Prospective, randomized, crossover comparison of sublingual apomorphine (3 mg) with oral sildenafil (50 mg) for male erectile dysfunction.

PURPOSE: We established the efficacy and safety of sublingual apomorphine compared with oral sildenafil in comparable groups of patients with erectile dysfunction (ED). MATERIALS AND METHODS: This prospective, randomized, crossover study included 77 heterosexual men with ED of various etiologies and severities. A total of 62 men were randomized but only 34 were evaluable for efficacy and tolerability. The study started with a run-in period of 2 to 4 weeks. The first 4 weeks of treatment were followed by a washout period of 4 weeks, after which patients changed to the alternate treatment for an additional 4-week period. The sequence of the 2 treatments was established by a randomization list in blocks in closed packets. The primary efficacy end point was the percent of attempts resulting in erection firm enough for intercourse. Additional variables were the percent of attempts resulting in intercourse and improvement in ED, as evaluated by the erectile function domain score of the International Index of Erectile Function questionnaire. RESULTS: Sildenafil was significantly more effective than apomorphine in regard to the percent of attempts resulting in erection firm enough for intercourse (85% vs 44%, p <0.0001) and actually resulting in intercourse (81% vs 43%, p <0.0001) as well as erectile function evaluated by the erectile function domain score of the International Index of Erectile Function (p <0.001). The incidence of adverse events was not significantly different for the 2 drugs. Although the number of patients was small, this study had strong statistical power due to the striking difference in results. CONCLUSIONS: Sildenafil was significantly more effective than apomorphine for ED. No statistical difference in adverse events was noted.

Preliminary report of a multicentric study on environmental risk factors in Ta-T1 transitional cell carcinoma of the bladder. A study from Gruppo Studi Tumori Urologici Foundation.

OBJECTIVE: The distribution of potential environmental risk factors among patients affected by superficial transitional cell carcinoma of the bladder (TCCB) has been analyzed. METHODS: Patients affected by superficial TCCB underwent TUR and early intravesical chemotherapy. Detailed data about age, sex, residence, employment, active and passive cigarette smoking, water resource and hair dye use were centralized. Analysis has been conducted on 474 patients affected by Ta-T1 G1-2 TCCB at medium risk for recurrence. Patients with primary single Ta G1-2, Tis or T1G3 tumors were excluded from the present analysis. RESULTS: Over 80% of the patients lived in urban areas, 22% were employed in industries presumed at risk for bladder cancer, 8% used hair dye and 75% were smokers. Bottled water was the only water resource in 42% of the patients. Employment in industry at risk (p = 0.01) and cigarette smoking (p = 0.04) resulted in being statistically related to tumor multiplicity. Moreover, the period of cigarette smoking was significantly longer in patients with recurrent tumors (p = 0.026). The municipal water supply represented the main water source in never-smokers (p = 0.01) rather than in smokers and in patients harboring T1 rather than Ta tumors (p = 0.03). CONCLUSIONS: Employment in industry at risk and cigarette smoking resulted in being related to tumor multiplicity. The length of exposure to cigarette smoking was related to the natural history of the tumor. A drinkable water source emerged as a risk factor in absence of cigarette smoking.

Prospective, randomized, crossover comparison of sublingual apomorphine (3 mg) with oral sildenafil (50 mg) for male erectile dysfunction.

PURPOSE: We established the efficacy and safety of sublingual apomorphine compared with oral sildenafil in comparable groups of patients with erectile dysfunction (ED). MATERIALS AND METHODS: This prospective, randomized, crossover study included 77 heterosexual men with ED of various etiologies and severities. A total of 62 men were randomized but only 34 were evaluable for efficacy and tolerability. The study started with a run-in period of 2 to 4 weeks. The first 4 weeks of treatment were followed by a washout period of 4 weeks, after which patients changed to the alternate treatment for an additional 4-week period. The sequence of the 2 treatments was established by a randomization list in blocks in closed packets. The primary efficacy end point was the percent of attempts resulting in erection firm enough for intercourse. Additional variables were the percent of attempts resulting in intercourse and improvement in ED, as evaluated by the erectile function domain score of the International Index of Erectile Function questionnaire. RESULTS: Sildenafil was significantly more effective than apomorphine in regard to the percent of attempts resulting in erection firm enough for intercourse (85% vs 44%, p <0.0001) and actually resulting in intercourse (81% vs 43%, p <0.0001) as well as erectile function evaluated by the erectile function domain score of the International Index of Erectile Function (p <0.001). The incidence of adverse events was not significantly different for the 2 drugs. Although the number of patients was small, this study had strong statistical power due to the striking difference in results. CONCLUSIONS: Sildenafil was significantly more effective than apomorphine for ED. No statistical difference in adverse events was noted.

Long-term outcome of antiandrogen monotherapy in advanced prostate carcinoma: 12-year results of a phase II study.

OBJECTIVE: To present the long-term outcome of patients with locally advanced or metastatic prostate carcinoma treated by first-line antiandrogen monotherapy. PATIENTS AND METHODS: From 1983 to 1990, 41 patients with advanced prostate carcinoma were treated with flutamide monotherapy until progression or the appearance of toxicity. Twenty-five patients (61%) had T3-T4N0M0 and 16 (39%) T2-4N0-3M1 prostate carcinoma. Consensus criteria were adopted to evaluate the response. Plasma testosterone and sexual function were recorded for the first 3 years. RESULTS: Flutamide was administered for up to 147 months; seven patients (17%) interrupted the treatment because of toxicity. There was an objective response in 17 (41%) patients; 20 (49%) had stable disease while four (10%) progressed. There were objective responses, lasting up to 150 months, in 82% of those with M0 and in 18% with M1 disease (P = 0.05). The median time to progression in patients with an objective response and stable disease was 45 and 16 months, respectively (P < 0.001). Thirty-one patients (76%) died from prostate cancer and 10 (24%) from unrelated diseases. The median survival was 67 and 36 months in patients with an objective response and stable disease, respectively (P < 0.001). There was an improvement in performance status in 85% and reduction in bone pain in 83% of the patients; sexual activity was maintained in 63%. CONCLUSION: Monotherapy with flutamide is well tolerated. Objective responses are more frequent in patients with locally advanced disease. Patients with an objective response within 6 months have a prolonged progression-free and overall survival.

Combination of intravesical chemotherapy and hyperthermia for the treatment of superficial bladder cancer: preliminary clinical experience.

The prevalence of superficial transitional cell carcinoma of the bladder (STCCB) is still increasing in spite of improved adjuvant chemotherapeutic and/or immunoprophylaxis approaches. Thus, there is certainly an urgent need to improve our ability to control this disease. Local hyperthermia has a therapeutical potential for the treatment of many solid tumors, especially when used in combination with other treatments, such as radiation and chemotherapy. In particular, a synergistic or, at least, supra-additive anti-tumor cell killing effect was documented when local hyperthermia was administered in combination with selected cytostatic drugs. Recently, advances in miniaturized technology have allowed the development of a system specifically designed for delivering an endovesical thermo-chemotherapy regimen in humans. In preliminary clinical experiences, insofar mainly carried out as mono-institutional investigations, the combined treatment using this system was demonstrated to be feasible, minimally invasive and safe when performed on out-patient basis. Moreover, the anti-tumoral efficacy seemed to be significantly enhanced when compared with that obtained using intravesical chemotherapy alone for both adjuvant (prophylaxis) and neo-adjuvant (ablative) approaches to superficial bladder cancer.

PSA and second-line therapy of hormone refractory prostate carcinoma.

The aim of the present study was to correlate PSA response with subjective response (bone pain and performance status), in patients treated for hormone refractory carcinoma of the prostate. Twenty-four patients were introduced into the study. Median PSA was 198 ng/ml. Symptom score, performance status and PSA were monitored monthly for 3 months and then 3-monthly. Sixteen patients (66%) showed a PSA response (median value 10 ng/ml). In 8 patients (33%) PSA was <4 ng/ml. Eight patients (33%) only had a subjective response. However, 75% of the patients with a PSA value <4 ng/ml had a subjective improvement. On the other hand, subjective response was 25% only in patients in whom PSA value decreased to <50% of the initial value but >4 ng/ml. In conclusion, PSA response is not always related to subjective improvement and does not always implicate a beneficial effect of the therapy for the patient.

An appraisal of telomerase activity in benign prostatic hyperplasia.

BACKGROUND: Prostate cancer is one of the commonest neoplasms in elderly males in developed countries. It is not clear which individuals are at high risk of developing aggressive adenocarcinoma of the prostate. Biomarkers are therefore urgently needed to identify such individuals. It had been suggested both by ourselves and others that prostatic telomerase activity may represent a valuable marker in this respect, particularly if applied to BPH, as tissue is readily available from both transurethral resection of prostates and transrectal ultrasound biopsy. METHODS: Tissue was collected prospectively from 46 patients with BPH who underwent TURP for clinically benign prostatic disease, and who were examined using the telomeric repeat amplification protocol (TRAP assay). RESULTS: Telomerase activity was not detected in any of 46 BPH samples, using TRAP assay conditions of 0.12, 1.2, and 12.0 microg protein. CONCLUSIONS: The study confirms that telomerase is not detectable in BPH samples. This would suggest that absence of telomerase activity may be a strong indicator of a lack of cancer. However further studies are necessary to confirm this.

Correlation between chronic prostatitis syndrome and pelvic venous disease: a survey of 2,554 urologic outpatients.

OBJECTIVES: In this study we evaluated the association between chronic prostatitis syndrome (CPS), varicocele and hemorrhoids as manifestations of a pelvic venous disease. METHODS: Our retrospective study was based upon 2,554 patients treated in two general urology clinics over the past 10 years. We have assessed the incidence of CPS among urological patients. RESULTS: We found 483 patients with CPS, representing 18.9% of the total number of visits at the outpatient clinic. In this group the percentage of varicocele and hemorrhoids was 14.69 and 8.48%, whereas in a control group these figures were 5.02 and 5.84%, respectively (p<0.001 and 0.1054). Such a difference is statistically significant and suggests a higher prevalence of varicocele in the CPS group, but this may be due to a methodological error of the retrospective study. CONCLUSION: Only a prospective study, which is of importance due to the frequency of the disease, can give a precise answer to this question.

[Conservative treatment of locally advanced bladder carcinoma: neoadjuvant chemotherapy, TUR and radiotherapy. Results in 40 patients]. / Trattamento conservativo del carcinoma vescicale localmente avanzato: chemioterapia neoadiuvante, TUR e radioterapia. Risultati su 40 pazienti.

PURPOSE: to assess the results of bladder preservation in infiltrating bladder cancer. The potential for neoadjuvant chemotherapy followed by extensive TUR and radiotherapy was investigated in 40 patients with T2-T4a G2-G3 bladder carcinoma. MATERIALS AND METHODS: from 1983 to 1995, 40 patients were submitted to bladder-sparing treatment consisting of neoadjuvant chemotherapy, extensive, TUR and radiotherapy. Most patients had T3G3 cancer. Cystectomy was not performed due to patient" choice in 29 cases (72.5%), for severe pulmonary or cardiovascular disease in disease in 9 patients (22.5) and age over 80 in 2 (5%) patients. A deep TUR-biopsy was performed before and after chemotherapy and an extensive TUR was repeated at the end of radiotherapy. In the first 30 patients chemotherapy consisted of 2-4 cycles of 70 mg/m2 cisplatin on fay 1, and 40 mg/m2 methotrexate on days 8 and 15. In the last 10 patients chemotherapy consisted of 3 cycles of CMV (100 mg/m2 cisplatin on day 2, 30 mg/m2 of vinblastine on days 1 and 8). Total dose of radiotherapy was 60-65 Gy. Recurrent superficial tumors were treated transurethrally. Radical cystectomy, when feasible, was considered for persistent or recurrent invasive disease. RESULTS: after chemotherapy, a clinical objective response was obtained in 27 patients (67.5%), 19 (47.5%) of whom showed a complete response. Thirteen (32.5%) patients showed no response and 5 (12.5%) progressed during chemotherapy. After extensive TUR of any residual mass and radiotherapy, a complete response was achieved in 6 patients who initially showed a partial response and in other 2 patients and stable disease after chemotherapy. Altogether, 27 patients (67.5%) presented had local recurrences, 3 patients underwent cystectomy. Fourteen patients (35%) are alive and 13 NED (65 months mean survival). Five patients died of unrelated disease. Twenty-one patients (52.5%) died of distant metastases (mean survival 28 months). Four patients presented distant metastases after vesical infiltrating recurrence and 4 patients had distant metastases in the absence of loco-regional recurrence. Twenty-two patients (55%) maintained an intact bladder. Patients with complete response to chemotherapy showed a low risk for developing recurrent infiltrating tumors and metastases. CONCLUSIONS: A complete tumor was maintained at 5 years in over 50% of the patients conservatively treated. Bladder salvage is feasible in selected patients.

The fate of patients with locally advanced bladder cancer treated conservatively with neoadjuvant chemotherapy, extensive transurethral resection and radiotherapy: 10-year experience.

PURPOSE: We assess the results of bladder preservation for infiltrating bladder cancer. The potential for neoadjuvant chemotherapy followed by extensive transurethral resection and radiotherapy was evaluated in 40 patients with T2-T4a G2-G3 bladder carcinoma. MATERIALS AND METHODS: From 1983 to 1995, 40 patients with bladder cancer underwent bladder sparing treatment, consisting of neoadjuvant chemotherapy, extensive transurethral resection and radiotherapy. Most patients had T3G3 cancer. A deep transurethral resection biopsy was performed before and after chemotherapy, and an extensive transurethral resection was repeated at the end of radiotherapy. Of the patients 30 received cisplatin and methotrexate and 10 also received vinblastine. Total dose of radiotherapy was 60 to 65 Gy. Recurrent superficial tumors were treated transurethrally. Radical cystectomy was considered for persistent or recurrent invasive disease. RESULTS: Complete response occurred in 19 patients (47.5%) after chemotherapy, and in 8 patients after transurethral resection and radiotherapy (67.5%). Within 10 years 8 responding patients (30%) had local recurrences and 3 underwent cystectomy. Of the patients 14 (35%) are alive, including 13 with no evidence of disease (mean survival 65 months), 5 died of unrelated disease and 21 (52.5%) died of distant metastases (mean survival 28 months). Of the 21 patients 14 had residual tumor after radiotherapy, 3 presented with distant metastases after vesical infiltrating recurrence and 4 had distant metastases in the absence of locoregional recurrence. In 22 patients (55%) the bladder was salvaged. Patients with complete response to chemotherapy had a low risk for recurrent infiltrating tumors and metastases. CONCLUSIONS: Complete tumor control was maintained at 5 years in more than 50% of the patients treated conservatively. Bladder salvage is feasible in select patients.

Local microwave hyperthermia and intravesical chemotherapy as bladder sparing treatment for select multifocal and unresectable superficial bladder tumors.

PURPOSE: The role of a combined regimen of local hyperthermia and topical chemotherapy in patients with multifocal and recurrent superficial bladder tumors not curable by transurethral resection was evaluated in a neoadjuvant organ sparing clinical study. MATERIALS AND METHODS: A total of 19 patients with multifocal, superficial grades 1 to 3 bladder tumors that recurred after intravesical chemoprophylaxis or immunoprophylaxis underwent local combined administration of microwave induced hyperthermia and intravesical chemotherapy as a debulking approach. Due to extensive superficial involvement of the bladder walls complete transurethral resection of all tumors seemed technically unfeasible in all cases and radical cystectomy was considered the treatment of choice. Endovesical hyperthermia at 42.5 to 46C was delivered using the SB-TS 101 system, based on a microwave transurethral applicator that irradiates the bladder filled with a circulating solution of mitomycin C. Patients underwent 8 weekly 1-hour sessions on an outpatient basis without anesthesia. When possible, after treatment patients underwent transurethral resection of residual tumors and all suspicious areas. RESULTS: After treatment transurethral resection appeared to be feasible and curative in 16 patients (84%). Histological study revealed complete and partial responses in 9 (47%) and 7 (37%) cases, respectively. Due to extensive residual tumors radical cystectomy was performed in 3 patients (16%). At a median 33-month followup 8 superficial transitional tumor recurrences were documented and easily eradicated by transurethral resection or laser therapy in patients in whom the bladder had been saved. CONCLUSIONS: Microwave induced hyperthermia combined with intravesical mitomycin C seems to be a feasible, safe and elective approach for conservative treatment of multifocal and recurrent superficial bladder tumors when other treatment strategies have failed.

Expression of different 17beta-hydroxysteroid dehydrogenase types and their activities in human prostate cancer cells.

The 17beta-hydroxysteroid dehydrogenase (17betaHSD) enzyme system governs important redox reactions at the C17 position of steroid hormones. Different 17betaHSD types (no. 1-4) have been identified to date in peripheral human tissues, such as placenta, testis, and breast. However, there is little information on their expression and activity in either normal or malignant prostate. In the present work, we have inspected pathways of 17beta-oxidation of either androgen or estrogen in human prostate cancer cells (LNCaP, DU145, and PC3) in relation to the expression of messenger RNAs (mRNAs) for 17betaHSD types 1-4. These cell systems feature distinct steroid receptor status and response to hormones. We report here that high expression levels of 17betaHSD4 were consistently observed in all three cell lines, whereas even greater amounts of 17betaHSD2 mRNA were detected solely in PC3 cells. Neither 17betaHSD1 nor 17betaHSD3 mRNAs could be detected in any cell line. From a metabolic standpoint, intact cell analysis showed a much lower extent of 17beta-oxidation of both androgen [testosterone (T)] and estrogen [estradiol (E2)] in LNCaP and DU145 cells compared to PC3 cells, where a greater precursor degradation and higher formation rates of oxidized derivatives (respectively, androstenedione and estrone) were observed. Using subcellular fractionation, we have been able to differentiate among 17betaHSD types 1-4 on the basis of their distinct substrate specificities and subcellular localization. This latter approach gave rise to equivalent results. PC3 cells, in fact, displayed a high level of microsomal activity with a low E2/T activity ratio and approximately equal apparent Km values for E2 and T, suggesting the presence of 17betaHSD2. Dehydrogenase specific activity with both E2 and T was also detected, although at lower levels, in LNCaP and DU145 cells. No evidence for reductase activity could be obtained in either the soluble or microsomal fraction of any cell line. As comparable expression levels of 17betaHSD4 were seen in the three cell lines, 17betaHSD2 is a likely candidate to account for the predominant oxidative activity in PC3 cells, whereas 17betaHSD4 may account for the lower extent of E2 oxidation seen in both LNCaP and DU145 cells. This is the first report on the expression of four different 17betaHSD types in human prostate cancer cells. It ought to be emphasized that for the first time, analysis of different 17betaHSD activities in either intact or fractionated cells harmonizes with the expression of relevant mRNAs species.

Adjuvant chemotherapy for superficial transitional cell bladder carcinoma: long-term results of a European Organization for Research and Treatment of Cancer randomized trial comparing doxorubicin, ethoglucid and transurethral resection alone.

PURPOSE: We compared the efficacy of transurethral resection alone or transurethral resection followed by bladder instillations of doxorubicin or ethoglucid for 1 year in patients with superficial bladder carcinoma, and followed them long term for the incidence of progression to muscle invasion. MATERIALS AND METHODS: A total of 443 patients with superficial transitional cell carcinoma of the bladder was randomized. After randomization of 206 patients the control arm was closed to patient entry based on the results of an interim analysis showing a significant difference in favor of those receiving adjuvant chemotherapy. RESULTS: Final analysis of treatment results for recurrence included 432 patients at a median followup of 3.4 years for time to first recurrence, 5 years for analysis of time to invasion (Category T2 disease or worse) and 10.7 years for duration of survival. Time to first recurrence was significantly prolonged by both drugs compared to transurethral resection alone (doxorubicin versus transurethral resection alone p < 0.001 and ethoglucid versus control p < 0.001). Recurrence rate per year was 0.30 for both adjuvant treatment arms and 0.68 for the resection only group. Progression to muscle invasion was rare (15.1% of cases) and not apparently different in the 3 treatment arms. Of the 423 patients death from any cause in 199 and from malignant disease in 59 was not correlated with treatment. However, there was a strong correlation between death from malignant disease, and T category and tumor grade. CONCLUSIONS: In regard to time to first recurrence and recurrence rate per year this study indicates that adjuvant chemotherapy with doxorubicin and ethoglucid using the indicated schedule is superior to transurethral resection alone. However, progression in stage or survival was not influenced by the treatment regimen.

Evaluation and follow-up of patients with N1-3 M0 or NXM1 prostate cancer in phase III trials.

OBJECTIVES: The aim of this discussion is to review the design and conduct of phase III trials in metastatic prostate cancer, to seek ways of improving their study design, accuracy, relevance to clinical practice, acceptability to patients, and ease of participation by clinicians. We also aim to try to set uniform definitions for the evaluation of the different endpoints used in clinical trials on metastasized prostate cancer. METHODS: The work was started by correspondence between the participants in the group for the year before the consensus meeting. Two comprehensive questionnaires were circulated and the answers were distributed to all the members of the group. The statements were finalized during the consensus meeting. RESULTS: There were some differing opinions concerning the methods of evaluation of endpoints for follow-up, such as time to tumor progression and time to treatment failure. After the consensus conference, there were no major disagreements within the group. CONCLUSIONS: The aim of phase III trials is to influence clinical management. To obtain a credible result they require a sound statistical basis with appropriate power and encompassing patients from small urologic practices as well as large or academic institutions. However, deviation from routine practice may affect the accrual rate, and the trial procedure should therefore be as similar as possible to routine management. Trials inevitably involve extra work and cost. Both should be kept to a minimum to encourage participation and hasten a timely conclusion. It is mandatory to create uniform ways of designing and evaluating clinical trials in prostate cancer.

A multicentre prospective study of prostatic volume in asymptomatic men in various continents.

Objective: To compare prostatic volumes in asymptomatic Asian men with similar controls in Europe. Patients and methods: Six centres (Beijing, Hong Kong, Jinan, Lisbon, Palermo and Stirling) independently selected asymptomatic men aged 55 y or more for assessment of prostatic volume using transrectal ultrasound (total=320 men) between 1992 and 1993. Results: Prostatic volumes in asymptomatic men were greater in Beijing than Hong Kong, Stirling and Palermo (P<0.05) and were smaller in Stirling than Beijing and Jinan (P<0.05). Conclusions: These results suggest that men from Stirling are less likely to have large prostates, but there is no evidence that men from any of the six cities are more likely to have small prostates. This small series may suggest that benign prostatic hyperplasia (BPH) is as common in China as in European cities. The differences may be due to some cities (Beijing, Jinan and Lisbon) having a greater proportion of high values, perhaps suggesting looser selection criteria. This may indicate an abandonment of traditional Asian foods with their presumptive beneficial effect in favour of a Western dietary style.

[The Urologic Cooperative Group of the EORTC. Structure, scope, research, results]. / Il gruppo cooperativo urologico dell'EORTC. Struttura, scopi, ricerche, risultati.

The European Organization for Research and Treatment of Cancer (EORTC) was founded in 1962. The first urological group was French-speaking and concentrated particularly on testicular tumours. Shortly after, an English-speaking group started its activities in Yorkshire, with main emphasis on prostate cancer, and a "bladder cancer group" attracted many urologists from Belgium and other European countries. In 1976 all these groups were fused into a one new urological group of which M. Pavone-Macaluso from Palermo, Italy, secretary of the French-speaking group, was chosen as secretary and then chairman of the unified group, whereas Ph. Smith from Leeds, UK, chairman of the English-speaking group, was elected as chairman and later as secretary of the new group. The two "founding fathers" celebrated the 10th and 20th anniversaries of the foundation of the group respectively in Leeds in 1986 and in Palermo in 1996. Later chairman were L. Denis, Belgium; F. Schröder, The Netherlands; D. Newling, UK; F. Debruyne, The Netherlands and R. Hall, UK. A. van der Meijden, The Netherlands, will take over in 1997. The present secretary is A.V. Bono from Varese, Italy. The present structure of the group consists of a variety of working parties (disease-orientated groups), with special interest in a given pathology (such as prostate cancer, superficial or advanced bladder cancer, etc.) and of other committees (chemotherapy, quality of life, quality control). All the activities are coordinated by a Data Centre in Brussels, that is responsible for the statistical support. In its 20 years of activity the group has made many contributions of significance which have coincided with a number of changes in the urological oncology and have obtained international recognition. The paper analyses in detail the most significant of the group's achievements in the various fields of urological oncology.

Genitourinary group phase II study of chemotherapy in stage T3-4 N0-X M0 transitional cell cancer of the bladder: prognostic factor analysis.

The aim of this study was to examine prognostic factors for survival of patients with invasive bladder cancer who had received neoadjuvant chemotherapy followed by further treatment. From 1986 to 1990, 149 eligible patients with T3-4 N0-X M0 bladder cancer were entered into a phase II trial of neoadjuvant chemotherapy, consisting of cisplatin and methotrexate. Patients received two or four courses of chemotherapy, depending on the absence or presence, respectively, of a major clinical response after two courses. 136 patients were evaluable for clinical response after two courses of chemotherapy, and 75 patients were evaluable for pathological response after two or four courses. A multivariate analysis, based on pretreatment variables and the post-treatment variables, clinical response and pathological response, showed that performance status, tumour size and clinical response after two courses of chemotherapy were the only independent prognostic factors for all eligible patients. A second multivariate analysis in the selected subgroup of patients, who underwent a cystectomy, showed that the G-cagetory and pathological response were the only independent prognostic factors. In conclusion, in this group of patients, the response to chemotherapy was a strong and independent prognostic factor in addition to other independent variables. However, it was not accurate or strong enough to allow an impact on the choice of locoregional therapy.