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.     

Initial tumor stage and grade as a predictive factor for recurrence in patients with stage T1 grade 3 bladder cancer

PURPOSE: We evaluated whether the risk of progression and the recurrence rate were different in patients with primary and nonprimary stage T1 grade 3 transitional cell carcinoma of the bladder. MATERIALS AND METHODS: Between 1983 and 1997, 75 patients were treated for stage T1 grade 3 transitional cell carcinoma of the bladder. Of these patients 68 (primary and nonprimary tumor in 58 and 14, respectively) without carcinoma in situ who had not undergone complete cystectomy immediately after diagnosis were included in the study. No maintenance regimen was used. Median followup was 100 months (range 9 to 217). RESULTS: The incidence of multiple tumors in patients with nonprimary tumors was significantly higher than in patients with primary disease (p = 0.035). However, the recurrence-free survival rate in patients with primary T1 GIII bladder tumor was significantly lower than that of patients with nonprimary T1 GIII bladder tumor (p = 0.0016). Multivariate analysis using Cox's proportional hazard regression model revealed that only initial tumor status had statistically significant effects on tumor recurrence (p = 0.007) and no other factors had a significant influence on recurrence-free survival. Progression-free and cancer specific survival rates were also significantly different between the 2 groups (p = 0.036 and 0.0307, respectively). CONCLUSIONS: Our study indicates that patients with primary stage T1 grade 3 bladder cancers have higher recurrence and progression potential than those with nonprimary disease despite the higher incidence of multiple tumors in patients with nonprimary tumors.     

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.     

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.     

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.     

Clinical outcomes following radical cystectomy for primary nontransitional cell carcinoma of the bladder compared to transitional cell carcinoma of the bladder

PURPOSE: The effect of bladder cancer histological subtypes other than transitional cell carcinoma (nonTCC) on clinical outcomes remains uncertain. We conducted a multi-institutional retrospective study of patients with bladder cancer treated with radical cystectomy to assess the impact of nonTCC histology on bladder cancer specific outcomes. MATERIALS AND METHODS: A total of 955 consecutive patients underwent radical cystectomy with bilateral pelvic lymphadenectomy for bladder cancer at 3 academic institutions. TCC was present in the radical cystectomy specimen in 888 patients (93%). NonTCC histology was present in 67 patients (7%), including squamous cell carcinoma in 26, adenocarcinoma in 13, small cell carcinoma in 10 and other nonTCC subtypes (ie spindle cell carcinoma, carcinosarcoma and undifferentiated carcinoma) in 18. For patients alive at last followup median followup was 39 and 23 months for patients with TCC and nonTCC histologies, respectively. Bladder cancer specific progression and survival were assessed using Kaplan-Meier and multivariate Cox proportional hazards analyses. RESULTS: Bladder cancer specific progression and mortality did not differ significantly between patients with SCC and TCC histologies. Patients with nonTCC and nonSCC bladder cancer were at significantly increased risk for progression and death compared to patients with TCC or SCC (p <0.001). This association remained statistically significant in patients with organ confined disease (stage pT2 or lower) and patients with nonorgan confined disease (stage pT3 or higher) (p <0.001). In a multivariate analysis nonTCC and nonSCC histology was associated with an increased risk of bladder cancer progression and death (OR 2.272 and 2.585, respectively, p <0.001), even after adjusting for final pathological stage, lymph node status, lymphovascular invasion and neoadjuvant or adjuvant treatments. CONCLUSIONS: NonTCC and nonSCC histological subtype is an independent predictor of bladder cancer progression and mortality in patients undergoing radical cystectomy for bladder cancer. Patients with bladder TCC and SCC share similar stage specific clinical outcomes.     

The effect of cystectomy, and perioperative methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy on the risk and pattern of relapse in patients with muscle invasive bladder cancer

PURPOSE: Trials have demonstrated decreased relapse with perioperative methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) chemotherapy in patients with muscle invasive bladder cancer. We evaluated whether the benefit of chemotherapy correlates with its effects on distant or pelvic relapse. MATERIALS AND METHODS: We retrospectively evaluated the records of all 107 patients who underwent cystectomy for muscle invasive bladder cancer at our institution between 1988 and 1994. Factors predicting relapse were identified and used to group patients at high or low risk. The outcome in each group with and without M-VAC chemotherapy was then analyzed in terms of overall, metastatic and pelvic relapse. Univariate analysis was performed using the Kaplan-Meier method and log rank statistic, and multivariate analysis was done using the Cox proportional hazards model. Median survival was 29 months for patients free of disease. RESULTS: Pathological stage T3 or greater according to the American Joint Committee on Cancer, tumor greater than 3 cm. and creatinine greater than 1.5-fold normal were independent poor prognostic factors in patients treated with cystectomy only. Patients with any of these factors or metastatic involvement of the pelvic lymph nodes were considered at high risk. All 35 low risk patients were treated with cystectomy only and had an excellent outcome with a 3-year relapse-free survival plus or minus standard error of 93% +/- 5%. The 3-year rates in 52 and 20 high risk patients treated without and with chemotherapy, respectively, were 42% +/- 8% versus 57% +/- 13% for relapse-free survival (p = 0.17), 38% +/- 9% versus 8% +/- 8% for pelvic failure (p = 0.02) and 39% +/- 9% versus 38% +/- 13% for distant metastases (not significant). Multivariate analysis of patients who underwent pelvic lymphadenectomy revealed that perioperative chemotherapy improved relapse-free survival and pelvic control but not metastatic control (p = 0.03, 0.02 and 0.31, respectively). CONCLUSIONS: Low risk patients have excellent disease control when treated with cystectomy only. Those with high risk features are at substantial risk for pelvic failure (38% at 3 years) after cystectomy only. Perioperative M-VAC chemotherapy has a profound impact on pelvic but not on metastatic failure.     

Transitional cell carcinoma of the bladder in young adults: presentation,natural history and outcome

PURPOSE: The natural history and prognosis of bladder cancer in young patients is not well defined. We analyzed our experience with such patients. MATERIALS AND METHODS: The medical records of 74 patients presenting with transitional cell carcinoma of the bladder at 40 years and younger were reviewed and compared with those of 75 patients diagnosed with bladder transitional cell carcinoma at 65 years old and older. RESULTS: Median followup was 28.1 months (range 1 to 155) and 34.7 (range 1 to 178) in young and old patients, respectively. Initial stage distribution was similar with 80% of patients presenting with superficial disease. No difference was observed in the disease-free progression or disease-free recurrence rate among the groups in patients initially presenting with stage Ta, Tis or T1 tumors. A significantly higher proportion of older versus younger patients underwent cystectomy (54% versus 23%). We did not observe a difference in pathological stage distribution or the rate of extravesical disease in young and old patients (47% and 45%, respectively). Younger patients who ultimately underwent radical cystectomy had significantly lower disease-free survival, mainly due to a higher rate of distant metastases than in the older group (41% versus 24%). The rate of local recurrence was similar. CONCLUSIONS: Bladder transitional cell carcinoma in young adults has a clinical stage distribution and natural history similar to that in older patients. Our study suggests that a subset of young patients who ultimately undergo radical cystectomy have particularly aggressive tumors, portending a poor outcome.     

UPPER TRACT RECURRENCES FOLLOWING RADICAL CYSTECTOMY: AN ANALYSIS OF PROGNOSTIC FACTORS, RECURRENCE PATTERN AND STAGE AT PRESENTATION

PURPOSE: We study the incidence and pattern of upper tract recurrences following radical cystectomy for bladder cancer, and analyze the prognostic factors. MATERIALS AND METHODS: A retrospective study was performed on 529 patients who underwent radical cystectomy and urinary diversion at Memorial Sloan-Kettering Cancer Center between July 1989 and June 1997. Data related to upper tract recurrence were analyzed. RESULTS: Of the 529 patients 16 (3%) had upper tract recurrence. Median followup was 16.9 months for the entire group and 49.1 months for patients with upper tract recurrence, with a median time to recurrence of 37.2 months. Of 12 upper tract recurrences 7 (58%) were locally advanced at surgery (p3a or greater with or without lymph node metastasis) and 5 of 16 patients with recurrence (31.3%) had bilateral tumors (2 synchronous and 3 metachronous). Overall survival from the time of diagnosis of upper tract recurrence after radical cystectomy was poor, with a median of 10 months (confidence interval 1 to 19). CONCLUSIONS: The incidence of upper tract recurrence following radical cystectomy is low (3%). However, the incidence of bilateral tumors (31.3%) and locally advanced stage at the time of operation (58%) is higher than expected for upper tract tumors in the general population. Survival of patients with upper tract recurrence is poor, with a median of 10 months.     

Cystectomy for transitional cell carcinoma of the bladder: results of a surgery only series in the neobladder era

PURPOSE: We studied the effect of radical cystectomy for transitional cell carcinoma of the bladder on survival and failure patterns when the 2 surgical standards cystectomy and neobladder were combined, when possible. MATERIALS AND METHODS: A consecutive series of patients undergoing radical cystectomy with pelvic lymph node dissection for transitional cell carcinoma of the bladder with curative intent was analyzed. Patients with neoadjuvant radiotherapy/chemotherapy were excluded. Pathological characteristics based on the 2002 TNM system, recurrence-free/overall survival and metastatic patterns were determined. RESULTS: A total of 788 patients with a mean age +/- SD of 65 +/- 10 years and a mean followup of 53.5 months who underwent surgery between 1986 and 2003 were analyzed. A neobladder was constructed in 75.4% of patients. Ten-year recurrence-free and overall survival rates were 59.1% and 44.9%, respectively. Positive lymph nodes were present in 143 patients (18%). The rate of recurrence-free survival at 5 years was 82.5% for pT2a pN0, 61.9% for pT2b and pT3a pN0, and 53.1% for pT3b pN0 disease. Local and distant failure rates were 4% and 9.5% for organ confined tumors, 15.9% and 19.2% for nonorgan confined tumors, and 20.4% and 45.1% in patients with positive lymph nodes, respectively. CONCLUSIONS: In patients with organ confined, lymph node negative transitional cell carcinoma excellent survival data can be achieved as long as the tumor is limited to the inner half of the detrusor. These data on a large group of patients support early aggressive surgical management for invasive bladder cancer. The results of this surgery only series may serve as a reference for other treatment modalities for bladder cancer.     

原发性膀胱小细胞癌(附4例报告)

目的 提高对膀胱小细胞癌的认识水平。方法 对4例膀胱小细胞癌的病理及临床资料进行回顾性分析。结果 4例患者中男3例，女1例，平均年龄69．5。其中3例行根治性膀胱全切加化疗，1例行姑息性膀胱全切。3例死于肿瘤复发，平均生存20个月，1例存活7年。结论原发性膀胱细胞癌恶性程度高、预后差，根治性膀胱全切加联合化疗可获得较好的疗效。     

Evidence supporting preoperative chemotherapy for small cell carcinoma of the bladder: a retrospective review of the M. D. Anderson cancer experience

PURPOSE: Neuroendocrine tumors of the bladder comprise a small subset of all bladder tumors. To improve our understanding of this tumor and define outcomes with current management, we performed a retrospective review of these cases. MATERIALS AND METHODS: We reviewed the records of 88 patients with small cell bladder carcinoma evaluated at our institution between 1985 and 2002. Of these patients 46 underwent cystectomy, including 25 who were treated with initial cystectomy and 21 who received preoperative chemotherapy. RESULTS: For patients treated with initial cystectomy median cancer specific survival (CSS) was 23 months, with 36% disease-free at 5 years. For patients receiving preoperative chemotherapy median CSS has not been reached (p = 0.026), although CSS at 5-years was 78% with no cancer related deaths observed beyond 2 years. Notably 7 of 25 patients treated with initial cystectomy received chemotherapy after surgery but their survival was no better than those treated with cystectomy alone. As others have observed, the pathological stage was higher than clinically appreciated for 56% of patients treated with initial cystectomy. Moreover, there were no cancer related deaths among patients with disease down staged to pT2 or less. CONCLUSIONS: Like other neuroendocrine tumors, small cell carcinoma of the bladder grows rapidly but is chemo-sensitive. Clinical under staging is the rule. Optimal results are achieved via integration of local and systemic treatment. Our results suggest that preoperative chemotherapy is the optimal strategy, even in the setting of clinically localized cancer. On the basis of these observations, we have initiated a trial in which 4 cycles of aggressive multiagent preoperative chemotherapy are followed by radical cystectomy.     

Intravesical bacillus Calmette-Guerin therapy for stage T1 grade 3 transitional cell carcinoma of the bladder: recurrence,progression and survival in a study of 57 patients

PURPOSE: Stage T1 grade 3 transitional cell carcinoma of the bladder is associated with a high risk of tumor recurrence and progression. We report our experience with stage T1 grade 3 bladder tumors treated with bacillus Calmette-Guerin (BCG) therapy in the last 10 years. MATERIALS AND METHODS: We analyzed the outcome in 57 consecutive patients treated with intravesical BCG for stage T1 grade 3 bladder cancer between 1991 and 2001. After initial transurethral resection all patients received a 6-week course of BCG therapy consisting of 1 instillation weekly. All patients underwent systematic biopsies at the end of the first BCG course. Patients with negative biopsies received maintenance BCG therapy, consisting of intravesical instillations each week for 3 weeks given 3, 6, 12, 18, 24, 30 and 36 months after the first course. Patients with residual tumor received a second course of 6 weekly instillations. Time to tumor recurrence and progression, and the rate of patient survival were retrospectively analyzed. RESULTS: Median followup was 53 months (range 9 to 110). Minimum followup was 2 years in 36 cases (63.2%) and 5 years in 28 (49.1%). After the first BCG course 50 patients (87.7%) had no residual disease, while 7 (12.3%) had residual tumor. The recurrence and progression rates were 42.1% and 22.8%, respectively. The rate of delayed cystectomy was 14%. The rate of disease specific survival was 87.7%. CONCLUSIONS: Our study confirms that BCG therapy is effective conservative treatment for patients with stage T1 grade 3 bladder tumors.     

Upper tract urothelial recurrence following radical cystectomy for transitional cell carcinoma of the bladder: an analysis of 1,069 patients with 10-year followup

PURPOSE: Risk factors for upper tract recurrence following radical cystectomy for transitional cell carcinoma of the bladder are not yet well-defined. We reviewed our population of patients who underwent radical cystectomy to identify prognostic factors and clinical outcomes associated with upper tract recurrence. MATERIALS AND METHODS: From our prospective database of 1,359 patients who underwent radical cystectomy we identified 1,069 patients treated for transitional cell carcinoma of the bladder between January 1985 and December 2001. Univariate analysis was completed to determine factors predictive of upper tract recurrence. RESULTS: A total of 853 men and 216 women were followed for a median of 10.3 years (maximum 18.5). There were 27 (2.5%) upper tract recurrences diagnosed at a median of 3.3 years (range 0.4 to 9.3). Only urethral tumor involvement was predictive of upper tract recurrence. In men superficial transitional cell carcinoma of the prostatic urethra was associated with an increased risk of upper tract recurrence compared with prostatic stromal invasion or absence of prostatic transitional cell carcinoma (p <0.01). In women urethral transitional cell carcinoma was associated with an increased risk of upper tract recurrence (p = 0.01). Despite routine surveillance 78% of upper tract recurrence was detected after development of symptoms. Median survival following upper tract recurrence was 1.7 years (range 0.2 to 8.8). Detection of asymptomatic upper tract recurrence via surveillance did not predict lower nephroureterectomy tumor stage, absence of lymph node metastases or improved survival. CONCLUSIONS: Patients with bladder cancer are at lifelong risk for late oncological recurrence in the upper tract urothelium. Patients with evidence of tumor involvement within the urethra are at highest risk. Surveillance regimens frequently fail to detect tumors before symptoms develop. However, radical nephroureterectomy can provide prolonged survival.     

Urethral tumor recurrence following cystectomy and urinary diversion: clinical and pathological characteristics in 768 male patients

PURPOSE: We evaluated the incidence and risks of urethral recurrence following radical cystectomy and urinary diversion in men with transitional cell carcinoma of the bladder. MATERIAL AND METHODS: Clinical and pathological results were evaluated in 768 consecutive male patients undergoing radical cystectomy with intent to cure for bladder cancer with a median followup 13 years, including 397 (51%) who underwent orthotopic urinary diversion with a median followup of 10 years and 371 (49%) who underwent cutaneous urinary diversion with a median followup of 19 years. Demographically and clinically these 2 groups were well matched with the only exception being longer median followup in the cutaneous group (p <0.001). Urethral recurrence was analyzed by univariate and multivariable analysis according to carcinoma in situ, tumor multifocality, pathological characteristics (tumor grade, stage and subgroup), the presence and extent of prostate tumor involvement (superficial vs stromal invasion) and the form of urinary diversion (cutaneous vs orthotopic). RESULTS: A total of 45 patients (6%) had urethral recurrence at a median of 2 years (range 0.2 to 13.6), including 16 (4%) with an orthotopic and 29 (8%) with a cutaneous form of urinary diversion. Carcinoma in situ and tumor multifocality were not significantly associated with an increased risk of urethral recurrence (p = 0.07 and 0.06, respectively). The presence of any (superficial and/or stromal invasion) prostatic tumor involvement was identified in 129 patients (17%). Prostate tumor involvement was associated with a significantly increased risk of urethral recurrence (p = 0.01). The estimated 5-year chance of urethral recurrence was 5% without any prostate involvement, increasing to 12% and 18% with superficial and invasive prostate involvement, respectively. Patients undergoing orthotopic diversion demonstrated a significantly lower risk of urethral recurrence compared with those undergoing cutaneous urinary diversion (p = 0.02). Patients without any prostate tumor involvement and orthotopic diversion (lowest risk group) demonstrated an estimated 4% year chance of urethral recurrence compared with a 24% chance in those with invasive prostate involvement undergoing cutaneous diversion (highest risk group). On multivariate analysis any prostate involvement (superficial and/or invasive) and urinary diversion form remained independent and significant predictors of urethral recurrence (p = 0.035 and 0.01, respectively). CONCLUSIONS: At long-term followup urethral tumor recurrence occurs in approximately 7% of men following cystectomy for bladder transitional cell carcinoma. Involvement of the prostate with tumor and the form of urinary diversion were significant and independent risk factors for urethral tumor recurrence. Patients undergoing orthotopic diversion have a lower incidence of urethral recurrence compared with those undergoing cutaneous diversion. Although prostate tumor involvement is a risk factor for urethral recurrence, it should not preclude orthotopic diversion, provided that intraoperative frozen section analysis of the urethral margin is without evidence of tumor.     

Surgical management of renal tumors 4 cm. or less in a contemporary cohort

PURPOSE: We evaluated a patient cohort with renal tumors 4 cm. or less treated with partial or radical nephrectomy. We compared patient and tumor characteristics, and survival in these 2 groups. MATERIALS AND METHODS: We retrospectively analyzed the records of 670 patients with a median age of 63 years treated surgically for renal cell carcinoma between July 31, 1989 and July 31, 1997. Renal tumors 4.0 cm. or less were noted in 252 patients (38%) who underwent a total of 262 procedures, including 183 radical (70%) and 79 partial (30%) nephrectomies. Ten patients required 2 operations each because of bilateral renal cell carcinoma. Median followup was 40 months. We compared clinicopathological parameters in the partial and radical nephrectomy groups using chi-square or Wilcoxon analysis as appropriate. Survival analysis was determined by the log rank test and Cox regression model. RESULTS: The partial and radical nephrectomy groups were comparable with respect to gender ratio, tumor presentation, histological classification, pathological stage and complication rate. Median tumor size was 2.5 and 3.0 cm. in the partial and radical nephrectomy groups, respectively (p = 0.0001). Resection was incomplete in 1 patient (1.3%) in the partial and none in the radical nephrectomy group. There was no local recurrence after either procedure, and no significant difference in disease specific, disease-free and overall survival (p = 0.98, 0.23 and 0.20, respectively). CONCLUSIONS: Patients with a small renal tumor have similar perioperative morbidity, pathological stage and outcome regardless of treatment with partial or radical nephrectomy. Therefore, partial nephrectomy remains a safe alternative for tumors of this size.     

Is there a therapeutic role for post-chemotherapy retroperitoneal lymph node dissection in metastatic transitional cell carcinoma of the bladder?

PURPOSE: We identified a subset of patients with bladder cancer (transitional cell carcinoma) and regional nodal metastasis to the retroperitoneal lymph nodes without detectable systemic dissemination. While the majority of these patients respond initially to chemotherapy, most have disease relapse at the same site within a year. We report the results of a phase II study exploring the potential benefit of retroperitoneal lymph node dissection in patients with transitional cell carcinoma of the bladder in whom disease has shown a significant response to chemotherapy. MATERIALS AND METHODS: A total of 11 patients with biopsy proven metastatic transitional cell carcinoma in the retroperitoneal lymph nodes and no evidence of visceral metastatic disease in whom disease showed a significant response to chemotherapy underwent complete bilateral retroperitoneal lymph node dissection. The end point of study was disease specific survival, calculated from the time of retroperitoneal lymph node dissection to death from transitional cell carcinoma of the bladder. RESULTS: Four patients underwent delayed retroperitoneal lymph node dissection. Seven patients underwent concurrent cystectomy, and pelvic and retroperitoneal lymph node dissection. There was no perioperative mortality. Nine patients had evidence of residual disease in the retroperitoneal nodes. Seven patients have recurrence outside of the original surgical field with a median time to recurrence of 7 months and 6 died at a median time to death of 8 months (range 5 to 14). One patient with retrocrural recurrence attained a complete response to salvage chemotherapy and remained disease-free 57 months after retroperitoneal lymph node dissection. For all 11 patients median disease specific and recurrence-free survival rates were 14 and 7 months, respectively. Four-year disease specific and recurrence-free survival rates were 36% and 27%, respectively. We stratified the patients based on the number of involved lymph nodes at retroperitoneal lymph node dissection and noted that viable tumor in no more than 2 lymph nodes correlated with greater disease specific and recurrence-free survival (p = 0.006 and 0.01, respectively). CONCLUSIONS: Retroperitoneal lymph node dissection can be safely performed for metastatic transitional cell carcinoma. Retroperitoneal lymph node dissection has curative potential, particularly in patients with viable tumor in no more than 2 lymph nodes after chemotherapy.     

膀胱小细胞癌的病理组织学特点及其诊治

目的:探讨膀胱小细胞癌病理组织学特点及其诊断与治疗。方法:回顾分析6例膀胱小细胞癌患者的临床和病理资料,6例患者行经尿道膀胱肿瘤电切术2例,膀胱部分切除术1例,行膀胱全切术2例,单纯化疗1例。5例患者接受2～6疗程化疗。结果:6例随访3个月～3年,1例患者术后生存2年至今,5例均因肿瘤转移死亡,平均生存时间14.8个月。结论:膀胱小细胞癌分化程度低、恶性程度高、易早期转移、预后差,主要依靠病理组织学检查确诊,现有治疗方法不足以将其治愈,手术联合化疗是目前主要的治疗方法,分子靶向治疗是未来治疗的主要手段。     

原发性膀胱小细胞癌诊治体会

目的 探讨膀胱小细胞癌的临床及病理特点.方法 回顾性分析9例膀胱小细胞癌的基本资料.男6例,女3例.年龄45～79岁,平均62岁.临床表现为肉眼血尿7例,排尿困难及下腹部疼痛2例.肿瘤直径0.5～7.0 cm,平均2.0 cm;多发2例,单发5例,全膀胱弥漫性生长2例.7例行尿脱落细胞学检查,阳性4例.9例均行手术治疗,其中4例术前诊断为浅表性者行TURBt,术后均定期行吡柔比星膀胱灌注,1例化疗3个周期;膀胱部分切除2例,均定期行吡柔比星膀胱灌注,1例化疗2个周期;根治性膀胱全切3例,静脉化疗2例.结果 术后病理检查:肿瘤细胞体积小,呈圆形,胞质稀少,核浓染,缺乏巢状结构.免疫组化染色:嗜铬素A(+)、神经元特异性烯醇化酶(+).诊断为小细胞癌,其中1例含移行细胞癌成分,1例合并前列腺癌.1例术前检查显示高血钙(3.15 mmol/L)和低血磷(0.61 mmol/L),术后1个月血钙及血磷恢复正常.保留膀胱者随访4例,3例分别于术后4、9、25个月死于转移,1例术后化疗者随访24个月未见复发及转移.膀胱全切3例中2例分别于术后2、28个月死亡,1例术后随访32个月未见肿瘤复发及转移.结论膀胱小细胞癌恶性程度高,预后差,根治性膀胱全切加全身化疗是主要的治疗方法,保留膀胱的手术应配合全身化疗.决定预后的是肿瘤的临床分期及治疗方法.

Abstract：

Objective To investigate the clinical and pathological features of small cell carcinoma of the urinary bladder. Methods The pathological and clinical data of 9 cases of small cell carcinoma were analyzed retrospectively. There were 6 males and 3 females, ages 45 to 79 years (mean age, 62 years). Clinical manifestations of 7 cases included gross hematuria and dysuria, the other 2 cases experienced lower abdominal pain. The mean tumor size was 2.0 cm (ranged, 0.5 to 7.0 cm). Two cases had multiple tumors and 5 cases had single tumors. The growth pattern in 2 cases was diffuse growth in the whole bladder. In 4 cases tumor cells were found in urine cytology. All 9 patients underwent surgical treatment, including TURBt. Four patients were diagnosed as superficial tumors before operation. All the patients underwent regular theprubicine irrigation in the bladder. One case underwent additional intravenous chemotherapy for 3 cycles. Partial cystectomy was performed in 2 cases, with regular theprubicine irrigation in bladder and 1 case underwent intravenous chemotherapy for 2 cycles. Radical cystectomy was performed in 3 cases, with 2 cases undergoing intravenous chemotherapy after operation. Results Pathological findings showed that tumor cells were small and round in shape. These hyperchromatic nuclei showed limited cytoplasm with lack of nesting characters. CgA and NSE were positive in immunohistochemistry. The final diagnosis was small cell carcinoma, with 1 case accompanied with transitional cell carcinoma and 1 case accompanied with prostate cancer. One case showed high preoperative serum calcium (3.15 mmol/L) and low serum phosphate (0.61 mmol/L), which returned to normal 1 month after operation. Four cases who′s bladder was preserved were followed up, 3 cases were alive for 4, 9 and 25 months after operation. The 1 case who underwent intravenous chemotherapy was followed up for 24 months and there was no sign of relapse or metastasis. In all the 3 cases with radical cystectomy, 2 cases died 2 and 28 months postoperativly. Another case with adjuvant chemotherapy was followed up for 24 months without recurrence or metastasis. Conclusions Small cell carcinoma of the urinary bladder is highly malignant with poor prognosis. Radical cystectomy in combination with systemic chemotherapy has better efficacy. Retained bladder surgery with systemic chemotherapy is an alternative choice. The most important factors which influence the prognosis of the tumor are clinical stage and therapeutic methods.     

膀胱小细胞癌1例报告并文献复习

目的 探讨膀胱小细胞癌的临床诊断、病理特征、治疗及预后,提高对该病的认识和诊治水平.方法 回顾性分析1例膀胱小细胞癌患者的临床资料,并复习相关文献,综合分析膀胱小细胞癌的诊断及治疗状况.结果 该患者行膀胱部分切除术,术后病理证实为膀胱小细胞神经内分泌癌,免疫组化染色显示肿瘤细胞表达神经内分泌标志物神经元特异性烯醇化酶（NSE）、突触素（Syn）、嗜铬颗粒蛋白A（CgA）.术后接受了4个疗程的化疗,死于癌复发和肺转移,术后生存时间为13个月.结论 膀胱小细胞癌罕见,恶性程度高,早期易发生转移,预后差,行根治性切除术加联合化疗或放疗可提高治愈率.