Original article
European consensus on diagnosis and treatment of germ cell
cancer: a report of the European Germ Cell Cancer
Consensus Group (EGCCCG)
H. J. Schmoll1*, R. Souchon, S. Krege, P. Albers, J. Beyer, C. Kollmannsberger, S. D. Fossa,
N. E. Skakkebaek, R. de Wit, K. Fizazi, J. P. Droz, G. Pizzocaro, G. Daugaard, P. H. M. de Mulder,
A. Horwich, T. Oliver, R. Huddart, G. Rosti, L. Paz Ares, O. Pont, J. T. Hartmann, N. Aass,
F. Algaba, M. Bamberg, I. Bodrogi, C. Bokemeyer, J. Classen, S. Clemm, S. Culine, M. de Wit,
H. G. Derigs, K. P. Dieckmann, M. Flasshove, X. Garcia del Muro, A. Gerl, J. R. Germa-Lluch,
M. Hartmann, A. Heidenreich, W. Hoeltl, J. Joffe, W. Jones, G. Kaiser, O. Klepp, S. Kliesch,
L. Kisbenedek, K. U. Koehrmann, M. Kuczyk, M. P. Laguna, O. Leiva, V. Loy, M. D. Mason,
G. M. Mead, R. P. Mueller, N. Nicolai, G. O. N. Oosterhof, T. Pottek, O. Rick, H. Schmidberger,
F. Sedlmayer, W. Siegert, U. Studer, S. Tjulandin, H. von der Maase, P. Walz, S. Weinknecht,
L. Weissbach, E. Winter & C. Wittekind
1Martin-Luther-University, Department of Hematology/Oncology, Halle, Germany
Received 26 September 2003; revised 2 March 2004; accepted 2 March 2004
Germ cell tumour is the most frequent malignant tumour type in young men with a 100% rise in the
incidence every 20 years. Despite this, the high sensitivity of germ cell tumours to platinum-based
chemotherapy, together with radiation and surgical measures, leads to the high cure rate of >_99% in
early stages and 90%, 75-80% and 50% in advanced disease with ‘good’, ‘intermediate’ and ‘poor’
prognostic criteria (IGCCCG classification), respectively. The high cure rate in patients with limited
metastatic disease allows the reduction of overall treatment load, and therefore less acute and long-
term toxicity, e.g. organ sparing surgery for specific cases, reduced dose and treatment volume of
irradiation or substitution of node dissection by surveillance or adjuvant chemotherapy according to
the presence or absence of vascular invasion. Thus, different treatment options according to prognos-
tic factors including histology, stage and patient factors and possibilities of the treating centre as well
may be used to define the treatment strategy which is definitively chosen for an individual patient.
However, this strategy of reduction of treatment load as well as the treatment itself require very high
expertise of the treating physician with careful management and follow-up and thorough cooperation
by the patient as well to maintain the high rate for cure. Treatment decisions must be based on the
available evidence which has been the basis for this consensus guideline delivering a clear proposal
for diagnostic and treatment measures in each stage of gonadal and extragonadal germ cell tumour
and individual clinical situations. Since this guideline is based on the highest evidence level available
today, a deviation from these proposals should be a rare and justified exception.
Key words: consensus on diagnosis and treatment, germ cell tumour, testicular cancer
Introduction
During the past two decades germ cell cancer has become the
‘model’ of a curable neoplasm. The major factor for the high
cure rate is the high level of sensitivity of germ cell cancer to
a variety of chemotherapeutic agents, in particular to cisplati-
num. Further aspects have also been important for the develop-
ment of the current treatment standards of germ cell cancer, in
particular, well-designed and well-conducted prospective ran-
domised trials highlighting clinically relevant questions in sur-
gical, radiotherapeutic and chemotherapeutic management of
germ cell cancer, as well as the integration of interdisciplinary
management into the treatment and clinical research of these
patients. Therefore, a large body of evidence from clinical
trials exists that allows physicians and patients to choose
*Correspondence to: European Germ Cell Cancer Consensus Group
(EGCCCG), c/o Prof. Hans-Joachim Schmoll, Martin-Luther-University,
Department of Hematology/Oncology, Ernst-Grube-Str. 40,
06120 Halle, Germany. Tel: +49-345-5572924;
E-mail: hans-joachim.schmoll@medizin.uni-halle.de
Annals of Oncology 15: 1377–1399, 2004
doi:10.1093/annonc/mdh301
q 2004 European Society for Medical Oncology

between different treatments which offer the best curative
option with the least amount of toxicity. However, due to the
multitude of available treatment options, decision making
regarding the optimal management of a patient has become
more complicated. This applies in particular to patients with
early stage disease who are often cured with minimal interven-
tion and who are at risk of being overtreated. Likewise,
patients with advanced, relapsed or refractory disease are diffi-
cult to treat and may not always receive optimal medical care.
Germ cell cancer is a rare disease that needs expert treat-
ment. Clear evidence has emerged that, in particular, patients
with advanced germ cell cancer benefit from the expertise of
their managing physician with improved survival [EBM III: 1].
{Evidence-based medicine (EBM): definitions of the levels and
characteristics of evidence originate from the US Agency for
Health Care Policy and Research [2]. Evidence of the state-
ments given in this paper are based on the criteria listed in
Table 1.} This expertise is dependent on the experience of the
physician which is probably best indicated by the number of
patients treated in the department [EBM III: 1]. A large patient
volume resulting in competence and experience even with rare
clinical scenarios is crucial and most patients being referred to
national reference centres with special experience in the field
of germ cell cancer benefit from the expertise. However, of
equal importance is that clear, comprehensive and up-to-date
consensus guidelines are available which represent the current
‘state of the art’ in diagnosis and treatment of germ cell cancer.
Therefore the European Germ Cell Cancer Consensus Group
(EGCCCG) has developed the following guidelines which iden-
tify the current standards in diagnosis and treatment of germ
cell cancer based on the available evidence published so far.
Patients and methods
On 22–23 November 2002, the European Consensus Conference on the
Diagnosis and Treatment of Germ Cell Cancer was organised by the
German Testicular Cancer Study Group (GTCSG) in Essen, Germany.
Medical, radiation and urological oncologists, as well as pathologists,
from several European countries were invited. The selection was based on
major scientific contributions in the field of diagnosis and treatment of
germ cell cancer. The purpose of this meeting was to define current ‘state
of the art’ treatment using the methodology of evidence-based medicine
(EBM) (Table 1) [2, 3]. In the 2 years prior to this meeting, members of
the GTCSG had reviewed the available literature according to EBM stan-
dards and published national German guidelines on the diagnosis and
treatment of germ cell cancer [4, 5]. These guidelines were sent to all the
invited participants prior to the conference and served, together with two
other EBM-based guidelines from other European countries [6, 7], as a
basis for the discussion. The resulting text was edited by the writing com-
mittee, reviewed and discussed by all participants. All listed participants
of the EGCCCG have agreed to this final consensus paper.
Diagnosis and staging
Clinical presentation of germ cell cancer
The majority of patients present with primary tumour in the
testis. Delay in diagnosing germ cell cancer may be caused
either by patients who may ignore symptoms too long or by
physicians who fail to define the correct diagnosis, e.g. mis-
classify a testicular mass as epididymitis [EBM III: 8] or back
pain as resulting from vertebral disc problems. Therefore, a
high level of suspicion should be maintained in young men
with any of these clinical features. In a minority of patients
the primary tumour manifestation is located extragonadally,
i.e. in the retroperitoneum or in the mediastinum. About
one-third of these patients will harbour intratubular germ cell
neoplasia (TIN) (synonym: carcinoma in situ, CIS). In another
third, ultrasonography of the testes reveals scar tissue indicat-
ing a ‘burned out’ testicular tumour which also has to be
removed. Therefore, only one-third of these patients have defi-
nitively a primary extragonadal germ cell tumour [EBM III: 9].
In all young men with retroperitoneal, supraclavicular or med-
iastinal mass, an underlying germ cell cancer should always
be considered [EBM III: 8–11].
The diagnosis is supported by elevated a-fetoprotein (AFP)
or b-human gonadotropin (b-HCG). In case of normal tumour
markers and suspicious testicles, the diagnosis of germ cell
cancer must be confirmed by tumour biopsy before treatment is
initiated. A histology of poorly or undifferentiated carcinoma
or poorly differentiated adenocarcinoma is highly suggestive of
the presence of germ-cell tumours. Such histologies should
undergo immunohistological evaluation, including germ cell
tumour specific markers and, if possible, the expression of iso-
chrome i(12p) which is specific for this tumour entity.
Diagnostic work up for a primary testicular tumour
When assessing the patient’s history the following risk factors
for the development of testicular tumours should be addressed:
contralateral testicular tumour [EBM IIA: 12–14], undes-
cended testis/cryptorchidism [EBM IIA: 15–17; EBM IIB:
18, 19] and testicular tumour among first-grade relatives, in
particular, in the father and/or brothers [EBM IIB: 20–22].
Table 1. Hierarchy of scientific evidence (declining from level IA to IV) according to the definition of US Agency for Health Care Policy and Research
by use of the Cochrane Collaboration [2]
Level Sources and characteristics of evidence
IA Evidence obtained from meta-analysis of randomised clinical controlled trials (RCT) and systematic reviews of RCT
IB Evidence obtained from at least one RCT
IIA Evidence obtained from at least one well-designed controlled study without randomisation
IIB Evidence obtained from at least one other type of well-designed quasi-experimental study
III Evidence obtained from well-designed non-experimental descriptive studies, such as comparative studies, correlation studies and case studies
IV Evidence obtained from expert committee reports or opinions and/or clinical experience of respected authorities without transparent proof
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