Elsevier

European Urology

Volume 53, Issue 3, March 2008, Pages 497-513
European Urology

Review – Testis Cancer
European Consensus Conference on Diagnosis and Treatment of Germ Cell Cancer: A Report of the Second Meeting of the European Germ Cell Cancer Consensus Group (EGCCCG): Part II

https://doi.org/10.1016/j.eururo.2007.12.025Get rights and content

Abstract

Objectives

The first consensus report that had been presented by the European Germ Cell Cancer Consensus Group (EGCCCG) in 2004 has found widespread approval by many colleagues throughout the world. In November 2006, the group met a second time under the auspices of the Department of Urology of the Amsterdam Medical Center, The Netherlands.

Methods

Medical oncologists, urologic surgeons, radiation oncologists as well as pathologists from several European countries reviewed and discussed the data that had emerged since the 2002 conference and incorporated the new data into updated and revised guidelines. As for the first meeting the methodology of evidence-based medicine (EBM) was applied. The results of the discussion were compiled by the writing committee. All participants have agreed to this final update.

Results

The second part of the consensus paper includes the treatment of metastasised disease, residual tumour resection, salvage therapy, follow-up, and late toxicities.

Conclusions

Whereas the vast majority of the recommendations made in 2004 remain valid 3 yr later, refinements in the treatment of early-stage as well as of advanced-stage testicular cancer have emerged from clinical trials. Despite technical improvements, expert clinical skills will continue to be one of the major determinants for the prognosis of patients with germ cell cancer. In addition, the particular needs of testicular cancer survivors have been acknowledged.

Section snippets

Treatment of patients with seminoma clinical stage (CS) IIA/B

Until now the standard treatment in CS IIA/B seminoma has been radiotherapy. Total doses in the range of 30–36 Gy seem reasonable. In CS IIA 30 Gy and in CS IIB 36 Gy, respectively, are administered homogeneously with single doses of 2 Gy at five fractions per week [1], [2], [3]. With modern radiation techniques this treatment results in a relapse-free survival at 6 yr of 95% for stage IIA and 89% for stage IIB [EBM IIB: 1]. Overall survival is close to 100% [1], [2], [3], [4]. The target volume

Treatment of patients with non-seminoma CS IIA/B

The cure rate for CS IIA and IIB non-seminoma is close to 98%. The vast majority of patients with marker elevations of α-fetoprotein (AFP), human chorionic gonadotropin (HCG), or lactic dehydrogenase (LDH) in CS IIA/B are treated according to the algorithms for patients with advanced disease, according to the International Germ Cell Cancer Consensus Group (IGCCCG) recommendations [19].

Only a few patients without marker elevations but with retroperitoneal lymph nodes 1–2 cm, suspected to have CS

Treatment of patients with advanced disease (Table 1)

For patients with a good prognosis, according to IGCCCG criteria [19], standard treatment is three cycles of BEP. In cases of contraindications against bleomycin four cycles of cisplatin and EP can be given [19], [44], [45], [46], [47], [48]. The efficacy of BEP, given for 5 d with EP 100 mg/m2 and cisplatin 20 mg/m2 each day, is equivalent to BEP with EP 165 mg/m2 applied during 3 d and cisplatin 50 mg/m2 during 2 d [EBM IB: 49]. However, BEP given over 3 d has increased long-term toxicity

Treatment of patients with brain metastases

Approximately 10% of all patients with advanced germ cell cancer present with brain metastases (ie, 1–2% of all patients with testicular cancer). At relapse, metastases in the CNS usually occur as part of a systemic relapse and rarely as an isolated sanctuary-site relapse after previously successful treatment. Patients who present with brain metastases at initial diagnosis have a long-term survival probability of 30–40%, whereas patients who develop metastases during first-line treatment or in

Monitoring of treatment results and further treatment

The prognostic value of a transient increase of tumour markers after initiation of first-line treatment as well as a delayed decrease of tumour markers according to their usual half-life is equivocal [EBM III: 71]. In patients with slow tumour marker decline and stable or regressing tumours, chemotherapy should be completed with three to four cycles, depending on the initial stage [19], [72], [73]. Patients with an unequivocal tumour marker increase during chemotherapy must be switched to

Seminoma

In patients with seminoma, residual masses present after chemotherapy and after radiotherapy should not necessarily be resected, irrespective of their size, but should be closely followed by imaging investigations and tumour marker determinations [78], [79], [80], [81], [82]. Fluorodeoxyglucose (FDG)-PET has a high prognostic value in patients with residual masses after treatment of seminoma. Patients with residual lesions of >3 cm in size that do not regress after therapy should undergo FDG-PET

Consolidation chemotherapy after secondary surgery

After resection of necrosis or teratoma no further treatment is required. When viable undifferentiated tumour is found, the role of further consolidation chemotherapy is uncertain. A retrospective analysis demonstrated an improved progression-free survival with adjuvant chemotherapy but failed to show an improvement in overall survival. Therefore, a wait-and-watch strategy may also be justified [EBM III: 107]. Patients in the good prognosis group, according to the IGCCCG classification, with

Salvage chemotherapy for relapsed or refractory disease

In patients who relapse or progress after first-line chemotherapy, the localisation and histology of the primary tumour, response to first-line treatment, duration of previous remissions as well as the levels of the tumour markers AFP and HCG at the time of relapse or progression are prognostic indicators [76], [71] (Table 2).

Salvage surgery

Residual masses after salvage chemotherapy should be resected within 4–6 wk after the normalisation of tumour markers or after a low-level marker plateau has been reached. The prognosis is markedly worse in patients after second- or third-line chemotherapy whose resected residual masses contain vital undifferentiated tumour. In these patients postoperative adjuvant chemotherapy does not improve survival and is therefore not indicated [96], [102].

Occasional patients with rising tumour markers

Late relapse

Late relapse is defined as any disease recurrence >2 yr after completion of first-line treatment. A pooled analysis of larger series published between 1989 and 2006 results in a crude incidence of 3.2% and 1.4% for patients with non-seminoma and seminoma, respectively [EBM III: 125]. Patients with late relapse after chemotherapy are particularly difficult to treat and should be managed differently from all other groups. If technically feasible, all patients with late relapse after chemotherapy

Follow-up and late toxicity

The aims of follow-up of patients with germ cell cancer are detection of relapse (including late relapse), diagnosis of second cancers as well as prevention, early diagnosis, and treatment of physical and psychological morbidity related to germ cell cancer or its therapy.

During the initial posttreatment phase follow-up consists of regular clinical examinations, monitoring of serum tumour markers, and imaging investigations. The frequency and type of examinations depend on the estimated risk of

Conflicts of interest

The authors have nothing to disclose.

Acknowledgements

This consensus document was made possible by the input of the participants of the 2006 consensus conference who discussed and prepared this update of the 2002 consensus meeting. All participants particularly wish to thank Dr. M. Pilar Laguna, Mrs. Sonja van Rees Vellinga, and Karin Plass for organizing the meeting.

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