Penile cancer is a rare but treatable condition that affects the penis, a vital organ for both urination and sexual function. When detected early, many cases can be successfully managed, making awareness and timely medical attention crucial for positive outcomes.

How Treatment Goals Are Set for This Rare Cancer

When someone receives a diagnosis of penile cancer, the treatment approach focuses on several key goals. The primary aim is to remove or destroy the cancerous cells while preserving as much normal tissue and function as possible. Doctors consider many factors when planning treatment, including where the cancer is located on the penis, how large the tumor has grown, and whether the cancer has spread beyond the penis to nearby tissues or lymph nodes.^[1]

Treatment selection also depends heavily on the stage of disease at diagnosis. Early-stage penile cancer, detected when the cancer is still confined to the surface layers of skin, often responds well to less invasive treatments. More advanced cases may require a combination of different treatment methods to achieve the best possible outcome. The patient’s age, overall health, and personal preferences also play important roles in deciding which treatment path to follow.^[4]

Because penile cancer is so rare in developed countries like the United States — affecting fewer than one in 100,000 men each year — medical societies have developed treatment guidelines based on the best available evidence. At the same time, researchers continue to explore new therapies through clinical trials, searching for more effective ways to treat this disease while minimizing side effects and preserving quality of life.^[6]

The psychological impact of penile cancer cannot be overlooked. Changes to such an intimate part of the body can affect a man’s self-image, relationships, and sexual function. Treatment teams today recognize these concerns and work to address both the physical and emotional aspects of care, offering support throughout the treatment journey and beyond.^[16]

Established Treatment Methods Used Today

The most common approach to treating penile cancer involves surgery, and the specific type of surgery depends on the extent and location of the cancer. For very early-stage disease where cancer affects only the foreskin, a simple circumcision — the removal of the foreskin — may be all that is needed. This procedure can eliminate the cancer while leaving the rest of the penis intact and functional.^[9]

When the cancer is present as a small, localized growth, doctors may perform a procedure called wide local excision. This involves cutting out the tumor along with a margin of healthy tissue around it to ensure no cancer cells are left behind. If a significant amount of tissue must be removed, surgeons can use a skin graft from another part of the body to cover the area and aid healing. Another surgical option for early cancers is Mohs surgery, a specialized technique where the surgeon removes the tumor in very thin layers, examining each layer under a microscope until no cancer cells remain. This method helps preserve as much normal tissue as possible.^[11]

For more advanced cancers, a partial penectomy may be necessary. This surgery involves removing part of the penis where the cancer is located. In cases where the cancer has grown extensively, a total penectomy — complete removal of the penis — may be required. When this happens, surgeons create a new opening in the area between the scrotum and anus (the perineum) to allow urination. If the cancer has spread to the lymph nodes in the groin, these nodes may also need to be surgically removed in a procedure called inguinal lymphadenectomy. This surgery has considerable morbidity and can cause significant side effects.^[6]

For very early-stage penile cancer, especially when the cancer affects only the outer layers of skin, doctors may recommend topical chemotherapy. This involves applying a cream containing cancer-fighting drugs directly to the affected area. One commonly used cream is 5-fluorouracil (5FU), which works by killing cancer cells in the skin. Another topical option is imiquimod, an immunotherapy cream that stimulates the body’s immune system to attack and destroy cancer cells. These creams allow treatment without surgery, though they must be applied consistently over several weeks.^[15]

Cryotherapy offers another non-surgical option for small, early-stage cancers. This treatment uses extreme cold to freeze and destroy cancer cells. A small device is placed directly on the affected area, and the freezing process kills the abnormal tissue. Similarly, laser surgery uses a focused beam of light as a cutting tool to remove surface lesions or abnormal tissue. Both methods can be effective for carefully selected early-stage cancers.^[15]

Radiation therapy uses high-energy rays to kill cancer cells and can be delivered in different ways. External beam radiation involves directing radiation beams from outside the body toward the tumor. In some cases, doctors use brachytherapy, where a radiation source is placed directly into or next to the tumor. This approach allows higher doses of radiation to reach the cancer while limiting exposure to surrounding healthy tissue. Radiation may be used as the primary treatment for early-stage disease or combined with surgery when cancer has spread to lymph nodes. Treatment typically continues for several weeks, with sessions scheduled five days per week.^[14]

The side effects of radiation to the penis can include skin changes, pain, swelling, and tissue damage that may affect urination or erectile function. Some men experience the formation of abnormal connections between organs called fistulas. While these side effects can be difficult, many gradually improve after treatment ends. Doctors may also prescribe medications called radiosensitizers, which make cancer cells more vulnerable to radiation, potentially improving treatment effectiveness.^[14]

Systemic chemotherapy involves drugs given intravenously or by mouth that travel throughout the body to kill cancer cells. This approach is typically reserved for advanced penile cancer that has spread to distant parts of the body. Chemotherapy may also be given before surgery (called neoadjuvant chemotherapy) to shrink tumors and make them easier to remove, or after surgery (called adjuvant chemotherapy) to eliminate any remaining cancer cells. Sometimes chemotherapy is combined with radiation therapy in an approach called chemoradiotherapy, where the two treatments work together to fight the cancer more effectively.^[9]

Chemotherapy drugs work by targeting rapidly dividing cells, but they can also affect normal cells that divide quickly, such as those in the hair follicles, digestive tract, and bone marrow. This leads to common side effects including hair loss, nausea, vomiting, diarrhea, fatigue, and increased risk of infections. The specific drugs used and the severity of side effects vary from person to person. Treatment teams monitor patients closely and can provide medications to help manage these side effects.^[9]

Innovative Therapies Being Tested in Research Studies

Because penile cancer is so rare in countries like the United States, clinical trials specifically designed for this disease are infrequent. However, patients with advanced or difficult-to-treat penile cancer may be eligible to participate in research studies testing new drugs, biological therapies, or surgical techniques. These trials are carefully designed to test whether new treatments are safe and more effective than current standard options.^[13]

Clinical trials typically progress through three phases. Phase I trials focus primarily on safety, determining the appropriate dose of a new treatment and identifying potential side effects in a small group of patients. Phase II trials expand to more patients and begin to evaluate whether the treatment shows signs of effectiveness against the cancer. Phase III trials involve large numbers of patients and directly compare the new treatment to current standard treatments to determine if it offers advantages.^[13]

One area of active investigation involves immunotherapy approaches that harness the body’s immune system to fight cancer. While not yet standard treatment for penile cancer, researchers are studying whether drugs that enhance immune responses might help patients with advanced disease. Some studies are examining checkpoint inhibitors, medications that remove brakes on the immune system, allowing immune cells to more effectively attack cancer cells. These drugs have shown promise in other cancers caused by viral infections, making them potentially relevant for penile cancers linked to human papillomavirus (HPV).^[12]

Scientists are also investigating targeted therapies that attack specific molecular pathways involved in cancer growth. These treatments differ from traditional chemotherapy because they specifically target abnormalities in cancer cells while causing less damage to normal cells. Researchers are working to identify which molecular changes are most common in penile cancer, with the hope of developing drugs that can specifically block these pathways. Some studies are testing drugs that target growth factor receptors or proteins involved in cell division.^[12]

Because human papillomavirus infection contributes to many penile cancers, treatments that specifically target HPV-positive cancers are under investigation. Research teams are studying whether therapies that work well in other HPV-related cancers, such as cervical or throat cancer, might also benefit men with penile cancer. This includes both drugs and treatment combinations designed to exploit the unique characteristics of virus-associated tumors.^[13]

Advanced surgical techniques continue to evolve as well. Surgeons are refining methods for reconstructive surgery after partial or total penectomy, using tissue from other parts of the body to create a functioning penis. These procedures, while complex, can significantly improve quality of life and body image for men who have undergone extensive cancer surgery. Clinical studies are evaluating outcomes and complications associated with different reconstructive approaches.^[12]

For men with disease that has spread to lymph nodes, researchers are studying whether less extensive lymph node surgery might be possible in certain cases. Techniques like sentinel lymph node biopsy, where only the first few lymph nodes that drain from the tumor are removed and examined, may help some patients avoid more extensive surgery and its associated complications. Ongoing trials are assessing which patients are good candidates for these more limited surgical approaches.^[13]

Some trials are investigating combinations of existing treatments used in new ways. For example, researchers are studying whether combining chemotherapy with immunotherapy might produce better results than either treatment alone. Others are testing whether giving radiation therapy in different doses or schedules could improve outcomes while reducing side effects. These combination approaches aim to attack cancer from multiple angles simultaneously.^[12]

An important consideration in advanced penile cancer treatment involves a specific genetic factor related to chemotherapy drugs. Some people carry variations in a gene called DPYD, which affects how the body processes certain chemotherapy drugs like fluorouracil and capecitabine. Patients with certain DPYD variants may experience severe, potentially life-threatening side effects from normal doses of these drugs. Genetic testing can identify these variants, allowing doctors to adjust drug doses or choose alternative treatments. This personalized approach helps maximize treatment effectiveness while minimizing dangerous complications.^[13]

Most Common Treatment Methods

• Surgery
  • Circumcision for cancer limited to the foreskin
  • Wide local excision with removal of tumor and surrounding healthy tissue margin
  • Mohs surgery removing cancer in thin layers examined under microscope
  • Partial penectomy removing part of the penis
  • Total penectomy with complete removal of penis and creation of new urinary opening
  • Inguinal lymphadenectomy for removal of lymph nodes in the groin
  • Reconstructive surgery to restore appearance and function
• Topical Treatments
  • 5-fluorouracil (5FU) chemotherapy cream applied to skin to kill cancer cells
  • Imiquimod immunotherapy cream that stimulates immune system against cancer
• Minimally Invasive Procedures
  • Cryotherapy using freezing to destroy cancer cells
  • Laser surgery using focused light beam to remove surface lesions
• Radiation Therapy
  • External beam radiation directed at tumor from outside body
  • Brachytherapy with radiation source placed directly in or near tumor
  • May be used alone for early disease or with surgery for advanced cancer
  • Radiosensitizers to enhance effectiveness of radiation
• Chemotherapy
  • Systemic drugs given intravenously or by mouth for advanced disease
  • Neoadjuvant chemotherapy before surgery to shrink tumors
  • Adjuvant chemotherapy after surgery to eliminate remaining cancer cells
  • Chemoradiotherapy combining chemotherapy with radiation
• Experimental Treatments in Clinical Trials
  • Immunotherapy drugs including checkpoint inhibitors
  • Targeted therapies attacking specific molecular pathways
  • Treatments specific to HPV-positive cancers
  • Novel surgical techniques and reconstruction methods
  • Combination approaches using multiple treatment types

Living With Treatment and Recovery

The journey through penile cancer treatment extends well beyond the medical procedures themselves. Many men face significant emotional and psychological challenges as they adjust to changes in their body and function. Feelings of anxiety, depression, embarrassment, or anger are common and completely understandable. Professional counseling, either individually or in groups, can provide valuable support during this difficult time.^[16]

Changes to sexual function are a major concern for many men treated for penile cancer. The impact on sexuality depends largely on the stage of cancer and type of treatment received. Men who undergo circumcision, wide local excision, or minimally invasive treatments often retain normal erectile function and the ability to have penetrative sex. Those who have a partial penectomy may still achieve erections, and enough of the penis often remains for sexual intercourse. Medications like sildenafil (Viagra) can help men who experience erectile difficulties after treatment.^[20]

For men who undergo total penectomy, penetrative intercourse is no longer possible, but this does not mean the end of intimacy or a satisfying relationship. Many couples find new ways to experience closeness and sexual pleasure. Open, honest communication with partners about feelings, concerns, and needs becomes especially important. Sex therapists who specialize in helping people cope with medical changes to sexual function can provide guidance and support.^[20]

Some men develop lymphedema, a condition where fluid accumulates causing swelling in the legs or genitals, particularly after lymph node surgery. This can be uncomfortable and may affect mobility. Treatment for lymphedema includes specialized massage techniques, compression garments, and exercises designed to improve lymph fluid drainage. Early intervention and proper management can help control symptoms and prevent complications.^[19]

Regular follow-up care after treatment is essential. Doctors will schedule periodic examinations to check for any signs that cancer has returned and to monitor for treatment-related complications. The frequency of these visits typically decreases over time if no problems are detected. Patients should report any new symptoms or concerns between scheduled appointments, as early detection of recurrence improves treatment options.^[17]

Building a support network helps many men cope with their diagnosis and treatment. This might include family members, friends, support groups specifically for penile cancer patients, or online communities where men can share experiences and advice. Organizations dedicated to male cancers offer resources, information, and connections to others who understand the unique challenges of this disease.^[16]