title: Improved prognosis of patients with intermediate- and poor-risk nonseminomatous germ cell tumours by optimizing combined treatment.
abstract: 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).
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: CRC Department of Medical Oncology, Western Infirmary, Glasgow, Scotland, UK. avassou@otenet.gr
authors.forename: G
authors.initials: G
authors.lastname: Pentheroudakis
authors.forename: J S
authors.initials: JS
authors.lastname: De Bono
authors.forename: S B
authors.initials: SB
authors.lastname: Kaye
authors.forename: A
authors.initials: A
authors.lastname: Simpson
authors.forename: J
authors.initials: J
authors.lastname: Paul
authors.forename: I
authors.initials: I
authors.lastname: Brown
authors.forename: B
authors.initials: B
authors.lastname: Pamenter
authors.forename: A
authors.initials: A
authors.lastname: Kirk
authors.forename: P
authors.initials: P
authors.lastname: Vasey
authors.forename: N
authors.initials: N
authors.lastname: Raby
authors.forename: D
authors.initials: D
authors.lastname: Kirk
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage; D005500:Follow-Up Studies; D018237:Germinoma / Q000188:drug therapy* / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012186:Retroperitoneal Neoplasms / Q000188:drug therapy* / Q000601:surgery; D012189:Retrospective Studies; D012307:Risk Factors; D016879:Salvage Therapy; D016019:Survival Analysis; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000601:surgery
chemical_list: D001761:Bleomycin; D005047:Etoposide; D002945:Cisplatin