EAU & ASCO: Penile Cancer 2023
See Original Guidelines
Background
- Penile cancer negatively impacts quality of life through
- Physical and emotional changes
- Feelings of mutilation
- Loss of masculinity
- Voiding and sexual dysfunction, which in turn can result in relationship breakdowns and withdrawal from society
- Lymphedema
Epidemiology
- Uncommon in industrialized countries
- More common in South America, Southeast Asia, and parts of Africa
- Race
- Highest incidence in white Hispanics, followed by Alaskans and Native American Indians, African Americans, white non-Hispanics.
- Increasing incidence in Western/developed countries most likely due to higher infection rates of HPV
Pathophysiology
Risk factors
- Human papilloma virus (HPV)
- Most important risk factor
- Most frequent HPV genotypes: HPV16 followed by HPV6
- Risk of penile cancer is increased in patients with condyloma acuminata
- Female sexual partners of patients with penile cancer have not been found to have an increased incidence of cervical cancer
- No general recommendation (except in a few countries) for HPV vaccination in males because of the different HPV-associated risk patterns in penile- and cervical cancer
- Since up to 50% of invasive penile carcinomas and 80% of preneoplastic lesions are HPV-associated, HPV vaccination is encouraged
- Phimosis
- Strongly associated with invasive penile cancer, due to associated chronic infections
- Smegma is not a carcinogen
- Neonatal circumcision reduces the incidence of penile cancer, but does not reduce the risk of Penile Intraepithelial Neoplasia
- Chronic penile inflammation
- Lichen sclerosus
- Ultraviolet A phototherapy
- Cigarette smoking
- Low level of education
- Low socio-economic status
Pathology
- >95% of penile cancers are squamous cell carcinomas (SCCs)
- Other malignant lesions of the penis
- Melanoma
- Mesenchymal tumors
- Lymphomas
- Metastases
- Penile metastases are frequently of prostatic, urinary bladder or colorectal origin
- Sarcoma
Penile Squamous Cell Carcinoma
- Usually arises from the epithelium of the inner prepuce or the glans
- Subtypes
- HPV-independent
- Usual
- Pseudohyperplastic
- Pseudoglandular
- Verrucous
- Caniculatum
- Papillary
- Sarcomatoid (Most aggressive and worse prognosis)
- Mixed
- HPV-associated
- Basaloid (most common among HPV-associated penile carcinomas)
- Warty
- Clear cell
- Lymphoepithelioma-like
- Mixed
- HPV-independent
- Penile intraepithelial neoplasia is considered the precursor lesion of penile SCC
- Clinical terms such as ‘Erythroplasia of Queyrat, Bowenoid papulosis and Bowen’s disease’ are discouraged
- Penile intraepithelial neoplasia is also classified as HPV-independent and HPV-associated
Grading
- The tumour, node, metastasis (TNM) classification for penile cancer includes tumour grade based on its prognostic relevance
- Highly observer-dependent and can be problematic, especially in large tumours which may be heterogeneous
- Based on
- Cytological atypica
- Keratinisation
- Intercellular bridges
- Mitotic activity
- Tumour margin
- Classified into
- Grade 1
- Grade 2
- Grade 3
- Sarcomatoid
- Grade 3 and sarcomatoid are considered poorly differentiated
TNM Staging
- Based on 8th edition of AJCC, last updated in 2017
Primary Tumor (T)
- 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: without lymphovascular invasion or perineural invasion and is not poorly differentiated
- T1b: 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
Regional Lymph Nodes (N)
- Clinical
- 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
- Pathological
- 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
Distant Metastasis (M)
- M0: No distant metastasis
- M1: Distant metastasis
Diagnosis and Evaluation
Penile biopsy
- In most cases, acquiring a punch biopsy (e.g., 2–3 mm) under local anaesthesia is sufficient to confirm the diagnosis.
- in cases where assessment of depth of invasion is necessary, an incisional biopsy which is deep enough to properly assess the degree of invasion and stage is preferable.
- Tissue sections determine the accuracy of histological diagnosis.
- Small lesions should be fully included
- Bigger lesions should have at least 3-4 blocks of tumour with the anatomical landmarks
- Second-opinion pathology review is recommended given the rarity of this cancer
- The pathology report must include
- Surgical procedure
- Anatomical site of the primary tumour
- Size of tumour
- Maximum thickness
- Histological type of SCC
- Grade
- Depth and extent of invasion
- Vascular invasion (venous/lymphatic)
- Perineural invasion
- Surgical margins
- HPV assessment
Management
- Patients should be referred to comprehensive referral centers for penile cancer
Prognosis
- Overall 5-year survival: 67%
- Localized disease: 81%
- Distant metastasis: 18%
- Prognostic factors
- Pathological subtype
- Peri-neural invasion
- Lymphovascular invasion
- Depth of invasion
- Grade in the primary tumour
- Extent of LN metastasis and extracapsular spread
- Extra-capsular extension in even one single LN carries a poor prognosis and is denoted as pN3