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  • Human papillomavirus infection appears to be the possible cause of 30% to 50% of penile cancer cases and appears to have a prognostic impact on clinical outcomes among patients with advanced disease.

  • Penile-preserving strategies should be strongly considered among patients with low-stage tumors, especially those limited to the skin and the distal glans penis.

  • The presence and the extent of metastasis to the ­inguinal region are the most important prognostic factors for survival in patients with squamous cell carcinoma of the penis.

  • Penile tumor T stage ≥ T1b, grade, lymphovascular invasion, and perineural invasion appear to be the most important pathologic prognostic factors for nodal spread. Their presence is used to determine the need for inguinal staging procedures among patients with no clinically apparent inguinal metastases.

  • Patients with bulky lymphadenopathy should undergo a multimodal therapeutic approach to include neoadjuvant platinum-based chemotherapy with paclitaxel, ifosfamide, and cisplatin (TIP) for four cycles followed by consolidation surgical lymph node dissection among responding patients.

  • Patients with relapsed or refractory penile cancer to platinum-based chemotherapy have poor outcomes with current therapy modalities, and every effort should be made to enroll these patients on novel therapeutic clinical trials.


Penile cancer most commonly affects men between 50 and 70 years of age. The tumor is not unusual in younger men; in one large series, 22% of patients were younger than 40 years, and 7% were younger than 30 years.1 In 2018, there were an estimated 1820 new cases in the United States.2 The annual incidence of penile cancer cases in total per year worldwide has been estimated at approximately 35,000.3 Penile cancer accounts for less than 1% of all malignant neoplasms among men in the United States and Europe,2,4,5 but it may represent up to 10% of cancers in men in some Asian, African, and South American countries.1 These differences are thought to be related to the prevalence of neonatal circumcision, human papillomavirus (HPV) infection, and cultural practices. Among uncircumcised tribes of Africa and within uncircumcised Asian cultures, penile cancer may amount to 10% to 20% of all malignant neoplasms in men.1 Squamous cell carcinoma (SCC) is the most common histologic subtype, accounting for more than 95% of cases (Table 46–1).6

Table 46–1Histopathology Subtypes of Penile Cancer


Lack of Circumcision

The risk of penile cancer varies according to circumcision practice, phimosis, HPV infection, and smoking.7–13 Neonatal circumcision has been considered a prophylactic measure that removes many of the risks of penile carcinoma because ...

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