Penile Cancer: The Basics
Charles Wood, MD
Updated by J. Taylor Whaley
Abramson Cancer Center of the University of Pennsylvania
Last Modified: March 28, 2011
What is penile cancer?
Penile cancer is a rare disease in which cancer cells develop within the skin and/or soft tissues of the penis.
Who gets penile cancer?
Penile cancer is rare in the United States and there are only about 1,300 new cases diagnosed annually. This translates into an occurrence of about 1 per 100,000 men in North America. In Asia, Africa, and South America, it is much more common with an incidence as high as 10 to 20 per 100,000 men. Circumcision just after birth, a procedure in which the covering of the tip of the penis is removed, appears to protect men from developing the disease. The risk of penile cancer is about 3 times higher for men who are uncircumcised, or are circumcised later in life. Phimosis, or an unretractable foreskin, has also been associated with up to a 10-fold increase in the risk of penile cancer. Possible mechanisms by which circumcision may decrease the incidence of penile cancer include avoiding the development of phimosis and preventing the retention of smegma (skin that has been shed combined with moisture and oil from skin). Poor hygiene, chronic retention of smegma, and having a sexually transmitted disease (such as HPV or human papilloma virus 16 or 18) may also increase a man's risk of developing cancer of the penis. Recent scientific advancements have produced human papilloma virus vaccines that may potentially play a role in the prevention of penile cancer, though the area remains controversial. Similar to anal, gynecologic, and other genital cancers, HPV infection has a strong association with penile cancer. Nearly 50% of patients that develop penile cancer have been found to have the HPV infection. The impact of HPV on prognosis has yet to be determined. In 2009, the FDA approved the use of the HPV vaccine in males aged 9 through 26 years. Although this vaccine is intended to reduce the rate of genital warts, vaccinating prior to initiation of sexual activity may have an effect on penile cancer. This topic remains on the forefront of active research. Smoking also appears to be associated with penile cancers and the incidence of penile cancer is approximately eight-fold higher in HIV-infected men. Most cancers of the penis are squamous cell carcinomas, which arise from the skin of the penis. Although rare, it is possible to get metastasis (tumors which have spread from other areas) to the penis.
What are the symptoms?
Penile cancer commonly 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. Although some penile cancers begin as pre-malignant lesions, the majority of penile cancers do not have premalignant lesions. The presentation for penile cancers can vary significantly from a small bump to very large, infected, and aggressive lesions. The cause for such a wide range of presentations can be explained in the delay in diagnosis. The average time interval from initial symptoms to evaluation by a health care physician approaches 10 months.
About half of men with penile cancer will have swollen groin lymph nodes at diagnosis. Only about half of these swollen nodes will be involved with tumor. This occurs because penile cancer lesions can often become infected and can also cause lymph node swelling. As the disease progresses, the cancer cells may form a raised lesion that can sometimes cause parts of the tissue of the penis to die and erode away. Spread of the disease is rare and symptoms in other parts of the body are uncommon.
How is it diagnosed?
After performing a physical examination, it is usually necessary to obtain a tissue sample, or biopsy, of the cancerous cells for examination under the microscope by the pathologist. Tissue is obtained by inserting a needle into the area of abnormal skin or tissue or by removing the entire tumor in a surgical procedure called a wide local excision. Cancers are described by the type of cells from which they arise. More than 95% of penile cancers are squamous cell carcinomas, a type of cell that is flat and thin and makes up the outer layer of the skin. Once the cancer is diagnosed, a procedure called a cystoscopy may be performed, in which a tiny camera (scope) is inserted through the opening of the penis and advanced all the way to the bladder to look for spread of cancer to the urethra (tube connecting the bladder to the penis) and/or bladder. An MRI of the penis may also be performed to determine if the tumor has spread to the deeper structures of the penis.
How is it staged?
Once a penile cancer is found, it is necessary to perform more tests to see if the tumor has spread so that appropriate treatment can be recommended. These may involve imaging studies such as CT scans or MRI scans, or procedures such as a cystoscopy (see above).
The extent of the tumor spread is also referred to as the "stage". The stage helps guide your doctor’s recommendations regarding the optimal treatment for the penile cancer as well as the prognosis. The staging system for penile cancer is the "TNM" system described by the American Joint Committee on Cancer. The "T" describes the size or invasiveness of the tumor; the "N" describes the spread of the tumor to any glands, or lymph nodes, near the tumor; and the "M" describes any distant spread, or metastasis, to other organs or sites of the body. 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. The different stages of penile cancer are as follows:
- Tis: carcinoma in situ, or a tumor that involves only the cells in which it began and has not spread to other tissues
- Ta: a tumor that has not invaded through the outmost layer of cells, or epithelium, that makes up the skin
- T1a: a tumor that has invaded through the epithelium to involve the connective tissue below the skin and is not described by the pathologist as poorly differentiated (how different it appear under the microscope from normal cells)
- T1b: a tumor that has invaded through the epithelium to involve the connective tissue below the skin and is determined to be poorly differentiated
- T2: a tumor that has invaded through the connective tissues to involve the corpus spongiosum or corpus cavernosum, the deep spongy tissues of the penis
- T3: a tumor that has invaded the urethra (the tube that connects the bladder and penis)
- T4: a tumor that has invaded other structures such as the bones of the pelvis
- N0: the cancer has not spread to glands or lymph nodes in the groin or pelvis
- N1: the cancer has spread to a single shallow gland or lymph node in the groin, called a superficial inguinal lymph node
- N2: the cancer has spread to more than one shallow gland or lymph node in the groin, either or one side or both sides of the groin
- N3: the cancer has spread to one or more deep glands or lymph nodes in the groin, called deep inguinal lymph nodes, or has spread to lymph nodes in the pelvis (such as internal iliac or hypogastric lymph nodes, external iliac lymph nodes, or obturator lymph nodes)
- M0: the cancer has not spread to distant organs or sites of the body
- M1: the cancer has spread to distant organs or sites of the body
- The different grades of penile cancer are as follows:
- G1: well-organized tumor cells; considered low grade
- G2-3: moderately-organized tumor cells; considered intermediate grade
- G4: poorly-organized tumor cells; considered high grade
The overall stage of the tumor (Stage I, II, III, or IV) is then based on a combination of the T, N, and M categories:
- Stage 0: Tis, N0, M0 and Ta, N0, M0
- Stage I: T1a, N0-1, M0
- Stage II: T1a, T2, or T3, N0, M0
- Stage IIIa: T1-3, N1, M0
- Stage IIIb: T1-3, N2, M0
- Stage IV; T4, N0-3, M0 or T1-4, N3, M0, or T1-4, N0-3, M1
A tumor may also be described as recurrent. This means that the tumor has come back after it was originally treated. It may return to the site where it first started or to other areas of the body.
What is the prognosis of penile cancer?
The prognosis is based largely on the stage of the tumor, as well as the grade. The most important prognostic factor that has demonstrated decreased survival is the presence of cancer cells within the inquinal lymph nodes. Patients with low grade and low stage tumors have an excellent prognosis and long-term survival. Patients with tumors that have not spread to the glands or lymph nodes have an excellent prognosis with cure rates of 80 to 100 percent. The survival rate decreases when the disease spreads to the lymph nodes in the groin, with survival rates below 50 percent at five years.
What are the recommended treatment options?
A partial or total penectomy can result in profound functional and psychosexual ramifications. This has prompted the development of several penile sparing procedures. If the tumor is diagnosed as a non-invasive cancer or early tumor, there are several options. Non-invasive cancers are generally addressed with local treatments, including circumcision, local excision, Moh's surgery, and topical chemotherapy. Very early tumors can be addressed with Laser surgery, Mohs' microsurgery and radiation therapy (which is described below). These techniques are occasionally used for very early tumors that have not invaded into the deeper tissues of the penis. Let’s review the possible treatment options.
Surgery forms the foundation of treatment and can involve excision of the primary tumor and foreskin only, the entire penis, and/or the lymph nodes in the groin and pelvis. Patients with small tumors (Tis), may be eligible for local excision or local ablative techniques like laser treatment, excisional or Moh’s surgery. Excisional surgery is a traditional simple surgical resection involves numbing the area with local anesthesia and removing the entire area of concern with a border or margin of healthy tissue, generally 3-10 mm. The skin is then closed with sutures (stitches) and the tissue is sent to a laboratory for a pathologist to ensure all the cancer has been removed. Moh’s surgery is a procedure performed by a trained specialist in the office under local anesthesia. With Moh’s surgery, very precise surgery is performed with attempts to remove the least amount of tissue while the margins, or edges, of the resection are examined under a microscope immediately to ensure all of the cancer is removed.
T1 tumors are treated with a partial penectomy (removal of part of the penis). Generally, a margin of 2 cm is required for adequate resection on a penectomy. In other words, 2 cm of normal penis is generally removed. Larger tumors generally require removal of the entire penis. For patients with T2 and higher tumors without lymph nodes that can be felt on exam or seen on imaging studies (node negative), surgical removal of the shallow nodes on both sides of the groin may be done in addition to resection of the primary tumor. This can sometimes result in severe swelling in the groin and legs. There are other options using less extensive lymph node removal, which have been studied. 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 to be 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 as opposed to all of the nodes of the groin (modified inguinal lymphadenectomy). Your surgeon will discuss which surgical options for the groin nodes are best for you. Surveillance of the groin nodes without immediate surgery to remove them appears to have a worse outcome that immediate surgery.
In men with positive nodes, removal of lymph nodes of both sides of the groin is recommended. A short period of surveillance with antibiotic treatment can be considered because in some people the enlarged nodes are due to infection. However, if antibiotics fail to resolve the enlarged nodes, resection of the nodes should be performed. If multiple groin lymph nodes are found to be involved with cancer, or if a patient presents with groin nodes that can be felt on exam or seen on imaging studies, the surgeon may also remove nodes from both the deep groin and pelvis to assess for further spread of disease. After removal of involved lymph nodes, chemotherapy and radiation therapy are often given additionally to ensure that all cancers cells have been eradicated. T4 tumors may require more extensive surgery with removal of part of the abdominal wall in addition to the groin lymph nodes and penis.
Radiation involves the use of high energy x-rays aimed at the tumor or the area from where the tumor was removed. Radiation can offer the advantage of penis preservation by avoiding a penectomy in some cases. Both external radiation (radiation that comes from a machine rotating around the patient) and brachytherapy (a procedure in which radioactive seeds are inserted directly into the tumor) can be used. Radiation therapy can be used alone for some T1 lesions and T2 lesions that are low grade, or it can be used with or without chemotherapy following surgery in patients who have advanced disease. Prior to the initiation of radiation, a circumcision should be performed. In advanced disease, poorly differentiated tumors, and when lymph nodes are involved, chemotherapy and radiation together is used to treat the pelvis and groin in order to help 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.
Topical medications are occasionally used to treat non-invasive penile cancers. 5- Fluorouracil (5-FU) is a type of chemotherapy often used intravenously for other types of cancer; however, it is also approved for topical use. The 5-FU cream is applied to the area twice daily for several weeks. Imiquimod is also an approved topical medication. This cream, which is thought to work by stimulating the immune system, is applied to the tumor five times a week for 6 weeks.
Chemotherapy is most commonly used in patients whose cancer has spread throughout the body to distant sites, and who need systemic therapy (therapy that reaches all parts of the body). Chemotherapy can be used in conjunction with radiation when the tumor involves the lymph nodes. This is based on its effectiveness in similar genital cancers. Once the cancer has spread to other organs, chemotherapy is used to try to stop symptoms and extend survival, but does not generally cure the cancer. Chemotherapy can also be used before surgery when patients present with more advanced disease, such as spread to the lymph nodes in the groin or pelvis. Drugs such as bleomycin, cisplatin, and methotrexate have been reported as achieving modest tumor responses in selected patients.
How will I be followed after my treatment?
Patients who have undergone treatment for penile cancer should be seen and carefully examined by a physician every 2 to 4 months for the first year. This is especially important for those patients who have not undergone removal of lymph nodes. The risk of developing spread to lymph nodes in the groin is greatest in the first 6 months after treatment. 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 which 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 once a patient has been in remission for 2 years or more.
References and Further Reading
American Cancer Society. Penile Cancer. www.americancancersociety.com
Crook J. Radiation Therapy for Cancer of the Penis. Urol Clin North Am. 2010 Aug;37(3):435-43.
Crook, J, Clement M, Grimard L. Radiation therapy in the management of the primary penile tumor: an update. World J Urol. 2009 Apr;27(2):189-96
Haffty, BG, Wilson, LD. Handbook of Radiation Oncology: Basic Principles and Clinical Protocoools. Jones and Bartlett Publishers (2008).
Hansen, EK & Roach, M. Handbook of Evidence-Based Radiation Oncology. Springer (2010).
Pagliaro LC, Crook J. Multimodality therapy in penile cancer: when and which treatments? World J Urol. 2009 Apr;27(2):221-5. Perez Mansur DB, Chao KSC. Penis and Male Urethra. In: Perez CA, Brady LW, Halperin EC, editors. Principles and Practice of Radiation Oncology. 5th ed. Philadelphia: Lippincott Williams & Wilkins; 2008. pp. 1519-1531.