Guidelines

Testicular Cancer

4. STAGING & CLASSIFICATION SYSTEMS

4.1. Staging

The 2016 Tumour, Node, Metastasis (TNM) classification of the International Union Against Cancer (UICC) is recommended to assess the anatomical extent of the disease (Table 4.1) [27].

Table 4.1: TNM classification for testicular cancer (adapted from UICC, 2016, 8th edn.) [27]

pT - Primary Tumour1

pTX

Primary tumour cannot be assessed (see note1)

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 more than 5 nodes positive, none more than 5 cm; or evidence of extranodal extension of tumour

N3

Metastasis with a lymph node mass more than 5 cm in greatest dimension

Pn - Regional Lymph Nodes – 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 of 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 node(s) or lung metastasis


M1b Distant metastasis other than non-regional lymph nodes and lung

S - Serum Tumour Markers (Pre chemotherapy)

SX

Serum marker studies not available or not performed

S0

Serum marker study levels within normal limits


S1

S2

S3


LDH (U/l)

< 1.5 x N and

1.5-10 x N or

> 10 x N or

hCG (mIU/mL)

< 5,000 and

5,000-50,000 or

> 50,000 or

AFP (ng/mL)

< 1,000

1,000-10,000

> 10,000

N indicates the upper limit of normal.

LDH = lactate dehydrogenase; hCG = human chorionic gonadotrophin; AFP = alpha-fetoprotein.

1 Except for pTis and pT4, where radical orchidectomy is not always necessary for classification purposes, the extent of the primary tumour is classified after radical orchidectomy; see pT. In other circumstances, TX is used if no radical orchidectomy has been performed.

The current “Carcinoma in situ” nomenclature is replaced by GCNIS.

* AJCC eighth edition subdivides T1 Pure Seminoma by T1a and T1b depending on size no greater than 3 cm or greater than 3 cm in greatest dimension [28].

** AJCC eighth edition considers the hilar soft tissue invasion as pT2, while the discontinuous involvement of the spermatic cord is considered as pM1 [28].

4.2. The Union for International Cancer Control prognostic groups

According to the 2016 TNM classification, the following prognostic groups are defined:

Table 4.2: Prognostic groups for testicular cancer (UICC, 2016, 8th edn.) [28]

Stage grouping

T

N

M

S

Stage 0

pTis

N0

M0

S0

Stage I

pT1-T4

N0

M0

SX

Stage IA

pT1

N0

M0

S0

Stage IB

pT2 - pT4

N0

M0

S0

Stage IS

Any pT/TX

N0

M0

S1-3

Stage II

Any pT/TX

N1-N3

M0

SX

Stage IIA

Any pT/TX

N1

M0

S0

Any pT/TX

N1

M0

S1

Stage IIB

Any pT/TX

N2

M0

S0

Any pT/TX

N2

M0

S1

Stage IIC

Any pT/TX

N3

M0

S0

Any pT/TX

N3

M0

S1

Stage III

Any pT/TX

Any N

M1a

SX

Stage IIIA

Any pT/TX

Any N

M1a

S0

Any pT/TX

Any N

M1a

S1

Stage IIIB

Any pT/TX

N1-N3

M0

S2

Any pT/TX

Any N

M1a

S2

Stage IIIC

Any pT/TX

N1-N3

M0

S3

Any pT/TX

Any N

M1a

S3

Any pT/TX

Any N

M1b

Any S

Stage IA: Patients have primary tumours limited to the testis and epididymis, with no evidence of microscopic vascular or lymphatic invasion by tumour cells on microscopy, no sign of metastases on clinical examination or imaging, and post-orchidectomy serum tumour marker levels within normal limits. Marker decline in patients with CS I disease should be assessed until normalisation.

Stage IB: Patients have a more locally invasive primary tumour, but no sign of metastatic disease.

Stage IS: Patients have persistently elevated (and usually increasing) serum tumour marker levels after orchidectomy, indicating subclinical metastatic disease (or possibly a second GCT in the remaining testis).

In population-based patient series from developed countries, 75-80% of seminoma patients, and about 
55%-64% of non-seminomatous germ cell tumour (NSGCT) patients have stage I disease at diagnosis [29,30]. True stage IS (persistently elevated or increasing serum tumour marker levels after orchidectomy) is found in about 5% of non-seminoma patients [29].

4.3. The International Germ Cell Cancer Collaborative classification for the prognostic-risk groups of metastatic testicular cancer

The 1997 IGCCCG defined a prognostic risk-factor system for metastatic GCT based on identification of clinically independent adverse factors. The classification has been revalidated on a contemporary cohort of metastatic testicular GCT treated with cisplatin/etoposide based first-line chemotherapy.

Compared to the 1997 figures, the five-year progression-free survival (PFS) of non-seminoma patients was unchanged for good- and intermediate-risk, but significantly improved for poor-risk patients (from 41% to 54%). The five-year overall survival (OS) was substantially better for all groups. In addition to the traditional components of the IGCCCG risk-prognostic groups previously described, older age (linear association) and lung metastasis were confirmed as negative factors for PFS [31].

In seminoma, the five-year PFS increased to 89% and 79% in good- and intermediate-risk patients with the corresponding OS rates of 95% and 88%. Lactate dehydrogenase (LDH) proved to be an additional adverse prognostic factor. Good-prognosis patients with LDH above 2.5 times the upper limit of normal (ULN) had a three-year PFS of 80% and a three-year OS of 92%, vs. 92% and 97% (in the group with lower LDH) [32].

Table 4.3: Prognostic-based staging system for metastatic germ cell cancer (IGCCCG) [31,32]*

Good-prognosis group

Non-seminoma

5-year PFS 90%

5-year survival 96%

All of the following criteria:

• Testis/retro-peritoneal primary

• No non-pulmonary visceral metastases

• AFP < 1,000 ng/mL

• hCG < 5,000 IU/L (1,000 ng/mL)

• LDH < 1.5 x ULN

Seminoma

5-year PFS 89%

5-year survival 95%

All of the following criteria:

• Any primary site

• No non-pulmonary visceral metastases

• Normal AFP

• Any hCG

• Any LDH

Intermediate-prognosis group

Non-seminoma

5-year PFS 78%

5-year survival 89%

Any of the following criteria:

• Testis/retro-peritoneal primary

• No non-pulmonary visceral metastases

• AFP 1,000 - 10,000 ng/mL or

• hCG 5,000 - 50,000 IU/L or

• LDH 1.5 - 10 x ULN

Seminoma

5-year PFS 79%

5-year survival 88%

All of the following criteria:

• Any primary site

• Non-pulmonary visceral metastases

• Normal AFP

• Any hCG

• Any LDH

Poor-prognosis group

Non-seminoma

5-year PFS 54%

5-year survival 67%

Any of the following criteria:

• Mediastinal primary

• Non-pulmonary visceral metastases

• AFP > 10,000 ng/mL or

• hCG > 50,000 IU/L (10,000 ng/mL) or

• LDH > 10 x ULN

Seminoma

No patients classified as “poor-prognosis”

* Pre-chemotherapy serum tumour markers should be assessed immediately prior to the administration of

chemotherapy (same day).

AFP = alpha-fetoprotein; hCG = human chorionic gonadotrophin; LDH = lactate dehydrogenase;
PFS = progression-free survival.