4. STAGING AND CLASSIFICATION SYSTEMS
4.1. TNM classification
The 8th edition of the UICC/AJCC TNM is the currently used classification system for penile cancer which was last updated in 2017 [73,83] Compared to the previous (7th) edition, some changes were introduced. The T1 category is stratified into two different risk groups depending on the absence or presence of lymphovascular invasion, perineural invasion, or poor differentiation (T1a vs. T1b, respectively, see Table 4.1) [84]. Furthermore, invasion into the urethra was previously classified as T3 disease. However, a tumour near the meatus may directly invade into the distal urethra through the corpus spongiosum, which is not associated with worse outcome. In addition, previous studies have shown that corpus spongiosum invasion is associated with a lower incidence of inguinal LN metastasis and has better survival compared to corpus cavernosum invasion. Therefore, invasion into the corpus spongiosum and corpus cavernosum is classified into T2 and T3, respectively [85,86]. Patients with T4 tumours have extension into adjacent tissues (e.g., prepubic fat, scrotum, spermatic cord, pubic bone, prostate).
The pN1 category was modified to include up to two unilateral inguinal LN metastases, while the pN2 category was modified to be three or more unilateral, or any bilateral LN metastases. This was based on data showing poor outcomes in cases involving three or more unilateral or bilateral LNs compared with those involving one or two unilateral LNs [86,87]. pN3 stage is defined as pelvic nodes (uni- or bilateral) or presence of extranodal extension (ENE) (inguinal or pelvic, regardless of the number of LN metastases) [73,83]. Further retroperitoneal LN spread cranial to the pelvic template is classified as extra-regional and therefore as distant metastases.
Table 4.1: UICC/AJCC 8th edition TNM clinical and pathological classification of penile cancer [73,83]
Clinical classification | ||
T - Primary Tumour | ||
TX | Primary tumour cannot be assessed | |
T0 | No evidence of primary tumour | |
Tis | Carcinoma in situ (Penile Intraepithelial Neoplasia – PeIN) | |
Ta | Non-invasive verrucous carcinoma* | |
T1 | Tumour invades subepithelial connective tissue | |
T1a | Tumour invades subepithelial connective tissue without lymphovascular invasion or perineural invasion and is not poorly differentiated | |
T1b | Tumour invades subepithelial connective tissue with lymphovascular invasion or perineural invasion or is poorly differentiated | |
T2 | Tumour invades corpus spongiosum with or without invasion of the urethra | |
T3 | Tumour invades corpus cavernosum with or without invasion of the urethra | |
T4 | Tumour invades other adjacent structures | |
N - Regional Lymph Nodes | ||
cNX | Regional lymph nodes cannot be assessed | |
cN0 | No palpable or visibly enlarged inguinal lymph nodes | |
cN1 | Palpable mobile unilateral inguinal lymph node | |
cN2 | Palpable mobile multiple or bilateral inguinal lymph nodes | |
cN3 | Fixed inguinal nodal mass or pelvic lymphadenopathy, unilateral or bilateral | |
M - Distant Metastasis | ||
cM0 | No distant metastasis | |
cM1 | Distant metastasis | |
Pathological classification | ||
The pT categories correspond to the clinical T categories. The pN categories are based upon biopsy or surgical excision | ||
pN - Regional Lymph Nodes | ||
pNX | Regional lymph nodes cannot be assessed | |
pN0 | No regional lymph node metastasis | |
pN1 | Metastasis in one or two inguinal lymph nodes | |
pN2 | Metastasis in more than two unilateral inguinal nodes or bilateral inguinal lymph nodes | |
pN3 | Metastasis in pelvic lymph node(s), unilateral or bilateral or extranodal extension of regional lymph node metastasis | |
pM - Distant Metastasis | ||
pM1 | Distant metastasis microscopically confirmed | |
G - Histopathological Grading | ||
GX | Grade of differentiation cannot be assessed | |
G1 | Well differentiated | |
G2 | Moderately differentiated | |
G3 G4 | Poorly differentiated Undifferentiated | |
*Including verrucous carcinoma.
4.2. Cancer stage grouping
In the UICC TNM 8th edition, stage II was newly subdivided into Stage IIA and Stage IIB based on T categories. Stage IIA is defined as T1b–2N0M0, while Stage IIB is defined as T3N0M0 [73] (Table 4.2).
Table 4.2 UICC TNM Stage/Prognostic Groups
Stage | T | N | M |
0 | Tis | N0 | M0 |
Ta | N0 | M0 | |
I | T1a | N0 | M0 |
IIA | T1b | N0 | M0 |
T2 | N0 | M0 | |
IIB | T3 | N0 | M0 |
IIIA | T1–3 | N1 | M0 |
IIIB | T1–3 | N2 | M0 |
IV | T4 | Any N | M0 |
Any T | N3 | M0 | |
Any T | Any N | M1 |