Multivariate analysis of clinical parameters of synchronous primary superficial bladder cancer and upper urinary tract tumor

PURPOSE: We determined the incidence and characteristic of synchronous upper urinary tract tumors (UUTTs) in patients with primary superficial bladder carcinoma and evaluated the characteristics of bladder tumors related to UUTTs. MATERIALS AND METHODS: We performed a retrospective study of 1,529 patients with primary superficial bladder carcinoma who underwent initial examination of the upper urinary tract with excretory urography. Data were analyzed by multivariate analysis using logistic regression. Variables evaluated and related to the incidence of UUTT were multiplicity, carcinoma in situ, bladder tumor size, localization of tumor in the bladder, and tumor grade and stage. RESULTS: A total of 28 patients (1.8%) had simultaneous bladder tumor and UUTT. UUTTs showed no preferred location and 17.9% were multiple. Of UUTTs 46% were invasive and almost 87% were grade 2 or 3. The only significant variable related to UUTT was bladder tumor in the trigone (RR 5.8, 95% IC 2.18 to 15.9, p <0.0005). Of 147 tumors located in the trigone 11 (7.5%) were associated with UUTT, corresponding to 41% of the UUTTs first diagnosed. If multiplicity and tumors in the trigone (551 cases) had been considered, 66.7% of tumors would have been diagnosed. CONCLUSIONS: Synchronous UUTT and superficial bladder tumor are uncommon but 46% are invasive. Considering the possible examination of the upper urinary tract only in patients with tumor in the trigone or with multiple bladder tumors 41.4% or 69% of UUTTs, respectively, would have been diagnosed. Patients with tumor in the trigone are at almost 6-fold higher risk for a synchronous tumor in the upper urinary tract.     

Natural history of positive urinary cytology after radical cystectomy

PURPOSE: The natural history and risk of disease progression in patients with positive urine cytology after radical cystectomy for urothelial carcinoma has not been adequately elucidated. MATERIALS AND METHODS: An institutional review board approved, retrospective review in patients undergoing radical cystectomy was performed to identify those with positive urinary cytology after radical cystectomy. Cox proportional hazards regression was used to determine factors associated with positive cytology after radical cystectomy and upper tract recurrence after positive cytology. Survival curves and probabilities were examined by Kaplan-Meier analysis. RESULTS: A total of 101 patients with at least a single positive urinary cytology result after radical cystectomy were identified. Ureteral involvement in the radical cystectomy specimen was significantly associated with subsequent positive cytology. At the first positive urinary cytology only 9 of 101 patients (9%) had documented urothelial recurrence but eventually 57 of 101 had radiographic evidence of urothelial recurrence. Median freedom from radiological evidence of urothelial recurrence after positive cytology was 2.1 years and ureteral involvement was associated with a higher likelihood of urothelial recurrence. Despite surgical and chemotherapeutic interventions median survival after urothelial recurrence was 2.1 years. CONCLUSIONS: Urine cytology may have a valuable role for detecting upper tract recurrence after radical cystectomy. Most patients with positive cytology after radical cystectomy eventually have radiological evidence of urothelial recurrence. These data may help clarify natural history in patients with positive cytology after radical cystectomy. Additionally, these data indicate the need for diligent evaluation for recurrent disease and potentially the role of early adjuvant therapy in patients with positive cytology after radical cystectomy.     

The fate of an unsatisfactory urine cytology test among patients with urothelial carcinoma

OBJECTIVE

To determine the outcome of patients with a urinary cytology test that is unsatisfactory (UUCyt) for evaluation (<50 urothelial cells) to guide the clinical decision‐making process, as currently there are no guidelines to aid in interpreting this result and directing further investigations.

PATIENTS AND METHODS

We retrospectively reviewed 142 patients, with 265 instances of UUCyt, in our bladder cancer database and by chart review. The cytology, cystoscopy and pathology results in the subsequent 12 months after a UUCyt result were reviewed, and the incidence of new and recurrent genitourinary tract cancers was calculated.

RESULTS

All patients had a previous history of, or developed, urothelial carcinoma during the follow‐up. There were 41 instances (16.3%) in which bladder cancer was evident at the time of the UUCyt and 29% of these tumours were high‐grade. There were another 44 instances (17.5%) in which new or recurrent bladder cancer developed in the subsequent year after a UUCyt test, and many (38.6%) of these tumours were high‐grade.

CONCLUSION

The incidence of urothelial carcinoma after a UUCyt was high (33.9%) with a substantial number of high‐grade (34%) tumours, implying that a UUCyt result cannot be interpreted as negative for malignancy. Therefore, in these cases, the urologist must depend on cystoscopy to make a diagnosis.     

Multitarget fluorescence in situ hybridization assay detects transitional cell carcinoma in the majority of patients with bladder cancer and atypical or negative urine cytology

PURPOSE: The multitarget fluorescence in situ hybridization (FISH) probe set UroVysion (Vysis, Downers Grove, Illinois), containing probes to chromosomes 3, 7 and 17, and to the 9p21 band, has been recently shown to have high sensitivity and specificity for detecting transitional cell carcinoma. In this study we retrospectively tested 120 urine samples from patients with atypical, suspicious and negative cytology for whom concurrent and followup bladder biopsy data were available. We evaluated the ability of FISH to identify malignant cells in cytologically equivocal or negative cases. MATERIALS AND METHODS: Archived slides from 120 voided (47) or instrumented (73) urine cytology specimens from patients with concurrent bladder biopsy and a minimum of 12 months of biopsy followup were subjected to hybridization with UroVysion. The cohort included patients with biopsy proven transitional cell carcinoma, which was grades 1 to 3 in 23, 35 and 24, respectively, and stages pTis in 3, pTa in 64, pT1 in 6, pT2 in 6 and pT4 in 3, while it showed negative histology in 38. Cytology findings were suspicious, atypical and negative for transitional cell carcinoma in 31, 49 and 40 cases, respectively. A positive FISH result was defined as 5 transitional cells or greater with a gain of 2 or more of chromosomes 3, 7 or 17, 12 cells or greater with 9p21 deletion, or 10% or greater of cells with isolated trisomy of 1 of chromosomes 3, 7 and 17. RESULTS: All except 12 of the 82 biopsy proven transitional cell carcinoma cases (11 pTa and 1 pT1 tumors) were positive by FISH (85% sensitivity). Sensitivity in patients with suspicious, atypical and negative cytology was 100%, 89% and 60%, respectively. Nine patients with atypical cytology had positive FISH in the setting of a negative concurrent bladder biopsy. However, 8 of these 9 patients (89%) had biopsy proven transitional cell carcinoma within 12 months following the date when the sample tested by FISH was obtained. The last of these patients with false-positive results had previously documented pTis disease, which was also present in the next bladder biopsy 15 months following the positive FISH result. The remaining 29 specimens from patients with negative biopsy and a negative 12-month followup tested negative by FISH (97% overall specificity). CONCLUSIONS: The UroVysion FISH assay provides high sensitivity and specificity to detect transitional cell carcinoma in cytologically equivocal and negative urine samples. These results emphasize the important role of this assay in the management of bladder cancer.     

Role of routine transurethral biopsy and isolated upper tract cytology after intravesical treatment of high‐grade non‐muscle invasive bladder cancer

Objectives: To investigate whether random bladder, and prostatic urethral biopsies and individual upper tract cytologies (restaging) provide useful clinical information in addition to cystoscopy and bladder cytology in assessing initial intravesical therapy response for high‐grade non‐muscle invasive bladder cancer. Methods: We retrospectively reviewed records of all patients who underwent restaging at our institution after treatment for high‐grade non‐muscle invasive bladder cancer (Ta, T1 and Tis) between January 2000 and October 2009. A total of 78 patients undergoing 116 consecutive restagings were included. The presence of intravesical cancer at restaging was assessed by cystoscopy, bladder wash cytology and random bladder biopsies, whereas ureteral and prostatic urethral disease was determined using upper tract barbotage cytology and prostatic urethral biopsies. Results: Indication for intravesical treatment was carcinoma in situ in 86, high‐grade T1 in 16 and high‐grade Ta in 14 cases. A total of 48 patients had primary disease and 68 had recurrence. Overall, 59 of 116 (50.9%) restagings showed positive bladder or prostatic biopsy and/or a positive cytology localized to the upper tract. Of the total number of recurrences, 12.9% (15 of 116) showed a negative cystoscopy and negative bladder cytology, and would have been missed on routine surveillance. A total of 23 of 116 (19.8%) restagings showed evidence of prostatic urethral and or ureteral disease. Conclusion: Roughly 25% of high‐grade non‐muscle invasive bladder cancer early recurrences after induction intravesical therapy would go unnoticed without the addition of random and directed prostate biopsies, and isolated upper tract cytologies to standard cystoscopy and bladder cytology.     

Endoscopic management of upper tract urothelial carcinoma in patients with a history of bladder urothelial carcinoma

PURPOSE: Endoscopic management of renal pelvis and ureteral urothelial carcinoma is gaining acceptance as a conservative treatment modality. Patients with a history of bladder urothelial carcinoma are at high risk for upper tract recurrence. We evaluate the role of endoscopic management of upper tract urothelial carcinoma in patients with a history of primary bladder urothelial carcinoma. MATERIALS AND METHODS: We retrospectively reviewed 90 patients with a history of primary bladder urothelial carcinoma who underwent endoscopic treatment of localized upper tract urothelial carcinoma between 1983 and 2004. RESULTS: Median patient age at diagnosis was 73 years (range 50 to 90). A total of 13 (14.4%) patients previously underwent cystectomy. With a median followup of 4.3 years (range 0.1 to 17), 105 upper tract urothelial carcinoma recurrences developed in 55 patients at a mean of 0.6 years (range 22 days to 5.9 years). Of these recurrences 76 were amenable to endoscopic management while 29 required nephroureterectomy. In 38 patients there were 91 bladder recurrences. At last followup 48 patients died, 17 of urothelial carcinoma at a median of 3.4 years (range 1 to 10). Cancer specific survival at 5 years for this cohort was 71.2%. Risk of death from urothelial carcinoma was significantly associated with stage (RR 3.23) and grade (RR 4.05) of upper tract urothelial carcinoma, imperative indication (RR 4.30), and treatment of bladder urothelial carcinoma with cystectomy (RR 3.34). CONCLUSIONS: Endoscopic management of upper tract urothelial carcinoma in patients with primary bladder urothelial carcinoma demonstrates a significant local recurrence rate. Furthermore, 5-year cancer specific survival is low. These patients represent a high risk cohort requiring strict ureteroscopic followup after endoscopic management is instituted.     

Chemoprevention for bladder cancer

PURPOSE: Bladder cancer is the most expensive cancer to treat and follow in the United States due to often extended courses of treatment coupled with the necessity for frequent surveillance examinations. Because direct exposure to carcinogens is implicated in bladder cancer development and many potentially protective compounds are concentrated in urine, bladder cancer is a logical target for chemoprevention. MATERIALS AND METHODS: We performed a MEDLINE search of the English language literature to identify reports of chemoprevention of bladder cancer. Study outcomes were evaluated and mechanisms of action were identified when possible. In cases of multiple reports of the same compound critical comparisons were performed. RESULTS: For most putative chemopreventive agents against bladder cancer the results of different studies are conflicting. Megadose vitamins, certain vitamin A analogues and pyridoxines have been associated with promising findings. For vitamins C and E and selenium, studies showing benefit are balanced by studies showing no benefit. Other compounds, such as soy, green tea and isothiocyanates, have been suggested by some studies to be protective and by others to be tumor promoting. CONCLUSIONS: For most bladder cancer chemopreventive agents studied to date results regarding efficacy vary, precluding the possibility of universal support by health care providers for this specific role. Megadose multivitamin supplements have demonstrated the ability to prevent bladder cancer recurrences in a single smaller study. Some analogues of vitamins A, B6, C and E have been shown to be beneficial in other disease processes, suggesting that these compounds may be advocated with the caveat that they do not have a specific protective role in bladder cancer. Data from randomized, prospective trials show a benefit in bladder cancer only after eliminating early or initial recurrences, suggesting the need for long-term administration of a chosen agent. Additional prospective trials with long-term followup, likely involving multiple institutions, are required before definitive recommendations can be made about chemoprevention for bladder cancer. In 2006 no oral agent can be recommended and to our knowledge the best chemopreventive strategy remains to be determined.     

Discrepancies between cytology, cystoscopy and biopsy in bladder cancer detection after Bacille Calmette-Guerin intravesical therapy

Objectives:   To evaluate discrepancies in the detection of Bacille Calmette-Guerin (BCG)-resistant bladder cancer by cystoscopy, bladder biopsy and urinary cytology.
Methods:   Between January 1992 and August 2006, 127 bladder cancer patients underwent a cycle of eight weekly BCG instillations. Four weeks after the last BCG instillation, urinary cytological analysis and cystoscopy with targeted biopsy in addition to eight–nine selected-site biopsies were performed.
Results:   Biopsy-proven cancer was found in 11/27 (40.7%), 5/42 (11.9%), and 11/58 (19.0%) of positive, suspicious, and negative cytology cases, respectively. Abnormal and normal cystoscopic findings correlated with a biopsy-proven cancer in 13/53 (24.5%) and 14/74 (18.9%) cases, respectively. The combination of a macroscopic cystoscopic suspicion and a positive cytology missed malignant cases in 15.9% of the cases. In 100 cases without biopsy-proven cancer, the rates of denuded urothelium at biopsy in the cases with positive and non-positive cytology were 7/16 (43.8%) and 16/84 (19.0%), respectively
Conclusions:   According to our study, routine biopsy is recommended in the evaluation of BCG treatment, even if the timing, limitations and disadvantages of the procedure should be taken into account.     

Association between urinary cytology and pathology for nontransitional cell malignancies of the urinary tract

PURPOSE: Because nontransitional cell carcinoma neoplasms of the urinary tract are rare in Western countries, we examined the association between urinary cytology and pathology evaluations for these tumors. MATERIALS AND METHODS: An institutional review board approved, retrospective review of a total of 55,946 cytology evaluations in 12,705 patients between 1992 and 2004 was performed for correlation with subsequent histopathology findings. Documented urothelial neoplasms were then correlated with previous cytology results. Nontransitional cell carcinomas were categorized as adenocarcinoma, squamous cell carcinoma and other, including small cell disease, sarcoma, melanoma or lymphoma. RESULTS: All 108 patients with cytology evaluations showing adenocarcinoma had histological evidence of cancer and 86% had adenocarcinoma in the urinary tract. All 110 patients with squamous cell carcinoma on cytology had cancer, including 47% with primary squamous cell disease. All 42 patients with other nontransitional cell carcinomas on cytology evaluation had cancer, of whom 64% had histological concordance. In a separate analysis of 70 patients who had pathologically confirmed adenocarcinoma 57% had positive prior cytology findings, of whom 19% had histological concordance. Of 85 patients with squamous cell carcinoma 81% had positive prior cytology findings, of whom 60% had histological concordance. Of 83 patients with other nontransitional cell carcinomas 70% had positive prior cytology findings, of whom 31% had histological concordance. CONCLUSIONS: In our series all patients with nontransitional cell carcinoma cytological results had cancer in the urinary tract. Thus, nontransitional cell carcinoma cytology findings mandate careful urinary tract evaluation. Concordance with histological subclassification on subsequent pathology evaluation ranges from 49% for squamous cell carcinoma to 86% for adenocarcinoma. A majority of patients with nontransitional cell carcinoma malignancies had positive prior cytology findings. However, the concordance with histological subclassification on prior cytology results ranges from 19% for adenocarcinoma to 60% for squamous cell carcinoma.     

Upper urinary tract tumors after primary superficial bladder tumors: prognostic factors and risk groups

PURPOSE: We evaluated the prognostic factors of primary superficial bladder cancer that may predict a metachronous upper urinary tract tumor. We also determined whether the incidence of upper urinary tract disease varies according to risk group based on primary superficial bladder tumor classification. MATERIALS AND METHODS: We studied disease evolution in a cohort of 1,529 patients with a primary superficial bladder tumor. To determine the prognostic factors of upper urinary tract cancer we performed multivariate analysis using Cox regression. Independent variables were grade, T stage, multiplicity, tumor size, carcinoma in situ association, previous or synchronous upper urinary tract tumor and intravesical instillation. We also performed the chi-square test and Kaplan-Meier survival analysis to assess the variable incidence of upper urinary tract tumors according to primary superficial bladder tumor risk group classification. RESULTS: The incidence of upper urinary tract cancer was 2.6%. The only factor prognostic for an upper urinary tract tumor was multiplicity (relative risk 2.7, 95% confidence interval [CI] 1.06 to 6.84). All patients with an upper urinary tract tumor had a previously recurrent primary superficial bladder tumor. In the low, intermediate and high risk groups the incidence of upper urinary tract cancer was 0.6% (relative risk 1), 1.8% (relative risk 3.1, 95% CI 0.4 to 23.9) and 4.1% (relative risk 8.3, 95% CI 1.1 to 61.6), respectively (chi-square and log rank tests p = 0.007 and p <0.05, respectively). CONCLUSIONS: A higher risk of upper urinary tract cancer must be expected in cases of multiple primary superficial bladder tumors. This finding supports the multicentricity theory of transitional cell carcinoma. Primary superficial bladder tumor classification by risk group is also useful for predicting the various risks of metachronous upper urinary tract cancer.     

预防肾盂输尿管癌术后再发膀胱癌的手术方法研究

目的探讨预防。肾盂输尿管癌术后再发膀胱癌的手术方法。方法对156例单纯。肾盂癌、单纯输尿管癌中获随访的139例患者资料进行同顾性总结。肾盂癌78例。输尿管癌61例。肿瘤细胞分级：G1 19例，G2 88例，G3 32例。肿瘤分期：Ta—T1 38例，T2 80例，T3～T4 21例。肿瘤直径0．8—6．0cm。结果139例均行根治性。肾、输尿管及管口周围部分膀胱壁（1．5—2．0cm）切除术。术后随访1～10年。再发膀胱癌55例，占39．6％。肾盂癌术中先用纱条结扎输尿管后游离切除患肾输尿管及管口周围部分膀胱者术后膀胱癌再发率18．5％（5／27），未先结扎输尿管者再发率27．5％（14／51）。术后当日膀胱灌注化疗者膀胱癌再发率32．3％（10／31）。术后3周开始膀胱灌注化疗者膀胱癌再发率34．9％（30／86）。术后当日及术后序贯膀胱灌注化疗者术后膀胱癌再发率20．0％（4／20），单纯术后序贯膀胱灌注化疗者膀胱癌再发率39．3％（26／66）。2者比较差异有统计学意义（P〈0．01）。结论术后当日及术后序贯膀胱灌注化疗可有效降低。肾盂输尿管癌术后膀胱癌的再发率，游离切除。肾输尿管前先结扎输尿管对预防肾盂癌术后再发膀胱癌可能有益。     

Independent predictors of metachronous bladder transitional cell carcinoma (TCC) after nephroureterectomy for TCC of the upper urinary tract

OBJECTIVE

To identify the prognostic factors predictive of metachronous bladder transitional cell carcinoma (TCC) in a multi‐institutional dataset of patients who had undergone nephroureterectomy (NU) for nonmetastatic upper urinary tract (UUT) TCC.

PATIENTS AND METHODS

The clinical and pathological data of 231 patients who had had NU for UUT‐TCC from 1989 to 2005 in three European centres were collected retrospectively, and analysed for clinical and pathological variables.

RESULTS

The median follow‐up was 38 months; during the follow‐up, bladder TCC was detected in 109 patients (47.2%), and was significantly more common in patients who had UUT‐TCC after previous bladder TCC (P < 0.001), in those with ureteric cancer (P = 0.022), and in those with pT2 UUT‐TCC (P = 0.017). On multivariate analysis, a previous history of bladder TCC was the only independent predictor of metachronous bladder TCC (hazard ratio 2.825; P < 0.001). The 5‐year probability of being free from metachronous bladder TCC was 45.5%. A history of bladder TCC (P < 0.001) and UUT tumour site (P = 0.01) were significantly associated with the probability of bladder recurrence‐free survival. On multivariate analyses, a previous history of bladder TCC (hazard ratio 2.226; P < 0.001) and the presence of ureteric TCC (1.562; P = 0.036) were independent predictors of the probabilities of being free from metachronous bladder TCC.

CONCLUSION

In this multi‐institutional study of patients who had had NU for UUT‐TCC, a history of bladder TCC was the only independent predictor of metachronous bladder TCC, while both a history of bladder TCC and the presence of ureteric tumours were predictive of the probabilities of being free from metachronous bladder TCC.     

Role of lymphadenectomy in the management of urothelial carcinoma of the bladder and the upper urinary tract

The role of lymphadenectomy has been controversial in urological malignancies. Urothelial carcinoma of the bladder and upper urinary tract has a high potential to spread through the lymphatic network compared with other malignancies, including renal cell carcinoma or prostate cancer. In urothelial carcinoma of the bladder, lymphadenectomy of pelvic nodes had been considered as the standard procedure when radical cystectomy was carried out. Recently, many investigators have examined the influence of its extent, and the majority of the studies have supported the beneficial role of extended lymphadenectomy in accurate staging or in improving patient survival. Although randomized controlled trials are required to establish a greater level of evidence, more urological surgeons have already noticed the necessity for extended lymphadenectomy in bladder cancer. In contrast to bladder cancer, there have been far fewer studies on urothelial carcinoma of the upper urinary tract. This might be because of the smaller number of the patients with urothelial carcinoma of the upper urinary tract and the lack of understanding of regional nodes. However, studies of lymph node mapping and the retrospective analyses with respect to the benefit of lymphadenectomy have been carried out in urothelial carcinoma of the upper urinary tract by some investigators, although the results are still controversial. However, the results from multi‐institutional studies by high volume centers have supported the beneficial role of lymphadenectomy in urothelial carcinoma of the upper urinary tract, as it has been proposed in bladder cancer. Thus, lymphadenectomy for urothelial carcinoma of the bladder and the upper urinary tract might have a potential role in staging and improving the oncological outcomes.     

慢性肾脏疾病对上尿路尿路上皮癌患者合并膀胱肿瘤风险的影响

目的 探讨慢性肾脏疾病(CKD)对上尿路尿路上皮癌(UUTUC)患者合并膀胱肿瘤风险的影响. 方法 UUTUC患者161例.男61例,女100例.平均年龄67(37～87)岁.既往有尿路移行细胞肿瘤病史者15例(9.3%).均行肾输尿管全长切除或输尿管下段切除术,病理检查证实为UUTUC.采用MDRD方程计算GFR,GFR＜60 ml/min者认为存在CKD.单因素和多因素分析性别、年龄、既往尿路上皮肿瘤病史、病变数目、肿瘤分期、分级、大小、是否合并CKD等临床病理因素对UUTUC患者合并膀胱肿瘤风险的影响. 结果 161例UUTUC患者中合并膀胱肿瘤20例(12.4%),合并CKD 93例(57.8%).单因素分析显示患者合并CKD(P=0.008)和既往尿路移行细胞肿瘤病史(P=0.001)是UUTUC患者合并膀胱肿瘤的危险因素,患者性别、年龄、病变数目、肿瘤分期、分级、大小与UUTUC患者合并膀胱肿瘤无显著相关性(P＞0.05).多因素分析显示CKD(HR 4.907,95%CI 1.206～19.959,P=0.026)和既往尿路上皮肿瘤病史(HR 6.444,95%CI1.699～24.445,P=0.006)是UUTUC患者合并膀胱肿瘤的独立危险因素.结论 UUTUC患者合并存在膀胱肿瘤并不少见.合并CKD和既往尿路上皮肿瘤病史是UUTUC患者合并膀胱肿瘤的独立危险因素.