The management of testicular cancer in Victoria, 1988-1993. Urology Study Committee of the Victorian Co-operative Oncology Group.

OBJECTIVES: To evaluate the patterns of care and management of testicular cancer in Victoria. DESIGN AND SETTING: Retrospective analysis of all cases of testicular cancer in Victoria from 1988 to 1993 identified through the Victorian Cancer Registry. MAIN OUTCOME MEASURES: Description of patient characteristics, staging investigations, initial management, and outcome. RESULTS: 667 eligible cases of testicular cancer were identified and questionnaires were returned for 633 of these patients (94.9% response rate). There were 357 (56.4%) patients with pure seminoma; 271 (42.8%) with non-seminomatous germ cell tumours, 3 (0.5%) with stromal tumours, and 2 (0.3%) with other tumours. The median age was 32 years (range, 0-80 years). Preoperative marker levels were not available for 8% of patients, and initial staging was considered inadequate in 6%. Surveillance programs used for patients with Stage I disease were considered inadequate in most. Relative survival at five years was 99% for patients with seminoma and 91% for non-seminoma. CONCLUSIONS: There was considerable variation in the investigation, treatment, and follow-up of these patients, which is likely to have resulted in unnecessary morbidity. Clinical practice guidelines should be developed and implemented to promote optimal management.

Primary malignant mediastinal germ cell tumours: a literature review and a study of 18 cases.

From 1957 to 1992, 18 cases of primary mediastinal germ cell tumours were referred to the Peter MacCallum Cancer Institute (PMCI). Six were seminomas, six were mixed germ cell tumours, two were embryonal cell carcinomas, three were teratocarcinomas and one was labelled an 'anaplastic germ cell tumour'. Two of the 18 patients were female. For seminomas, surgical (and in one case chemotherapeutic) debulking, followed by radiotherapy produced the best results. Mediastinal doses ranged from 30 to 40 Gy. Local control was achieved in those patients receiving mediastinal radiotherapy. Four patients currently survive disease-free. The non-seminomatous germ cell tumours showed a significantly poorer survival, and only two of 12 patients remain alive in remission at 110 and 130 months after diagnosis. Survival has been updated as of November 1997. Attention is focused on the anterior position of the primary germ cell tumours in the mediastinum. A review of the literature up to and including 1997 is presented.

A phase II trial of cisplatin and interferon alpha 2b in patients with advanced bladder cancer.

Twenty-two patients with advanced transitional cell bladder cancer were treated in a phase II trial exploring the possible synergy of cisplatin and interferon alpha 2b. Of the 20 evaluable patients, 7 (35%) had a partial response to the treatment, and only 6 patients were able to complete the full planned six cycles of treatment. Response rates, duration of responses, and overall survival of our patients are not superior to those expected by cisplatin alone.

Has lymphography a role in early stage testicular germ cell tumours?

A retrospective study was performed of 183 newly diagnosed seminoma cases and 73 newly diagnosed non-seminomatous germ cell tumours (NSGCT) presenting from 1985 to 1989 to a tertiary referral cancer hospital. The purpose was to assess the contribution of bipedal lymphography (LG) to the management of these patients. As the main value of LG is in detecting small retroperitoneal lymph node (LN) metastases, analysis concentrated upon early stage disease, specifically N0 and N1a LN disease. Comparison between LG results, abdominopelvic computed tomography (APCT), final clinical stage and treatment outcome was performed. We found that with the LG and APCT criteria used (filling defects > 2 mm and LN diameter > 20 mm, respectively), LG was much more sensitive in disease detection. However, with modern techniques APCT can reliably detect disease 10 mm or greater. In addition, tumour marker status, primary tumour vascular invasion status and initial clinical examination were each more important in staging NSGCT disease than LG alone. Thus, LG is now rarely used in our institution but we will have to monitor our excellent survival data to confirm that this change in policy is warranted.

The importance of bleomycin in combination chemotherapy for good-prognosis germ cell carcinoma. Australasian Germ Cell Trial Group.

PURPOSE: In an effort to maintain the excellent long-term results achieved with combination chemotherapy for good-prognosis germ cell carcinoma, but to reduce the toxicities encountered, a randomized trial was conducted comparing cisplatin and vinblastine with or without bleomycin. PATIENTS AND METHODS: Two hundred eighteen assessable patients with a good prognosis were randomized to receive induction chemotherapy with cisplatin 100 mg/m2 intravenously (IV) day 1 and vinblastine 6 mg/m2 IV days 1 and 2 every 3 weeks (PV) with or without bleomycin 30 mg intramuscularly (IM) weekly (PVB) for a maximum of 12 weeks. Once maximum response was achieved, patients with a complete remission (CR) received two courses of consolidation chemotherapy, while those with residual abnormalities and normal tumor markers underwent surgical resection whenever possible. RESULTS: Toxicities encountered in this study were clearly greater for those patients who received bleomycin, with significantly more leukopenia, thrombocytopenia, anemia, alopecia, and renal and pulmonary toxicities. The proportion of patients who achieved CR and had no evidence of disease (resection of all viable malignancy) was 89% for PV and 94% for PVB (P = .29). After a minimum of 4 years of follow-up, relapses have occurred in 7% of patients who received PV and 5% who received PVB. A total of five patients on each therapy arm were successfully treated with further salvage chemotherapy and surgery. Thus, deaths from progressive malignancy have occurred in 15% of patients on PV and 5% on PVB (P = .02), a rate that was partly offset by the higher proportion of toxic deaths with PVB (P = .06). CONCLUSION: Despite the toxicities encountered with bleomycin in cisplatin-based combination chemotherapy for these patients, complete deletion of this drug compromises therapeutic efficacy.

Oral methotrexate for superficial transitional cell carcinoma of the bladder.

A total of 22 patients with superficial transitional cell carcinoma of the bladder, uncontrolled cystoscopically and unsuitable for or having failed intravesical therapy, received 50 mg. oral methotrexate per week for 12 months. Of the patients 7 (32%) achieved or remained in complete remission and 5 achieved a partial response, while 4 remained stable, 3 had progression and 3 were not evaluable. Patients who were still alive had a median followup of 2.5 years. Two patients with complete remission had relapse at 16 and 26.4 months, and 5 were disease-free at 34.5, 31.3, 18.6, 17.8 and 16.8 months, respectively. The methotrexate was generally well tolerated but 2 patients discontinued therapy because of dyspnea (1 subsequently died of respiratory failure that was possibly related to the methotrexate) and 1 because of persistent grade 2 mucositis. Grade 3/4 toxicities occurred in 3 patients: 1 each with reversible increases in creatinine and aspartate aminotransferase, and 1 with gastric bloating. There was little hematological toxicity. Reversible skin lesions developed in 4 patients. This oral treatment may provide an effective alternative to intravesical therapy but can be associated with severe toxicity.

Time trends in accuracy of classification of testicular tumours, with clinical and epidemiological implications.

Initial classifications of 1009 testicular tumours were reviewed as part of a population based survey of all testicular neoplasms in Victoria, Australia, between 1950 and 1978. All reviews were made by one of two pathologists at the Peter MacCallum Cancer Institute, using the system of the British Testicular Tumour Panel. Accuracy of diagnosis varied markedly over the time period and with pathological category. Seven cases were initially designated malignancies but were determined to be non-malignant conditions upon review. In each decade, review reduced the proportion of seminomas and increased the proportion of non-seminoma germ cell tumours (NSGCT) and non germ cell tumours. Reclassification resulted in changed age specific incidences of seminoma and NSGCT, most noticeably in 1950-59. Trends in age standardised incidence of seminoma and NSGCT were not affected by reclassification although the values were. The trend in age standardised incidence of non germ cell tumours was affected by reclassification. The implications of the changes in classification for epidemiological studies and clinical management are discussed.

Samarium-153-labelled EDTMP for bone metastases from cancer of the prostate.

A Phase I dose-escalation trial of a bone seeking phosphonate labelled with Samarium-153 was conducted on heavily pretreated patients with widespread bony metastases from cancer of the prostate. The bone marrow dose was calculated initially on a 4:1 uptake of cortical to cancellous bone, but subsequent information suggested the distribution was approximately equal so that the marrow received about three times the dose that has been prescribed. As a result, what were at first thought to be doses of 0.5 Gy, 1.0 Gy and 1.5 Gy were probably 1.5 Gy, 3.0 Gy and 4.5 Gy respectively. Three patients were treated at each dose level. The dose was repeated in the first three. Pain relief was delayed for 2 weeks, and was maximal by 4 weeks. All but one patient gained some benefit but this was transitory, lasting only 4-6 weeks in most. A recalculated dose of 3 Gy proved the most effective. The major toxicity was to platelets. Thrombocytopenia was fatal in four cases (two with repeat doses). All patients died but three survived more than 6 months with the help of third line hormonal measures and local radiotherapy to maintain comfort. A second group of five patients, not previously irradiated, were given 153Sm-EDTMP to a marrow dose of 3 Gy and all have survived for more than 4 months and achieved minimal to excellent relief of pain. The technique is recommended as initial therapy in unirradiated patients with good bone marrow function and with significant pain above and below the diaphragm, making half-body irradiation less likely to be a useful palliative procedure.

Trebling of the incidence of testicular cancer in victoria, Australia (1950-1985).

Changes in the incidence of testicular cancer in Victoria, Australia were studied from 1950 to 1985. Cases from the period 1950 to 1978 were derived from many sources (1116 cases). Emphasis was placed on diagnostic reliability; 97% of cases were confirmed histologically, and of these, 86% were reviewed at the Peter MacCallum Cancer Institute. For the years 1982 to 1985, Victorian Cancer Registry data were used. The incidence rose by a factor of 2.9 from 1.44 (95% confidence interval [CI], 1.15 to 1.73) per 100,000 in 1950 to 1954 to 4.16 (95% CI, 3.73 to 4.59) per 100,000 in 1982 to 1985. Between 1950 to 1954 and 1965 to 1969, there was a sharp rise, followed by a plateau or dip, then a further rise. Among seminomas, the rates rose in most adult age groups, whereas among nonseminomas, the rise was concentrated in younger age groups. There was a significant trend to earlier age of occurrence among nonseminomas (P = 0.0004) but not among seminomas (P = 0.89). Cohort analysis revealed a trend toward increasing rates for both seminomas and nonseminomas, and confirmed the trend toward earlier age of onset for nonseminomas. Disproportionate increases were observed for the 1915 to 1924 cohort of seminomas and the 1930 to 1939 cohort of nonseminomas. Analysis of available data from other Australian states indicated comparable rising incidence in New South Wales, Tasmania, and Western Australia.

Laterality, maldescent, trauma and other clinical factors in the epidemiology of testis cancer in Victoria, Australia.

Clinical factors were studied in a population based survey of 1,116 cases of testicular neoplasms in Victoria, Australia, between 1950 and 1978. The ratio of right to left sided tumours was 54:46, but the left side predominated among sarcomas (P = 0.006), and in older men. The relative risk (RR) for men with unilateral maldescent was 15 (CI 10-23) and for men with bilateral maldescent 33 (CI 20-55) (odds ratio 1.4, CI 0.5-4, P = 0.7). Calculations per testis in men with unilateral maldescent showed an elevated risk for both the maldescended testis (RR 28, CI 19-41, P less than 0.0001) and the normally descended testis (RR 3, CI 1.2-6, P = 0.04). The RR for men with abdominal maldescent was 55 (CI 36-83) compared to 7 (CI 4-11) for those with inguinal maldescent (odds ratio 8, CI 3-20, P less than 0.0001). Seminomas were more common than nonseminomas (NSGCT) in men with a history of maldescent (odds ratio 1.7, CI 1.1-3, P = 0.02) and also among corrected cryptorchids compared to uncorrected (P = 0.005). Seminomas were diagnosed at an earlier median age in men with corrected cryptorchid testes compared to uncorrected (P = 0.03) and in men with corrected cryptorchid testes compared to normally descended (P = 0.001). Maldescent was also associated with hernia (P = 0.04). Twenty-eight per cent of patients recorded a history of trauma with a higher proportion among NSGCT than among seminomas (P = 0.03). Prior malignancies were reported in nine patients, compared to 3.6 expected; prostate cancer (2) and malignant melanoma (2) were the greatest contributors to the excess.

Neo-adjuvant (pre-emptive) cisplatin therapy in invasive transitional cell carcinoma of the bladder.

Following 2 pilot studies which showed 57 and 61% response rates to intravenous cisplatin for transitional cell carcinoma of the bladder prior to definitive treatment, the West Midlands Urological Research Group (WMURG) and the Australian Bladder Cancer Study Group (ABCSG) independently began randomised trials to test the survival benefit of neo-adjuvant intravenous cisplatin prior to radiotherapy in T2-T4 M0 transitional cell carcinoma of the bladder. Both trials failed to recruit their target numbers of 250 patients in the West Midlands and 320 in Australia. Since they had similar treatment protocols and eligibility criteria, they were combined in an overview analysis, achieving a total number of 255 patients. Each treatment group was compared with its own control group and the differences were pooled to give an overall result. There was no difference in survival between treated and control patients. The odds ratio was 1.13 with the control groups faring marginally better than the chemotherapy groups. Even with 255 patients the 95% confidence interval of the odds ratio was wide (0.80-1.57). Although there is no clear evidence of a clinically worthwhile benefit from neo-adjuvant cisplatin, this approach must be tested in a larger study using combination treatments with greater activity in metastatic disease.

The management of invasive bladder cancer: a review of selected Australasian studies in radiotherapy, chemotherapy and cystectomy.

Since 1968, studies have been conducted in Australia and New Zealand to improve the results of treatment for invasive bladder cancer. The prognostic value of clinical stage and of ureteric obstruction has been confirmed. Radiotherapy has been established as appropriate treatment for the majority of patients with bladder cancer, most of whom are elderly and suffer from other health problems. There has been no additional benefit from radiosensitizers in increasing the effectiveness of radiotherapy such as hyperbaric oxygen or misonidazole, or from irradiation of the para-aortic nodes, all of which can result in additional toxicity without increasing tumour control. Pre-emptive chemotherapy with cisplatin has had no obvious impact on improving survival. Elective total cystectomy has shown the prognostic value of tumour downstaging by pre-operative pelvic radiotherapy. Although younger patients are usually selected for total cystectomy and urinary diversion, there is no evidence that, stage for stage, elective total cystectomy confers a survival advantage compared with radical pelvic radiotherapy.