Friday, June 27, 2014

Penile Cancer: Basics of Diagnosis and Staging

Penile cancer, in general, refers to cancer of the skin of the penis.  Most of these cancers (95%) are squamous cell carcinoma (SCC), similar to skin cancers elsewhere on the body.  Men can also develop cancers of the urethra (or inner lining of the penis), but this is a distinct and separate entity.  In the United States, penile cancer is relatively rare affecting only about 1,600 men - about 0.2% of the nearly 1 million male cancers diagnosed each year.  The incidence of penile cancer varies around the world and can reach as high as 20% of all male cancers in some African countries and Brazil.

The variation in the incidence of penile cancer is related to risk factors.  The best known risk factors for penile cancer include:

  • phimosis (circumcision is protective of penile cancer in regions where rates are high)
  • poor hygiene (obesity may be a risk factor if it prevents good hygiene)
  • smegma (trapped male penile secretions)
  • tobacco use
  • Human Papilloma Virus (HPV) 16*, 18, 31 and 33
The worldwide rates of penile cancer are decreasing and this is attributed to improved education regarding hygiene, improving socioeconomic status and may be attributed to increasing rates of circumcision.

Penile cancer most often present as a lesion on the penis.  The majority of cancers appear on the glans (or head) or the prepuce (foreskin) of the penis.  

48% Glans
21% Prepuce
9% Gland and Prepuce
6% Coronal Sulcus
2% Shaft

There are a number of pre-malignant lesions that may dispose a man to later development of penile cancer.  The lesions range from the dysplastic to carcinoma-in-situ to frank squamous cell carcinoma.  We review some of the more common lesions below:


Balanitis Xerotica Obliterans (BXO)

Balanitis Xerotica Obliterans (BXO)

Appears as a whitish plaque on glans or prepuce
Can cause meatal stenosis 
4-8% will progress to SCC 
Treatment: topical steroid cream, circumcision, meatotomy (opening of the urethral meatus) if needed


solitary or multiple whitish plaques often associated with chronic irritation
10-20% will progress to SCC
Treatment: surgical excision w/ long term F/U
Condyloma Accuminata

Condyloma accuminata (veneral warts)

Associated with HPV 6 and 11
Flat lesions, can be identified easily as they turn white with 5% acetic acid soaks
Treatment: topical podophyllin, CO laser ablation, IFN injection

Buschke-Lowenstein tumor (verrucous carcinoma)

Also associated with HPV 6 and 11
Locally destructive, but does not metastasize 
Treatment: local excision

Carcinoma in situ (CIS)

carcinoma in situ (CIS)
Carcinoma in situ is classified by its appearance and location on the penis.

Erythoplasia of Queyrat 

red, velvety, well demarcated lesion of glans/prepuce
10-33% progress to invasive SCC
Not associated with visceral malignant disease
Treatment: local excision/circumcision, laser fulgration, topical 5FU

Bowens disease 

sharply defined plaques of scaly erythema on shaft
5% progress to invasive SCC
Metastases are rare but are reported
Bowens disease is associated with an increased risk of concomitant visceral malignancy (commonly prostate or bladder cancer)
Treatment: local excision, close follow up

Diagnosis and Evaluation

Most lesions present while localized to the penis.  Physical examination is of paramount importance as staging (depth of spread; see below) is most important in determining prognosis.  Lesions that are mobile and in the skin have a better prognosis than lesions that are fixed or growing into the deeper structures of the penis.  The first location of spread for penile cancer is to the lymph nodes in the groin.  50% of patients with have enlarged lymph nodes in the groin at the time of presentation.  However, only 50% of these patients will have cancer in the lymph nodes as these lymph nodes are often "reactive" to inflammation or super-infection in the penile lesion.  Interestingly, 20% of patients without palpable lymph nodes will eventually be determined to have metastatic cancer.

The most important step in the evaluation of a penile lesion is biopsy.  Biopsy can either be incisional (a sampling) or excisional (the whole lesion is removed).  Both dermatologists and urologists are proficient in biopsy in most hospitals.  Biopsy is essential to rule out or confirm a diagnosis of SCC, assess the depth of invasion (stage), determine grade (aggressiveness) of the cells and evaluate for microscopic vascular invasion (predictive of distant recurrence).  Depth of invasion, or tumor stage, is the most important factor in the initial evaluation of penile cancers.    

Staging of the Primary Tumor (T-stage) 
Tx – cannot be assessed
T0 – no primary tumor
Tis – CIS
Ta – noninvasive verrucous carcinoma
T1 – subepithelial connective tissue invasion
T1a: no LVI, NOT poorly differentiated 
T1b: + LVI, grade 3-4 (poorly differentiated)
T2 – invaded corpus spongiosum, cavernosum
T3 – invades urethra
T4 – other adjacent structures

Interestingly, stage and grade are highly correlated.  Grade describes the aggressiveness of the cancer under the microscope and high grade cancers are more likely to be locally invasive and more likely to have spread to the lymph nodes in the groin.  Up to 25% of low-grade tumors will have lymph node involvement; 40-90% of high-grade tumors will have positive lymph nodes.  Nodal stage is determined by the size and location of enlarged and involved lymph nodes.

Nodal Stage (N-Stage)
NX cannot be assessed
N0 – no palpable or visibly enlarged inguinal nodes
N1 – palpable, mobile unilateral inguinal lymph node (single lymph node)
N2 – palpable, mobile multiple or bilateral inguinal lymph nodes
N3 – extranodal extension of LN mets or pelvic lymph nodes (uni/bilateral)


American Cancer Society. Cancer Facts & Figures 2014. Atlanta: American Cancer Society; 2014.

Penile Cancer. American Cancer Society.

Pettaway, Lance and Davis.  Tumors of the Penis.  Campbell-Walsh Urology , Tenth Edition. 2012. Eds Wein, Kavoussi, Novick, Partin, and Peters.  Chapter 34, 901-933.e9


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