High-dose sequential chemotherapy (HDS) versus PEB chemotherapy as first-line treatment of patients with poor prognosis germ-cell tumors: mature results of an Italian randomized phase II study.

BACKGROUND: In the late 1990s, the use of high-dose chemotherapy (HDCT) and stem-cell rescue held promise for patients with advanced and poor prognosis germ-cell tumors (GCT). We started a randomized phase II trial to assess the efficacy of sequential HDCT compared with cisplatin, etoposide, and bleomycin (PEB). PATIENTS AND METHODS: Patients were randomly assigned to receive four cycles of PEB every 3 weeks or two cycles of PEB followed by a high-dose sequence (HDS) comprising HD-cyclophosphamide (7.0 g/m(2)), 2 courses of cisplatin and HD-etoposide (2.4 g/m(2)) with stem-cell support, and a single course of HD-carboplatin [area under the curve (AUC) 27 mg/ml × min] with autologous stem-cell transplant. Postchemotherapy surgery was planned on responding residual disease in both arms. The primary end point was progression-free survival (PFS). The study was designed to detect a 30% improvement of 5-year PFS (from 40% to 70%), with 80% power and two-sided α at 5%. RESULTS: From December 1996 to March 2007, 85 patients were randomized: 43 in PEB and 42 in HDS arm. Median follow-up was 114.2 months [interquartile range (IQR): 87.7-165.8]. Complete or partial response with normal markers (PRm-) were obtained in 28 (65.1%) and 29 (69.1%) patients, respectively. Five-year PFS was 55.8% [95% confidence interval (CI) 42.8-72.8] and 54.8% (95% CI 41.6%-72.1%) in PEB and HDS arm, respectively (log-rank test P = 0.726). Five-year overall survival was 62.8% (95% CI 49.9-79.0) and 59.3% (95% CI 46.1-76.3). One toxic death (PEB arm) was recorded. CONCLUSIONS: The study failed to meet the primary end point. Furthermore, survival estimates of conventional-dose chemotherapy higher than expected should be accounted for and will likely limit further improvements in the first-line setting. CLINICALTRIALS.GOV: NCT02161692.

Modified cisplatin, etoposide, and ifosfamide (PEI) salvage therapy for male germ cell tumors: long-term efficacy and safety outcomes.

BACKGROUND: Since 1985, we introduced a modified combination of etoposide, ifosfamide, and cisplatin (PEI) as second-line therapy of adult male germ cell tumors with the aim to reduce toxic effect while maintaining efficacy over the original regimen. PATIENTS AND METHODS: Patients received four cycles of ifosfamide at 2.5 g/m(2) on days 1-2, etoposide, and cisplatin at 100 and 33 mg/m(2), respectively, on days 3-5 every 21 days, followed by surgery. Results were stratified according to the International Germ Cell Consensus Classification Group-2 (IGCCCG-2). RESULTS: From February 1985 to January 2012, 189 patients were treated. 72.6% were IGCCCG-2 intermediate-to-very high risk. Thirty-five patients (18.5%) had a complete response, 67 (35.4%) a marker normalization (PRm-). Median follow-up was 122.1 months (inter-quartile range [IQR]: 71.4-232.0). Two-year progression-free and 5-year overall survival were 34.3% [95% confidence interval (CI) 28.1% to 41.9%] and 42.1% (95% CI 35.3% to 50.2%), respectively. Survival estimates compared favorably with those obtained by conventional dose chemotherapy (CDCT) regimens in each prognostic category. 70.4% of grade 3-4 neutropenia (25.5% febrile neutropenia), 48.1% thrombocytopenia, 21.2% anemia, 3.2% neurotoxic effect, and no severe renal toxic effect were recorded. CONCLUSION: Dose-modified Italian PEI should be considered as an appropriate benchmark for CDCT in the first salvage setting.

Interferon adjuvant to radical nephrectomy in Robson stages II and III renal cell carcinoma: a multicentric randomized study.

PURPOSE: Because interferon gave promising results in the management of metastatic renal cell carcinoma in the 1980s, a multicentric randomized controlled trial was planned to compare adjuvant recombinant interferon alfa-2b (rIFNalpha2b) with observation after radical nephrectomy in patients with Robson stages II and III renal cell carcinoma. Overall and event-free survival were to be evaluated together with prognostic factors. PATIENTS AND METHODS: Overall and event-free survival curves for 247 patients (124 controls and 123 treated) were estimated by the Kaplan-Meier method and compared using the log-rank test. Cox's multiple regression models were adopted to perform a joint analysis of treatment and prognostic factors. RESULTS: The 5-year overall and event-free survival probabilities were 0.665 and 0.671, respectively, for controls and 0.660 and 0.567, respectively, for the treated group; the differences were not statistically significant (2P = .861 for overall and 2P = .107 for event-free survival with the log-rank test). Regarding prognostic factors, only grade, pT, and pN demonstrated a significant prognostic role. First-order interactions of treatment with pT and pN category were investigated; a significant interaction was found between pN and treatment. A harmful effect of rIFNalpha2b in the 97 treated pN0 patients and a protective effect in the 13 treated pN2/pN3 patients were statistically significant. CONCLUSION: Adjuvant rIFNalpha2b is not indicated after radical nephrectomy for renal cell carcinoma. The protective effect in the small group of pN2/pN3 patients requires further investigation.

Orchiectomy alone in clinical stage I nonseminomatous testis cancer: a critical appraisal.

Sixty-two consecutive patients with clinical stage I nonseminomatous testicular cancer were entered into a prospective study to receive no treatment after orchiectomy until clinical evidence of recurrent disease. Of 59 evaluable cases, 41 (69.5%) remained continuously disease free for a median duration of 30 months (range, 18 to 46 months), and evidence of metastatic disease developed in 18 patients (30.5%) from 2 to 36 months after orchiectomy. The median disease-free interval for relapsing patients was 6 months. Retroperitoneal metastases developed in ten patients; seven patients had pulmonary metastases, and one patient had progressive elevation of the serum alpha-fetoprotein level. Relapses were significantly more frequent in patients with either embryonal carcinoma, infiltrating testicular cancer (pT greater than 1), peritumoral vascular invasion, or in those who underwent transscrotal biopsy. One patient with relapse refused salvage therapy and died. The remaining 17 patients have been rendered disease free with cisplatin combination chemotherapy and/or surgery. However, two patients showed further recurrence, with one in the lung and the other one also in the retroperitoneal nodes. In our opinion, surveillance following orchiectomy will provide useful information in clinical stage I nonseminomatous testicular cancer, but it is a difficult study. For the time being, it should be restricted to specialized centers only. In the meanwhile, retroperitoneal lymphadenectomy remains the standard treatment.

Viable malignant cells after primary chemotherapy for disseminated nonseminomatous germ cell tumors: prognostic factors and role of postsurgery chemotherapy--results from an international study group.

PURPOSE: To assess the value of postsurgery chemotherapy in patients with disseminated nonseminomatous germ-cell tumors (NSGCTs) and viable residual disease after first-line cisplatin-based chemotherapy. PATIENTS AND METHODS: The outcome of 238 patients was reviewed. Tumor markers had normalized in all patients before resection. A multivariate analysis of survival was performed on 146 patients. RESULTS: The 5-year progression-free survival (PFS) rate was 64% and the 5-year overall survival (OS) rate was 73%. Three factors were independently associated with both PFS and OS: complete resection (P <.001), < 10% of viable malignant cells (P =.001), and a good International Germ Cell Consensus Classification (IGCCC) group (P =.01). Patients were assigned to one of three risk groups: those with no risk factors (favorable group), those with one risk factor (intermediate group), and those with two or three risk factors (poor-risk group). The 5-year OS rate was 100%, 83%, and 51%, respectively (P <.001). The 5-year PFS rate was 69% (95% confidence interval [CI], 62% to 76%) and 52% (95% CI, 40% to 64%) in postoperative chemotherapy recipients and nonrecipients, respectively (P <.001). No significant difference was detected in 5-year OS rates. After adjustment on the three prognostic factors, postoperative chemotherapy was associated with a significantly better PFS (P <.001) but not with better OS. Patients in the favorable risk group had a 100% 5-year OS, with or without postoperative chemotherapy. Postoperative chemotherapy appeared beneficial in both PFS (P <.001) and OS (P =.02) in the intermediate-risk group but was not statistically beneficial in the poor-risk group. CONCLUSION: A complete resection may be more critical than recourse to postoperative chemotherapy in the setting of postchemotherapy viable malignant NSGCT. Immediate postoperative chemotherapy or surveillance alone with chemotherapy at relapse may be reasonable options depending on the completeness of resection, IGCCC group, and percent of viable cells. Validation is necessary.

Unusual malignant tumours in 49 patients with HIV infection.

Between December 1986 and December 1988, the Italian Cooperative Group on AIDS-Related Tumours documented 49 HIV-related tumours other than malignant lymphomas (ML) and Kaposi's sarcomas (KS), predominantly among HIV-infected intravenous drug abusers (IVDA). Of 12 germinal testicular tumours collected, six were seminomas, two of which were pure embryonal and the other four embryonal mixed. Cervical carcinoma was observed in nine IVDAs (intraepithelial in eight and advanced, with rapid progression, in one). Lung cancer associated with HIV infection was reported in eight patients, of whom four had an adenocarcinoma, two a small cell carcinoma, one an epidermoid carcinoma and one a mesothelioma. All patients with non-small-cell-lung cancer (SCLC) were at stage III, while those with SCLC and mesothelioma had limited disease. Five out of eight presented with limited disease at onset. The median age was low; lung cancer occurred predominantly in young adults, of whom all but one were smokers. Three patients could not be treated; four died while on treatment because of progression of the neoplasia and one died of an overdose. Acute lymphoblastic leukaemia (ALL) was diagnosed in five patients. The immunophenotype was always Burkitt-like (L3), and acute myeloblastic leukaemia (M2) was diagnosed in one. Of the central nervous system (CNS) tumours, two cases of glioblastoma and one of medulloblastoma were described. Two cases of young adults with multiple myeloma and two cases of colorectal carcinoma were also reported. One case of chronic lymphocytic leukaemia, one anorectal carcinoma, one oral carcinoma, one pancreatic carcinoma, one thymoma, one kidney carcinoma, one malignant melanoma and thyroid carcinoma were also found.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological markers in transurethral biopsies from bladder-cancer - preliminary-results.

A biologic profile including proliferative.activity, evaluated as H-3-thymidine labeling index (H-3-dT LI), DNA ploidy, p53 tumor-suppressor gene and P-glycoprotein (P-170), as an expression of the multidrug resistance gene, was defined for 50 primary transitional cell carcinomas of the bladder. H-3-dT LI was evaluated by autoradiography on histologic sections after incubation of fresh tumor biopsies with H-3-thymidine. Ploidy was defined by flow cytometric analysis of DNA content on nuclei suspensions obtained from frozen material. Expression of p53 protein and P-170 glycoprotein was detected by immunohistochemistry using the PAb1801 and C219 monoclonal antibody respectively, on sections from paraffin-embedded tumor biopsies. Invasive tumors showed a higher median H-3-dT LI (12.7% vs 4.2%) and a higher frequency of aneuploidy (73% vs 43%) and more frequently expressed p53 (82% vs 36%) than superficial tumors. Further analysis showed that proliferative activity was higher in invasive than in superficial cancers only in p53-positive or aneuploid tumors and not in p53-negative or diploid tumors. Moreover, proliferative activity and p53 overexpression, but not ploidy, were directly related to histologic grading and tumor stage. Generally, P-170 was not significantly related to any biologic or clinico-pathologic factor. Kinetic and phenotypic biologic markers are differently related to clinico-pathologic factors. A panel of biologic features can be easily evaluated on small transurethral biopsies at diagnosis, during endocavitary treatment or follow-up in bladder cancer patients.

High dose chemotherapy with carboplatin, VP 16 +/- ifosfamide in germ cell tumors: the Italian experience.

This schedule has shown an interesting activity with nearly 40% of the patients achieving CR. Moreover 4 patients experienced an inversion rate (CR with ABMT when they never achieved this status before). In terms of toxicity, this schedule seems feasible with 2/28 toxic deaths, which is in the lower part of the range of major solid tumors ABMT programs. But even if the rationale is proper, a better patients' selection is required. The CCR (continuous Complete Remission) rate is overimposable to other main studies previously published, but all our CCR were obtained in responding patients (Sensitive Relapses or unresectable PR). We may suggest that earlier transplantation is advisable when less tumor bulky is present and less clonal eterogeneity. The exact maximum tolerated dose of Carboplatin/VP 16/Ifosfamide programs has not yet clearly pointed out. The lack of major life-threatening episodes and neuro/nephrotoxicity may allow us to explore higher Carboplatin doses. Anyway the ultimate answer to the utility of ABMT trials must come from a randomized study in responding patients.

Intravesical electromotive administration of drugs for treatment of superficial bladder cancer: a comparative Phase II study.

OBJECTIVES: To evaluate the efficacy of electromotive administration (EMDA) of intravesical mitomycin-C (MMC) in patients with superficial bladder tumors and to evaluate the toxicity of the treatment. METHODS: Thirteen patients with multifocal Stages Ta-T1 and G1-G2 transitional cell carcinoma (TCC) of the bladder, primary or recurrent (group A), received MMC 40 mg (retained in the bladder for 2 hours) once a week for 8 weeks. Fifteen patients with the same characteristics (group B) were treated with EMDA/MMC at a current of 15 mA for 20 minutes once a week for 8 weeks. All lesions in the bladder except one (marker) were resected in each patient. RESULTS: In group A, 5 of 12 patients (41.6%) demonstrated complete macroscopic and histologic disappearance of the marker lesion (complete response [CR]). In group B, 6 of 15 patients (40%) had a similar CR. Recurrence rate in responders was 60% in group A versus 33% in group B after 7.6 and 6 months, respectively. Disease-free interval was 14.5 months in the EMDA/MMC group compared to 10.5 months in the MMC group. Side effects were few. CONCLUSIONS: In intermediate risk patients with TCC of the bladder, EMDA/MMC was not superior to MMC alone with a CR rate of 41% versus 41.6%. In responders, a lower recurrence rate and a longer disease-free interval were observed in the EMDA/MMC group.

Retroperitoneal lymphadenectomy in clinical stage I nonseminomatous germinal testis cancer.

Thirty-six consecutive patients underwent retroperitoneal lymphadenectomy for clinical stage I nonseminomatous germinal testis cancer from January 1980 to August 1981. Retroperitoneal lymphnode metastases were pathologically documented in 8 cases (22.2%). No patient received adjuvant therapy following surgery. The disease relapsed in 4 patients (11.1%) always in the lung, from 5 to 7 months after lymphadenectomy. The pulmonary disease was minimal in 3 cases and bulky (1 lung nodule greater than 2 cm) in 1 patient. All the relapsed patients entered continuous complete remission with cisplatin, vinblastine and bleomycin (plus surgery in one case). All the 36 patients in this series are alive and disease-free after a follow-up period of 40-60 months from lymphadenectomy. Antegrade ejaculation was lost by 10 out of 13 cases who had undergone the bilateral lymphadenectomy (77%) and by 2 of the 21 adult patients who had had the unilateral dissection (9.5%). Unilateral retroperitoneal lymphadenectomy is recommended in patients with negative intra-operative findings who undergo surgery for clinical stage I nonseminomatous testis cancer.

The importance of gonadothropin assays in the clinical follow up patients with germinal tumors of the testis.

Clinical-hormone studied were done on 34 patients with germinal tumors of the testis. The gonadotropin titres varied from normal to highly elevated values. Only in 4 cases (11.77%), however, were the gonadotropin titres above 10,000 mouse units/24 hours. These 4 were among the 9 cases (26.47%) with positive pregnancy tests. Gynaecomastia was present in 4 patients (11.77%). Total estrogens were assayed in these 4 cases and were found to be high. Gynaecomastia is attributed to excess estrogens. Elevated gonadotropin titres were found predominantly in cases of embryonal carcinoma, teratocarcinoma and choriocarcinoma, as well as in the most advanced clinical stages. As regards the correlation between gonadotropin titres and course of the tumor, it was found that the higher the titre the worse the prognosis. The results suggest that hormonal assays are of value in the clinical follow-up of testicular germinal tumors and should therefore be carried out in association with other clinical parameters.

[Description of 5 cases of rhabdomyosarcoma of the testis]. / Descrizione di 5 casi di rabdomiosarcoma del testicolo

The paper reports 5 cases of paratesticular rhabdomyosarcoma in patients of 10 to 18 years of age out of 438 cases of testicular tumours admitted to the Istituto Naxionale per lo Studio e la Cura dei Tumori in Milan (1.14%). Two cases were far advanced and died within a few months despite chemotherapy and radiotherapy. Only one of the three operated patients was cured and is still living 4 years after treatment. This patient had negative nodes and a full course of post-operative chemotherapy. The causes of failure in the other two cases are believed to be: not performing retroperitoneal lymphadenectomy in one and not giving post-operative chemotherapy in both. It is concluded that radical orchiectomy, retroperitoneal lymphadenectomy (followed by radiotherapy in N+ cases) and post-operative chemotherapy are the treatment of choice for operable paratesticular rhabdomyosarcoma.

[Evaluation of 178 mediastinoscopies (author's transl)]. / Valutazione di 178 mediastinoscopie

Of the 178 consecutive mediastinoscopies performed at the Istituto Nazionale per lo Studio e la Cura dei Tumori of Milan from 1967 to 1974 145 were performed for diagnostic purposes and 33 for the pre-operative evaluation of resectability in cases of proven lung carcinoma. Mediastinoscopy is a very useful procedure for obtaining a definite pathological diagnsis in indeterminate mediastinal and pulmonary lesions. In succases, mediastinoscopy should precede any attempt at therapy, as 1/3 primary mediastinal lymph node lesions are benign and about 30% of suspected mediastinal tumors or lymphomas are actually misdiagnosed lung cancers (mainly oat-cell carcinomas). As to the role of mediastinoscopy in the assessment of lung cancer resectability, the current view is that it plays a part together with tomography and bronchoscopy in the clinical staging of this neoplasm, but it is no longer relied upon alone. It is mandatory in every case of suspected or probable mediastinal invasion and the criteria for inoperability are the following: spread to high paratracheal or contralateral nodes, direct invasion of the mediastinal fat, fixity of the neoplasm to the trachea or vertebral bodies. In such cases mediastinoscopy will prevent a useless exploratory thoracotomy.

[Controlled pilot study with combination chemotherapy in testicular carcinomas (author's transl)]. / Studio pilota con due associazioni chemioterapiche nei carcinomi testicolari

In 24 previously untreated patients with advanced testicular carcinoma, the combination of adriamycin, vincristine and methotrexate (AVM) was tested in a prospective randomized study against a combination of non-cross resistant drugs including vinblastine, bleomycin and mithramycin (VBM). Complete and partial (greater than 50%) remission was observed in 4 out of 13 patients treated with AVM and in 3 out of 11 given VBM. In one patient receiving AVM and in two patients treated with VBM, the response at the level of previous inoperable retroperitoneal metastatic lymph nodes allowed a subsequent radical lymph node dissection. After cross-over a partial response for 6 months was obtained in only one patient treated with VBM while none was observed in 4 patients receiving AVM. Both combinations were well tolerated. However, their therapeutic activity seems to be definitely lower with respect to treatment with vinblastine followed by continuous infusion with bleomycin.

Vinblastine plus bleomycin continuous infusion chemotherapy of stage III testicular carcinomas.

Thirty-four consecutive patients with stage III testicular carcinomas were treated with vinblastine, 8 mg/m2 given in 2 fractions on day 1 and 2, followed by continuous intravenous administration of bleomycin, 15 mg/m2 in 1000 cc of 5% glucose and distilled water over a 24-hour period for 5 successive days beginning on day 2. This cycle was repeated every 28-35 days as toxicity permitted. Complete remission occurred in 18% and complete plus partial remission in 79%. Only 2 of 22 patients with advanced abdominal disease achieved a complete remission. After cytoreductive surgery the complete remission rate was increased to 39%. Median survival of complete responders at 3 years has not been reached, and it has been shown to be significantly superior to that of partial (p less than 0.01) and nonresponders (p less than 0.01). Toxic effects consisted mainly in severe leukopenia, stomatitis, adynamic ileum and osteoarticular pain. One drug-related death due to sepsis with agranulocytopenic fever was observed. Probably because of different patient selection, this report could not reproduce the results reported by Samuels et al. with equivalent drug dosage, but it was confirmed that this regimen is able to achieve a high overall response rate and a prolonged median survival in complete responders. The consistent success of this aggressive combination in inducing a high percentage of partial responses has opened the way for a better definition of the role of surgery for the treatment of advanced testicular carcinoma at out Institute.

Postsurgical policy in stage I testicular seminoma: cost and benefit of prophylactic irradiation in a long-term experience.

The definitive cure rate for clinical stage 1 testicular seminoma is very close to 100%, and prophylactic irradiation of the regional lymph nodes is associated with a low morbidity. Nevertheless, in recent years a "wait-and-see" policy has been proposed by some researchers. We analysed the cost/benefit ratio of radiotherapy (RT) by review of the case histories of 299 patients treated at the Department of Radiotherapy of the Istituto Nazionale per lo Studio e la Cura dei Tumori in Milan from January 1968 to December 1989. The 5-year overall survival was 99% (97.5% at 10 years), while the 10-year disease-free survival was 96%. The recurrence rate was 2.3%, but no patient relapsed in the irradiated areas. Acute toxicity was very moderate with only 4 (1.3%) serious radiation sequelae occurring 6 to 27 years after treatment. However, 9 second malignancies (3%) were observed. Lastly, we have calculated the costs for our National Health Service comparing surveillance policy and prophylactic irradiation.

Estrogen receptors and MPA treatment in metastatic renal carcinoma. A preliminary report.

Ten previously untreated patients with metastatic renal carcinoma underwent transperitoneal radical nephrectomy followed by high dosage MPA treatment. Estrogen receptors were determined in the specimen of all cases by the dextran-coated charcoal method: both the neoplastic tissue and the healthy parenchyma were tested. The disease progressed in 8 cases, and 2 patients are alive without any evidence of progressive disease 12 and 27 months after the operation. Very low receptor levels were detected in these 2 cases and one of them could be defined as borderline with our threshold criterion. However, receptors were undetectable in the neoplastic tissue from 4 of 8 patients who progressed. These questionable results justified the start of a prospective multicentric trial to study in a large number of cases both hormone receptors and clinical response to hormone therapy in human renal cancer.

Lobectomy with bronchoplastic procedures for lung cancer.

From April 1970 to October 1977, 19 patients with lung cancer of the upper lobar bronchus orifice underwent radical lobectomy with major bronchus resection. Sleeve lobectomy was accomplished in 11 cases and wedge lobectomy in the remaining 8. The length of the free bronchial margin in the surgical specimen was less than 1 cm in 3 cases, but limited pulmonary reserve did not allow pneumonectomy. Squamous carcinoma was diagnosed in 14 patients, adenocarcinoma in 2, oat-cell carcinoma in 2, and large cell carcinoma in one. Most cases (70%) were pathological stage I. There was one operative death due to anastomotic leakage (5%), and another patient required pneumonectomy completion. Of 13 patients with non oat-cell carcinoma and adequate bronchial resection, none had local recurrence: 3 patients developed distant metastases, and 10 are alive and disease-free after a follow-up period ranging from 16 to 104 months. The authors conclude that in selected lung cancer patients lobectomy with bronchoplastic procedures is superior to pneumonectomy for tissue sparing advantages.

Preoperative irradiation and surgery for esophageal cancer: causes of failure.

Twenty-seven patients with squamous esophageal cancer underwent small volume, low-dose, concentrated radiotherapy followed by esophageal resection whenever possible (esophagectomy for tumors of the thoracic esophagus and esophagogastrectomy for tumors of the lower esophagus). Curative resectability was 70% (19/27) with 4 operative deaths (21%). Recurrence rate was 66% after a mean period of 16 months, and the failure pathway was nodal in 53% of the cases. Historical comparison of the data suggests that preoperative irradiation increases the curative resectability rate without changing the early recurrence rate or failure pathway. Tumors with deeper invasion of the esophageal wall, which benefit by preoperative irradiation, are probably related to greater nodal diffusion, which is partly outside of the volume that may be resected or irradiated.

[Long-term results and planning of therapy of seminal tumors of the testis]. / Risultati a distanza e pianificazione terapeutica dei tumori seminali del testicolo

The paper retrospectively reviews the modalities and the long-term results of treatment of 200 consecutive patients with pure seminoma and of 125 patients with testicular carcinomas admitted to the Istituto Nazionale per lo Studio e la Cura dei Tumori of Milan from 1929 to Jan 1973. Radical orchiectomy with high ligation of the spermatic cord at the internal inguinal ring was performed in all previously untreated patients. Those who had had a scrotal operation performed elsewhere were radically reoperated upon. Lymphography and cobalt 60 telecurietherapy were introduced in 1960 and new treatment plans were employed for the irradiation of the deep lymphnodes. Since 1968 all operable carcinomas have undergone bilateral retroperitoneal lymphadenectomy and since 1964 all patients with advanced disease have been treated with chemotherapy (single agent or combination). Survival rates were calculated by the actuarial method. The new treatment modalities proved to be significantly superior to the old ones. In pure seminoma a 92% cure rate was obtained in NO patients after prophylactic irradiation of retroperitoneal nodes (2,500-3,000 rad in 3 weeks). In NI-3 patients the cure rate was as high as 75% after radical irradiation of retroperitoneal nodes (3,500-4,000 rad in 4 weeks) as well as prophylactic irradiation of mediastinum and both supraclavicular fossae. Extended radical radiotherapy (combined with chemotherapy in some patients) cured 2/6 N4 and 3/8 M1 patients. According to the old modalities of treatment, figures were respectively 72% in NO cases, 40% in N1-3 and 0% in N4 and M1 patients. In carcinomas, the cure rate after retroperitoneal lymphadenectomy was 91% in N--patients and 47% in N+ cases. In N+ patients post-operative radiation was also performed (4,000-5,000 rad in 5 weeks). After radiotherapy alone (without lymphadenectomy) the rates were 62% in NO and 28% in N1-2 patients. In primary inoperable patients (N3-4 and M1) chemotherapy, with or without radiation, significantly prolonged the survival rate. It is concluded that radiotherapy is the treatment of choice for pure seminoma and in N4 and M1 cases a full course of chemotherapy must be combined with extensive irradiation. Retroperitoneal lymphadenectomy is mandatory in all operable cases of testicular carcinoma while adjuvant chemotherapy may further improve the prognosis in N+ cases. For inoperable carcinomas chemotherapy (plus radiotherapy) is the treatment of choice. The new multiple drug regimens are providing encouraging results.