Combination of gemcitabine and carboplatin in urothelial cancer patients unfit for cisplatin due to impaired renal or cardiac function

PURPOSE: Combination of gemcitabine and carboplatin is the accepted treatment for metastatic urothelial cancer patients unfit for cisplatin-based chemotherapy. MATERIALS AND METHODS: Gemcitabine 1000 mg/m² (days 1, 8) and carboplatin AUC-4.5 (day 1) were given every 21 days to 23 patients with creatinine clearance < 60 mL/min, cardiac ejection fraction < 45% or active ischemia. Patient characteristics included: median age 73 (56-86) years; primary site: bladder 17 (73%), upper tract 6 (27%) patients; Bajorin's prognostic groups: good 6 (26%), intermediate 11 (48%) and poor 6 (26%) patients. Data was retrospectively documented. Patients were followed until they expired. RESULTS: We obtained objective responses in 8 (34.7%) patients, (95% CI, 16.3-57.2%), including one patient with complete response. The median progression-free survival was 4 (0.2-16.5+) months and the overall survival 8.6 (0.2-45.3+) months. At time of analysis, 4 patients (17%) remained disease free; 3 of them underwent resection of residual disease. Toxicity included: infection in 9 (39%) patients; among them, one died from pneumonia; bleeding > grade 2 in 3 (13%) patients and fatigue grade 3 in 2 (9%) patients. Hematologic toxicity included grade 4 thrombocytopenia in 2 (9%) patients and grade 4 neutropenia in 3 (13%) patients. Five (22%) patients discontinued therapy due to toxicity. CONCLUSIONS: Combination of gemcitabine and carboplatin demonstrated clinical activity in patients with advanced urothelial cancer unfit for cisplatin. It was associated with considerable toxicity. Resection of residual disease is feasible in this population.

Results from three municipal hospitals regarding radical cystectomy on elderly patients

OBJECTIVE: Radical cystectomy is the standard treatment for invasive bladder carcinoma in elderly patients at major surgical centers. As yet no data are available as to the question whether radical surgery on the genitourinary tract of patients over 75 can also be carried out at municipal hospitals with comparable intra and postoperative morbidity, and respective mortality. MATERIALS AND METHODS: 452 radical cystectomies and urinary diversions as ileum conduits or ileum neobladders due to transitional cell carcinoma were carried out at three municipal hospitals between 1992 and 2004. At the time of the surgery, 44 patients (9.7 percent) were > 75 (75-84) (Group-1), by comparison 408 patients were younger than 75 (35-74) (Group-2). Comparisons are to be made between the groups for 30 day mortality, 30 day reoperation rate, early complication rate (< 3 months), late complication rate (> 3 months), progression-free survival, and overall survival. The results are to be discussed in view of the international literature. Mean follow-up was 49 months (median: 38 months). RESULTS: The perioperative mortality in Group-1 was 2.3 percent compared to 2.5 percent in Group-2 (p = 0.942). There was no significant difference in the perioperative mortality with regard to the different case load of the evaluated hospital. There were no significant group differences regarding the 30 day reoperation rate, early and late complications. Progression-free and overall survival of all patients after 5 years was 56.1 percent and 53.6 percent respectively; here again the differences between the age groups was not significant (p = 0.384 and p = 0.210). Our results for patients > 75 do not differ from the published data of large clinics with a high cystectomy frequency. CONCLUSIONS: Our data confirm that radical cystectomy on elderly patients can also be carried out in municipal hospitals with acceptable mortality and morbidity rates. Of prime importance is a careful...

The role of squamous differentiation in patients with transitional cell carcinoma of the bladder treated with radical cystectomy

OBJECTIVE: We aim at determining the prognostic value of squamous differentiation in patients with transitional cell carcinoma (TCC) of the bladder that were treated with radical cystectomy. MATERIALS AND METHODS: From January 1993 to January 2005, we retrospectively selected 113 patients. Correlations among squamous differentiation with other clinical and pathological features were assessed by both chi-square and Fisher tests. The Kaplan-Meier method was used to evaluate survival curves and statistical significance was determined by the log-rank test. Multivariate analysis was performed through a Cox proportional hazards regression model. RESULTS: Squamous differentiation was observed in 25 (22.1 percent) of the 113 patients. This finding was significantly related only to the pathological stage. Mean follow-up after cystectomy was 31.7 ± 28.5 months. Disease recurrence occurred in 16 (64 percent) and 30 (34 percent) patients with and without squamous differentiation (log-rank test, p = 0.001), and mortality occurred in 10 (40 percent) and 14 (16 percent) of the patients with and without squamous differentiation respectively. Univariate analysis revealed that pathological stage, squamous differentiation, tumor size and lymph node involvement were significant predictors of cancer-specific survival. However, only squamous differentiation and tumor size were independent prognostic variables on multivariate analysis. CONCLUSIONS: Squamous differentiation was an independent prognostic factor for cancer specific survival in patients with bladder cancer treated with radical cystectomy. Further studies with a larger number of patients are necessary to confirm these results.

A fourteen-year review of radical cystectomy for transitional cell carcinoma demonstrating the usefulness of the concept of lymph node density

OBJECTIVE: We studied the long-term outcome of radical cystectomy for transitional cell carcinoma and evaluated prognostic factors for disease specific survival. MATERIALS AND METHODS: A retrospective review was carried out for all cystectomies performed for transitional cell carcinoma between 1989 and 2002. Disease specific survival was correlated to patient, pathological and operative factors as well as to adjuvant therapy. RESULTS: Of the 133 cystectomies included, 100 were male and 33 were female patients. The median age was 69 years (range 43 to 86). The median follow up was 20 months (range 0 to 158). With univariate analysis, pT stage, N stage, lymph node density, carcinoma in-situ, surgical margin and post-operative radiotherapy to distant metastasis were predictive of disease specific survival. On the other hand, with multivariate analysis, only pT stage, lymph node density and post-operative radiotherapy to distant metastasis were predictive of disease specific survival. Within the group of node positive disease, lymph node density also predicted disease specific survival with both univariate and multivariate analyses. Patients with lymph node density 20 percent or below showed better disease specific survival. CONCLUSIONS: pT stage and lymph node density were found to be the most important predictive factors for disease specific survival after cystectomy in the Asian population.

17-year follow-up of a randomized prospective controlled trial of adjuvant intravesical doxorubicin in the treatment of superficial bladder cancer

PURPOSE: To evaluate the efficacy of adjuvant intravesical doxorubicin in superficial transitional cell carcinoma of the urinary bladder on long-term follow-up. MATERIALS AND METHODS: Between July 1986 and November 1991, all patients harboring superficial bladder cancers (Ta or T1) with one or more of these criteria (stage > a, grade > 1, size > 1 cm, multiple or recurrent tumors) were randomized to receive either 50 mg doxorubicin or no adjuvant therapy. Patients with recurrences were allowed to receive doxorubicin or other intravesical agents. Recurrence, progression and survival were analyzed. RESULTS: There were 82 patients included (64 males and 18 females). The mean age was 64 years. Forty-six patients were randomized to the doxorubicin group and 36 to the control group. Final analysis was made at median follow-up of 45, 128 and 131.5 months for recurrence, progression and survival, respectively. Recurrence free, progression free and disease specific survival did not differ significantly between groups. The 10-year Kaplan-Meier estimates for recurrence free, progression free and disease specific survival were 67 percent, 84 percent and 92 percent, respectively for the doxorubicin group, and were 50 percent, 89 percent and 97 percent, respectively for the control group. Tumor size predicted recurrence (p = 0.013) and grade predicted progression (p = 0.004) with multivariate analysis. CONCLUSIONS: Adjuvant intravesical doxorubicin could not be shown to improve recurrence, progression and survival of superficial bladder cancer, compared with control on long-term follow-up. Tumor size and grade were shown to be prognostic factors for recurrence and progression, respectively.