicity was nearly universal; cheilosis, conjunctivitis, pruritus, joint and eye pain, flashing lights, and erythrocyte sedimentation rate (ESR) over 60 were all noted. The lack of positive results and the frequency and severity of toxicity led to termination of the study.

The usefulness of serum acid phosphatase in monitoring patients with advanced prostate carcinoma.

The usefulness of serum acid phosphatase (SAP) in monitoring patients with advanced prostate carcinoma has been questioned. We reviewed a series of 59 patients with stage D2 prostate carcinoma. All patients had extended follow-up through at least one clinical relapse, or death. Responses to a variety of therapies were characterized as absent, subjective, or objective. All patients with an elevated pre-treatment SAP that fell to normal following therapy had prolonged survivals and improved prognoses. Conversely, all patients with an elevated SAP which did not normalize following therapy had poorer survivals. Among 36 objective responses to therapy, the SAP was elevated prior to or simultaneous with disease progression in 33 (93% sensitivity). In each ease where the pretreatment SAP normalized following therapy, any subsequent elevation in SAP above normal was always associated with clinical evidence of disease progression (100% specificity). Changes in SAP following therapy correlate well with both disease regression and disease progression in patients with advanced prostatic carcinoma.

Prognostic factors in invasive bladder carcinoma in a prospective trial of preoperative adjuvant chemotherapy and radiotherapy.

Clinical and pathologic factors were analyzed in 40 patients with localized muscle-invasive bladder carcinoma treated in a prospective bladder-preserving program consisting of transurethral tumor resection, neoadjuvant chemotherapy (methotrexate, cisplatin, and vinblastine [MCV]), and 4,000 cGy radiotherapy with concurrent cisplatin. Patients with biopsy-proven complete response after chemotherapy and 4,000 cGy radiation received full-dose radiotherapy (6,480 cGy) with cisplatin. Cystectomy was recommended to patients with residual disease. Distant metastasis rate was associated with tumor stage and size: 0% in T2 patients, 39% in T3-4 patients (P = .035), 6% for tumors less than 5 cm, and 59% for tumors greater than or equal to 5 cm (P = .002). Risk of bladder tumor recurrence was higher in patients with tumor-associated carcinoma in situ (CIS; 40%) than those without CIS (6%; P = .075). Papillary tumors and solid tumors both had similar treatment outcomes. By multivariate analysis, tumor stage T2 (P = .04) and absence of CIS (P = .03) were significant predictors of complete response; CIS was predictive of local bladder recurrence (P = .07); and tumor size (P = .03), response after chemoradiotherapy (P = .02), and vascular invasion (P = .08) were associated with distant metastasis. Six of eight local bladder tumor recurrences were superficial tumors. The low actuarial distant metastasis rate of T2 patients (0% at 3 years), the 3-year actuarial overall survival rates for T2 (89%) and T3-4 (50%) patients, and the similar treatment outcomes for papillary versus solid tumors are encouraging when compared with published historical controls. These results provide preliminary evidence (median follow-up, 30 months) that the current chemoradiotherapy regimen may have beneficial effects in the treatment of muscle-invasive bladder carcinoma. The true efficacy of neoadjuvant chemotherapy remains to be proven by ongoing randomized trials.