[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.

Current views on intravesical treatment and chemoprophylaxis of superficial bladder cancer. The present role of epirubicin and doxorubicin.

Since 1972, a large number of studies have shown that intravesical treatment with doxorubicin (adriamycin) is effective against carcinoma in situ and multiple papillary tumors. Furthermore, it significantly reduces the recurrence rate after transurethral resection. Its efficacy has been compared with that of Bacillus Calmette-Guerin (BCG), which is the only treatment accepted by the US Food and Drug Administration for therapy of carcinoma in situ (Tis). In more recent years, a few studies have been performed using intravesical epirubicin in the hope that different properties of the molecule might enhance the activity of the anthracyclines, but produce fewer and milder side-effects. After weekly instillations of epirubicin (50 mg in 50 ml of sterile water) a complete response is achieved in 47% of patients with a histologically proven papillary marker lesion. The prophylactic efficacy of even a single instillation of epirubicin within 6 hours after transurethral resection (TUR) was proved in a randomized study (30863) of the EORTC (European Organization for Research on Therapy of Cancer) Urological Group. A randomized Italian trial (Blinst 4) of chemoprophylaxis after TUR investigated the efficacy of different intravesical administration schedules of epirubicin (50 mg in 50 ml of sterile water). All treatment regimens were more effective than no treatment. The sequential intravesical combination of epirubicin and interferon-alpha-2b has shown, in our personal experience, encouraging clinical results and our laboratory data suggest the synergic activation of the local immune response.

Monocytoid B-cell lymphoma of the prostate.

A case of a primary malignant non-Hodgkin's lymphoma of the prostate, with the histological and immunohistochemical features of monocytoid B-cell lymphoma, is presented. The tumor histology was identical to that described in the forms of node-based monocytoid B-cell lymphoma being composed of a dense, monomorphous lymphoid infiltrate with ovoid nuclei and rather abundant, pale cytoplasm. Phenotypic analysis revealed high expression of B markers 4KB5 and L26, and negativity for T-associated antigens. This unusual localization broadens the spectrum of extra-nodal sites of monocytoid B-cell lymphoma.

The role of epipodophyllotoxin derivatives in bladder cancer.

Past and present experiences with podophyllin derivatives in bladder cancer are described. A preliminary study of teniposide was conducted in 1975 at the Institute of Urology, University of Palermo, in patients with advanced or superficial bladder cancer. In 18 patients with advanced bladder cancer, teniposide was administered intravenously (IV), followed in seven patients by peptichemio or doxorubicin. One complete response (CR) and four partial responses (PRs) were achieved. In 24 patients with superficial tumors, teniposide at a dose of 50 mg dissolved in 30 mL normal saline was administered intravesically as ablative therapy or as prophylaxis following transurethral resection (TUR). Of 12 patients in the ablative therapy group, two CRs and two PRs were achieved. Only 2 patients of 12 in the prophylaxis group relapsed within 6 months. In five cases, teniposide was administered in combination with peptichemio. In recent years, the Urological Group of the European Organization for the Research and Treatment of Cancer (EORTC) has performed a phase II study in which teniposide was used in combination with cisplatin given IV in the treatment of advanced bladder cancer. The EORTC group has also performed a randomized study to compare intravesical teniposide versus thiotepa versus no treatment other than initial resection. A brief report on both studies is given. In December 1987, a study was initiated to evaluate intravesical etoposide use in the prophylaxis of recurrences of superficial transitional cell carcinoma of the bladder. Intravesical etoposide (200 mg dissolved in 50 mL saline solution) was administered at weekly intervals for the first month after TUR and then monthly for 11 months. Of 38 evaluable patients, 20 had recurrences at a mean follow-up of 14 months. No systemic toxicity was noted.

Treatment of bladder cancer with intravesical instillation of adriamycin.

Intravesical treatment with adriamycin has been extensively employed in the last decade. In the treatment of carcinoma in situ complete responses have been reported in about 60% of cases. Its efficacy is probably lower in the therapy of multiple or diffuse low stage transitional cell carcinoma that is too extensive to be completely resected by conventional transurethral surgery. In such circumstances, including cancer in situ, adriamycin compares favorably with other local forms of treatment. The prophylactic use of intravesical instillation of Adriamycin has been studied more extensively. Preliminary results of controlled randomized trials implemented from the EORTC Urological Group show that adriamycin instillations significantly reduce recurrence rate after TUR. The treatment is well tolerated. Systemic absorption is virtually absent, and no severe drug-related side effects have ever been reported. Chemical cystitis is occasionally observed, especially if multiple instillations are started immediately after TUR, or in the presence of additional inflammatory conditions, such as previous irradiation or bacterial cystitis.

Cooperative studies of chemoprophylaxis after transurethral resection of bladder tumors.

Large cooperative trials are more likely than series studied by small groups to bring about significant progress in the field of intravesical adjuvant chemotherapy of superficial bladder tumor. Multicenter randomized trials involving large numbers of patients have been conducted in Europe by the EORTC Urological Group. The Group's main objectives were to compare the efficacy of thio-TEPA, VM-26, epodyl, Adriamycin, and cisplatin, against no treatment, and to study the prophylactic effect of oral pyridoxine and evaluate the main prognostic factors. The results obtained so far are reported. Preliminary information is also given about the Blinst study, a multicenter open investigation of local chemotherapy with doxorubicin (Adriamycin), with special reference to evaluation of the importance of different modalities of treatment with a single drug.

Local chemotherapy in bladder cancer treatment.

Intravesical chemotherapy can be employed either in a therapeutic aim or as an adjuvant prophylactic treatment after TUR. In this paper a discussion is presented about various controversial points that need to be clarified with regard to topical chemotherapy, with special reference to the selection of the drug and to various modalities of treatment. Some results are presented from the literature and from the author's personal experience, with emphasis on the randomized clinical trials performed by EORTC and by other workers or groups.