Concomitant carcinoma in situ is a feature of aggressive disease in patients with organ-confined TCC at radical cystectomy

OBJECTIVES: Carcinoma in situ (CIS) is a nonpapillary, high-grade, potentially aggressive, and unpredictable manifestation of transitional cell carcinoma (TCC) of the bladder. The aim of this study was to assess whether presence of concomitant CIS has a detrimental effect on cancer control after radical cystectomy. METHODS: The records of 812 consecutive patients who underwent radical cystectomy and pelvic lymphadenectomy for bladder TCC at three US academic centres were reviewed. Ninety-nine of 812 (12%) patients had CIS only at radical cystectomy and were excluded from the analyses. RESULTS: Three hundred thirty of the 713 (46.3%) patients had concomitant CIS at radical cystectomy. Patients with TCC involvement of the urethra were more likely to have concomitant CIS than not (61% vs. 40%, p=0.018). Concomitant CIS was significantly more common in patients with lower cystectomy stages and higher tumour grades. In univariate, but not multivariate, analysis, patients with concomitant CIS versus those without were at increased risk of disease recurrence (p=0.0371). In patients with organ-confined disease, concomitant CIS was an independent predictor of disease recurrence (p=0.048 and p=0.012, respectively) but not bladder cancer-specific mortality (p=0.160 and p=0.408, respectively) after adjusting for the effects of standard postoperative features. CONCLUSIONS: Concomitant CIS in the cystectomy specimen is common, and patients with concomitant CIS are at increased risk of urethral TCC involvement. The presence of concomitant CIS appears to confer a worse prognosis in patients with non-muscle-invasive TCC treated with radical cystectomy.     

Tumor recurrence in the remnant urothelium of females undergoing radical cystectomy for transitional cell carcinoma of the bladder: long-term results from a single center

PURPOSE: We analyzed the risk factors and incidence of secondary TCC of the remnant urothelium in women following radical cystectomy for TCC of the bladder. MATERIALS AND METHODS: A total of 85 women with a mean age of 64.5 years with clinically localized TCC of the bladder underwent radical cystectomy between 1992 and 2004. Orthotopic bladder substitution was performed in 46 females, while 39 underwent nonorthotopic urinary diversion. Of the entire cohort 22 (26%) patients underwent cystectomy for multifocal or recurrent TCC. Followup examinations were performed at 6-month intervals. RESULTS: Mean followup in the entire cohort was 49.8 months (median 42). Intraoperative frozen sections obtained from the urethra and distal ureters were negative for TCC and CIS in all patients. Four women (4.7%) had TCC in the remnant urothelium at a mean of 56 months postoperatively. These patients had undergone cystectomy for multifocal or recurrent TCC (4 of 22 or 18%). No secondary TCC was seen in the 63 patients with solitary invasive or nonrecurrent bladder cancer (p <0.05). Urethral recurrence was found in 2 patients (4.3%) 65 and 36 months after orthotopic neobladder surgery, respectively. In the orthotopic group 1 patient (2.1%) had an upper urinary tract tumor 76 months after surgery, while in the nonorthotopic group 1 (2.5%) was found to have an upper urinary tract tumor 48 months postoperatively. CONCLUSIONS: Recurrent or multifocal TCC may represent a risk factor for secondary TCC of the remnant urothelium after cystectomy. In our series all recurrent tumors were late recurrences (more than 36 months postoperatively). Because the rate of urethral recurrence in the current series corresponds to that reported in men (2% to 6%), urethra sparing cystectomy with orthotopic bladder replacement does not appear to compromise the oncological outcome in women.     

Radical transurethral resection and chemotherapy in the treatment of muscle-invasive bladder cancer: a long-term follow-up

OBJECTIVE: To evaluate the treatment of patients with muscle-invasive bladder cancer (T2-T4a) by radical transurethral resection (TUR) and cisplatin-methotrexate systemic chemotherapy. PATIENTS AND METHODS: Fifty patients with transitional cell carcinoma (TCC) of the bladder (nine T2, 36 T3 and five T4a) were treated by 'complete' TUR of the bladder tumour followed by 2-6 cycles of cisplatin (70 mg/m2) and methotrexate (40 mg/m2) chemotherapy. The median (range) tumour size was 3 (1-7 cm). In six patients, attempted TUR at the dome of the bladder led to intraperitoneal perforation; the tumour was excised by partial cystectomy in these patients. The latest follow-up results from 57 patients treated by radical TUR and methotrexate alone, reported previously, are included. RESULTS: At the first evaluation cystoscopy immediately after completing chemotherapy, 38 patients were tumour-free, eight had persistent muscle-invasive TCC and four had Ta, T1+CIS disease. With an overall median follow-up of 47 months, 10 additional patients relapsed with muscle-invasive carcinoma in the bladder after a median interval of 15.6 months; three patients developed Ta, T1 tumours, three Ta, T1 + CIS, and six CIS only. Six of the 10 recurrent invasive tumours were at the same site, but four were at a different site in the bladder. Although during follow-up 12 patients developed superficial recurrence that required endoscopic treatment, the bladder was preserved (free of muscle-invasive cancer) in 37 of 50 patients. In 30 of these 37, this was achieved with no need for salvage radiotherapy or cystectomy. Six patients died from metastatic TCC with no tumour in the bladder. CONCLUSION: In this selected group of patients, muscle-invasive bladder cancer was controlled by TUR and systemic chemotherapy, preserving normal bladder function in 60% of patients without apparently comprising overall survival.     

Efficacy of intravesical bacillus Calmette-Guerin for carcinoma in situ of bladder

Three months after an initial 6-week course ofintravesical bacillus Calmette-Guerin (BCG) given between January 1990 and March 2005, 94 (90%) out of 104 patients with carcinoma in situ (CIS) of the bladder achieved a complete response (CR). The 5- and 10-year recurrence-free rates were 67 and 60%, respectively (median follow-up 42 months). Three months after a second course ofintravesical BCG given to 23 patients who failed the initial induction course for CIS was evaluated. Of these, 96% achieved a CR, and the 5- and 10-year recurrence-free rates were 56 and 28%,respectively (median follow-up 23 months). Only one patient who received a second course of BCG therapy showed disease progression. Two of the 4 patients with BCG-refractory CIS of the bladder achieved CR after intravesical gemcitabine therapy and maintained a tumor-free status beyond 6 months. Five of the 16 patients showing disease progression had upper urinary tract cancer, 4 had recurrent or muscle invasive bladder cancer, 6 had prostatic involvement of CIS, and one patient had urethral recurrence. Three of the 16 patients died. Bladder preservation was achieved in 97 of the 104 patients, although 7 patients ultimately underwent radical cystectomy and urinary diversion for aggressive disease. In conclusion, some patients may be managed safely by repeated endoscopic resection and intravesical therapy with cystectomy postponed until objective evidence of progression exists.     

Phase II study of intravesical therapy with AD32 in patients with papillary urothelial carcinoma or carcinoma in situ (CIS) refractory to prior therapy with bacillus Calmette-Guerin (E3897): a trial of the Eastern Cooperative Oncology Group

ObjectiveTo assess the safety and effectiveness of AD32, a doxorubicin analogue with little systemic exposure when administered intravesically, in patients with recurrent or refractory superficial urothelial carcinoma (formerly called transitional cell carcinoma [TCC]), or carcinoma in situ (CIS), who have failed prior BCG-based immunotherapy.MethodsEligible patients received six weekly doses (800 mg) of intravesical AD32 and were evaluated at 12-week intervals for 24 months or until date of worsening disease. Primary analysis was the proportion of all patients recurrence-free at 12 months. Treatment-related and GU-specific toxicities were also examined. All participating institutions submitted the protocol for Institutional Review Board (IRB) approval.ResultsThe study was halted due to unavailability of study drug after accrual of 48 of a planned 64 patients; 42 were included in the analysis. Of these, 28 (67%) were still alive after median follow-up of 61.1 months. Of 21 TCC patients, 18 (85.7%) experienced disease recurrence (median time to recurrence, 5.3 months). Of the 5 CIS patients with complete response (CR), 3 (60%) experienced disease recurrence; (median time to recurrence, 37.3 months). Recurrence-free rates at 12 and 24 months were 20% (90% CI, 7.8%, 36.1%) and 15% (90 CI, 4.9%, 30.2%), respectively, for patients with TCC and 80% (90% CI, 31.4%, 95.8%) at both intervals for CIS patients with CR. Infection was the most common treatment-related toxicity; no grade 4 or higher toxicity was observed. The most common GU-specific toxicity was increased frequency/urgency.ConclusionsAD32 is safe and active for treatment of recurrent or refractory superficial bladder carcinoma. The agent awaits more complete characterization when drug production problems can be solved.     

Treatment of Bacillus Calmette-Guerin refractory superficial bladder cancer: further intravesical therapy

We here report our clinical experience with salvage therapy for patients with bacillus Calmette-Guerin (BCG)-refractory superficial bladder cancer and discuss current approaches to the disease, especially focusing on bladder preservation. First, we evaluated the efficacy of an initial 6-week course of intravesical BCG in 93 patients with carcinoma in situ (CIS) of the bladder. Of these, 91% achieved a complete response (CR) at the evaluation at 3 months. The 2- and 5-year recurrence-free rates were 71 and 67%, respectively (mean follow-up 39 months). These results support the intravesical BCG as a first-line therapy for CIS. Next, we assessed the efficacy of a second course of intravesical BCG for 16 patients who failed the initial induction course for CIS. Of these, 94% achieved CR at the evaluation at 3-month, and the 2- and 5-year recurrence-free rates were 62 and 46%, respectively (mean follow-up 28 months). None of the patients who received a second course had disease progression. Thus, a second course of BCG therapy seems to be a reasonable option for CIS patients failing the initial course. We also report our initial experience with intravesical gemcitabine therapy for 3 patients with BCG-refractory CIS of the bladder and 1 patient with recurrent multiple tumors. Gemcitabine (1500 mg in 100 ml saline) was given in the bladder for 1 hour twice weekly for a total of 12 treatments. The treatment was associated with minimal bladder irritation and systemic absorption, and was well tolerated except in a 90-year-old man who discontinued therapy because of grade 2 toxicity. Two patients achieved CR and maintained a tumor-free status beyond 14 months, suggesting that the intravesical gemcitabine is a promising salvage therapy for BCG-refractory superficial bladder cancer.     

Photodynamic therapy.

The preliminary data suggest that red-light whole-bladder photodynamic therapy is safe and effective in the treatment of Tis and may be useful in the prophylactic management of superficial bladder cancer. Theoretically, whole-bladder photodynamic therapy has the advantage of higher efficacy after a single treatment than most conventional modalities for superficial bladder cancer. In patients with Tis, the complete response rate is 88%, and 25% have recurrences during a mean follow-up of 20 months (range 12-60). In patients undergoing prophylaxis, the recurrence rate is 31% and the median time to recurrence is 18 months. Importantly, none of the high-risk patients treated with whole-bladder photodynamic therapy has developed disease progression in stage or grade at the time of recurrences. Whole-bladder therapy also has the potential advantage of repeat treatment without increased tumor resistance or increased morbidity. Data from the present phase II-III clinical trials involving a large number of patients will define the role of photodynamic therapy in the management of superficial bladder cancer.     

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.     

Photodynamic therapy of superficial bladder tumors

Photodynamic therapy (PDT), using hematoporphyrin derivative (HPD) and the red light (wavelength 630 nm) of an argon-dye laser as the source of excitation energy was performed on 46 patients with superficial bladder tumors. Two methods of laser irradiation, (1) focal PDT using a 400 micron quartz fiber through a cystourethroscope in 22 patients with superficial bladder tumors and (2) whole bladder wall total PDT using a motor-driven laser light scattering device in 24 patients with multifocal carcinoma in situ and/or dysplasia of bladder mucosa associated with multicentric concurrent superficial tumors, were used. The patients in (2) had been referred for total cystectomy, and 19 of these 24 patients had a history of several transurethral resections, hyperthermia and/or instillation therapy. HPD 2-4 mg/kg was i.v. injected 48 to 72 hours before PDT. Judging from the results of 60 protrusions treated by focal PDT, the light power should be 200 mW/cm2 for 5-10 minutes or more and the total light energy should be 100 J/cm2 or more in tumors up to 2 cm in size. With focal PDT, 4 of the 22 patients had no recurrence with the mean tumor free time of 20.8 months. In 6 of the 24 patients treated with total PDT using 10, 20 or 30 J/cm2 of light energy, there was no recurrence with a mean tumor-free time of 7.5 months and there was no significant relationship between the recurrence rate and total light energy used.     

Intravesical bacille Calmette-Guérin in the treatment of carcinoma in situ or high-grade superficial bladder carcinoma after radiotherapy for bladder carcinoma

OBJECTIVE: To evaluate the effectiveness and tolerance of endovesical bacille Calmette-Guérin (BCG) after pelvic radiation therapy for bladder cancer in patients with recurrence as carcinoma in situ (CIS) and/or high-grade superficial bladder cancer. PATIENTS AND METHODS: In a prospective study, 13 patients were treated with weekly instillations of 81 mg BCG Connaught for 6 weeks. for CIS and/or high-grade superficial bladder carcinoma. All had been treated previously with radical radiation therapy for bladder carcinoma. RESULTS: Five patients had no recurrences and six patients retained their bladders, within a median follow-up of 74.5 months. Five patients progressed; two underwent radical surgery and are alive after 75 months of follow-up, and three died from the disease (two were high-risk surgical patients and one had metastatic disease). Another two patients died from intercurrent disease without bladder cancer. Eight patients were alive at a mean (SD range) follow-up of 85 (12, 65-97) months. CONCLUSION: Intravesical BCG is useful for controlling CIS and/or high-grade superficial bladder carcinoma in irradiated bladders and has an acceptable local tolerance: more than a third of patients were free of disease and preserved their bladders. This proportion is acceptable in patients currently scheduled for cystectomy.     

Partial cystectomy: a contemporary review of the Memorial Sloan-Kettering Cancer Center experience and recommendations for patient selection

PURPOSE: Partial cystectomy is a bladder sparing procedure that has been used to treat invasive bladder cancer in highly selected patients. This study analyzes the outcomes of partial cystectomy in a contemporary cohort of patients to identify appropriate selection criteria for the procedure. MATERIALS AND METHODS: Records were reviewed for 58 patients with a primary bladder tumor who had undergone partial cystectomy at Memorial Sloan-Kettering Cancer Center from 1995 to 2001. Information was collected on tumor size, histology, location, presence of carcinoma in situ (CIS), multifocality, neoadjuvant treatment, clinical stage, pathological stage and disease status. RESULTS: For the 58 patients analyzed, overall 5-year survival was 69% with a mean followup of 33 months (range 1 to 83). Of the patients 43 (74%) are alive with an intact bladder, 39 (67%) are currently disease-free with an intact bladder and 32 (55%) have been continuously disease-free with an intact bladder. Seven patients experienced a superficial recurrence and were treated successfully while 15 patients experienced an advanced recurrence. On univariate analysis CIS and multifocality were related to superficial recurrence, and lymph node involvement and positive surgical margin were related to advanced recurrence. On multivariate analysis concomitant CIS (odds ratio 7.05, p = 0.004) and lymph node involvement (odds ratio 4.38, p = 0.031) were predictors of advanced recurrence. CONCLUSIONS: In highly selected patients with invasive bladder cancer, partial cystectomy offers acceptable outcomes. Concomitant CIS and presence of metastases to regional lymph nodes predict advanced recurrence.     

Light penetration in bladder tissue: implications for the intravesical photodynamic therapy of bladder tumours

OBJECTIVES: To assess (i) the optical properties and depth of penetration of varying wavelengths of light in ex-vivo human bladder tissue, using specimens of normal bladder wall, transitional cell carcinoma (TCC) and bladder tissue after exposure to ionizing radiation; and (ii) to estimate the depth of bladder wall containing cancer that could potentially be treated with intravesical photodynamic therapy (PDT), assuming satisfactory tissue levels of photosensitizer. Materials and methods The study included 11 cystectomy specimens containing invasive TCC (five from patients who had previously received external-beam bladder radiotherapy, but with recurrent TCC) and three 'normal' bladders removed from patients treated by exenteration surgery for extravesical pelvic cancer. Full-thickness bladder wall and tumour samples were taken from these specimens and using an 'intravesical' and a previously validated interstitial model, the optical penetration depths (i.e. the tissue depth at which the light fluence is 37% of incident) were calculated at wavelengths of 633, 673 and 693 nm. RESULTS: There were no significant differences in light penetration between normal and tumour-affected bladder tissue at each wavelength. There were significant differences in light penetration among wavelengths; light at 693 nm penetrated approximately 40% further than light at 633 nm (P < 0.002). The light currently used in bladder PDT (633 nm) has a mean (SEM) optical penetration depth of 4.0 (0.1) mm within TCC. In addition, at this wavelength, there was 29% greater light penetration in previously irradiated than in unirradiated bladder wall (P = 0.001). This did not occur in the tumour-affected bladder. CONCLUSIONS: Bladder tissue is relatively more translucent than other human tissues and there is therefore great potential for PDT in the treatment of bladder cancer. As there is no difference in light penetration between TCC and normal bladder tissue, a tumour-specific response with diffuse illumination of the bladder will depend on drug localization within the tumour. The currently used wavelength of 633 nm can be expected to exert a PDT effect within bladder tumour up to a depth of 20 mm. Increasing the wavelength will allow deeper pathology to be treated.     

Genetic alterations and biological pathways in human bladder cancer pathogenesis

Human bladder cancers are heterogeneous. For example, at first presentation papillary transitional cell carcinomas (TCCs) are typically superficial and often multifocal. Papillary TCCs frequently recur, but most never progress to invasive TCC. In contrast, bladder carcinoma in situ (CIS) usually presents as a solitary flat lesion and, if left untreated, invariably progresses to invasive TCC. Some TCC are already invasive at the time of presentation. Squamous cell carcinoma (SCC) tends to present at a later stage than most TCCs and has a relatively aggressive clinical course. Multiple genetic alterations have been identified in invasive human bladder cancers and are present in different combinations and in different frequencies in the different manifestations of bladder cancer described above. A high percentage ( approximately 67%) of superficial papillary TCCs show early losses involving chromosome 9q, while very few show either a TP53 or a CDKN2/16 mutation. Thus, loss of 9q may be the earliest event in initiation of papillary TCC. In contrast, bladder CIS and SCC show relatively low percentages of 9q loss. However, approximately 65% of bladder CIS contain a TP53 alteration and approximately 67% of bladder SCC contain a CDKN2/p16 alteration. Mutations in these two tumor suppressor genes have powerful implications for loss of genome stability and cell growth regulation, respectively, consistent with the aggressive phenotypes of these cancers. Thus, these data suggest a model of bladder cancer pathogenesis in which the predominant genetic alteration may be the "initiating event" in cancer pathogenesis and may play a role in determining the biological potential of the tumor.     

Histopathological and immunohistochemical study of papillary urothelial neoplasms of low malignant potential and grade associated with extensive invasive low-grade urothelial carcinoma

OBJECTIVE: To report five cases of papillary urothelial neoplasm of low malignant potential (UNLMP) and papillary urothelial carcinoma of low grade (UCLG) associated with extensive muscle invasion, and to investigate the clinical and histopathological presentation and their immunohistochemical properties. MATERIALS AND METHODS: Consecutive cystectomy and correlating transurethral resection (TUR) of urinary bladder tumour specimens were reviewed to identify cases of UCLG having extensive invasion into the urinary bladder wall. All specimens were stained immunohistochemically, as were those from 10 control cases having reactive urothelium or superficial UNLMP. The clinical charts were reviewed. RESULTS: Of a total of 95 cystectomy cases there were four of UNLMP or UCLG with extensive invasion. An additional case was added from our consultation file. All five cases had biopsies misdiagnosed as benign lesions or prostatic adenocarcinoma. The superficial invasive components consisted of UCLG conforming to the previously described entities of nested transitional cell carcinoma (TCC), microcystic or deceptively benign-appearing TCC. Immunostaining for cytokeratin 20, MIB-1 and p53 was similar to reactive epithelia, whereas E-cadherin immunoreactivity was slightly different, with focal negativity compared with extensive immunoreactivity in invasive vs noninvasive UCLG. Four patients developed distant metastases; three died within a follow-up of 3 years. CONCLUSIONS: UNLMP and UCLG that widely and deeply invade the bladder accounted for 4% of urothelial carcinoma (UC) in cystectomy specimens and commonly pose diagnostic problems in superficial TUR specimens. From this study with few cases the diagnosis of this entity in superficial biopsies is aided by an awareness of it and by identifying 'benign appearing' nests of urothelial cells which are deeply seated in the stroma. Immunostaining is unlikely to be very useful.     

Upper tract transitional cell carcinoma following cystectomy for bladder cancer.

PURPOSE: We assessed the incidence of upper urinary tract tumors (UUTTs) after cystectomy for invasive or superficial transitional cell carcinoma (TCC) of the bladder. The risk factors, patients' characteristics and evolution of those who developed UUTTs are analyzed. MATERIALS AND METHODS: From August 1980 to February 1994, 568 radical cystectomies were performed for TCC of the bladder: in 469 instances (82.5%) due to invasive tumor (T2-T4), and in 99 cases (17.5%) for superficial tumor (Ta, T1, Tis). All patients were followed for at least 5 years or until death. A retrospective study of patients who developed UUTTs has been performed. A revision of bladder tumor and UUTT characteristics, and the intervals between both is also evaluated. RESULTS: 26 patients (4.5%) developed UUTTs: 11 of the 99 patients cystectomized for superficial TCCs (11.1%); 6 of the 392 patients with primary invasive TCC (1.5%), and 9 of the 77 (11.6%) patients with invasive tumors and a prior history of superficial TCC. The interval to the development of UUTT was higher after cystectomy for superficial tumor. TCCs of the bladder that subsequently developed UUTTs were high grade in 84%, multifocal in 80%, or had carcinoma in situ in 65%, tumor in the prostatic urethra in 52%, and involvement of the distal ureter in 57%. Twenty-two UUTTs (84%) were located in the calyces or the renal pelvis, 3 were bilateral (11.5%), 14 multiple (58%) and 4 superficial (16%). With a median follow-up time of 18 (range 3-103) months, 14 patients (53.8%) died of tumor, 2 were alive with disease, 2 were lost for follow-up, and 8 (30%) were alive and free of disease. CONCLUSIONS: We found that patients cystectomized for superficial or invasive TCC with a prior history of superficial TCC have a higher incidence of UUTTs. These cases require follow-up with annual urography or loopography.     

Outcome of radical cystectomy for bladder cancer according to the disease type at presentation

OBJECTIVE: To examine whether the outcome of cystectomy for invasive transitional cell carcinoma (TCC) of the bladder was influenced by the type of disease at initial presentation. PATIENTS AND METHODS: The charts of 76 patients treated for TCC by radical cystectomy from 1987 to 1997 in our unit were reviewed. The patients were divided into three groups: group 1 comprised 43 patients with primary invasive disease; group 2 included 12 patients with progression of an initial superficial bladder tumour after failure of conservative treatment; and group 3 comprised 21 patients who had a radical cystectomy for superficial TCC, with a high risk of progression after attempts at conservative treatment. The pathological findings on transurethral resection and cystectomy specimens, cancer-specific survival and the time to progression were compared among the three groups. RESULTS: The rate of pT0 in cystectomy specimens was 16%, 41% and 24% in groups 1, 2 and 3, respectively. Under-staging occurred in 24% of cases in group 3. The 10-year cancer-specific survival rates were 48%, 47% and 82% in groups 1, 2 and 3, respectively. The cancer-specific survival rate and progression rate were not significantly different between groups 1 and 2, but were significantly lower/higher in these patients than in group 3 (P < 0.01). CONCLUSIONS: These data suggest that the prognosis of superficial TCC which progresses despite conservative management is no better than that of invasive TCC at initial presentation, despite the closer follow-up received by the former patients. Early identification of this group of patients may improve the cancer-specific survival, as early cystectomy for high-risk superficial TCC yields better results.     

Plasmacytoid transitional cell carcinoma of urinary bladder: a clinicopathologic study of 9 cases

In this report, we summarized the clinicopathologic features of 9 cases of plasmacytoid transitional cell carcinoma (TCC) of the urinary bladder, a rare variant of TCC. All 9 patients were men with a mean of age 64.3 years (range, 46 to 81 y). All but 1 patient presented with gross hematuria; the remaining patient had urgency and microscopic hematuria. Cystoscopic findings revealed a dominant solid mass with surrounding multiple papillary lesions in 6 cases and multiple masslike lesions in 3 other cases. The initial diagnosis of plasmacytoid TCC was made on transurethral resection in 8 cases and cystoscopic biopsy in 1. One patient had TNM stage I disease, 2 had stage II disease, 3 had stage III disease, and 3 had stage IV disease. Four patients were treated by radical cystectomy with chemotherapy, 2 by radical cystectomy alone, 1 each by chemotherapy or intravesical bacillus Calmette-Guerin infusion alone, and 1 did not receive any further therapy. Microscopically, all tumors contained plasmacytoid cells, which composed 30% to 100% of the entire tumor. Eight of 9 cases were associated with high-grade TCC, and transitional cell carcinoma in situ was present in 4 cases. The plasmacytoid tumor cells were characterized by eccentrically located nuclei and abundant eosinophilic cytoplasm. Interestingly, plasmacytoid transitional cell carcinoma in situ was noted in 1 case. Immunohistochemical staining demonstrated that both plasmacytoid and conventional TCC components were positive for cytokeratins 7 and 20. The mean Ki-67 labeling index was 30% (range, 10% to 50%), and p53 expression in the majority of cases was low (5% to 10%), except for in 2 cases (70% and 80%). The mean follow-up in 8 patients was 24.5 months (range, 5 to 47 mo); the other patient was lost to follow-up. Five patients died of disease from 5 to 36 months, 2 patients were alive with disease at 30 and 47 months, and 1 patient was alive and well at 36 months with no evidence of disease. In summary, plasmacytoid TCC tends to present at an advanced stage and to have a poor prognosis. Morphologic recognition and distinction from other plasmacytoid malignant neoplasms is critical for its clinical management and immunohistochemical studies may be required for differential diagnosis.     

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. This revised version was published online in August 2006 with corrections to the Cover Date.     

Intravesical bacillus Calmette-Guèrin for the treatment of superficial bladder cancer in renal transplant patients

BACKGROUND: Intravesical instillations with bacillus Calmette-Guérin (BCG) is considered the treatment of choice in the prophylaxis of high-grade superficial bladder carcinoma and in the treatment of carcinoma in situ (CIS) of the bladder. METHODS: There is no previous experience with BCG treatment in patients with renal transplantation. Theoretically, immunosuppression is a contraindication because of the risk of severe morbidity and sepsis. We present our experience with endovesical BCG in three renal transplant patients, under immunosuppressive treatment, with high-grade superficial bladder cancer and CIS. RESULTS: Two patients are free of disease at 17 and 60 months. One patient developed disease recurrence and underwent a radical cystectomy. There was neither change in renal function nor any clinical evidence of tuberculous infection. CONCLUSIONS: Intravesical BCG in superficial bladder cancer and/or CIS is a valid option, with no added morbidity to renal transplant patients.     

When intravesical measures fail. Indications for cystectomy in superficial disease.

The indications for intravesical therapy for superficial bladder cancer include multifocal or recurrent tumors, lamina propria invasion, CIS, and superficial involvement of the prostatic urethra. Tumor-free success rates approach 70% in most series. Intravesical therapy is usually administered as a 6-week course with a re-evaluation of the bladder at the 3-month interval. If disease persists, a second 6-week course of therapy is administered. If tumor recurs or persists at the 6-month evaluation, treatment is considered to have failed, and another form of therapy is instituted (Fig. 1). In the 30% of patients failing an adequate course of intravesical therapy, cystectomy may be indicated for uncontrollable superficial disease not amenable to transurethral resection, persistent grade III lesions, lamina propria invasion, persistent CIS, persistent involvement of the prostatic urethra, and persistence of tumor in a nonfunctioning bladder. Rarely, cystectomy may be indicated because of severe adverse effects related to intravesical therapy.