Cancer specific outcomes in patients with pT0 disease following radical cystectomy

PURPOSE: We assessed clinical outcomes in patients found to have no evidence of disease, ie pT0, in the cystectomy specimen following radical cystectomy for transitional cell carcinoma. MATERIALS AND METHODS: Between 1984 and 2003, 955 consecutive patients underwent bilateral pelvic lymphadenectomy and radical cystectomy for bladder cancer at 3 institutions, namely The Johns Hopkins Hospital, University of Texas Southwestern Medical Center and Baylor College of Medicine. Excluding nonTCC histology and patients with missing data resulted in 888 evaluable cases. Primary end points were recurrence-free survival and bladder cancer specific survival. RESULTS: Final pathological evaluation revealed absent transitional cell carcinoma in the cystectomy specimen, ie pT0, in 59 patients (7%), of whom 2 (3%) had pathologically positive lymph nodes. Transurethral resection stage or clinical stage data were available on 56 patients (95%), including Tis in 5 (9%), Ta in 2 (4%), T1 in 18 (32%), T2 in 29 (52%) and T3 in 2 (4%). Overall 6 recurrences (10%) were noted, including cTis in 1 case, cT1 in 1, cT2 in 3 and cT3 in 1. Median followup in patients with pT0 disease was 56 months (range 3 to 183). Three patients (5%) died of bladder cancer and another 4 (7%) died of other causes. Five and 10-year bladder cancer progression-free and cancer specific survival estimates in patients with pT0 disease were 90% and 81%, and 95% and 85%, respectively. CONCLUSIONS: Despite excellent clinical outcomes in the majority of patients with no evidence of tumor on final pathological evaluation not all patients with pT0 disease in the cystectomy specimen are cured of bladder cancer. These events may even occur in patients with nonmuscle invasive or muscle invasive organ confined pathology at staging transurethral resection. Further study is needed to identify prognostic factors in this population.     

Superficial (pT2a) and deep (pT2b) muscle invasion in pathological staging of bladder cancer following radical cystectomy

PURPOSE: We compared and evaluated clinical outcomes in patients with pathological superficial (pT2a) and deep (pT2b) invasion of bladder muscle with transitional cell carcinoma following radical cystectomy and urinary diversion. MATERIALS AND METHODS: From 1971 to 2001, 311 of 1,359 patients (23%), including 244 males (78%) and 67 females, were found to have pathological muscle invasive (pT2) bladder cancer following radical cystectomy. Of this group 147 patients (47%) had pT2a (superficial) and 164 (53%) had pT2b (deep) muscle invasive tumors. Overall 242 patients had no evidence of lymph node metastasis, including 127 with pT2a (86%) and 115 with pT2b (70%). A total of 69 patients (22%) had lymph node involvement, including 20 with pT2a (14%) and 49 with pT2b (30%). At a median followup of 14.3 years (range 0 to 30.1) clinical outcomes were determined, including recurrence-free and overall survival, and local vs distant recurrence. RESULTS: In the 311 patients with pT2 tumors 10-year recurrence-free and overall survival rates were 72% and 47%, respectively. There was a significantly higher risk of node positive disease with pT2b vs pT2a tumors (30% vs 14%, p <0.001). No significant difference was observed in 10-year recurrence-free survival in patients with pT2a node negative vs pT2b node negative tumors (84% vs 72%, p = 0.091). When comparing pT2a node positive vs pT2b node positive tumors, no significant difference was observed in 10-year recurrence-free survival (50% vs 48%, p = 0.84). Recurrence-free survival was significantly higher in patients with pT2 lymph node negative tumors than in those with pT2 lymph node positive tumors (79% vs 49%, p <0.001). Furthermore, these differences remained significant when stratified by pT2a and pT2b node negative vs positive disease. Local pelvic recurrence developed in 10 of 311 patients (3%) with pT2 disease, while 69 (22%) had distant metastatic disease. In patients with recurrence the local or distant recurrence site was not associated with tumor stage (pT2a vs pT2b p = 0.24) or lymph node status (node negative vs positive p = 0.37). CONCLUSIONS: In muscle invasive (pT2) bladder cancer treated with radical cystectomy there is a higher risk of lymph node positive disease in deep muscle (pT2b) vs superficial (pT2a) invasion. However, no apparent difference was observed in recurrence-free survival between pT2a (superficial) vs pT2b (deep) muscle invasive tumors when controlling for lymph node status. Recurrence-free survival is significantly improved in patients with pT2 lymph node negative tumors compared to survival in those with pT2 lymph node positive tumors. Patients with muscle invasive (pT2), lymph node negative tumors have excellent clinical outcomes following cystectomy, while those with muscle invasive (pT2), lymph node positive tumors have higher recurrence rates and should be considered for adjuvant treatment protocols.     

Pathological findings of gynecologic organs obtained at female radical cystectomy

PURPOSE: Historically anterior pelvic exenteration has been the recommended treatment for invasive urothelial carcinoma in women undergoing radical cystectomy. We evaluated the pathological features of reproductive organs removed during exenteration to determine the incidence of malignant pathology in these organs and the need for removal. MATERIALS AND METHODS: We reviewed the records of all patients who underwent radical cystectomy between January 1994 and December 2000. Of these 382 patients, we identified 68 females who underwent radical cystectomy for urothelial carcinoma. We reviewed preoperative, operative and pathological findings, including bladder, lymph nodes, uterine and adnexal pathology, in these female patients. RESULTS: Median patient age was 64 years (range 35 to 86). Gynecologic organs were present in 40 of the 68 surgical specimens (59%). The reasons for absent gynecologic pathology were previous hysterectomy in 26 cases and the preservation of organs during orthotopic urinary diversion creation in 2. Malignancy was identified in 3 specimens, including invasive urothelial carcinoma in 2 (5%). In these 2 cases invasion was clearly identified intraoperatively. Low grade stromal sarcoma of the uterus was present in 1 specimen (2%). CONCLUSIONS: In the absence of clinical suspicion radical hysterectomy at cystectomy rarely improves cancer control. Furthermore, secondary malignancies are rare. The functional impact of preserving gynecologic organs is a subject of ongoing study.     

Stage specific follow-up strategy after cystectomy for carcinoma of the bladder

BACKGROUND: Follow-up strategies after cystectomy for carcinoma of the bladder should be determined according to the risk of recurrence, which is stage dependent. We aimed to develop follow-up protocol for monitoring patients with carcinoma of the bladder for tumor recurrence and diverted urinary tract complications after radical cystectomy. METHODS: The records of 351 patients with carcinoma of the bladder who underwent cystectomy between 1979 and 1999 were reviewed for dates and presenting symptoms of local and distant recurrences. The results of imaging studies and blood tests were also reviewed. Based on the division of patients into pathological stages of pT1 and lower, pT2, and pT3 and higher groups, we proposed a new follow-up schedule for carcinoma of the bladder. RESULTS: The risk of metastasis was related to the pathological stage of the primary tumor. Recurrence developed in 10 of 124 patients (8%) with pT1 or lower, 17 of 101 patients (17%) with pT2, and 55 of 101 patients (54%) with pT3 or higher disease at a median of 11 (range 6-186), 10 (1-40) and 7 (1-76) months, respectively. Recurrences in patients with pT3 or higher were found earlier and more frequently than those with pT2 or lower. Of 82 patients with metastases, 54 initially were symptomatic, and three of pT1 or lower, six of pT2, and 19 of pT3 or higher were asymptomatic. Based on these results we proposed a stage specific follow-up protocol. CONCLUSIONS: A stage-driven follow-up strategy for monitoring patients after radical cystectomy can reduce medical expenses while efficiently detecting recurrences and complications.     

Outcomes in patients with pathological carcinoma in situ only disease at radical cystectomy

PURPOSE: Pathological stage influences patient outcome after radical cystectomy. We present our experience with patients who have only transitional cell carcinoma in situ of the bladder (pCIS-only) on final pathological examination after radical cystectomy. MATERIALS AND METHODS: Between August 1995 and June 2003, 576 patients underwent radical cystectomy at our institution. Of these patients 54 were pathological stage CIS-only on final cystectomy specimen. Four patients simultaneously had invasive transitional cell carcinoma of the ureter or renal pelvis and were excluded from evaluation. Variables examined included demographic characteristics, preoperative pathological stage, high risk features and followup parameters. RESULTS: Of the 50 patients with pCIS-only 44 (88%) were disease-free at last followup. Mean followup was 37.2 months (range 3.6 to 93.5). Of the 50 patients 21 had focal CIS while 29 had multifocal disease. There was no difference in disease recurrence between these 2 groups (9.5% vs 13.7%, p = 0.8). There were 9 patients with proximal urethral CIS involvement, of whom metastatic disease developed in 3. Only 1 of the 8 patients (12.5%) with ureteral orifice involvement had recurrence. Of the 50 patients 22 had muscle invasive disease on initial transurethral resection without residual invasive disease at cystectomy. This subset fared significantly worse after radical cystectomy than the 28 patients with less than stage T2 disease on transurethral bladder tumor resection (22.7% vs 3.6% metastasis, p < or = 0.05). CONCLUSIONS: The outcome of patients who have pCIS-only after radical cystectomy is not uniform. Patients may be at higher risk for recurrence if disease extends to the proximal urethra. In addition, patients demonstrating invasion on clinical staging (stage T2 or greater) but subsequent pCIS-only disease have a worse prognosis compared to those with superficial clinical staging. Patients with CIS-only on clinical and pathological staging have an excellent disease-free survival with radical cystectomy even with the presence of multifocal disease.     

Prognostic risk stratification of pathological stage T2N0 bladder cancer after radical cystectomy

Study Type – Therapy (individual cohort) Level of Evidence 2b What’s known on the subject? and What does the study add? Patients with urothelial carcinoma of the bladder (UCB) and pathological (p) stage T2N0 disease exhibit a range of clinical outcomes with an overall estimated 10–25% experiencing recurrence and death after radical cystectomy (RC). Nomograms to prognosticate UCB post‐RC have been developed in heterogeneous datasets of patients across different stages and do not address factors unique to pT2N0 disease. A user‐friendly prognostic risk model was devised for patients with pT2N0 UCB undergoing RC based on residual pathological stage at RC (pT2a, pT2b, OBJECTIVE ? To stratify risk of pathological (p) T2N0 urothelial carcinoma of the bladder after radical cystectomy (RC) based on pathological factors to facilitate the development of adjuvant therapy trials for high‐risk patients.

PATIENTS AND METHODS

? The study comprised 707 patients from a database of patients with pT2N0 urothelial carcinoma of the bladder who had undergone RC and not received perioperative chemotherapy. ? The effect of residual pT‐stage at RC, age, grade, lymphovascular invasion and number of lymph nodes removed on recurrence‐free survival was evaluated using Cox regression analyses. A weighted prognostic model was devised with significant variables.

RESULTS

? The median follow up was 60.9 months. In multivariable analyses, residual disease at RC (pT2a: hazard ratio (HR) 1.740, P = 0.03; for pT2b: HR 3.075, P < 0.001; both compared with P = 0.09) and lymphovascular invasion (HR 2.234, P < 0.001) were associated with recurrence‐free survival (c = 0.70). ? Three risk groups were devised based on weighted variables with 5‐year recurrence‐free survival of 95% (95% CI 87–98), 86% (95% CI 81–90) and 62% (95% CI 54–69) in the good‐risk, intermediate‐risk and poor‐risk groups, respectively (c = 0.68). The primary limitation is the retrospective and multicenter feature.

CONCLUSIONS

? A prognostic risk model for patients with pT2N0 bladder cancer undergoing RC with generally adequate lymph node dissection was constructed based on residual pathological stage at RC, grade and lymphovascular invasion. ? These data warrant validation and may enable the selection of patients with high‐risk pT2N0 urothelial carcinoma of the bladder for adjuvant therapy trials.     

Correlation between clinical and pathological staging in a series of radical cystectomies for bladder carcinoma

OBJECTIVE: To analyse the rate of concordance between the clinical and pathological Tumour-Nodes-Metastasis staging systems in a homogeneous series of patients who had undergone radical cystectomy for locally advanced or recurrent multifocal superficial bladder carcinoma. PATIENTS AND METHODS: The clinical data of 156 patients who had undergone radical cystectomy and bilateral iliaco-obturator lymphadenectomy for bladder cancer in our department were analysed retrospectively. RESULTS The clinical stage of the primary tumour was carcinoma in situ in three patients (1.9%), cT1 in 67 (42.9%), cT2 in 70 (44.9%), cT3 in five (3.2%) and cT4 in nine (5.8%). Clinical lymph node involvement was detected in 19 patients (12.2%). The differences between clinical and pathological stages were statistically significant (P < 0.001), the concordance was moderate (kappa = 0.27, P < 0.001). Of the 70 patients with < or = cT1, 40 (57%) were reconfirmed as having pathological stage < or = T1; of the 70 with cT2, 16 (23%) had pT2 carcinoma. Of the 140 patients with clinically organ-confined (< or =T2) neoplasms, 70 (50%) had been understaged after radical cystectomy. The clinical and pathological systems were statistically overlapping for locally advanced cases only. Pathological lymph node involvement was diagnosed in 45 patients (28.8%); this was foreseen with pelvic computed tomography in 19 (12%) only (P < 0.001). All patients designated cN+ were also pN+. CONCLUSION: These data confirm the high risk of clinical understaging of both local extension of the primary tumour and lymph node involvement.     

Recurrence and progression of stage T1, grade 3 transitional cell carcinoma of the bladder following intravesical immunotherapy with bacillus Calmette-Guerin

PURPOSE: 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). MATERIALS AND METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.     

Prognostic significance of lymphovascular invasion of bladder cancer treated with radical cystectomy

PURPOSE: We determined the prognostic significance of lymphovascular invasion (LVI) in patients treated for invasive transitional cell carcinoma of the bladder with radical cystectomy. MATERIALS AND METHODS: From August 1971 to June 2004, 2,005 patients underwent radical cystectomy for primary bladder cancer with intent to cure. All patients with nontransitional cell carcinoma histology, palliative procedures, unknown lymphovascular status, less than pT1 pathological stage, or any neoadjuvant or adjuvant chemotherapy/radiation therapy were excluded, leaving 702 comprising the study cohort. Of the 702 patients 249 (36%) had LVI. RESULTS: Median followup was 11.0 years (range 8 days to 23.2 years). Overall 5 and 10-year survival was 51% and 34%, while 5 and 10-year recurrence-free survival was 66% and 64%, respectively. Ten-year recurrence-free survival in patients without LVI was 74% compared with 42% in those with LVI (p <0.0001). Similarly 10-year overall survival was 43% in patients without LVI compared with 18% in those with LVI (p <0.0001). In the organ confined/lymph node negative and lymph node positive pathological subgroups survival outcomes were significantly worse if LVI was present. Although a trend was observed, LVI status was not statistically significant in patients with extravesical node negative disease. Stepwise Cox regression analysis revealed that pathological subgroup (organ confined, extravesical and lymph node positive) (p <0.0001) and LVI status (p = 0.0004) were independent prognostic variables for recurrence-free and overall survival. CONCLUSIONS: Lymphovascular invasion appears to be an important and independent prognostic variable in patients with invasive bladder cancer treated with radical cystectomy. LVI status should be determined in cystectomy specimens, which may provide further risk stratification in patients following radical cystectomy.     

Combination chemotherapy of ifosfamide, 5‐fluorouracil,etoposide and cisplatin as perioperative treatment in lymph node positive bladder carcinoma patients treated by radical cystectomy

Objectives: To evaluate the efficacy and toxicity of perioperative combination chemotherapy with ifosfamide, 5‐fluorouracil, etoposide and cisplatin (IFEP) in bladder cancer patients with regional lymph node metastases treated by radical cystectomy. Methods: We reviewed the medical records of 183 consecutive patients who underwent radical cystectomy for invasive urothelial carcinoma of the bladder. Of those, 26 patients with regional lymph node metastasis who were regarded as being rendered surgically disease‐free (pT1‐4, N1‐2, cM0) and treated with perioperative IFEP chemotherapy were the subjects of the present study. Results: Median follow‐up of 26 patients was 49 months (range 4–150). Grade 3 and 4 bone marrow toxicities were seen in 15 and four patients, respectively. Neither chemotherapy‐related death nor febrile neutropenia occurred. The 5‐year overall and cancer‐specific survival rate was 60% and 68%, respectively. The overall survival rate of the patients with pT4 disease was significantly worse than that of patients with pT1‐3. There were four N2 patients who survived for over 5 years free of disease. Conclusions: Perioperative IFEP therapy appeared to be effective in the treatment of lymph node positive bladder cancer patients who underwent radical cystectomy. Further study may be warranted.     

Grading the invasive component of urothelial carcinoma of the bladder and its relationship with progression-free survival

Although grading is valuable prognostically in pTa and pT1 papillary urothelial carcinoma, it is unclear whether it provides any prognostic information when applied to the invasive component in muscle-invasive carcinoma. The authors analyzed 93 cases of muscle-invasive urothelial carcinoma of the bladder treated with radical cystectomy for which follow-up information was available. Each case was graded using the Malmstr?m grading system for urothelial carcinoma, applied to the invasive component. Pathologic stage, lymph node status, and histologic invasion pattern were also recorded and correlated with progression-free survival. Thirty-four cases (37%) were pT2, 40 (43%) were pT3, and 19 (20%) were pT4. Of the 77 patients who had a lymph node dissection at the time of cystectomy, 34 (44%) had metastatic carcinoma to one or more lymph nodes. The median survival for pT2, pT3, and pT4 stages was 85, 24, and 29 months, respectively (p = 0.0001). Lymph node-negative and lymph node-positive patients had a median survival of 63 and 23 months, respectively (p = 0.0001). Fifteen patients (16%) were graded as 2b and 78 patients (84%) were graded as 3. Median survival of patients graded as 2b was 34 months compared with 31 months for patients graded as 3 (p value not significant). Three invasive patterns were recognized: nodular (n = 13, 14%), trabecular (n = 39, 42%), and infiltrative (n = 41, 44%). The presence of any infiltrative pattern in the tumor was associated with a median survival of 29 months, compared with 85 months in tumors without an infiltrative pattern (p = 0.06). Pathologic T stage and lymph node status remain the most powerful predictors of progression in muscle-invasive urothelial carcinoma. In this group of patients histologic grade, as defined by the Malmstr?m system and as applied to the invasive component, provided no additional prognostic information. An infiltrative growth pattern may be associated with a more dismal prognosis.     

Downstaging to non-invasive urothelial carcinoma is associated with improved outcome following radical cystectomy for patients with cT2 disease

Introduction

Pathologic stage is a critically important prognostic factor after radical cystectomy (RC) that is used to guide the use of secondary therapies. However, the risk of disease recurrence, for patients clinically diagnosed with muscle-invasive tumors who are found not to have muscle-invasive disease at RC are poorly defined. Therefore, we reviewed the long-term outcomes in patients who were downstaged to non-invasive urothelial carcinoma at time of RC.

Methods

We identified 1,177 consecutive patients with muscle-invasive urothelial carcinoma of the bladder who underwent radical cystectomy at our institution between 1980 and 1999 without neoadjuvant therapy. Postoperative disease recurrence and survival were estimated using the Kaplan?CMeier method and compared using the log rank test. Cox proportional hazard regression models were used to analyze the impact of pathologic stage on survival.

Results

Pathologic downstaging to non-muscle invasive disease was identified in 538 (45.7?%) patients. The 10-year cancer-specific survival was 84.1, 77.4, 71.1 and 58.5?% for those with pT0, pTis, pT1 and pT2 tumors, respectively. On multivariate analysis, the risk of cancer-specific mortality was significantly decreased for patients with non-muscle invasive disease than those with organ-confined muscle invasion (RR?0.39; p?=?0.002). There was no difference in disease-specific mortality among patients who had non-invasive (pT0, pTa, or pTis) disease (p?=?0.19).

Conclusions

Downstaging from clinical muscle-invasive bladder cancer to non-muscle invasive disease at RC is associated with a significant reduction in cancer-specific mortality. However, even patients with residual non-muscle invasive disease may suffer disease recurrence and require continued surveillance after surgery.     

Complications of radical cystectomy for nonmuscle invasive disease: comparison with muscle invasive disease

PURPOSE: Radical cystectomy is gold standard treatment for muscle invasive bladder cancer and is an option for many patients with nonmuscle invasive disease at high risk for disease progression. We assessed the early complications of radical cystectomy among patients with nonmuscle invasive compared to those with muscle invasive disease. MATERIALS AND METHODS: We reviewed the records of 304 consecutive patients who underwent radical cystectomy from December 1995 to July 2000. We evaluated complications that occurred within 30 days of the procedure. Cases were stratified into nonmuscle invasive (PO, Pa, P1 and PIS, N0) or muscle invasive (P2-4, N0-3) tumors based on final specimen pathology. The 2 groups were then compared with respect to age, gender, race, American Society of Anesthesiologists score, type of urinary diversion, estimated blood loss, operative time and length of stay, and major and minor complications. RESULTS: Of the 293 available patients 105 (36.8%) had nonmuscle invasive specimen pathology. Overall major and minor complications occurred in 4.9% and 30.4% of cases, respectively. Independent t test revealed no significant difference between groups in terms of age (p = 0.85), gender (p = 0.77), race (p = 1.0), American Society of Anesthesiologists (p = 0.32), type of urinary diversion (p = 0.33), estimated blood loss (p = 0.31), operative time (p = 0.41), length of stay (p = 0.75), or presence of major (p = 0.78) or minor (p = 0.79) complications. CONCLUSIONS: The early morbidity associated with radical cystectomy for nonmuscle invasive disease is similar to but not less than that associated with muscle invasive tumors. These acceptable risks as well as the potential benefits should be discussed with patients with nonmuscle invasive bladder cancer at high risk for disease progression.     

An interval longer than 12 weeks between the diagnosis of muscle invasion and cystectomy is associated with worse outcome in bladder carcinoma

PURPOSE: The standard of care for muscle invasive transitional cell carcinoma of the bladder is radical cystectomy. Definitive therapy may often be delayed for various reasons. We assessed whether pathological stage and survival correlated with the length of time between diagnosis of muscle invasion and cystectomy. MATERIALS AND METHODS: The records of 290 consecutive patients who underwent radical cystectomy between February 1987 and July 2000 were reviewed. Of 265 (91.4%) cystectomies performed for transitional cell carcinoma data were available for 247 (85.2%) and 189 (65.2%) patients were identified who underwent surgery for muscle invasive disease (T2 or greater). The interval between diagnosis of muscle invasion and cystectomy was calculated for each patient. Patients were divided into groups based on time to surgery as group 1-less than 4 weeks, 2-4 to 6 weeks, 3-7 to 9 weeks, 4-10 to 12 weeks, 5-13 to 16 weeks, and 6-greater than 16 weeks. Exploratory univariate and multivariate analyses were performed to test the association of time lag with clinical features and postoperative survival. RESULTS: Mean patient age was 66 years (range 37 to 84) and overall 3-year Kaplan-Meier estimated survival was 59.1% +/- 4% (median followup 36 months). For all patients mean interval from diagnosis to cystectomy was 7.9 weeks (range 1 to 40). Extravesical disease (P3a or greater) or positive nodes were identified in 84% (16 of 19) of patients when the delay was longer than 12 weeks, compared with 48.2% (82 of 170) in those with a time lag of 12 weeks or less (p < 0.01). Similarly 3-year estimated survival was lower (34.9% +/- 13.5%) for patients with a surgery delay longer than 12 weeks compared to those with a shorter interval 62.1% +/- 4.5% (hazards ratio 2.51, 95% CI 1.30-4.83, p = 0.006). When adjusted for nodal status, and clinical and pathological stages the interval was still statistically significant (adjusted hazards ratio 1.93, 95% CI 0.99-3.76, p = 0.05). CONCLUSIONS: In patients undergoing radical cystectomy a delay in surgery of greater than 12 weeks was associated with advanced pathological stage and decreased survival. Although this relationship persisted after adjusting for nodal status, and clinical and pathological stages, the presence of lymph node metastasis remained the strongest predictor of patient outcome.     

Radical cystectomy and orthotopic urinary diversion in male patients with pT4a urothelial bladder carcinoma: Oncological outcomes

The aim of the present study was to evaluate the oncological outcomes of radical cystectomy followed by orthotopic urinary diversion in male patients with urothelial bladder carcinoma involving prostatic stroma (pT4a). A total of 1964 patients with urothelial bladder carcinoma who underwent cystectomy between 1971 and 2008 were retrospectively analyzed. Among them, male patients with pT4aN0M0 disease at cystectomy and orthotopic urinary diversion were identified and included in the analysis. Exclusion criteria were perioperative mortality and primary urethrectomy. The outcomes were urethral recurrence, local recurrence, recurrence‐free survival and overall survival. Univariate and log–rank statistics were used to examine associations between variables and outcome. A total of 33 patients (1.7%) entered the study with a median age of 71 years. Median follow up was 4.8 years (range 0.1–21 years). A total of two urethral recurrences (6%) occurred at a median of 2.4 years after cystectomy. No patient had local recurrence. The 5‐year recurrence‐free survival and overall survival was 56% ± 10% and 56% ± 9%, respectively. The probability of urethral and local recurrence after orthotopic diversion in pT4a urothelial bladder carcinoma patients is low. Thus, orthotopic urinary diversion appears to be oncologically safe in this patient population.     

Does pathological sub stratification of T2 bladder cancer predict outcome in a contemporary pure urothelial carcinoma cohort?

IntroductionStudies evaluating outcomes in bladder cancer sub stratified into T2a and T2b pathologic staging have demonstrated inconsistent results. Survival outcomes in a cohort of pure urothelial carcinoma patient undergoing radical cystectomy were evaluated to determine the prognostic value of T2 sub staging.MethodsUsing our prospectively maintained institutional cystectomy database, we identified patients with pure urothelial carcinoma of the bladder, either pT2aN0 or pT2bN0. We excluded any patients with variant histology, patients that underwent neoadjuvant chemotherapy, and patients that had margin positive disease. Demographic and clinicopathologic data were collected, and Cox proportional hazard regression assessed overall survival (OS), cancer specific survival (CSS), and recurrence free survival (RFS).ResultsFrom 2001 to 2019, we identified 1,929 patients that underwent radical cystectomy, 61 patients had pT2a and 65 had pT2b pure urothelial carcinoma that met inclusion criteria. Only age (P = 0.02) and the initial transurethral resection of bladder tumor pathology (P < 0.01) were notably different when comparing the clinical characteristics of patients with pT2a and pT2b. No differences were noted in OS, CSS, or RFS between the 2 groups on Kaplan-Meier analysis. On univariate Cox regression analysis, age, TURBT stage, cystectomy pathology stage, carcinoma in situ, and lymphovascular invasion status, and Bacillus Calmette-Guérin therapy status was not found to be significant factors for OS, CSS, or RFS between patients with pT2aN0 or pT2bN0 tumors.ConclusionPrior studies have sub stratified pT2a and pT2b, studying survival outcomes with equivocal results. Many of these studies included variant histology or use of chemotherapy in the analysis. Here, we identified a pure urothelial cohort to compare survival outcomes between pT2a and pT2b and found no difference in OS, CSS, and RFS.     

Laparoscopic cystectomy with extracorporeal-assisted urinary diversion: experience with 34 patients

OBJECTIVES: Open radical cystectomy remains the gold standard for nonmetastatic muscle invasive bladder cancer. Laparoscopic cystectomy has been described as a feasible procedure and is still being evaluated. We describe our initial experience with this laparoscopic surgical approach in 34 patients. METHODS: From February 2002 to October 2004, 18 men and 16 women underwent laparoscopic cystectomy with extracorporeal-assisted urinary diversion for transitional cell carcinoma of the bladder (n=27), invasive cervical carcinoma (n=4), and atrophic bladder (n=3). We report here on specific technical details and present initial results of our series. RESULTS: The mean operating time was 244 min, the mean blood loss 325 ml, and the transfusion rate 5.9%. All procedures were completed laparascopically without conversion to open techniques. No major complications occurred during or after the operation. In case of urothelial malignancy (n=27), the histopathologic analysis of the removed specimen revealed organ-confined transitional cell carcinoma of the bladder in 66.7% (pT1:14.8%; pT2: 51.9%) and locally advanced disease in 33.3% (pT3: 25.9%; pT4: 7.4%). In two cases final histology proved positive surgical margins. Extended lymphadenectomy detected lymph node metastasis in two patients. CONCLUSIONS: We demonstrate that the combination of laparoscopic cystectomy and extracorporeal urinary diversion is possible and remains a safe, feasible, and repeatable surgical technique. To determine the oncologic outcome long-time follow-up will be necessary.     

Radical cystectomy for clinically muscle invasive bladder cancer: does prior non-invasive disease affect clinical outcomes?

Purpose

To compare clinical and pathologic outcomes of radical cystectomy for muscle invasive bladder cancer in relation to prior history of non-invasive urothelial carcinoma.

Materials and methods

Retrospective data collected from 1,150 patients managed by radical cystectomy for urothelial carcinoma of the bladder from the Canadian Bladder Cancer Network were analysed. Patients with clinical stage T2 or more were included and divided into two groups: (Group 1) patients with prior history of non-invasive urothelial carcinoma (N?=?365) and (Group 2) patients with clinical muscle invasive cancer de novo (N?=?785). Variables analysed included patient age, gender, pathologic stage, adjuvant chemotherapy, recurrence and mortality.

Results

Both groups were nearly equal in mean age and gender distribution, with mean ages of 67.2 and 66.7?years, and 79.7 and 79.5%, respectively (P?=?0.4 and 0.9, respectively). The presence of preoperative hydronephrosis was 20.8 and 32.6% (P?=?0.0007) for groups 1 and 2, respectively. The rate of higher pathological stage (T3 or T4) was 36.3 and 58% (P?<?0.0001), positive lymph nodes were 20.1 and 28.8% (P?=?0.002), and lymphovascular invasion was 31.7 and 46.2% (P?=?0.0001) for groups 1 and 2, respectively. The rate of adjuvant chemotherapy was 15.5 and 23.3% (P?=?0.002) for groups 1 and 2, respectively. None of the sampled patients received neoadjuvant chemotherapy. The overall survival (OS) and disease-specific survival (DSS) rates at 5?years were 62 and 70% for group 1 and 51 and 60% for group 2, respectively, while at 10?years, OS and DSS were 46 and 66% for group 1 and 35 and 49% for group 2, respectively (P?=?0.0001 and 0.0002, respectively). Using multivariate analysis examining factors affecting recurrence and survival, we found that previous non-invasive bladder tumour history was associated with a significantly reduced risk of mortality and recurrence (Hazard ratio of 0.7 for all risks, P?=?0.0002).

Conclusion

Our retrospective study suggests that patients with non-invasive urothelial carcinoma of the bladder that progress to muscle invasion and require radical cystectomy appear to have better pathologic and clinical outcome than patients presenting with clinical muscle invasive disease de novo.     

T1G3 bladder cancer--indications for early cystectomy

OBJECTIVES: To review our experience with early radical cystectomy in patients with T1G3 Transitional Cell Carcinoma of bladder (TCC). PATIENTS AND METHODS: Thirty patients, who underwent early radical cystectomy over a 10-year period for clinical stage T1G3 TCC bladder, were studied. Of these 21 (70%) had radical cystectomy without treatment with intravesical chemo/immunotherapy. The number of tumours, presence or absence of Carcinoma In-Situ (CIS) and the pathological stage of the cystectomy specimen were recorded in each patient. Disease specific survival was determined in the subgroups using Kaplan-Meier estimates. RESULTS: Seventeen patients underwent radical surgery for a single tumour without concomitant CIS (Group A). The other 13 had multiple tumours with or without concomitant CIS or a single tumour with CIS (Group B). The disease was upstaged after cystectomy in 1 (6%) patient in Group A compared to 7 (55%) in Group B, (p = 0.009). Nine (53%) had pT0 disease in Group A compared to 0% in Group B, (p = 0.0017). The 5-year cancer specific survival rates were 92% in Group A and 82% in Group B. CONCLUSIONS: In patients with multiple T1G3 tumours with or without associated CIS, or in those with single T1G3 tumour with associated CIS the incidence of the disease being already muscle invasive at the time of clinical diagnosis is 55%. Early radical cystectomy should be advocated in this group. Conversely, for a single T1G3 tumour without associated CIS, conservative bladder preserving strategy with immuno-chemotherapy and close surveillance is justified.     

Harnblasenkarzinompatienten im klinischen Tumorstadium T2

Background

Few and partially contradictory data are available regarding the prognostic signature of downstaging of muscle-invasive clinical tumour stages in patients treated with radical cystectomy.

Materials and methods

Clinicopathological parameters of 1,643 patients (study group, SG) treated with radical cystectomy due to muscle-invasive urothelial bladder cancer were summarized in a multi-institutional database. Patients of the SG fulfilled the following conditions: clinical tumour stage T2 N0 M0 and no administration of neoadjuvant radiation or chemotherapy. Cancer-specific survival (CSS) rates were calculated referring to pathological tumour stages in cystectomy specimens (pT2) (mean follow-up: 51 months). Furthermore, a multivariable model integrating clinical information was developed in order to predict the probability of downstaging.

Results

A total of 173 patients (10.5%) of the SG presented with downstaging in pathological tumour stages (pT0: 4.8%, pTa: 0.4%, pTis: 1.3%, pT1: 4.1%); 12 of these patients had positive lymph nodes (7%, in comparison with 21% pN+ of pT2 tumours and 43% of >pT2 tumours). Patients with tumour stages pT2 had CSS rates after 5 years of 89, 69 and 46%, respectively (p<0.001). In a multivariable Cox model the presence of pathological downstaging resulted in a significant reduction of cancer-specific mortality (HR 0.30; 95% CI 0.18–0.50). By logistic regression analysis the date of TURB (benefit for more recent operations) was identified as the only independent predictor for downstaging of muscle-invasive clinical tumour stages. Age, gender, grading and associated Tis in the TURB did not reveal any significant influence.

Conclusion

Patients with muscle-invasive clinical tumour stages and downstaging in cystectomy specimens represent a subgroup with significantly enhanced CSS rates. Further trials that integrate the parameters tumour size, stages cT2a vs cT2b and focality are required in order to define the independent prognostic signature of downstaging of tumour stages more precisely.