Explaining Penile Cancer Basics

Penile cancer is a rare malignancy that forms in the tissues of the penis. While the diagnosis can be psychologically and physically challenging, it is highly treatable when detected early. The American Cancer Society estimates that penile cancer accounts for less than 1% of cancers in men in the United States, affecting about 2,000 men annually.

The most common type is squamous cell carcinoma, which begins in the flat skin cells of the glans (head) or foreskin. Less common types include melanoma, basal cell carcinoma and sarcoma.

Key risk factors include:

• HPV infection: Human papillomavirus is detected in about half of all penile cancer cases.
• Phimosis: A condition where the foreskin cannot be fully retracted, leading to chronic inflammation.
• Smoking: Tobacco use increases the risk of developing penile cancer.
• Age: Most cases occur in men over age 60.

Diagnosis

Accurate diagnosis is the first step toward effective treatment. The process typically begins with a physical examination of the penis and groin area to check for lumps or abnormalities.

Biopsy A biopsy is the only way to definitively confirm cancer. A urologist removes a small sample of tissue from the suspicious area for laboratory analysis. The type of biopsy depends on the lesion’s size and location:

• Incisional biopsy: Removal of a portion of the lump.
• Excisional biopsy: Removal of the entire lump.

Imaging and Staging Once cancer is confirmed, imaging tests such as CT scans, MRIs or ultrasounds are used to determine if the cancer has spread to lymph nodes or other organs.

The cancer is then staged from stage 0 (carcinoma in situ) to stage 4 (metastatic disease). Staging guides the treatment plan, particularly determining whether the lymph nodes in the groin (inguinal nodes) need to be removed.

Treatment Options

Treatment plans are highly personalized, depending on the stage of the cancer and the patient's overall health. A multidisciplinary team — often including a urologist, medical oncologist and radiation oncologist — should review the case.

Surgery is the primary treatment for most penile cancers.

• Mohs surgery: A precise technique used for early-stage, small tumors where thin layers of skin are removed and examined until only cancer-free tissue remains. This maximizes the preservation of healthy tissue.
• Circumcision: If the cancer is confined to the foreskin, a circumcision may be the only treatment required.
• Wide local excision: Removal of the tumor along with a margin of healthy skin.
• Penectomy: In more advanced cases, partial or total removal of the penis may be necessary. Surgeons prioritize preserving as much length as possible to maintain urinary function standing up.
• Lymph node dissection: If there is a risk the cancer has spread, lymph nodes in the groin may be surgically removed.

Radiation Therapy High-energy beams are used to kill cancer cells. This is often an option for patients who cannot undergo surgery or for those with smaller tumors who wish to preserve the penis. It may also be used after surgery to kill remaining cells.

Chemotherapy

• Topical: For very early stage or pre-cancerous lesions, a cream (such as 5-fluorouracil or imiquimod) is applied directly to the skin.
• Systemic: Intravenous drugs (like cisplatin, paclitaxel or ifosfamide) circulate throughout the body to treat cancer that has spread to lymph nodes or distant organs.

Immunotherapy (Emerging Options) For advanced cases, immunotherapy is a rapidly evolving frontier. Drugs like Keytruda (pembrolizumab) or Libtayo (cemiplimab) help the body's immune system recognize and attack cancer cells. Recent clinical trials (such as the HERCULES trial) have shown promising results for combining immunotherapy with chemotherapy in advanced stages.

Keytruda plus platinum-based chemotherapy was found to be both safe and efficacious in treating penile squamous cell carcinoma (PSCC), according to findings from the phase 2 HERCULES trial presented at the 2024 American Society of Clinical Oncology Annual Meeting.

Dr. Fernando Cotait Maluf, of Hospital Beneficência Portuguesa de São Paulo and Hospital Israelita Albert Einstein, São Paulo, Brazil, presented the data at the conference. In the presentation, Maluf noted that PSCC has up to a 10 times higher incidence in low-income countries in Africa, Asia and Latin America. He added that advanced PSCC is a disease for which no improvements have been made of late, and prognosis is poor, with an overall survival of approximately six to seven months.

“Platinum-based chemotherapy has been considered the standard of care. … Immune checkpoint inhibitors have been associated with efficacy in different tumor types, including HPV16-positive tumors, such as cervical and head and neck squamous cell carcinoma,” Maluf explained.

Side Effects

The side effects of treatment can be significant, impacting both physical function and emotional well-being. It is vital to discuss these potential outcomes with a care team before treatment begins.

• Sexual Dysfunction: Surgery can affect sensation and the ability to achieve an erection. Even with penis-sparing techniques, scar tissue may cause curvature or discomfort.
• Lymphedema: Removal of lymph nodes in the groin can lead to fluid buildup and swelling in the legs and scrotum. This is a common, long-term side effect that often requires management with compression garments and physical therapy.
• Urinary Changes: If a significant portion of the penis is removed, the urethral opening may need to be relocated (perineal urethrostomy), requiring the patient to sit while urinating.
• Psychological Impact: Changes to the appearance of the genitalia can lead to anxiety, depression or body image issues. Counseling and support groups are essential components of recovery.
• Systemic Side Effects: Chemotherapy can cause fatigue, nausea, hair loss and increased risk of infection. Immunotherapy may cause immune-related side effects such as skin rashes or inflammation of organs.

Conclusion

A diagnosis of penile cancer requires prompt and aggressive management, but the outlook for early-stage disease is favorable. The five-year relative survival rate for localized penile cancer is approximately 80%, according to the American Cancer Society. However, this rate drops significantly if the cancer spreads to the inguinal lymph nodes, underscoring the importance of early detection and thorough lymph node evaluation.

Patients are encouraged to be active participants in their care. This includes asking about clinical trials, seeking a second opinion at a high-volume cancer center, and establishing a survivorship plan that includes regular follow-up exams to monitor for recurrence.

Reference

1. “Keytruda Plus Chemo May Improve Penile Cancer Outcomes,” CURE; https://www.curetoday.com/view/keytruda-plus-chemo-may-improve-penile-cancer-outcomes

Editor's note: This article is for informational purposes only and is not a substitute for professional medical advice, as your own experience will be unique. Use this article to guide discussions with your oncologist. Content was generated with AI, reviewed by a human editor, but not independently verified by a medical professional.

For more news on cancer updates, research and education, don’t forget to subscribe to CURE®’s newsletters here.