Penile Cancer

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What is Penile Cancer ?

About the penis

The penis is the external genital organ of a man. It is made up of three chambers of spongy tissue that contain smooth muscle and many blood vessels and nerves. The corpora cavernosa makes up two of the chambers that are located on both sides of the upper part of the penis. The corpus spongiosum is located below the corpora cavernosa and surrounds the urethra, the tube through which urine and semen leave the body at an opening called the meatus. At the tip of the penis, the corpora cavernosa expands to form the head of the penis, or glans.

About penile cancer

Cancer begins when normal cells change and grow uncontrollably, forming a mass called a tumor. A tumor can be benign (noncancerous) or malignant (cancerous, meaning it can spread to other parts of the body). Penile cancer is a rare form of cancer that occurs mostly in uncircumcised men (men who have a foreskin, the piece of skin covering the head of their penis). Circumcision is the removal of the foreskin and may reduce the risk of penile cancer.

Types of penile cancer

There are several types of penile cancer, including:

Epidermoid/squamous cell carcinoma. Ninety-five percent (95%) of penile cancer is epidermoid, or squamous cell, carcinoma. This means that the cells look like the tissues that make up skin when looked at with a microscope. Squamous cell carcinoma can begin anywhere on the penis; however, most develop on or under the foreskin. When found at an early stage, epidermoid carcinoma can usually be cured.

Basal cell penile cancer. Under the squamous cells in the lower epidermis (one of the layers of the skin tissues that cover the penis) are round cells called basal cells. These can sometimes become cancerous. This is also called non-melanoma skin cancer. Less than 2% of penile cancers are basal cell cancers.

Melanoma. The deepest layer of the epidermis contains scattered cells called melanocytes, which make the melanin that gives skin color. Melanoma starts in melanocytes, and it is the most serious type of the skin cancer. This cancer sometimes occurs on the surface of the penis. 

Sarcoma. About 1% of penile cancers are sarcomas, which are cancers that develop in the tissues that support and connect the body, such as blood vessels, smooth muscle, and fat.

Risk Factors and Prevention

A risk factor is anything that increases a man’s chance of developing cancer. Although risk factors often influence the development of cancer, most do not directly cause cancer. Some people with several risk factors never develop cancer, while others with no known risk factors do. However, knowing your risk factors and talking about them with your doctor may help you make more informed lifestyle and health care choices.

The following factors can increase a person’s risk of developing penile cancer:

Human papillomavirus (HPV) infection. The most important risk factor for penile cancer is infection with this virus. HPV is most commonly passed from person to person during sexual activity. There are different types, or strains, of HPV, and some strains are more strongly associated with certain types of cancers. Reduce your risk of HPV infection by limiting the number of sex partners, because having many partners increases the risk of HPV infection. Using a condom cannot fully protect you from HPV during sex. HPV vaccines protect against certain strains of the virus. 

Smoking. Smoking may contribute to the development of penile cancer, especially in men who are also infected with HPV. 

Age. Penile cancer is most common in men older than 50. About 20% of the time, patients with penile cancer are younger than 40.

Smegma. Smegma is a thick substance that can build up under the foreskin and is caused by dead skin cells, bacteria, and oily secretions from the skin. Smegma may contain small amounts of cancer-causing substances. Uncircumcised men should pull back (retract) the foreskin and thoroughly wash the penis on a regular basis to make sure that smegma does not cause irritation of the penis.

Phimosis. Phimosis occurs when the foreskin becomes tight or constricted and is difficult to retract, therefore causing a buildup of smegma. Men with phimosis are less likely to be able to thoroughly clean the penis.

HIV/AIDS infection. Infection with human immunodeficiency virus (HIV), the virus that causes acquired immune deficiency syndrome (AIDS), is a risk factor. When a person is HIV-positive, their immune system is less able to fight off early-stage cancer.

Psoriasis treatment. Men who have been treated with the drug psoralen combined with ultraviolet (UV) light have a higher risk of developing penile cancer.

Circumcision. Circumcision may provide some protection from penile cancer because removing the foreskin helps keep the area clean. Epidermoid/squamous cell carcinoma of the penis almost never occurs in men who are circumcised. However, it is important to note that circumcision alone cannot prevent penile cancer.

Personal hygiene. Men who carefully and completely clean under the foreskin on a regular basis can lower their risk of developing penile cancer.

Symptoms and Signs : Men with penile cancer may experience the following symptoms or signs. Sometimes, men with penile cancer do not show any of these symptoms. Or, these symptoms may be caused by a medical condition that is not cancer. If you are concerned about a symptom or sign on this list, please talk with your doctor.

A growth or ulcer on the penis, especially on the glans or foreskin, although it can also occur on the shaft

Changes in the color of the penis

Skin thickening on the penis

Persistent discharge with a foul odor beneath the foreskin

Blood coming from the tip of the penis or from under the foreskin

Unexplained pain in the shaft or tip of the penis

Irregular or growing bluish-brown flat lesions or marks beneath the foreskin or on the penis

Reddish, velvety rash beneath the foreskin

Small, crusty bumps beneath the foreskin

Swollen lymph nodes in the groin

Irregular swelling at the end of the penis

Your doctor will ask you questions about the symptoms you are experiencing to help find out the cause of the problem, called a diagnosis. This may include how long you’ve been experiencing the symptom(s) and how often.

If cancer is diagnosed, relieving symptoms and side effects remains an important part of cancer care and treatment. This may also be called symptom management, palliative care, or supportive care. Be sure to talk with your health care team about symptoms you experience, including any new symptoms or a change in symptoms.

Diagnosis : Doctors use many tests to diagnose cancer and find out if it has metastasized (spread). Some tests may also determine which treatments are likely to be the most effective. For most types of cancer, a biopsy (see below) is the only way to make a definitive diagnosis of cancer. If a biopsy is not possible, the doctor may suggest other tests that will help make a diagnosis. Imaging tests may be used to find out whether the cancer has metastasized. Your doctor may consider these factors when choosing a diagnostic test:

Age and medical condition

Type of cancer suspected

Severity of symptoms

Previous test results

In addition to a physical examination, the following tests may be used to diagnose penile cancer:

Biopsy. A biopsy is the removal of a small amount of tissue for examination under a microscope. Other tests can suggest that cancer is present, but only a biopsy can make a definite diagnosis. The sample removed from the biopsy is analyzed by a pathologist (a doctor who specializes in interpreting laboratory tests and evaluating cells, tissues, and organs to diagnose disease).

Fine needle aspiration/biopsy. A fine needle aspiration is a specific type of biopsy. First, the skin is often made numb with an anesthetic (a medication to block the awareness of pain) cream, followed by an injection of local anesthetic into the area near the tumor. The doctor will insert a thin needle into the tumor and remove some cells and fluid. The procedure may be repeated two or three times to obtain samples from different areas of the tumor. The samples will then be sent to a laboratory, where a pathologist will determine if the cells are cancerous (called positive for cancer), non-cancerous (called benign or negative for cancer), or undetermined (called non-diagnostic).

Sentinel lymph node biopsy. This is another type of biopsy. It is important to know if cancer cells have spread to other areas beyond the penis. In this technique, the doctor removes one or a few sentinel lymph nodes—the first lymph node(s) into which the lymph system drains into near to the tumor—to check for cancer cells. Lymph nodes are the tiny, bean-shaped organs that help fight infection. In the case of penile cancer, the sentinel lymph nodes are located just under the skin in the groin. If cancer cells are detected, it means that the disease may have spread to other lymph nodes in the region or to other parts of the body through the blood and lymph vessels. However, there is a chance that a sentinel lymph node biopsy may not find cancer cells in the lymph nodes, when in fact the cancer has spread.

Inguinal (groin) lymph node dissection. This is the most accurate way to find out whether the cancer has spread to any lymph nodes near the penis. In this procedure, the lymph nodes near the penis are removed and checked for cancer. This procedure provides more information than the removal of a single lymph node or a group of lymph nodes. However, after this procedure, some men may have problems with wound healing and long-lasting and possibly severe lymphedema (leg swelling). Research to find ways to prevent these side effects is ongoing. 

X-ray. An x-ray is a way to create a picture of the structures inside of the body, using a small amount of radiation.

Computed tomography (CT or CAT) scan. A CT scan creates a three-dimensional picture of the inside of the body with an x-ray machine. A computer then combines these images into a detailed, cross-sectional view that shows abnormalities or tumors. Sometimes, a contrast medium (a special dye) is injected into a patient’s vein to provide better detail. A CT scan helps find out if the cancer has spread to lymph nodes in the groin, pelvis, and the abdomen and also allows the doctor to see if the cancer has spread to the lungs, liver, and other tissues.

Magnetic resonance imaging (MRI). An MRI uses magnetic fields, not x-rays, to produce detailed images of the body. A contrast medium may be injected into a patient’s vein to create a clearer picture.

Positron emission tomography (PET) scan. A PET scan is a way to create pictures of organs and tissues inside the body. A small amount of a radioactive substance is injected into a patient’s body. This substance is absorbed mainly by organs and tissues that use the most energy. Because cancer tends to use energy actively, it absorbs more of the radioactive substance. A scanner then detects this substance to produce images of the inside of the body. However, PET scans have not been approved for use in men with penile cancer, and research studies have not shown that PET scans increase survival or otherwise provide any benefit for men with penile cancer.

Stages and Grades : Grading and staging are ways of describing how fast-growing the cancer is and how much it has grown, including where the cancer is located and if or where it has spread. Doctors use diagnostic tests to determine the cancer's grade and stage, so grading and staging may not be complete until all the tests are finished. Knowing the grade and stage helps the doctor to decide what kind of treatment is best and helps predict a patient's prognosis (chance of recovery).

Grading : Histologic grade describes how much the cancer cells look like normal tissue under a microscope. A tumor's grade is described using the letter “G” and a number. Grade is important because it helps to predict the likelihood that the cancer has spread. In general, the lower the grade, the better the prognosis.

GX: The tumor grade cannot be identified.

G1: Describes cells that look more like normal tissue cells (called well differentiated).

G2: The cells are somewhat different from normal cells (called moderately differentiated).

G3: Describes tumor cells that look very much like each other, but don’t look very much like normal cells (called poorly differentiated).

G4: The tumor cells barely look like normal cells (called undifferentiated).

Staging : There are different stage descriptions for different types of cancer. One tool that doctors use to describe the stage is the TNM system. This system judges three factors: the tumor itself, lymph nodes around the tumor, and if the tumor has spread to the rest of the body. The results are combined to determine the stage of cancer for each person. There are five stages of penile cancer: stage 0 (zero) and stages I through IV (one through four). The stage provides a common way of describing the cancer so doctors can work together to plan the best treatments.

TNM is an abbreviation for tumor (T), node (N), and metastasis (M). Doctors look at these three factors to determine the stage of cancer:

How large is the primary tumor, where is it located and what is the grade of the tumor (see Grading above)? (Tumor, T)

Has the tumor spread to the lymph nodes near the tumor? (Node, N)

Has the cancer metastasized (spread) to other parts of the body? (Metastasis, M) 

Tumor. Using the TNM system, the "T" plus a letter and/or number (0 to 4) is used to describe the size and location of the tumor. Some stages are also divided into smaller groups that help describe the tumor in even more detail. This helps the doctor develop the best treatment plan for each patient. Specific tumor stage information is listed below:

TX: The primary tumor cannot be evaluated.

T0: There is no tumor.

Tis: An early cancer that has not spread to other tissue. This is also called carcinoma in situ.

Ta: The tumor is a noninvasive, verrucous (wart-like) carcinoma, which looks somewhat like a small piece of broccoli or cabbage.

T1a: The tumor has grown into the subepithelial connective tissue (tissue below the top layers of skin). The tumor has not grown into blood or lymph vessels, and the tumor grade (see above) is G2 or lower.

T1b: The tumor has grown into the subepithelial connective tissue. The tumor has grown into blood or lymph vessels, and/or the tumor grading is G3 or higher.

T2: The tumor has grown into the corpus spongiosum or corpora cavernosum (internal chambers of the penis).

T3: The tumor has grown into the urethra.

T4: The tumor has grown into other nearby structures.

Node. The “N” in the TNM staging system stands for lymph nodes near the cancer (called regional lymph nodes). The regional lymph nodes for penile cancer are located in the groin and the pelvis. Lymph nodes in other parts of the body are called distant lymph nodes. Staging places cancers that have spread to regional lymph nodes and cancers that have spread to distant lymph nodes in separate categories. The N in TNM staging only refers to the regional lymph nodes.

If the doctor evaluates the lymph nodes before the biopsy or surgery, based on a physical examination and/or other tests, the letter “c” (for “clinical” staging) is placed in front of the N. If the doctor evaluates the lymph nodes after a biopsy or surgical removal of the lymph nodes, which is more accurate, the letter “p” (for “pathologic” staging) is placed in front of the N. The information below describes the pathologic staging.

pNX: The regional lymph nodes cannot be evaluated.

pN0: Cancer has not spread to the regional lymph nodes.

pN1: Cancer has spread to a single inguinal lymph node (lymph node in the groin).

pN2: Cancer has spread to more than one inguinal lymph node on the same side or both sides of the body.

pN3: The cancer has spread to one or more inguinal (groin) lymph nodes, and it has grown from that lymph node into the surrounding tissue in the groin, and/or the cancer has spread beyond the lymph nodes in the groin or pelvis, on the same side or both sides of the body.

Distant metastasis. The “M” in the TNM system indicates whether the cancer has spread from the penis to other parts of the body.

MX: Distant metastasis cannot be evaluated.

M0: There is no distant metastasis.

M1: There is metastasis to parts of the body other than the penis and the regional lymph nodes.

Cancer stage grouping

Doctors assign the stage of the cancer by combining the T, N, and M classifications.

Stage 0: The cancer has not grown below the superficial (surface) layer of skin, and it has not spread to lymph nodes or distant parts of the body (Tis or Ta; N0, M0).

Stage I: A low-grade cancer has grown just below the superficial layer of skin. It has not spread to lymph nodes or distant parts of the body (T1a, N0, M0).

Stage II: The cancer is invasive and is high grade and/or has grown into blood or lymph vessels and/or into the internal chambers of the penis and/or the urethra. There is no spread to lymph nodes or distant parts of the body (T1b, T2, or T3; N0, M0).

Stage IIIa: The cancer has grown no further than the urethra, and has spread to a single groin lymph node, but has not spread to distant parts of the body (T1, T2, or T3; N1, M0).

Stage IIIb: The cancer has grown no further than the urethra, and has spread to more than one groin lymph node, but it has not spread to pelvic lymph nodes or distant parts of the body (T1, T2, or T3; N2, M0).

Stage IV: Any of the following:

The cancer has grown into nearby tissues (T4, any N, any M).

The cancer has spread to one or more inguinal (groin) lymph nodes, and it has grown from that lymph node into the surrounding tissue in the groin (any T, N3, any M).

The cancer has spread to at least one lymph node in the pelvis (any T, N3, any M) and/or to distant lymph nodes outside the pelvis or to other parts of the body (any T, any N, M1).

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