The prognostic impact of perioperative blood transfusion on survival in patients with bladder urothelial carcinoma treated with radical cystectomy

PURPOSE: The aim of our study was to assess the influence of perioperative blood transfusion (PBT) on survival outcomes following radical cystectomy (RC) and pelvic lymph node dissection (PLND). MATERIALS AND METHODS: We reviewed and analyzed the clinical data of 432 patients who underwent RC for bladder cancer from 1991 to 2012. PBT was defined as the transfusion of allogeneic red blood cells during RC or postoperative hospitalization. RESULTS: Of all patients, 315 patients (72.9%) received PBT. On multivariate logistic regression analysis, female gender (p=0.015), a lower preoperative hemoglobin level (p=0.003), estimated blood loss>800 mL (p4 packed red blood cell units was an independent predictor of overall survival (p=0.007), but not in cancer specific survival. CONCLUSIONS: Our study was not conclusive to detect a clear association between PBT and survival after RC. However, the efforts should be made to continue limiting the overuse of transfusion especially in patients who are expected to have a high probability of PBT, such as females and those with a low preoperative hemoglobin level and history of neoadjuvant chemotherapy.

Preoperative Underweight Patients with Upper Tract Urothelial Carcinoma Survive Less after Radical Nephroureterectomy

The prognostic impact of body mass index (BMI) in patients with upper tract urothelial carcinoma (UTUC) is an ongoing debate. Our study aimed to investigate the prognostic role of BMI in patients treated with radical nephroureterectomy (RNU) for UTUC from a multi-institutional Korean collaboration. We retrospectively reviewed data from 440 patients who underwent RNU for UTUC at four institutions in Korea. To avoid biasing the survival estimates, patients who had previous or concomitant muscle-invasive bladder tumors were excluded. BMI was categorized into approximate quartiles with the lowest quartile assigned to the reference group. Kaplan-Meier and multivariate Cox regression analyses were performed to assess the influence of BMI on survival. The lower quartile BMI group showed significantly increased overall mortality (OM) and cancer specific mortality (CSM) compared to the 25%-50% quartiles and upper quartile BMI groups. Kaplan-Meier estimates showed similar results. Based on multivariate Cox regression analysis, preoperative BMI as a continuous variable was an independent predictor for OM and CSM. In conclusion, preoperative underweight patients with UTUC in Korea survive less after RNU. Preoperative BMI may provide additional prognostic information to establish risk factors.

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.

Clinical Significance of Lymph Node Dissection in Patients with Muscle-Invasive Upper Urinary Tract Transitional Cell Carcinoma Treated with Nephroureterectomy

We investigated the value of lymph node dissection in patients with cN0 muscle-invasive transitional cell carcinoma of the upper urinary tract (UUT-TCC). Medical records of 152 patients with cN0 muscle-invasive UUT-TCC, who underwent nephroureterectomy between 1986 and 2005, were reviewed. Sixty-three patients (41.4%) underwent lymph node dissection. The median number of lymph nodes harvested was 6 (range, 1 to 35), and from these, lymph node involvement was confirmed in 9 patients (14.3%). Locoregional recurrence (LR) and disease-recurrence (DR) occurred in 29 patients and 63 patients, respectively. Fifty-five patients (36.2%) had died of cancer at the last follow-up. The number of lymph nodes harvested was associated with the reduction of LR (chi-square(trend)=6.755, P=0.009), but was not associated with DR (chi-square(trend)=1.558, P=0.212). In the survival analysis, N stage (P=0.0251) and lymph node dissection (P=0.0073) had significant influence on LR, but not on DR or disease-specific survival. However, the number of lymph nodes harvested did not affect LR-free, DR-free, or disease-specific survival. We conclude that lymph node dissection may improve the control of locoregional cancer, as well as staging accuracy, in cN0 muscle-invasive UUT-TCC, but that it does not clearly influence survival.

Prognostic Impact of Peripelvic Fat Invasion in pT3 Renal Pelvic Transitional Cell Carcinoma

Renal pelvic transitional cell carcinoma (TCC), which invades beyond muscularis into peripelvic fat or the renal parenchyma, is diagnosed as stage pT3 despite its structural complexity. We evaluated the prognostic impact of peripelvic fat invasion in pT3 renal pelvic TCC. Between 1986 and 2004, the medical records on 128 patients who were surgically treated for renal pelvic TCC were retrospectively reviewed. Sixty patients with pT3 disease were eligible for the main analysis. The prognostic impact of various clinicopathological factors was analyzed using univariate and multivariate analyses. On univariate analysis, sex, age, concomitant bladder tumors, concomitant ureter tumors, lymphadenectomy, adjuvant chemotherapy, tumor grade, multiplicity, renal parenchymal invasion, and carcinoma in situ did not influence the disease-specific survival (p>0.05). By contrast, peripelvic fat invasion, lymph node invasion, and lymphovascular invasion were each significantly associated with disease-specific survival (p<0.05). Multivariate analysis showed that peripelvic fat invasion (p=0.012) and lymph node invasion (p=0.004) were independent prognostic factors. In conclusion, peripelvic fat invasion is a strong prognostic factor in pT3 renal pelvic TCC. Thus, systemic adjuvant therapy should be considered in the presence of peripelvic fat invasion, even if the lymph nodes are not involved.

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...

Pathological staging of muscle invasive bladder cancer: is substaging of pT2 tumors really necessary?

OBJECTIVE: Compare clinical outcomes in patients having urothelial tumors invading less than one half of the depth of bladder muscle and greater than one half of bladder muscle and, to determine various clinical variables as predictive factors for survival. MATERIALS AND METHODS: According to our inclusion criteria, 57 patients among cases with T2 bladder tumor were selected. Thirty-five patients (61.4 percent) had pT2a (Group-1) and 22 patients (38.6 percent) had pT2b (Group-2) muscle invasive tumors. Mean follow up time was 7.3 years for Group-1, and 6.1 years for Group-2. Multivariate analysis was performed in order to identify possible correlation of clinical variables like age, gender, grade of primary tumor, appearance of local and/ or distant metastasis with patient outcome. RESULTS: Five year recurrence-free and overall survival rates were 69.1 percent and 44.3 percent for patients with pT2a tumor, whereas these ratios were 66.1 percent and 43 percent, respectively for patients with pT2b tumor (p = 0.896; p = 0.975). Mean overall and progression-free survival times were 87.7 ± 13.8 and 116 ± 13.12 months for Group-1, while they were 73.8 ± 13.7 and 88.85 ± 12.55 months for Group-2, respectively. On both univariate and multivariate analysis, age was noticed as an independent predictive factor for survival. CONCLUSIONS: The depth of muscle invasion in bladder tumors has no prognostic significance. Recurrence of the disease either locally or at distant sites dramatically shortens patients' life. Being older than 60 years old during the time of radical surgery, is also a bad prognostic factor for overall and progression-free survival.

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.

Carcinoma of the renal pelvis and ureter

OBJECTIVE: To assess the occurrence of upper urinary tract urothelial tumors (UUTT) in Brazil. MATERIALS AND METHODS: We performed a clinical and histopathologic study of 33 patients who were diagnosed with a malignant neoplasm in the renal pelvis or ureter in the period of 1994 to 2004, in a single institution. RESULTS: Among the patients with upper urinary tract carcinoma, 70 percent were males and 30 percent females, with mean age of 65 ± 16 years (ranging from 31 to 91 years). Nineteen patients presented renal pelvis tumor (58 percent), 9 ureteral tumor (27 percent) and 5 synchronic pelvic and ureteral tumors (15 percent). Renal pelvis tumors represented 2.8 percent of all the urothelial neoplasms, and 11.4 percent of all renal neoplasms treated in the same period. Ureteral tumors represented 1.6 percent of all the urothelial malignancies surgically managed in these 11 years. Tobacco smoking was the most common risk factor, and analgesic abuse was not reported by those patients. Most carcinomas were high-grade and muscle-invasive. Mean time to diagnosis was 7 months, being hematuria the most common symptom. CONCLUSIONS: A high association was also found between UUTT and bladder urothelial carcinoma. UUTT were mostly seen in men in their seventies and related to a high overall and cancer-related mortality rate. The overall disease-specific survival was 40 percent, much lower than found in most of the reported series.

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.