Testicular Cancer

4. STAGING & PROGNOSIS

4.1. Staging

The 2025 Tumour, Node, Metastasis (TNM) classification of the International Union Against Cancer (UICC) is recommended to assess the anatomical extent of the disease (Table 1) [31].

Table 1: TNM classification for testicular cancer (adapted from UICC, 2025, 9th edn.) [31]

N indicates the upper limit of normal.
AFP = alpha-fetoprotein, hCG = human chorionic gonadotrophin; LDH = lactate dehydrogenase.
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.
*AJCC 8th edition subdivides T1 Pure Seminoma by T1a and T1b depending on size no greater than 3cm or greater than 3cm in greatest dimension.
**AJCC 8th edition notes that the discontinuous involvement of the spermatic cord is considered as pM1.[32].

4.2. The Union for International Cancer Control prognostic groups

The following table (Table 2) lists prognostic groups defined by the 2025 TNM classification.

Table 2: Prognostic groups for testicular cancer (UICC, 2025, 9th edn.) [31]

In population-based patient series from developed countries, 75-80% of SGCT patients, and 55-64% of NSGCT patients had CS I disease at diagnosis [33,34]. Stage IS, i.e. persistently elevated or increasing serum tumour marker levels after radical orchidectomy, was found in approximately 5% of NSGCT patients [33].

4.3. Risk factors for relapse in clinical stage I germ cell tumours

4.3.1. SGCT

Primary testicular tumour size and stromal invasion of the rete testis have been considered the prognostic risk factors associated with relapse in CS I SGCT. Two systematic reviews (SRs) assessed the prognostic value of both risk factors [35,36]. While tumour size (continuous or dichotomised) and rete testis invasion (RTI) were associated with a higher risk of relapse, both SRs highlighted the low quality of the studies included and concluded that the level of evidence was low to justify the use of both risk factors to drive adjuvant treatment decisions in routine practice.

Two large series re-assessed prognostic risk factors in CS I SGCT patients under surveillance. A multi-institutional retrospective series including 1,016 patients and an additional validation cohort of 285 patients identified primary testicular tumor size (size < 2cm, 2-5cm, and > 5), RTI (pagetoid + stromal invasion) and lymphovascular invasion (LVI) to be associated with risk of relapse [37,38]. A three-tier risk stratification was compiled, including a small proportion of high-risk patients (2.3%) with tumour size > 5cm and both RTI and LVI present who had a five-year cumulative probability of relapse of 44%.

A large prospective series from Denmark [39] including 924 patients with central pathology review identified invasion of the testicular hilum (rete testis and hilar soft tissue), LVI and elevated HCG and LDH prior to orchiectomy as independent predictors of relapse. In contrast to previous studies, tumour size was not identified as a risk factor. A six-tier risk stratification was developed and the estimated five-year probability of relapse ranged from 6% in patients without risk factors to 62% in patients with all four risk factors, which was 22% of the patient population. Both series demonstrated that the vast majority of patients with CS I SGCT are cured by orchiectomy alone, as the overall relapse rate was 14.7% and 16%, supporting active surveillance as the preferred adjuvant strategy.

4.3.2. NSGCT

For CS I NSGCT, invasion of the primary tumour into blood or lymphatic vessels, i.e. LVI, has long been described to be strongly associated with the risk of relapse [40-42]. According to historical figures, relapse risk for patients with LVI-positive tumours was 50% versus 15% in patients with LVI-negative tumours.

A Danish study of more than 400 patients with central pathology review identified tumour size, invasion of the hilar soft tissue and presence of embryonal carcinoma as additional risk factors [39]. Depending on the combination of factors, relapse risk ranged from < 5% to > 85%.

4.4. The International Germ Cell Cancer Collaborative Group (IGCCCG) classification for the prognostic risk groups of metastatic germ cell cancer

The 1997 IGCCCG defined a prognostic risk-factor system for metastatic GCT based on identification of clinically independent adverse factors [43]. The classification has been revalidated on a contemporary cohort of metastatic TGCT treated with cisplatin/etoposide based first-line chemotherapy [44].

Compared to the 1997 figures, the five-year progression-free survival (PFS) of NSGCT 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 prognastic risk groups previously described, older age (linear association) and lung metastases were confirmed as negative factors for PFS [44].

For SGCT, revalidation of the IGCCCG classification showed that the five-year PFS increased to 89% and 79% in good- and intermediate-risk patients with corresponding OS rates of 95% and 88%. Lactate dehydrogenase (LDH) over 2.5 times the upper limit of normal (ULN) was identified as a possible adverse prognostic factor in regard to shorter three-year PFS; however, overall three-year survival was not affected [40].

Table 3: Prognostic-based staging system for metastatic germ cell cancer (IGCCCG) [40, 44]*

* Prechemotherapy 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.