Estimated new cases and deaths from penile (and other male genital) cancer in the United States in 2024:[1]
Penile cancer is rare in most developed nations, including the United States, where the rate is less than 1 per 100,000 men per year. Some studies suggest an association between human papillomavirus (HPV) infection and penile cancer.[2-5] Observational studies have shown a lower prevalence of penile HPV in men who have been circumcised (odds ratio, 0.37; 95% confidence interval, 0.16–0.85).[6] Some, but not all, observational studies also suggest that male newborn circumcision is associated with a decreased risk of penile cancer.[7,8] According to published data, if the relationship is causal, the number needed to treat was about 909 circumcisions to prevent a single case of invasive penile cancer.[9]
When diagnosed early (stage 0, stage I, and stage II), penile cancer is highly curable. Curability decreases sharply for stage III and stage IV disease. Because of the rarity of this cancer in the United States, clinical trials specifically for penile cancer are infrequent. Patients with stage III and stage IV cancer are candidates for phase I and phase II clinical trials testing new drugs, biological therapy, or surgical techniques to improve local control and distant metastases.
The selection of treatment depends on the following:[10,11]
The DPYD gene encodes an enzyme that catabolizes pyrimidines and fluoropyrimidines, like capecitabine and fluorouracil. An estimated 1% to 2% of the population has germline pathogenic variants in DPYD, which lead to reduced DPD protein function and an accumulation of pyrimidines and fluoropyrimidines in the body.[12,13] Patients with the DPYD*2A variant who receive fluoropyrimidines may experience severe, life-threatening toxicities that are sometimes fatal. Many other DPYD variants have been identified, with a range of clinical effects.[12-14] Fluoropyrimidine avoidance or a dose reduction of 50% may be recommended based on the patient's DPYD genotype and number of functioning DPYD alleles.[15-17] DPYD genetic testing costs less than $200, but insurance coverage varies due to a lack of national guidelines.[18] In addition, testing may delay therapy by 2 weeks, which would not be advisable in urgent situations. This controversial issue requires further evaluation.[19]
Virtually all penile carcinomas are of squamous cell origin and include the following subtypes:
Although they are less common subtypes, warty carcinoma and basaloid carcinoma appear to be more highly associated with human papillomaviruses (HPV), particularly HPV 16, than typical squamous cell carcinoma or verrucous carcinoma of the penis.[3-5]
Neuroendocrine carcinomas can also be seen.[6]
The AJCC has designated staging by TNM (tumor, node, metastasis) classification to define penile cancer.[1]
| Stage | TNM | Description |
|---|---|---|
| T = primary tumor; N = regional lymph node; M = distant metastasis; cN = clinical N; PeIN = penile intraepithelial neoplasia; pN = pathological N. | ||
| aReprinted with permission from AJCC: Penis. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 701–14. | ||
| 0is | Tis, N0, M0 | Tis = Carcinoma in situ (PeIN). |
| N0 = cN0, no palpable or visibly enlarged inguinal lymph nodes; pN0, no lymph node metastasis. | ||
| M0 = No distant metastasis. | ||
| 0a | Ta, N0, M0 | Ta = Noninvasive localized squamous cell carcinoma. |
| N0 = cN0, no palpable or visibly enlarged inguinal lymph nodes; pN0, no lymph node metastasis. | ||
| M0 = No distant metastasis. | ||
| Stage | TNM | Description |
|---|---|---|
| T = primary tumor; N = regional lymph node; M = distant metastasis; cN = clinical N; pN = pathological N. | ||
| aReprinted with permission from AJCC: Penis. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 701–14. | ||
| I | T1a, N0, M0 | T1a = Tumor is without lymphovascular invasion or perineural invasion and is not high grade (i.e., grade 3 or sarcomatoid). |
| N0 = cN0, no palpable or visibly enlarged inguinal lymph nodes; pN0, no lymph node metastasis. | ||
| M0 = No distant metastasis. | ||
| Stage | TNM | Description |
|---|---|---|
| T = primary tumor; N = regional lymph node; M = distant metastasis; cN = clinical N; pN = pathological N. | ||
| aReprinted with permission from AJCC: Penis. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 701–14. | ||
| IIA | T1b, N0, M0 | T1b = Tumor exhibits lymphovascular invasion and/or perineural invasion or is high grade (i.e., grade 3 or sarcomatoid). |
| N0 = cN0, no palpable or visibly enlarged inguinal lymph nodes; pN0, no lymph node metastasis. | ||
| M0 = No distant metastasis. | ||
| T2, N0, M0 | T2 = Tumor invades into corpus spongiosum (either glans or ventral shaft) with or without urethral invasion. | |
| N0 = cN0, no palpable or visibly enlarged inguinal lymph nodes; pN0, no lymph node metastasis. | ||
| M0 = No distant metastasis. | ||
| IIB | T3, N0, M0 | T3 = Tumor invades into corpora cavernosum (including tunica albuginea) with or without urethral invasion. |
| N0 = cN0, no palpable or visibly enlarged inguinal lymph nodes; pN0, no lymph node metastasis. | ||
| M0 = No distant metastasis. | ||
| Stage | TNM | Description |
|---|---|---|
| T = primary tumor; N = regional lymph node; M = distant metastasis; cN = clinical N; ENE = extranodal extension; pN = pathological N. | ||
| aReprinted with permission from AJCC: Penis. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 701–14. | ||
| IIIA | T1–3, N1, M0 | T1 = Glans: Tumor invades lamina propria; Foreskin: 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 perineural invasion and is not high grade (i.e., grade 3 or sarcomatoid). | ||
| –T1b = Tumor exhibits lymphovascular invasion and/or perineural invasion or is high grade (i.e., grade 3 or sarcomatoid). | ||
| T2 = Tumor invades into corpus spongiosum (either glans or ventral shaft) with or without urethral invasion. | ||
| T3 = Tumor invades into corpora cavernosum (including tunica albuginea) with or without urethral invasion. | ||
| N1 = cN1, palpable mobile unilateral inguinal lymph node; pN1, ≤2 unilateral inguinal metastases, no ENE. | ||
| M0 = No distant metastasis. | ||
| IIIB | T1–3, N2, M0 | T1 = Glans: Tumor invades lamina propria; Foreskin: 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 perineural invasion and is not high grade (i.e., grade 3 or sarcomatoid). | ||
| –T1b = Tumor exhibits lymphovascular invasion and/or perineural invasion or is high grade (i.e., grade 3 or sarcomatoid). | ||
| T2 = Tumor invades into corpus spongiosum (either glans or ventral shaft) with or without urethral invasion. | ||
| T3 = Tumor invades into corpora cavernosum (including tunica albuginea) with or without urethral invasion. | ||
| N2 = cN2, palpable mobile ≥ unilateral inguinal nodes or bilateral inguinal lymph nodes; pN2, ≥3 unilateral inguinal metastases or bilateral metastases, no ENE. | ||
| M0 = No distant metastasis. | ||
| Stage | TNM | Description |
|---|---|---|
| T = primary tumor; N = regional lymph node; M = distant metastasis; cN = clinical N; ENE = extranodal extension; PeIN = penile intraepithelial neoplasia; pN = pathological N. | ||
| aReprinted with permission from AJCC: Penis. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 701–14. | ||
| IV | T4, Any N, M0 | T4 = Tumor invades into adjacent structures (i.e., scrotum, prostate, pubic bone). |
| cNX = Regional lymph nodes cannot be assessed. | ||
| cN0 = No palpable or visibly enlarged inguinal lymph nodes. | ||
| cN1 = Palpable mobile unilateral inguinal lymph node. | ||
| cN2 = Palpable mobile ≥ unilateral inguinal nodes or bilateral inguinal lymph nodes. | ||
| cN3 = Palpable fixed inguinal nodal mass or pelvic lymphadenopathy unilateral or bilateral. | ||
| pNX = Lymph node metastasis cannot be established. | ||
| pN0 = No lymph node metastasis. | ||
| pN1 = ≤2 unilateral inguinal metastases, no ENE. | ||
| pN2 = ≥3 unilateral inguinal metastases or bilateral metastases, no ENE. | ||
| pN3 = ENE of lymph node metastases or pelvic lymph node metastases. | ||
| M0 = No distant metastasis. | ||
| Any T, N3, M0 | TX = Primary tumor cannot be assessed. | |
| T0 = No evidence of primary tumor. | ||
| Tis = Carcinoma in situ (PeIN). | ||
| Ta = Noninvasive localized squamous cell carcinoma. | ||
| T1 = Glans: Tumor invades lamina propria; Foreskin: 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 perineural invasion and is not high grade (i.e., grade 3 or sarcomatoid). | ||
| –T1b = Tumor exhibits lymphovascular invasion and/or perineural invasion or is high grade (i.e., grade 3 or sarcomatoid). | ||
| T2 = Tumor invades into corpus spongiosum (either glans or ventral shaft) with or without urethral invasion. | ||
| T3 = Tumor invades into corpora cavernosum (including tunica albuginea) with or without urethral invasion. | ||
| T4 = Tumor invades into adjacent structures (i.e., scrotum, prostate, pubic bone). | ||
| N3 = cN3, palpable fixed inguinal nodal mass or pelvic lymphadenopathy unilateral or bilateral; pN3, ENE of lymph node metastases or pelvic lymph node metastases. | ||
| M0 = No distant metastasis. | ||
| Any T, Any N, M1 | Any T = See descriptions above in this table, stage IV, Any T, N3, M0. | |
| cNX = Regional lymph nodes 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. | ||
| pNX = Lymph node metastasis cannot be established. | ||
| pN0 = No lymph node metastasis. | ||
| pN1 = ≤2 unilateral inguinal metastases, no ENE. | ||
| pN2 = ≥3 unilateral inguinal metastases or bilateral metastases, no ENE. | ||
| pN3 = ENE of lymph node metastases or pelvic lymph node metastases. | ||
| M1 = Distant metastasis present. | ||
Stage 0 penile cancer is defined by the following TNM classifications:[1]
Carcinoma in situ of the penis is referred to as erythroplasia of Queyrat when it occurs on the glans, and Bowen disease when it occurs on the penile shaft. These precursor lesions progress to invasive squamous cell carcinoma in 5% to 15% of cases. In case series studies, human papillomavirus DNA has been detected in most of these lesions.[2,3] With no data from clinical trials in this disease stage, treatment recommendations are largely based on case reports and case series involving limited numbers of patients.
Treatment options:
Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
Stage I penile cancer is defined by the following TNM classification:[1]
Stage I penile cancer is curable.[2]
Treatment options:
Because of the high incidence of microscopic node metastases, elective adjunctive inguinal dissection of clinically uninvolved (negative) lymph nodes in conjunction with amputation is often used for patients with poorly differentiated tumors. Lymphadenectomy can carry substantial morbidity, such as infection, skin necrosis, wound breakdown, chronic edema, and even a low, but finite, mortality rate. The impact of prophylactic lymphadenectomy on survival is not known. For these reasons, opinions vary on its use.[9-12]
Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
Stage II penile cancer is defined by the following TNM classifications:[1]
Treatment options:
Because of the high incidence of microscopic node metastases, elective adjunctive dissection of clinically uninvolved (negative) lymph nodes in conjunction with amputation is often used for patients with poorly differentiated tumors. Lymphadenectomy can carry substantial morbidity, such as infection, skin necrosis, wound breakdown, chronic edema, and even a low, but finite, mortality rate. The impact of prophylactic lymphadenectomy on survival is not known.[8-11]
To reduce the morbidity associated with prophylactic lymphadenectomy, dynamic sentinel node biopsy is used in patients with stage T2 clinically node-negative penile cancer. One retrospective single-institution study of 22 patients reported a false-negative rate of 11%.[12]
Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
Stage III penile cancer is defined by the following TNM classifications:[1]
Inguinal adenopathy in patients with penile cancer is common but may be the result of infection rather than neoplasm. If palpable enlarged lymph nodes exist 3 or more weeks after removal of the infected primary lesion and completion of a course of antibiotic therapy, bilateral inguinal lymph node dissection should be performed.
In cases of proven regional inguinal lymph node metastasis without evidence of distant spread, bilateral ilioinguinal dissection is the treatment of choice.[2-5] Because many patients with positive lymph nodes are not cured, clinical trials may be appropriate.
Treatment options:
Because of the high incidence of microscopic node metastases, adjunctive inguinal dissection of clinically uninvolved (negative) lymph nodes in conjunction with amputation is often used for patients with poorly differentiated tumors. Lymphadenectomy can carry substantial morbidity, such as infection, skin necrosis, wound breakdown, chronic edema, and even a low, but finite, mortality rate. The impact of prophylactic lymphadenectomy on survival is not known. [3,4,9,10]
To reduce the morbidity associated with prophylactic lymphadenectomy, dynamic sentinel node biopsy is used in patients with stage T2 and stage T3 clinically node-negative penile cancer. One retrospective single-institution study of 22 patients reported a false-negative rate of 11%.[11]
Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
Stage IV penile cancer is defined by the following TNM classifications:[1]
No standard treatment exists that is curative for patients with stage IV penile cancer. Therapy is directed at palliation, which may be achieved either with surgery or radiation therapy.
Treatment options:
Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
Patients with locally recurrent disease can be treated with surgery or radiation therapy. If the initial treatment of radiation therapy fails, patients often undergo penile amputation. Patients with nodal recurrences not controlled by local measures are candidates for phase I and phase II clinical trials testing new biological and chemotherapeutic agents.[1-5]
Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
General Information About Penile Cancer
Updated statistics with estimated new cases and deaths for 2024 (cited American Cancer Society as reference 1).
Added Fluorouracil dosing as a new subsection.
This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages.
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of penile cancer. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.
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PDQ® Adult Treatment Editorial Board. PDQ Penile Cancer Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/penile/hp/penile-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389381]
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