Improved prognosis of patients with intermediate- and poor-risk nonseminomatous germ cell tumours by optimizing combined treatment.

OBJECTIVE: To assess whether the optimal use of combined treatment with chemotherapy and appropriately timed surgical intervention by a specialized team might improve the outcome for patients with poor- and intermediate-prognosis (International Germ Cell Consensus Classification, IGCCC) nonseminomatous germ cell tumours (NSGCTs). PATIENTS AND METHODS: Between 1984 and 1998, 47 patients with intermediate (16) and poor prognosis (31) NSGCT were treated; 43 had a testicular and four a retroperitoneal primary. RESULTS: Of the 47 patients only seven (15%) had a complete radiological response after primary chemotherapy; 36 (77%) required surgery after chemotherapy (29 para-aortic lymphadenectomy, 13 resection of pulmonary metastases, two each excision of supraclavicular and retrocrural lymph nodes and one resection of brain metastases; 13 required surgery at more than one site). There was no surgical mortality, with postoperative wound pain the commonest morbidity. On pathology, the resected masses were mature teratoma in 13, necrosis in 12 and malignant disease in 11 patients, the resection being complete in 30. There were microscopically positive margins in the other six patients, all but one having viable residual cancer. Of the 47 patients, 18 needed treatment for relapse, with four having surgery for growing mature teratoma, six chemotherapy plus surgery and eight salvage chemotherapy alone. Of 31 patients, 22 (71%) with a poor and 13 of 16 with an intermediate prognosis were alive at a median (range) follow-up of 94 (41-171) months; of all 47, 34 (72%) remain in complete remission. Ten patients died from disease progression. The presence of residual malignant disease at the resection margin was significantly associated with poorer survival (hazard ratio 7.21, P = 0.0016). Prognostic factors, e.g. number of involved sites, IGCCC group and viable tumour in resected masses, were not significant. The 5-year overall and relapse-free survival (95% confidence interval) was 81 (69-93)% and 57 (43-71)%, respectively. CONCLUSION: The optimal delivery and timing of chemotherapy and surgical resection by a specialist team of oncologists, urological and cardiothoracic surgeons is critical in treating poor-risk NSGCT and might be responsible for improving the outcome of these patients. The detection of residual malignant disease after chemotherapy by positron emission tomography should be investigated to identify those who might benefit from further systemic treatment before complete surgical resection.

Bilateral testicular cancer: a preventable problem? Experience from a large cancer centre.

OBJECTIVE: To report a retrospective review of patients with a testicular germ cell tumour treated in a large cancer centre who developed a second tumour, as 1.8-5% of such patients will subsequently develop a new primary tumour in the contralateral testis. PATIENTS AND METHODS: From a database of 570 men treated for testicular cancer in the West of Scotland between 1989 and 1998, all those who developed bilateral testicular tumours were identified. RESULTS: Nineteen men (3.3%) developed a second primary testicular malignancy; the mean age at diagnosis of the first tumour was 29.5 years, with the mean (range) interval to diagnosis of the second tumour of 76 (11-181) months (except for one man with synchronous tumours). The first tumour was teratoma in 11 and seminoma in seven; one patient had synchronous bilateral teratoma. The second primary was teratoma in 10 and seminoma in eight. Known risk factors for carcinoma in situ were present in nine patients, i.e. a small atrophic contralateral testis in five, a family history of testicular cancer in two, a history of infertility in two and unilateral undescended testis in one. Two patients had had contralateral testicular biopsies at the first diagnosis; both were negative for intratubular germ cell neoplasia (IGCN). Eight patients had chemotherapy to treat the first tumour and 14 for the second. All underwent bilateral orchidectomy. Overall, 18 of 19 men are alive and disease-free, with a median follow-up of 51 months. Pathology for 12 of the second testicular tumours was available for review; there was no IGCN in any of the slides from three patients, it was only present focally around the tumour in seven, and was diffuse in two patients. CONCLUSIONS: Chemotherapy for the first testicular tumour does not eliminate the risk of developing a contralateral tumour. Despite careful follow-up, in most patients the second primary tumour was not diagnosed early enough to avoid chemotherapy. The focal nature of IGCN in the second testis in most patients questions the value of biopsy of the contralateral testis. Improved methods of detecting patients at risk of second testicular tumours are needed.