All About Penile Cancer
What is the penis?
The penis is an external male sex organ that is also part of the urinary system. It is made of skin, nerves, smooth muscle, and blood vessels. The parts of the penis are the glans, shaft, corpus cavernosum, corpus spongiosum, meatus, and urethra. The glans (head) is the tip of the penis that is covered by skin called mucosa. This mucosa is the skin that is removed when a male is circumcised. The main part of the penis is the shaft and houses the corpus cavernosum and the corpus spongiosum. The corpus cavernosum is the two cylinder-shaped tissues that run along the sides of the penis. The corpus spongiosum is the sponge-like tissue that is in the front of the penis and ends at the glans. The urethra is inside the corpus spongiosum. The urethra is a thin tube that connects to the bladder and it excretes urine and semen to the outside of the body. The opening on the glans of the penis where semen and urine exit the body is called the meatus.
What is penile cancer?
Normally, cells in the body will grow and divide to replace old or damaged cells in the body. This growth is highly regulated, and once enough cells are made to replace the old ones, normal cells stop dividing. Tumors occur when cells continue to grow in an uncontrolled way. Tumors can either be benign or malignant. Benign tumors do not spread beyond the part of the body where they started (metastasize) and do not invade nearby tissues. Malignant tumors can invade and damage other tissues around them. They also may spread to other parts of the body, often through the bloodstream or through the lymphatic system where the lymph nodes are found.
Over time, the cells of a malignant tumor become more abnormal and appear less like normal cells. This change in how cancer cells look is called the tumor grade. Cancer cells are described as being well-differentiated, moderately-differentiated, poorly-differentiated, or undifferentiated. Well-differentiated cells look normal and like the cells from which they started. Undifferentiated cells have become so abnormal that it can be hard to tell what types of cells they started from.
Penile cancer can either be in or on the penis. Almost all cases of penile cancer start in the skin cells of the penis. Most of these cancers develop from the squamous cells, which are flat skin cells.
The earliest stage of squamous cell cancer in the penis is called carcinoma in situ and only affects the top layers of skin. Carcinoma in situ of the glans is called erythroplasia of Queyrat. If it is on the shaft, it is called Bowen disease. Squamous cell cancers start anywhere on the penis but most often on the foreskin of uncircumcised men or on the glans. They are slow-growing and the earlier they are diagnosed, the greater the cure rate. More rare types of penile cancer include melanoma, basal cell carcinoma, adenocarcinoma, and sarcoma.
What causes penile cancer and am I at risk?
Each year, there are about 2,210 new cases of penile cancer diagnosed in the United States. In Asia, Africa, and South America, it is diagnosed more often. There are a number of risk factors that can lead to penile cancer. However, having one or more risk factors does not mean that you will get penile cancer. You could also have no risk factors and get penile cancer. Circumcision just after birth, a procedure in which the skin covering the tip of the penis is removed, appears to protect men from getting the disease. Phimosis, or an unretractable foreskin, is also associated with an increase in the risk of penile cancer. It is thought that circumcision decreases the chance of penile cancer because there is less retention of smegma (skin that has been shed combined with moisture and oil from the skin). Poor hygiene, chronic retention of smegma, and having a sexually transmitted disease (such as HPV or human papillomavirus 16 or 18) may also increase a man's risk of penile cancer. Smoking and HIV can increase a man’s risk of penile cancer. Men who have been treated for a skin condition called psoriasis with medications called psoralens and UV (ultraviolet) light have been found to have a higher rate of penile cancer. It is important that a man receiving this treatment covers his genitals during exposure to UV light.
How can I prevent penile cancer?
To prevent penile cancer, it is best to avoid known risk factors such as smoking, and contraction of HPV and HIV. There are HPV vaccines for men and women. It is also important for men to practice proper hygiene. Uncircumcised men should retract the foreskin when washing their penis. Although not having a circumcision is a risk factor in penile cancer, studies do not necessarily find the circumcision will prevent penile cancer.
What screening tests are used for penile cancer?
There are no specific screening tests for penile cancer. However, cancer of the penis can be visible. If a man finds any type of lesion, wart, blister, sore, ulcer, white patch, or any other abnormality he should have it looked at by a medical provider. Most likely it is not cancer, but it could be an infection, sexually transmitted disease, or some other type of condition that should be treated. Most likely, if it is cancer and it is found early, it can be treated early with little or no damage to the penis.
What are the signs of penile cancer?
Penile cancer often presents as a lump, mass, or ulcer on the penis. Lesions can be raised and wart-like or flat. The penile lesion can be sore and inflamed, and there may be itching and burning in the region as well. Generally, penile cancers affect the head or foreskin of the penis rather than the shaft of the penis. Penile cancers can look very different, anything from a small bump to a very large, infected, and aggressive lesion. Diagnosis can be delayed since penile cancer can look so different for each person.
Some men with penile cancer will have swollen groin lymph nodes at diagnosis. Penile cancer lesions can often become infected and cause lymph node swelling. Without treatment, the cancer cells may form a raised lesion that can sometimes cause parts of the tissue of the penis to die and erode. The spread of the disease is rare and symptoms in other parts of the body are uncommon.
How is penile cancer diagnosed?
After a physical examination, you will likely need a biopsy (tissue sample) of the cancerous cells to be looked at under a microscope by a pathologist. To get tissue, a provider inserts a needle into the area of abnormal skin or tissue, or removes the entire tumor in a surgical procedure called a wide local excision. In some cases, a procedure called a cystoscopy may be done, in which a tiny camera (scope) is inserted through the opening of the penis and all the way to the bladder to look for the spread of cancer to the urethra (tube connecting the bladder to the penis) and/or bladder. A CT, MRI, or ultrasound of the penis may be done to see if the tumor has spread to the deeper parts of the penis.
How is penile cancer staged?
Once penile cancer is found, more tests will be done to see if the tumor has spread and so that a treatment plan can be made. The staging of a cancer describes how much it has grown before the diagnosis is made. Staging is the extent of disease. Keep in mind that penile cancer rarely spreads, but it is possible.
The staging system for penile cancer is the "TNM" system described by the American Joint Committee on Cancer.
- "T" describes the size or invasiveness of the tumor.
- "N" describes the spread of the tumor to any glands, or lymph nodes, near the tumor.
- "M" describes any distant spread or metastasis to other organs or sites of the body.
This is then interpreted as a stage somewhere from I (one) denoting more limited disease to IV (four) denoting more advanced disease. Grade, or how well the tumor cells are organized, is also used in making treatment decisions but is not included in the official "TNM" staging system.
These staging systems can be hard to understand but they help providers determine the extent of the cancer and make treatment decisions. The stage of cancer, or extent of disease, is based on the information gathered through the various tests done (described above) as the diagnosis and work-up of the cancer is being performed. Your healthcare provider will use the results of the diagnostic work-up to assign the TNM result. The TNM breakdown is quite technical, and the entire staging system is outlined at the end of this article.
How is penile cancer treated?
The goal of the treatment of penile cancer is to not only remove all of the cancer but also to prevent the cancer from coming back (recurrence) and to maintain as much of the function and form of the penis. Changes to the size, shape, and function of the penis can cause distress. It has become common in recent years to use the most organ-sparing treatment possible. The most common treatment for penile cancer is surgery. Surgery may be used with radiation and/or chemotherapy, called adjuvant therapy.
Surgery
Surgery can be useful in all stages of penile cancer. There are many different types of surgeries that can be done. For early-stage penile cancer, excisional surgery can be used. The area is numbed with local anesthesia and the entire lesion with a border or margin of healthy tissue is removed with a scalpel (surgical knife). The skin is then closed with sutures (stitches). The tissue is sent to a laboratory for a pathologist to make sure all the cancer has been removed. If the cancer is only on the foreskin, a circumcision (foreskin removal) may be done. This is like an excisional surgery.
In some cases, a glansectomy is done. A glansectomy is the removal of part or all of the tip of the penis. A skin graft from another part of the body may be used to rebuild the tip of the penis.
Moh’s surgery is a procedure done by a trained specialist in the office under local anesthesia. With Moh’s surgery, very precise surgery is done to remove the least amount of tissue while the margins, or edges, of the resection are looked at under a microscope right away to make sure all of the cancer is removed.
Penectomy, removal of part or all of the penis, can be used to treat penile tumors. Earlier stage tumors are treated with partial penectomy in which part of the penis is removed. Removal of the entire penis and the roots that extend into the pelvis, also called a total penectomy, may be used for larger tumors. The removal of the entire penis will change how a man urinates. The surgeon will create an opening between the scrotum and the anus called a perineal urethrostomy. The urethral sphincter will remain so a man will be able to control when he wants to urinate.
Some patients may also need to have their lymph nodes biopsied or removed. This can lead to severe swelling in the groin and legs. There are other options using less extensive lymph node removal. One option is to have a selective dissection of the groin nodes using a sentinel mapping technique (where a dye or radioactive material is used to find the lymph nodes most likely involved with cancer such that only they are removed). If these nodes are negative, further dissection is not needed. It may also be possible to only remove some of the nodes instead of all of the nodes of the groin (modified inguinal lymphadenectomy). Your surgeon will talk to you about your options.
In men with positive nodes, removal of lymph nodes of both sides of the groin is recommended. You may be given antibiotics before surgery to see if the enlarged lymph nodes are caused by infection. If this doesn’t work, resection of the nodes should be done. If multiple groin lymph nodes are cancerous, or if a patient has groin nodes that can be felt on an exam or seen on imaging studies, the surgeon may also remove nodes from both the deep groin and pelvis to look for spread of disease. After removal of these lymph nodes, chemotherapy and radiation therapy are often given to ensure that all cancer cells have been killed.
The treatment of advanced tumors may need a surgery called emasculation. This surgery removes the penis and often the scrotum and testicles. Men who have this surgery will need a testosterone supplement since the testicles are removed.
Radiation Therapy
Radiation can also be used to treat penile cancer.
Radiation is the use of high-energy x-rays. These x-rays are like those used for x-rays, but they have a much higher energy. The high energy of x-rays in radiation therapy damages the DNA of cells. Cancer cells divide faster than healthy cells, and so their DNA is more likely to be damaged than normal cells. Also, cancer cells are less able to repair damaged DNA than normal cells are, so cancer cells are killed more easily by radiation than normal cells are. Radiation therapy kills cancer cells while killing fewer cells in normal, healthy tissue.
Before radiation, a circumcision should be performed. This is done to manage the swelling and tightening of the foreskin that can be caused by radiation therapy. Radiation can help preserve the penis by avoiding a penectomy in some early-stage cases.
Both external radiation (radiation that comes from a machine rotating around the patient) and brachytherapy (a procedure in which radioactive material is placed into the tumor) can be used. There are two types of brachytherapy that can be used:
- Interstitial: In the operating room, hollow needles are placed into the penis and held in place with a plastic holder. Radioactive pellets are placed in the needles and left in for different periods of time. This can be done over many days. When treatment is done, the pellets and needles are removed.
- Plesiobrachytherapy: A plastic cylinder is placed over the penis and another cylinder that contains a source of radiation is placed over top of the first cylinder. Treatment is often given several days in a row and is used only for tumors that are near the surface of the penis.
Radiation therapy can be used alone, or it can be used with or without chemotherapy following surgery in patients who have advanced disease. In advanced disease, poorly differentiated tumors, and when lymph nodes are involved, chemotherapy and radiation are used together to treat the pelvis and groin. This is done to prevent the cancer from returning in the pelvis, groin, or penis. The radiation and chemotherapy are given after the lymph nodes in the groin have been removed by the surgeon. Radiation may also be used in advanced disease to slow the growth of the cancer and manage symptoms.
Before starting radiation, speak to your provider about the side effects of radiation. Some may affect the skin on your penis, and it is important to perform good hygiene. Ask your provider about proper hygiene. Some less common but serious side effects can be skin necrosis (death), trouble urinating, and trouble getting an erection.
Chemotherapy
Chemotherapy is most often used when the cancer has spread throughout the body to distant sites, and for patients who need systemic therapy (therapy that reaches all parts of the body). Chemotherapy may be used with radiation when the tumor involves the lymph nodes. Once the cancer has spread to other organs, chemotherapy is used to try to help manage side effects and slow the growth of the cancer, but does not cure the cancer. Chemotherapy can also be used before surgery when patients have more advanced disease, such as spread to the lymph nodes in the groin or pelvis. Because penile cancer is rare, there is no standard chemotherapy regimen used for penile cancer. The chemotherapies used vary due to the lack of research. The most commonly used chemotherapies are: cisplatin, ifosfamide, fluorouracil, capecitabine, mitomycin C and paclitaxel. The two most common regimens are cisplatin/fluorouracil, and TIP (paclitaxel, ifosfamide, and cisplatin).
Topical chemotherapy medications, like fluorouracil (5-FU), can be used to treat non-invasive penile cancers. The 5-FU cream is applied to the area as directed by your provider. Imiquimod is also an approved topical medication. This cream, which is thought to work by stimulating the immune system, is applied directly to the skin.
Local Treatments
In some cases, a laser light is used to destroy cancer cells in small lesion(s) rather than use a scalpel. Cryosurgery, the freezing and removal of cancerous cells and tissue, may also be used. Both laser surgery and cryosurgery are useful techniques but are not used as often.
Clinical Trials
There are clinical research trials for most types of cancer, and at every stage of the disease. Clinical trials are designed to determine the value of specific treatments. Trials are often designed to treat a certain stage of cancer, either as the first form of treatment offered, or as an option for treatment after other treatments have failed to work. They can be used to evaluate medications or treatments to prevent cancer, detect it earlier, or help manage side effects. Clinical trials are extremely important in furthering our knowledge of this disease. It is through clinical trials that we know what we do today, and many exciting new therapies are currently being tested. Talk to your provider about participating in clinical trials in your area. You can also explore currently open clinical trials using the OncoLink Clinical Trials Matching Service.
Follow-Up Care and Survivorship
Follow-up care for patients who have been treated for penile cancer will depend on the extent of the cancer and how it was treated. Patients are often seen every 3-6 months for the first 2 years and then once a year for years 3-5. No matter how often you are being seen it is very important to notify your provider of any new symptoms you are having. These could be caused by the treatment you received or could be signs of recurrence. Going to all scheduled appointments is important for patients who have not undergone removal of lymph nodes, since there is a risk of spread of the cancer to the lymph nodes. The cornerstone of follow-up care is physical examination, although sometimes imaging studies such as ultrasound of the groin may detect spread of cancer to lymph nodes even before those nodes can be felt on examination. CT scanning of the pelvis is also helpful in detecting abnormal nodes that cannot be detected on physical examination. If a patient has undergone removal of the penis, reconstruction of the penis by plastic surgery may be considered.
Fear of recurrence, sexuality issues, financial impact of cancer treatment, employment issues and coping strategies are common emotional and practical issues experienced by penile cancer survivors. Your healthcare team can identify resources for support and management of these practical and emotional challenges faced during and after cancer.
Cancer survivorship is a relatively new focus of oncology care. With nearly 17 million cancer survivors in the US alone, there is a need to help patients transition from active treatment to survivorship. What happens next, how do you get back to normal, what should you know and do to live healthy going forward? A survivorship care plan can be a first step in educating yourself about navigating life after cancer and helping you communicate knowledgeably with your healthcare providers. Create a survivorship care plan today on OncoLink.
Resources for More Information
The American Cancer Society
Dedicated to helping persons who face cancer. The ACS supports research, patient services, early detection, treatment and education. The ACS maintains a national database of patient support services, support groups and resources.
www.cancer.org
Imerman’s Angels
Dedicated to providing personalized connections that enable one-on-one support among cancer fighters, survivors and caregivers.
www.imermanangels.org
Cancer Support Community
An international non-profit dedicated to providing support, education and hope to people affected by cancer.
www.cancersupportcommunity.org
Appendix: Complete Penile Cancer Staging
American Joint Committee on Cancer, TNM Staging for Penile Cancer. (8th ed., 2017)
Primary Tumor (T) | Description |
|---|---|
TX | Primary tumor cannot be assessed |
T0 | No evidence of primary tumor |
Tis | Carcinoma in situ (penile intraepithelial neoplasia) |
Ta | Noninvasive localized squamous cell carcinoma |
T1 | Glans: tumor invades lamina propria. Forsekin: Tumor invades dermis, lamina propria, or dartos fascia. Shaft: Tumor invades connective tissue between epidermis and corpora regardless of location. All sites with or without lymphovascular invasion or perineural invasion and is or is not high grade. |
T1a | Tumor is without lymphovascular invasion or perinueral invastion or is high grade. |
T1b | Tumor exhibits lymphovascular invasion and/or perineural invasion or is high grade. |
T2 | Tumor invades corpus spongiosum or cavernosum with or without urethral invasion. |
T3 | Tumor invades into corpora cavernosum with or without urethral invasion. |
T4 | Tumor invades other adjacent structures. |
Regional Lymph Nodes (N) | Clinical Stage Definition |
|---|---|
cNX | Regional lymph nosed cannot be assessed |
cN0 | No palpable or visibly enlarged inguinal lymph nodes. |
cN1 | Palpable mobile unilateral inguinal lymph node |
cN2 | Palpable mobile ≥2 unilateral inguinal nodes or bilateral inguinal lymph nodes. |
cN3 | Palpable fixed inguinal nodal mass or pelvic lymphadenopathy unilateral or bilateral |
Lymph Nodes (N) | Pathologic Stage Definition |
|---|---|
pNX | Regional lymph nodes cannot be assessed |
pN0 | No lymph node metastasis |
pN1 | ≤2 unilateral inguinal metastases, no ENE |
pN2 | ≥3 unilateral inguinal metastases or bilateral metastases |
pN3 | Extranodal extension of lymph node metastases or pelvic lymph node metastases |
Distant Metastasis (M) | Description |
|---|---|
M0 | No distant metastasis |
M1 | Distant Metastasis |
Stage | T | N | M |
|---|---|---|---|
Stage 0is | Tis | N0 | M0 |
Stage 0a | Ta | N0 | M0 |
Stage I | T1a | N0 | M0 |
Stage IIA | T1b | N0 | M0 |
Stage IIIA | T1-3 | N1 | M0 |
Stage IIIB | T1-3 | N2 | M0 |
Stage IV | T4 | Any N | M0 |
References
Algan, O and Crook J. Primary and Adjuvant Radiation Therapy in the Management of Penile Cancer. 2014. P173-198.
American Cancer Society. Penile Cancer. Found at: https://www.cancer.org/cancer/penile-cancer.html
Hegarty PK et al. Penile cancer: organ-sparing techniques. British Journal of Urology. 2014; 114:799-805.
National Institute of Health. National Cancer Institute Penile Cancer Treatment (PDQ®). Found at: http://www.cancer.gov/types/penile
NCCN. Guidelines Version 2.2021. American Joint Committee on Cancer (AJCC) TNM Staging System for Penile Cancer (8th ed., 2017)
Van Poppel H., et al. Penile Cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology. 2013. 24:115-124.
Wang J et al. Treatment for Metastatic Penile Cancer After First-line Chemotherapy Failure: Analysis of Response and Survival Outcomes. Urology. 2015 May;85(5):1104-1110.