P. H. Smith

Prognostic factors in superficial bladder tumors. A study of the European organization for research on treatment of cancer: Genitourinary tract cancer cooperative group

A randomized clinical trial was performed on 308 patients with stage T1 carcinoma of the bladder to compare the efficacy of transurethral resection alone or followed by bladder instillations of thiotepa or VM-26 (teniposide) for 1 year. With the recurrence rate as the primary end point of interest the data from this trial were used to assess the prognostic importance of the following factors at entry into the study: number of tumors, prior recurrence rate, tumor size, grade, age, treatment group assigned and, finally, the interval between transurethral resection at entry into the study and the start of intravesical treatment. Using multivariate statistical techniques we found that the number of tumors at presentation was the most important prognostic factor followed by, in order of importance, the recurrence rate at entry and the size of the largest tumor. Of particular note was the discovery that patients with less than 1 recurrence per year at entry had a prognosis similar to patients with primary tumors, while those with a higher recurrence rate did uniformly poorly. These results show that patients with stage T1 carcinoma of the bladder form a heterogeneous group and that more aggressive therapy should be considered for patients with a poor prognosis.

Adjuvant Chemotherapy of Superficial Transitional Cell Bladder Carcinoma:Preliminary Results of a European Organization for Research onTreatment of Cancer Randomized Trial Comparing Doxorubicin Hydrochloride, Ethoglucid and Transurethral Resection Alone

Patients with superficial transitional cell carcinoma of the bladder were entered in a randomized clinical trial to compare the efficacies of transurethral resection alone or followed by bladder instillation of doxorubicin hydrochloride or ethoglucid (Epodyl) for 1 year. Results showed that adjuvant chemotherapy with the selected drugs prolonged the mean interval between recurrences. Mild systemic toxicity and chemical cystitis were observed in 3 and 3 per cent, respectively, of the patients given ethoglucid, and in 5 and 4 per cent, respectively, of those taking doxorubicin.

A Comparison of the Effect of Diethylstilbestrol with Low Dose Estramustine Phosphate in the Treatment of Advanced Prostatic Cancer: Final Analysis of a Phase III Trial of the European Organization for Research on Treatment of Cancer

In a randomized phase III trial performed by the Urological Group of the European Organization for Research on Treatment of Cancer low dose estramustine phosphate (280 mg. twice daily for 8 weeks and 140 mg. twice daily thereafter) was compared to diethylstilbestrol (1 mg. 3 times daily) in patients with stages T3 to T4, M0 or M1 prostatic cancer. Of 248 patients entered 227 were evaluable for analysis: 115 received estramustine phosphate and 112 received diethylstilbestrol. The best response of the local tumor as assessed by palpation was seen in patients receiving diethylstilbestrol. There was no significant difference between treatments for response rate of metastases, interval to local progression, distant progression, over-all survival and death of carcinoma of the prostate. Duration of survival was correlated with the assessment of local response as determined by palpation. The response of distant lesions also was correlated closely with survival. Diethylstilbestrol (1 mg. 3 times daily) was associated with a significantly worse degree of cardiovascular toxicity than estramustine phosphate. This finding was especially obvious in patients who had no history of cardiovascular disease. Gastrointestinal toxicity occurred in 25 patients treated with estramustine phosphate, including 6 in whom cessation of treatment was necessary. Further studies are required to determine the optimum dose of diethylstilbestrol and estramustine phosphate, and to establish the best form of hormonal treatment for prostatic carcinoma.

Tryptophan Metabolites, Pyridoxine (Vitamin B(6)) and Their Influence on the Recurrence Rate of Superficial Bladder Cancer

This double-blind randomised phase III trial was designed to assess the effect of pyridoxine administration on the recurrence of Ta and T1 transitional cell tumours of the bladder. The trial accrued 291 patients and showed no significant difference between the pyridoxine and placebo treatment groups with respect to the time to first recurrence or the recurrence rate. Adjustment for the main prognostic factors, namely the recurrence rate prior to entry, the number of tumours at entry, the G grade and the levels of the tryptophan metabolites kynurenine plus acetyl kynurenine at entry do not change the overall conclusions.

A Phase II Study of Intravesical Mitomycin C in the Treatment of Superficial Bladder Cancer

Twenty-three patients with histologically proven superficial bladder cancer (Tis, Ta, T1) were treated with intravesical instillations of Mitomycin C at a dose of 20 mg in 20 ml of water 3 times weekly for 21 instillations. Seventeen patients (77%) showed complete disappearance of all known disease and a further 4 showed partial responses. In 8 patients toxic effects developed (thrombocytopaenia 1, chemical cystitis 2, skin rash 3, urinary tract infection 2). All resolved rapidly on stopping the treatment but were severe enough in 5 patients to prevent them from receiving a full course of treatment.

Orchidectomy versus Zoladex® plus Eulexin® in patients with metastatic prostate cancer (EORTC 30853)

A total of 327 patients with metastatic prostate cancer have been randomized to either orchidectomy or treatment with goserelin (Zoladez) 3.6 mg depot preparation combined with flutamide (Eulexin) 250 mg t.i.d. in a phase III study (EORTC 30853). A small but statistically significant difference in time to subjective and objective progression of disease was found in favour of the combination treatment. However, time from objective progression to death was longer in the group initially allocated to orchidectomy. Thus no difference was found in overall survival between the two treatment groups. The clinical significance of these differences requires further follow up and analysis.

Orchidectomy vs. Zoladex plus Flutamide in Patients with Metastatic Prostate Cancer

Treatment with bilateral orchidectomy was compared with Zoladex, 3.6 mg depot, plus flutamide, 250 mg t.i.d., in a randomized prospective study by the European Organization for Research and Treatment of Cancer (EORTC). Small but statistically significant differences in time to subjective and objective progression of disease were found in favor of Zoladex plus flutamide. However, time from objective progression to death was longer in the orchidectomy group. The clinical significance of these differences requires further follow-up and analysis. No difference was found in overall survival between the 2 treatment groups.

Testicular Cancer and Other Tumors of the Genitourinary Tract

G. Pizzocaro, A. Milani, and M. Pasi National Tuma Instituti Milan Italy Pre-treatment classification of tumors (clinical staging) primarily depends on the natural history of the disease, and should be a guide to the proper application of actual therapeutic modalities. Today there is a need to reclassify testicular tumors as follows: stage I (no evidence of metastases); small volume stage II (subdiaphragmatic lymph node metastases not larger than 5 cm); and advanced disease. Advanced disease can usually be subdivided into small volume advanced disease (lymph node metastases no larger than 5 cm and-or pulmonary metastases no larger than 2 cm and low levels of serum tumor markers) and bulky advanced disease (larger metastases, or AFP > 1,000 ng/ml and beta-HCG > 10,000 mUI/ml). The special circumstances in the subdivision of advanced disease are: persistent elevation of serum tumor markers only with no clinical evidence of metastases (occult disease); very bulky disease (lymph node metastases> 10 cm or lung metastases> 5 cm); or extrapulmonary metastases (liver, brain, bone, skin, etc.)

Adjuvant Therapy of T1 Bladder Carcinoma: Preliminary Results of an EORTC Randomized Study

This paper reports the preliminary results of an ongoing clinical trial in patients with category T1 bladder cancer who are randomized after transurethral resection to receive either thiotepa, VM-26, or no treatment. While there are no significant differences between the three treatment groups with respect to the time until first recurrence, thiotepa has significantly reduced the recurrence rate as compared to either VM-26 (P = 0.03) or no treatment (P = 0.04) among the 215 patients for whom follow-up information is currently available.

Clinical Bladder Cancer

Understanding the Disease.- Chairmans Summary.- Some Aspects of the Pathology of Bladder Cancer.- Urinary Cytology Today.- Bladder Tumor - Diagnosis.- Staging of Bladder Cancer.- Transurethral Ultrasonography - Bladder Cancer Staging and Other Clinical Application.- Therapeutic Approaches.- Chairmans Summary.- Dynamic Evaluation of Bladder Cancer.- Bladder Cancer - Surgery.- Radiation Therapy of Carcinoma of the Urinary Bladder.- Chemotherapy.- Chemotherapy for Urinary Bladder Cancer: Developments, Trends, and Future Perspectives.- Intravesical Chemotherapy for Superficial Bladder Tumors.- Progress in the Chemotherapeutic Treatment of Advanced Bladder Cancer.- Immunology.- Chairmans Summary.- Host Evaluation of Patients with Bladder Cancer.- Chemoimmune Prophylaxis of Superficial Bladder Cancer.- Prospective Studies.- Chairmans Summary.- Intravesical Chemoprophylaxis of Superficial Bladder Cancer.- Prospective Studies of the EORTC Urological Group.- The Philosophy of National Bladder Cancer Project Studies.- List of Contributors.