Latest Recommendations of the European Germ Cell Cancer Group on Diagnosis and Treatment of Germ Cell Cancer

Localization of the tumour
Size
Multiplicity
Extension of the tumour (pT category according to UICC)
Histopathological type (WHO)
In seminoma: presence of syncytiotrophoblasts
In spermatocytic seminoma: any sarcomatous elements
In pluriform tumours: description and percentage of each individual component
Presence of TIN
Immunohistochemistry: AFP and hCG for detection of yolk sac tumour and choriocarcinoma CD31/FVIII for vascular invasion (pluripotency-related markers such as OCT4, NANOG, LIN28, AP-2 gamma for TIN, seminoma, embryonal cell carcinoma)
Table 1.2 shows the different types of germ cell tumours according to the WHO classification.
Table 1.2
WHO classification of germ-cell tumours of the testis [10]
Histological type
ICD-O-M
Intratubular germ cell neoplasia, unclassified
9064/2
Others
Tumours of one histological type (pure forms)
 Seminoma
9061/3
  (Subtype) Seminoma with syncytiotrophoblastic cells
 
 Spermatocytic seminoma
9063/3
  (Subtype) Spermatocytic seminoma with sarcoma
 
 Embryonal carcinoma
9070/3
 Yolk sac tumour
9071/3
Trophoblastic tumours
 Choriocarcinoma
9100/3
 Trophoblastic neoplasms other than choriocarcinoma
 
 Monophasic choriocarcinoma
 
 Placental site trophoblastic tumour
9104/1
Teratoma
9080/3
 Dermoid cyst
9084/0
 Monodermal teratoma
 
 Teratoma with somatic type malignancies
9084/3
Tumours of more than one histological type (mixed forms)
 
 Mixed embryonal carcinoma and teratoma
9081/3
 Mixed teratoma and seminoma
9085/3
 Choriocarcinoma and teratoma/embryonal carcinoma
9101/3
 Others
 
WHO World Health Organization
The clinical stage is defined by the UICC TNM classification (Table 1.3). Patients with metastatic disease are classified according to the classification of the International Germ Cell Cancer Collaborative Group (IGCCCG), which also pays regard to the elevation of tumour markers (Table 1.4).
Table 1.3
TNM classification – UICC 2009 [11]
pT
Primary tumour
 pTX
Primary tumour cannot be assessed
 pT0
No evidence of primary tumour (e.g. histological scar in testis)
 pTis
Intratubular germ cell neoplasia (carcinoma in situ)
 pT1
Tumour limited to testis and epididymis without vascular/lymphatic invasion: tumour may invade tunica albuginea but not tunica vaginalis
 pT2
Tumour limited to testis and epididymis with vascular/lymphatic invasion, or tumour extending through tunica albuginea with involvement of tunica vaginalis
 pT3
Tumour invades spermatic cord with or without vascular/lymphatic invasion
 pT4
Tumour invades scrotum with or without vascular/lymphatic invasion
N
Regional lymph nodes clinical
 NX
Regional lymph nodes cannot be assessed
 N0
No regional lymph node metastasis
 N1
Metastasis with a lymph node mass 2 cm or less in greatest dimension or multiple lymph nodes, none more than 2 cm in greatest dimension
 N2
Metastasis with a lymph node mass more than 2 cm but not more than 5 cm in greatest dimension, or multiple lymph nodes, any one mass more than 2 cm but not more than 5 cm in greatest dimension
 N3
Metastasis with a lymph node mass more than 5 cm in greatest dimension
pN
Pathological
 pNX
Regional lymph nodes cannot be assessed
 pN0
No regional lymph node metastasis
 pN1
Metastasis with a lymph node mass 2 cm or less in greatest dimension and 5 or fewer positive nodes, none more than 2 cm in greatest dimension
 pN2
Metastasis with a lymph node mass more than 2 cm but not more than 5 cm in greatest dimension; or more than 5 nodes positive, none more than 5 cm; or evidence or extranodal extension of tumour
 pN3
Metastasis with a lymph node mass more than 5 cm in greatest dimension
M
Distant metastasis
 MX
Distant metastasis cannot be assessed
 M0
No distant metastasis
 M1
Distant metastasis
 M1a
Non-regional lymph nodes(s) or lung
 M1b
Other sites
S
Serum tumour markers
 Sx
Serum marker studies not available or not performed
 S0
Serum marker study levels within normal limits
LDH (U/l) hCG (mlU/ml) AFP (ng/ml)
 S1
<1.5 × N and <5,000 and <1,000
 S2
1.5–10 × N or 5,000–50,000 or 1,000–10,000
 S3
>10 × N or >50,000 or >10,000
N indicates the upper limit of normal for the LDH assay
Except for pTis and pT4, where radical orchiectomy is not always necessary for classification purposes, the extent of the primary tumour is classified after radical orchiectomy; see pT in other circumstances. TX is used if no radical orchiectomy has been performed
According to the 2002 TNM classification, stage I testicular cancer includes the following substages:
Stage IA
pT1
NO
MO
S0
Stage IB
pT2, pT3, or pT4
NO
MO
S0
Stage IS
Any pT/TX
NO
MO
S1–3
AFP alpha-fetoprotein, hCG human gonadotropin, LDH lactate dehydrogenase, UICC International Union Against Cancer
Table 1.4
IGCCCG prognostic grouping classification [12]
Prognosis
5-year survival
Non-seminoma
Seminoma
Good
90 %
Testis or primary extragonadal retroperitoneal tumour
Any primary localization
No non-pulmonary visceral metastases
No non-pulmonary visceral metastases
Low markers
Any marker level
 AFP <1,000 ng/ml
 ß-hCG <1,000 ng/ml (<5,000 IU/l)
 LDH <1.5 × normal level
Intermediate
75 %
Testis or primary extragonadal retroperitoneal tumour
Any primary localization
No presence of non-pulmonary visceral metastases
Presence of non-pulmonary visceral metastases (liver, CNS, bone, intestinum)
Any marker level
Intermediate markers
 AFP 1,000–10,000 ng/ml and/or
 ß-hCG 1,000–10,000 ng/ml (5,000–50,000 IU/l) and/or
 LDH 1.5–10 × normal level
Poor
50 %
Primary mediastinal germ cell tumour with or without testis or
Primary retroperitoneal tumour and
Presence of non-pulmonary visceral metastases (liver, CNS, bone, intestinum) and/or
High markers
 AFP >10,000 ng/ml and/or
 ß-hCG >10,000 ng/ml (50,000 IU/l) and/or
 LDH >10 × normal level
AFP a-fetoprotein, ß-hCG human chorionic gonadotropin, CNS central nervous system, IGCCCG International Germ Cell Cancer Collaborative Group, LDH lactic dehydrogenase
Spiral computerized tomography (CT) scans of the thorax, abdomen and pelvis remain the staging procedures of choice. Magnetic resonance tomography (MRT) can be an alternative, but should be done only at institutions with special expertise in evaluating testis cancer patients [13]. Positron electron tomography (PET) has no role as a staging procedure [14, 15]. Imaging of brain or bones only is mandatory in patients with visceral metastases or in case of symptoms.
AFP, hCG and LDH should be performed before and after orchiectomy. To define a clinical stage I, marker normalization is mandatory. Therefore in case of still elevated markers post-orchiectomy several marker controls might be necessary before finally to define the clinical stage. If markers do not normalize, it is declared as stage IS disease. In patients with metastatic disease, pre-chemotherapy markers instead of pre-orchiectomy markers should be used to allocate the IGCCCG category [12, 16].
Because further treatment might influence the hormonal status and fertility of the patient a baseline assessment including testosterone, luteinising hormone (LH), follicle-stimulating hormone (FSH) and, if possible, a semen analysis should be performed.
Patients should also be informed about cryoconservation.

1.5 Treatment of Patients with Seminoma CSI

Rete testis infiltration and tumour size >4 cm have been recognized as risk factors for occult retroperitoneal lymph node metastases in a retrospective analysis [17]. A metaanalysis of patients managed by surveillance showed a 5-year relapse rate of 12 % in patients without any risk factor, a relapse rate of 16 % in case of one risk factor and of 32 % in patients with both risk factors. Based on these data, a risk-adapted strategy was recommended with surveillance for patients without any risk factors and adjuvant treatment in those with one or two risk factors. Options for adjuvant therapy are a single course of carboplatin (AUC 7) or paraaortal/paracaval radiation with 20 Gy. Recent data about the induction of secondary malignancies after adjuvant radiotherapy reduced the choice of this strategy [1820]. Since the latest prospective series from the Canadian Group could not validate the rete testis infiltration and tumour size >4 cm as risk factors, many physicians already favour surveillance independent of any risk factor [21]. On the other hand, a prospective Spanish trial could at least confirm the negative predictive value of these factors [22]. Therefore, no definitive recommendation can be given.

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Nov 17, 2016 | Posted by in ONCOLOGY | Comments Off on Latest Recommendations of the European Germ Cell Cancer Group on Diagnosis and Treatment of Germ Cell Cancer

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