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Original Articles: Bladder Cancer: Neoadjuvant Cisplatin Chemotherapy Before Radical Cystectomy in Invasive Transitional Cell Carcinoma of the Bladder: A Prospective Randomized Phase III Study

ABSTRACTFrom November 1984 to April 1989, 122 patients with clinical T2-4a Nx-2 M0 transitional cell carcinoma of the bladder were entered in a prospective randomized trial to compare survival between a control group of 60 patients treated only with radical cystectomy (arm A) and a group of 62 patients treated with 3 cycles of 100 mg./m2. neoadjuvant cisplatin before radical cystectomy (arm B). Secondary objectives of the trial were comparison of the disease-free interval and time to death, significance of response of the primary tumor to cisplatin, pattern of relapse and toxicity. As of April 1993 after a median followup of 78.2 months (range 48 to 101) no difference in survival between the control patients and those who received neoadjuvant cisplatin has been observed. The overall direct survival is 37.3% for arm A and 35.5% for arm B. The survival rate of the 109 patients who complied with the protocol is 38.2% for 55 patients of the control group and 40.7% for 54 patients of the cisplatin group. Survi...

Long-term follow-up of a randomized prospective trial comparing a standard 81 mg dose of intravesical bacille Calmette-Guérin with a reduced dose of 27 mg in superficial bladder cancer.

Objectives To determine the efficacy of a three‐fold reduced dose (RD, 27 mg) of intravesical bacille Calmette‐Gue´rin (BCG) against the standard dose (81 mg) in patients with superficial bladder cancer, assessing recurrence, progression and differences in toxicity.

Improving the safety of BCG immunotherapy by dose reduction

The preliminary results of a randomized, multicentre, prospective trial conducted by the Spanish Oncology Group (CUETO) are presented. The primary aim of the trial was to determine whether or not lowering the dose of bacillus Calmette-Guérin (BCG) could reduce toxicity without compromising efficacy. From February 1991 to June 1992, 500 patients with superficial bladder cancer (TaG2-3, T1G1-3) entered the trial. Of these patients, 252 were included in group A (BCG, 81 mg) and 248 in group B (BCG, 27 mg). There were no significant differences in clinical and pathological characteristics between the two groups. Following treatment, significant differences arose between groups A and B in local severe toxicity (22.6 vs. 4.2%, respectively; p < 0.01). Systemic toxicity was more common in group A than in group B (p < 0.01): pulmonary effects (2.3 vs. 0.4%), fever (26.9 vs. 12.9%) and malaise (16.2 vs. 8.4%), all p < 0.01. Regarding efficacy, 204 patients in group A and 210 in group B were evaluated after a mean follow-up of 18.6 months. No significant differences in recurrence rate (18.1 vs. 19.5%) or progression rate (2.4 vs. 4.8%) were found. However, in patients with superficial bladder cancer with high risk of recurrence and progression (carcinoma in situ and G3), caution must be exercised in selecting the dose.

Primary Cisplatin, Methotrexate and Vinblastine Aiming at Bladder Preservation in Invasive Bladder Cancer: Multivariate Analysis on Prognostic Factors

PURPOSE Although radical cystectomy is the standard therapy for invasive bladder cancer, cisplatin based multi-drug chemotherapy has proved to be effective for advanced transitional cell urothelial carcinoma. The potential for bladder preservation with neoadjuvant chemotherapy is currently under investigation. MATERIALS AND METHODS A phase 2 protocol is presented for conservative treatment of muscle invasive transitional cell carcinoma of the bladder consisting of primary cisplatin, methotrexate and vinblastine chemotherapy followed by reevaluation for bladder sparing surgery and surveillance. A total of 61 patients completed the protocol with a mean followup of 41.4 months. RESULTS Initial complete response to chemotherapy associated with tumor stage, size and configuration was noted in 20 patients (33%). Bladder preservation, intended only for the complete response group, was achieved in 16 patients (26%) but only 11 (18%) were alive with the bladder intact at study closure. Disease-free 5-year survival rate was 47% (95% confidence interval 65 to 26%). Tumor stage (p = 0.0007), size (p = 0.0003), response to chemotherapy (p = 0.002), patient age (p = 0.039) and tumor grade (p = 0.048) influenced survival. Multivariate analysis revealed response to chemotherapy (beta = 0.988, p = 0.034) and tumor size (beta = 0.978, p = 0.042) to be the only independent predictors. CONCLUSIONS Induction of cisplatin, methotrexate and vinblastine chemotherapy is helpful in identifying patients with a greater chance for survival among those with locally advanced bladder cancer. However, a bladder preservation strategy based on this therapy is only of limited success.

Pseudosarcomatous Myofibroblastic Proliferation of the Bladder: Report of 2 Cases and Literature Review

We report 2 cases of pseudosarcomatous myofibroblastic proliferations of the bladder unrelated to urological trauma. To our knowledge, these cases represent the longest followup (12 and 19 years, respectively) reported in the literature, which confirms the long-term benign nature of an entity that may be clinically and even pathologically mistaken as malignancy. A review of the literature revealed a female predominance (3:1), 50% of the cases manifested in the first 2 decades of life and mean age was significantly lower in male patients (p < 0.005). These facts suggest the existence of a hormonal factor in the pathogenesis of this entity. A predilection for fundus, and the posterior and lateral walls also is demonstrated. In light of the complex embryogenesis of the cloacal territory, it could be hypothesized that this lesion arises from embryonal mesenchymal remnants of the endodermally derived urinary tract.

Long-term follow-up of a randomized prospective trial comparing a standard 81mg dose of intravesical bacille calmette-guérin with a reduced dose of 27mg in superficial bladder cancer.1: BJU Int 2002;89:671–680.

Abstract Objectives: To determine the efficacy of a three-fold reduced dose (RD, 27 mg) of intravesical bacille Calmette-Guerin (BCG) against the standard dose (81 mg) in patients with superficial bladder cancer, assessing recurrence, progression, and differences in toxicity. Patients and Methods: Five hundred patients with superficial bladder cancer (Ta, T 1 , Tis) were enrolled and randomly assigned to be treated after transurethral resection of all visible lesions with intravesical BCG Connaught strain (weekly × six and thereafter fortnightly × six) either with the standard or RD instillation. Results: All but one of the 500 patients were evaluable for efficacy and toxicity (252 in the standard arm and 247 in the RD arm). The median follow-up was 69 months (maximum 104); 71 (28%) patients in the standard arm and 76 (31%) in the RD arm developed recurrences; the median time to recurrence has not yet been attained, but at 5 years the mean (sd) percentage of recurrence-free patients was 70.5 (3.12) and 70.4 (3.1) for the standard and RD arms, respectively. In patients presenting with multifocal tumours, the standard dose was more effective against recurrences than the RD ( P = 0.0151). In those with G3 and high-risk tumours overall, the superiority of the standard dose was marginal ( P = 0.060 and P = 0.082). Twenty-nine (11.5%) tumours in the standard arm and 33 (13.3%) in the RD arm progressed to invasive disease; the median time to progression has not yet been attained, but the percentage of progression-free patients at 5 years was 88.8 (2.23) and 86.9 (2.31) for the standard and RD arms, respectively. The standard dose was more effective than the RD against progression only in patients with multifocal disease ( P = 0.048). Twelve (4.8%) cystectomies were performed in the standard and 15 (6.1%) in the RD arm. Currently, 106 (21.2%) patients have died, but only 38 (7.6%) from bladder cancer, i.e., 20 (7.9%) in the standard and 18 (7.5%) in RD arm. Overall the disease-specific death rate was lower for those patients who completed the scheduled treatment. The cause-specific survival at 5 years did not differ between the arms ( P = 0.76) but there was a trend toward better cause-specific survival for patients with multifocal tumours in the standard arm. Toxicity differed between the arms, significantly more patients having no toxicity in the RD arm, and fewer having delayed instillations or withdrawing. However, severe systemic toxicity occurred even in patients treated with the RD, in a similar proportion to those receiving the standard dose. Conclusion: Overall, the RD gave similar results for recurrence and progression but with significantly less toxicity. However, patients with multifocal tumours fared better with the standard dose and there was a trend towards better recurrence rates in patients with high-risk tumours. We recommend continuing to use the standard dose for high-risk tumours, whereas we consider the RD safe and effective for intermediate-risk lesions and for maintenance schedules.

Extrarenal Retroperitoneal Angiomyolipoma

The clinical and pathological findings in a patient with extrarenal angiomyolipoma arising in the perinephric space are presented. This location has been reported only rarely and sets forth some diagnostic and therapeutic difficulties that are also discussed.

INTRATHORACIC KIDNEY AND VERTEBRAL FUSION: A MODEL OF COMBINED MISDEVELOPMENT

We report a case of right intrathoracic kidney associated with a complex somite malformation that comprised vertebral fusion and right intrathoracic supernumerary ribs. The interpretation of this association as a disease model of nature allows us to propose a unifying hypothesis on the pathogenesis of this form of renal dystopia.

Metastasising Carcinoma of the Urinary Bladder Presenting as a Retro-Orbital Mass

A 61-year-old man presented with macroscopic haematuria. Infiltrating transitional cell carcinoma of the urinary bladder was diagnosed after transurethral resection, and he was treated first with three doses of cisplatinum (100 mg/m2 at three week intervals) and then by radical cystectomy. Eleven months later he complained of progressive diplopia, which was found on computed tomography to be caused by a retro-orbital metastatic mass. There was no evidence of a space occupying lesion in the brain or of other metastases. The patient died four weeks later and permission for necropsy was refused. Despite the fact that carcinoma of the urinary bladder rarely metastasis in this way, urologists should be aware that it can happen.

Kaposi’s Sarcoma of the Penis as an Initial Urological Manifestation of AIDS

Kaposi’s sarcoma of the penis is an initial manifestation of AIDS and the practising urologist should be aware of this form of presentation. We report 2 young intravenous drug abusers with this tumor