Penile carcinoma

Penile carcinoma is a rare malignancy with an annual incidence of 0.1 to 0.7 per 100,000 men, accounting for fewer than 1% of male cancers in the United States. 

Behaves similarly to squamous cell carcinoma in other parts of the skin.

Patients tend to delay seeking medical attention, with 15-50% delaying medical attention for more than 1 year from onset.

Average delay time to seek treatment is 8 months.

Approximately 1250 men each year have a cancer of the penis.

Accounts for 0.4-0.6% of all malignancies in the United States and Europe.

Incidence decreasing.

Incidence is highest among Hispanics, followed by Alaskan Native Americans and African Americans.

Represents 20-30% of all cancers diagnosed in men who live in Asia, Africa, and South America.

In India, the age-adjusted incidence of penile cancer ranges from 0.7-2.3 cases per 100,000 men in urban men and 3 cases per 100,000 men in rural men.

In Brazil the incidence of penile cancer is 8.3 cases per 100,000 population.

In Uganda 1% of men developing the disease by age 75.

Incidence increases in men aged 60 years or older and peaks in men aged 80 years.

Delay in diagnosis can result in poor functional outcomes and reduced survival.

There are two molecularly divergent pathways for penile carcinogenesis: HPV induced and non HPV induced.

Estimated 50-80% of penile cancers are HPV-induced

The tumor is not unusual in younger men, with 22% of patients younger than 40 years, and 7% younger than 30 years.

Herpes viral infections have not been associated with the development of penile cancers.

HPV has been detected in 1/3-1/2 of penile cancers.

The more keratinized subtypes of penile carcinoma, such as usual and verrucous cancers have lower HPV detection compared with warty

and basaloid varieties.

HPV associated penile cancers have somewhat less aggressive course with a better prognosis.

Malignancy found on the skin or in the tissues of the penis.

Squamous cell carcinoma usually originating in the glans or foreskin is the most common type, occurring in 9 out of 10 cases.

Very rare in Europe and North America.

Occurs in about one in 100,000 men in the US.

Accounts for 0.2% of cancers and 0.1% of deaths from cancer among males in the United States.

In some parts of Africa and South America it accounts for up to 10% of cancers in men.

Cause is unknown.

Risk factors include: human papillomavirus infection, smoking, smegma, phimosis, poor hygiene, UV light exposure advancing, age, lack of circumscision, AIDS increased number of sexual partners, lack of condom use, presence of balanatis or lichen sclerosus..

Phimosis is present in at least 25-75% of patients.

HPV-16 and HPV-18 have been found in one third of men with penile cancer.

Associated with smoking and chewing tobacco.

Circumcision protective, as this lesion is rare in men undergoing this procedure as a neonate.

The disease is found more frequently when circumcision is delayed until puberty.

Adult circumcision offers little or no protection.

Lesions can originate anywhere on the penis, but most are found on the glans (48%) and prepuce (21%).

May be related to chronic exposure of carcinogens contained in smegma that collects within the prepuce.

Lesions can range from an subtle induration to a small excrescense or papule, can be exophytic, flat or ulcerated.

Itching or burning under the foreskin or an ulceration of the glans are the most common presenting symptoms.

Approximately 90% of squamous cell cancers of the penis are in the distal portion of the penis.

Pain is rarely present.

May initially form on the corona of the glans and spread across the glans and into the prepuce.

Phimosis may conceal the cancer.

Metastasizes in a stepwise fashion, spreading first to the inguinal nodes, then to tell the pelvic nodes, and finally to periaortic nodes.

In rare cases, an inguinal mass ulcerates, drains, or bleeds

No specific laboratory studies or tumor markers are diagnostic.

MRI and ultrasonography are useful for local cancer staging and for assessing the inguinal lymph nodes.

These studies may be helpful for detecting tumor invasion into the corpora.

Both MRI and CT scanning can demonstrate enlarged pelvic and retroperitoneal lymph nodes.

Biopsy for diagnosis may be an excisional one if the cancer is small or the lesion is confined to the prepuce and a circumcision is acceptable.

The biopsy should contain tissue beneath the tumor to help stage the disease.

Needle aspiration of enlarged lymph nodes may aid in planning therapy.

Sentinel node biopsy may help in staging and therapy decisions.

Low levels of E-cadherin and high expression of MMP-9 represented independent risk factors for nodal disease.

Most lesions are low grade, but correlation between grade and survival is lacking.

High-grade disease is associated with regional lymph node metastases.

The strongest predictor for survival is the presence or absence of nodal metastases.

Stage I – Cancer has only affected the glans and/or foreskin.

Stage II – Cancer has spread to the shaft of the penis.

Stage III – Mobile inguinal lymph nodes which are operable

Stage IV – Fixed inguinal lymph nodes or distant metastasis.

Prognosis varies widely with stage of disease.

Prognosis more frequently depends on locoregional spread than the development of distal disease.

Overall 5-year survival rate for all stages of penile cancer is about 50%.

Buck fascia, which surrounds the corpora, acts as a temporary barrier to metastases.

When the cancer penetrates the Buck fascia and the tunica albuginea the cancer has access to the vasculature and systemic spread is possible.

Metastases to the femoral and inguinal lymph nodes are the earliest path for tumor dissemination.

Lymphatics of the prepuce join with those from the shaft and drain into the superficial inguinal nodes.

Cancer cells have access to lymph nodes in both inguinal areas.

The lymphatics of the glans join those draining the corpora.

At the base of the penis lymphatics drain to both the superficial and deep pelvic lymph nodes.

The superficial inguinal nodes drain to the deep inguinal nodes and then to the pelvic nodes.

Multiple cross connections between lymph vessels, permit bilateral penile lymphatic drainage.

Metastatic enlargement of the regional nodes leads to skin necrosis, chronic infection, and, eventually, death from sepsis or hemorrhage.

Distant metastases are usually associated with regional node involvement, and may involve lung, liver and brain.

Tumors vary from well-differentiated keratinizing tumors to solid anaplastic carcinomas with scant keratinization.

SEER program data on 1605 men diagnosed with penile cancer CIS was diagnosed in 37% of this population, localized disease was diagnosed in 39%, regional disease was present in 13%, distant disease was present in 2.3%, and unstaged disease remained in 7.9%.

Older age at diagnosis was associated with a higher stage of disease.

The mean time until death from cancer was 66.6 months in those with CIS, 50.1 months in those with localized disease, 32.4 months in those with regional disease, and 7.4 months in those with distant metastases.

Flat ulcerative lesions tend to metastasize to the lymph nodes earlier and are therefore associated with a lower 5-year survival rate.

Cancers larger than 5 cm and those involving more than 75% of the shaft are associated with a high prevalence of nodal metastases and a lower survival rate.

Fatal in most untreated patients within 2 years.

Recurrence rate of 28% and lymph node metastases are found in 28-39% depending upon the extent and grade of the lesion.

The mortality rate is 20-38% with a 10-year survival rate of 78%.

Treatment depends on the stage.

Treatment is associated with continual mutilation changes to the quality of life.

Surgical options include wide local excision, microsurgery, laser surgery, circumcision, amputation of the penis.

For patients with locally advanced disease, with regional lymph node involvement or unresectable bulky primary tumors, induction chemotherapy, possibly before radical surgery is recommended.

Multiple neoadjuvant chemotherapies for locally advanced disease, with regional lymph node involvement or unresectable bulky primary tumor,have objective responses of about 50%, but relapses occur in the majority of cases, and long-term remission is rare.

Primary goal in the management is to eliminate the malignancy while preserving a cosmetically acceptable and functional penis.

Three types of surgical procedures exist with the treatment of squamous cell carcinoma of the penis: penis sparing surgery, partial penectomy, and total penectomy.

Treatment for penile carcinoma include partial penectomy, local excision, topical chemotherapy, laser ablation, circumcision, glansectomy, and glans resurfacing.

Penis sparing surgery involves preserving the length of the penis and using a split thickness skin graft or full thickness skin graft, a rotation flap, or an advancement flap to cover the excised portion of the penis.

Penis spending surgery attempts to provide a normal appearance and function of the penis and minimizes psychological effects of the procedure.

Penis sparing surgery only available to patients with carcinoma in situ or tumor stage T1.

Partial penectomy results in shortened penis but preserves the phallic structure and the ability to void while standing.

Partial penectomy associated with the local recurrence rate of 7-14%.

Partial penectomy considered for patients with stage T2 or higher.

Total penectomy is performed on patients with extensive tumor involvement of the corporate cavernosa or invasive disease at the base of the penis.

Total penectomy removes the corpora cavernosa to the ischial rami, dissecting the urethra from corporate cavernosa, and bringing the urethra to the skin in the perineum.

The local recurrence rate for total penectomy less than 5% in squamous cell carcinoma of the penis.

Inguinal metastases can be removed with inguinal dissection and in many instances can be a curative surgery.

Complications of inguinal dissections include skin flap necrosis, skin flap infections, and leg edema.

Inguinal resection is performed in patients who have palpable inguinal nodes,

Inguinal dissection should be considered in patients with a high likelihood of microscopic nodal disease, as early regional lymphadenectomy for microscopic disease is associated with a 92% disease free survival at five years ( McDougal WS et al).

In patients with a deferred inguinal node dissection until lymph nodes become palpable, only 33% of patients are disease-free at five years (McDougal WS et al).

Intraepithelial neoplasms can be treated with topical 5-fluorouracil.

Penile intraepithelial neoplasia (PIN) refers to an alteration of the penile squamous epithelium characterized by dysplastic changes with an intact basement membrane.

Penile intraepithelial neoplasia a precursor lesion to invasive squamous cell cancer.

PIN associated with lichen sclerosis and chronic inflammation and may or may not be related to HPV.

Candidates for radiation therapy include young men with lesions smaller than 3cm, superficial, exophytic lesions or noninvasive cancers on the glans or coronal sulcus, patients who refuse surgery or who have metastatic disease and need some form of palliative therapy.

Circumcision is recommended prior to initiating radiation therapy for cancers involving the prepuce.

Radiation may be associated with will penile swelling, irritation, desquamation, phimosis, urethral fistula, urethral strictures, penis necrosis, pain and infection.

Most widely accepted external beam radiation schedule for cancers smaller than 4 cm is 4,000 cGy in 20 fractions over 4 weeks to the shaft of the penis.

Local control rate with external beam radiation in carefully selected patients varies from 60-90%.

If local recurrence or significant adverse effects occur with radiation salvage surgery may be utilized.

Brachytherapy techniques may also be employed.

If circumcision is performed, and the tumor is smaller than 4 cm with less than 1 cm of corporal invasion radiation can provide local control rates with penile preservation ranging from 58-89%.

Chemotherapy agents are used to treat patients with metastases beyond the pelvic and inguinal lymph nodes.

The most commonly used drugs include cisplatin, bleomycin, methotrexate, and fluorouracil, paclitaxel, ifosfamide.

The standard surgical therapy for the primary cancer is local excision and either partial or total penectomy.

With small penile tumors confined to the prepuce, circumcision is the treatment of choice.

Surgical treatment of cancers larger than 1.5 cm have a recurrence rate of 50%.

While margins of 2 cm have traditionally been considered necessary to reduce local recurrences, recent evidence has shown that such wide margins may not be needed.

When the cancer involves the glans and distal shaft  a partial amputation of the penis with a 2-cm margin is necessary.

Local wedge resection is associated with a recurrence rate of 50%.

Total penectomy is performed if adequate margins cannot be achieved with lesser surgery. considered.

Mohs surgery is applicable in some patients.

Inguinal node resection in patients with no evidence of adenopathy is controversial as the incidence of occult metastases in patients who have no palpable adenopathy is 20%-25%.

Since the cure rate among patients with positive inguinal nodes approaches 80% the decision to perform an inguinal lymphadenectomy often depends on the grade of the cancer and its local extent.

Cancers that have invaded through the basement membrane are much more likely to have nodal metastases than superficial tumors.

Bilateral lymphadenectomy is necessary when the nodes are palpable or appear abnormal on CT scanning or MRI.

With involvement of only 1-2 inguinal lymph nodes, cure is possible in nearly 75% with only lymphadenectomy, and almost 20% of patients with limited pelvic lymph node involvement can be cured.

Clinically negative lymph nodes do not always mean that metastases has not occurred, as 20% of patients have occult inguinal metastases.

30% of those with positive inguinal nodal disease have pelvic node involvement.

High-grade and high-stage cancers are likely to have nodal disease with 80%-100% of these patients having positive nodes.

Only 24% of patients with well-differentiated cancer will have nodal metastases.

61%-75% of patients with T2 cancers have nodal metastases.

5%-10% of patients with T1 disease will have nodal metastases.

Nodal metastases occur in a significant number of patients with low stage and low-grade disease.

Mortality rate of penile surgery followed by lymphadenectomy is less than 1%.

Sentinel node biopsy may spare the need for bilateral inguinal lymphadenectomy.

Surgical margin of 0.5-1 cm is adequate.

Penile epithelial neoplasia represents a dysplastic premalignant lesion.

Moh’s surgery provides effective, long-term local control for patients with localized penile cancer.

 

 

Moh’s surgery demonstrated overall survival (OS) of 97.7% and recurrence-free survival of 93.0%.

 

 

Treatment is associated with continual mutilation changes to the quality of life.

 

 

Treatment for penile carcinoma include partial penectomy, local excision, topical chemotherapy, laser ablation, circumcision, glansectomy, and glans resurfacing.

 

 

Patients with Ta, Tis, T1, and T2 disease are considered candidates for Mohs surgery.

 

 

Lesions were predominantly located on the glans (41.9%).

 

 

No patient had a positive surgical margin after Mohs surgery. 

 

 

OS was 97.7%, with 1 death from non-cancer related causes.