Penile Cancer Treatment (PDQ®): Treatment - Health Professional Information [NCI]

General Information About Penile Cancer

Incidence and Mortality

Estimated new cases and deaths from penile (and other male genital) cancer in the United States in 2024:[1]

• New cases: 2,100.
• Deaths: 500.

Risk Factors

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.[2,3,4,5] 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]

Treatment Overview

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]

• Size.
• Location.
• Invasiveness.
• Stage of the tumor.

Fluorouracil dosing

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.[12,13,14] Fluoropyrimidine avoidance or a dose reduction of 50% may be recommended based on the patient's DPYD genotype and number of functioning DPYD alleles.[15,16,17]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]

References:

1. American Cancer Society: Cancer Facts and Figures 2024. American Cancer Society, 2024. Available online. Last accessed June 21, 2024.
2. Del Mistro A, Chieco Bianchi L: HPV-related neoplasias in HIV-infected individuals. Eur J Cancer 37 (10): 1227-35, 2001.
3. Griffiths TR, Mellon JK: Human papillomavirus and urological tumours: I. Basic science and role in penile cancer. BJU Int 84 (5): 579-86, 1999.
4. Poblet E, Alfaro L, Fernander-Segoviano P, et al.: Human papillomavirus-associated penile squamous cell carcinoma in HIV-positive patients. Am J Surg Pathol 23 (9): 1119-23, 1999.
5. Frisch M, van den Brule AJ, Jiwa NM, et al.: HPV-16-positive anal and penile carcinomas in a young man--anogenital 'field effect' in the immunosuppressed male? Scand J Infect Dis 28 (6): 629-32, 1996.
6. Castellsagué X, Bosch FX, Muñoz N, et al.: Male circumcision, penile human papillomavirus infection, and cervical cancer in female partners. N Engl J Med 346 (15): 1105-12, 2002.
7. Schoen EJ, Oehrli M, Colby C, et al.: The highly protective effect of newborn circumcision against invasive penile cancer. Pediatrics 105 (3): E36, 2000.
8. Neonatal circumcision revisited. Fetus and Newborn Committee, Canadian Paediatric Society. CMAJ 154 (6): 769-80, 1996.
9. Christakis DA, Harvey E, Zerr DM, et al.: A trade-off analysis of routine newborn circumcision. Pediatrics 105 (1 Pt 3): 246-9, 2000.
10. Mark JR, Hurwitz M, Gomella LG: Cancer of the urethra and penis. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 11th ed. Wolters Kluwer Health, 2019, pp 1136-44.
11. Chao KS, Perez CA: Penis and male urethra. In: Perez CA, Brady LW, eds.: Principles and Practice of Radiation Oncology. 3rd ed. Lippincott-Raven Publishers, 1998, pp 1717-1732.
12. Sharma BB, Rai K, Blunt H, et al.: Pathogenic DPYD Variants and Treatment-Related Mortality in Patients Receiving Fluoropyrimidine Chemotherapy: A Systematic Review and Meta-Analysis. Oncologist 26 (12): 1008-1016, 2021.
13. Lam SW, Guchelaar HJ, Boven E: The role of pharmacogenetics in capecitabine efficacy and toxicity. Cancer Treat Rev 50: 9-22, 2016.
14. Shakeel F, Fang F, Kwon JW, et al.: Patients carrying DPYD variant alleles have increased risk of severe toxicity and related treatment modifications during fluoropyrimidine chemotherapy. Pharmacogenomics 22 (3): 145-155, 2021.
15. Amstutz U, Henricks LM, Offer SM, et al.: Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Dihydropyrimidine Dehydrogenase Genotype and Fluoropyrimidine Dosing: 2017 Update. Clin Pharmacol Ther 103 (2): 210-216, 2018.
16. Henricks LM, Lunenburg CATC, de Man FM, et al.: DPYD genotype-guided dose individualisation of fluoropyrimidine therapy in patients with cancer: a prospective safety analysis. Lancet Oncol 19 (11): 1459-1467, 2018.
17. Lau-Min KS, Varughese LA, Nelson MN, et al.: Preemptive pharmacogenetic testing to guide chemotherapy dosing in patients with gastrointestinal malignancies: a qualitative study of barriers to implementation. BMC Cancer 22 (1): 47, 2022.
18. Brooks GA, Tapp S, Daly AT, et al.: Cost-effectiveness of DPYD Genotyping Prior to Fluoropyrimidine-based Adjuvant Chemotherapy for Colon Cancer. Clin Colorectal Cancer 21 (3): e189-e195, 2022.
19. Baker SD, Bates SE, Brooks GA, et al.: DPYD Testing: Time to Put Patient Safety First. J Clin Oncol 41 (15): 2701-2705, 2023.

Cellular Classification of Penile Cancer

Virtually all penile carcinomas are of squamous cell origin and include the following subtypes:

• Verrucous carcinoma.[1]
• Warty carcinoma (verruciform).[2]
• Basaloid carcinoma.[3]

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.[3,4,5]

Neuroendocrine carcinomas can also be seen.[6]

References:

1. Schwartz RA: Verrucous carcinoma of the skin and mucosa. J Am Acad Dermatol 32 (1): 1-21; quiz 22-4, 1995.
2. Bezerra AL, Lopes A, Landman G, et al.: Clinicopathologic features and human papillomavirus dna prevalence of warty and squamous cell carcinoma of the penis. Am J Surg Pathol 25 (5): 673-8, 2001.
3. Cubilla AL, Reuter VE, Gregoire L, et al.: Basaloid squamous cell carcinoma: a distinctive human papilloma virus-related penile neoplasm: a report of 20 cases. Am J Surg Pathol 22 (6): 755-61, 1998.
4. Gregoire L, Cubilla AL, Reuter VE, et al.: Preferential association of human papillomavirus with high-grade histologic variants of penile-invasive squamous cell carcinoma. J Natl Cancer Inst 87 (22): 1705-9, 1995.
5. Rubin MA, Kleter B, Zhou M, et al.: Detection and typing of human papillomavirus DNA in penile carcinoma: evidence for multiple independent pathways of penile carcinogenesis. Am J Pathol 159 (4): 1211-8, 2001.
6. Vadmal MS, Steckel J, Teichberg S, et al.: Primary neuroendocrine carcinoma of the penile urethra. J Urol 157 (3): 956-7, 1997.

Stage Information for Penile Cancer

American Joint Committee on Cancer (AJCC) Stage Groupings and Definitions of TNM

The AJCC has designated staging by TNM (tumor, node, metastasis) classification to define penile cancer.[1]

Definitions of TNM Stages 0is and 0a^a

Stage	TNM	Description
T = primary tumor; N = regional lymph node; M = distant metastasis; cN = clinical N; PeIN = penile intraepithelial neoplasia; pN = pathological N.
a Reprinted 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 = Carcinomain 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.

Definitions of TNM Stage I^a

Stage	TNM	Description
T = primary tumor; N = regional lymph node; M = distant metastasis; cN = clinical N; pN = pathological N.
a Reprinted 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.

Definitions of TNM Stages IIA and IIB^a

Stage	TNM	Description
T = primary tumor; N = regional lymph node; M = distant metastasis; cN = clinical N; pN = pathological N.
a Reprinted 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.

Definitions of TNM Stages IIIA and IIIB^a

Stage	TNM	Description
T = primary tumor; N = regional lymph node; M = distant metastasis; cN = clinical N; ENE = extranodal extension; pN = pathological N.
a Reprinted 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.

Definitions of TNM Stage IV^a

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.
a Reprinted 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 = Carcinomain 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.

References:

1. Penis. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. Springer; 2017, pp 701–14.

Treatment of Stage 0 Penile Cancer

Stage 0 penile cancer is defined by the following TNM classifications:[1]

• Tis, N0, M0
• Ta, N0, M0

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:

1. Surgical excision can result in scarring, deformity, and impaired function. To minimize these effects, Mohs micrographic surgery, which involves the excision of successive horizontal layers of tissue with microscopic examination of each layer in frozen section, has been used in patients with in situ and invasive penile cancers.[4,5][Level of evidence C3]
2. Topical application of fluorouracil cream has been effective in cases of erythroplasia of Queyrat [6] and Bowen disease.[7][Level of evidence C3]
3. Imiquimod 5% cream is a topical immune response modifier that has been effective with good cosmetic and functional results.[8,9,10][Level of evidence C3]
4. Laser therapy with Nd:YAG or CO₂ lasers has also resulted in excellent cosmetic results.[11][Level of evidence C3]
5. Cryosurgery has resulted in good cosmetic results in patients with erythroplasia of Queyrat and verrucous penile carcinoma.[12,13][Level of evidence C3]

Current Clinical Trials

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.

References:

1. Penis. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. Springer; 2017, pp 701–14.
2. Cupp MR, Malek RS, Goellner JR, et al.: The detection of human papillomavirus deoxyribonucleic acid in intraepithelial, in situ, verrucous and invasive carcinoma of the penis. J Urol 154 (3): 1024-9, 1995.
3. Rubin MA, Kleter B, Zhou M, et al.: Detection and typing of human papillomavirus DNA in penile carcinoma: evidence for multiple independent pathways of penile carcinogenesis. Am J Pathol 159 (4): 1211-8, 2001.
4. Mohs FE, Snow SN, Messing EM, et al.: Microscopically controlled surgery in the treatment of carcinoma of the penis. J Urol 133 (6): 961-6, 1985.
5. Moritz DL, Lynch WS: Extensive Bowen's disease of the penile shaft treated with fresh tissue Mohs micrographic surgery in two separate operations. J Dermatol Surg Oncol 17 (4): 374-8, 1991.
6. Goette DK, Carson TE: Erythroplasia of Queyrat: treatment with topical 5-fluorouracil. Cancer 38 (4): 1498-502, 1976.
7. Tolia BM, Castro VL, Mouded IM, et al.: Bowen's disease of shaft of penis. Successful treatment with 5-fluorouracil. Urology 7 (6): 617-9, 1976.
8. Danielsen AG, Sand C, Weismann K: Treatment of Bowen's disease of the penis with imiquimod 5% cream. Clin Exp Dermatol 28 (Suppl 1): 7-9, 2003.
9. Micali G, Nasca MR, Tedeschi A: Topical treatment of intraepithelial penile carcinoma with imiquimod. Clin Exp Dermatol 28 (Suppl 1): 4-6, 2003.
10. Schroeder TL, Sengelmann RD: Squamous cell carcinoma in situ of the penis successfully treated with imiquimod 5% cream. J Am Acad Dermatol 46 (4): 545-8, 2002.
11. van Bezooijen BP, Horenblas S, Meinhardt W, et al.: Laser therapy for carcinoma in situ of the penis. J Urol 166 (5): 1670-1, 2001.
12. Michelman FA, Filho AC, Moraes AM: Verrucous carcinoma of the penis treated with cryosurgery. J Urol 168 (3): 1096-7, 2002.
13. Sonnex TS, Ralfs IG, Plaza de Lanza M, et al.: Treatment of erythroplasia of Queyrat with liquid nitrogen cryosurgery. Br J Dermatol 106 (5): 581-4, 1982.

Treatment of Stage I Penile Cancer

Stage I penile cancer is defined by the following TNM classification:[1]

• T1a, N0, M0

Stage I penile cancer is curable.[2]

Treatment options:

1. For lesions limited to the foreskin, wide local excision with circumcision may be adequate therapy for control.
2. For infiltrating tumors of the glans with or without involvement of the adjacent skin, the choice of therapy is dictated by tumor size, extent of infiltration, and degree of tumor destruction of normal tissue. Equivalent therapeutic options include:
   • Penile amputation.[3]
   • Radiation therapy (i.e., external-beam radiation therapy and brachytherapy).[4,5]
   • Microscopically controlled surgery.[6]
3. Nd:YAG laser therapy has offered excellent control/cure with preservation of cosmetic appearance and sexual function (under clinical evaluation).[7,8]

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.[9,10,11,12]

Current Clinical Trials

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.

References:

1. Penis. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. Springer; 2017, pp 701–14.
2. Harty JI, Catalona WJ: Carcinoma of the penis. In: Javadpour N, ed.: Principles and Management of Urologic Cancer. 2nd ed. Williams and Wilkins, 1983, pp 581-597.
3. Lynch DF, Pettaway CA: Tumors of the penis. In: Walsh PC, Retik AB, Vaughan ED, et al., eds.: Campbell's Urology. 8th ed. Saunders, 2002, pp 2945-2947.
4. Chao KS, Perez CA: Penis and male urethra. In: Perez CA, Brady LW, eds.: Principles and Practice of Radiation Oncology. 3rd ed. Lippincott-Raven Publishers, 1998, pp 1717-1732.
5. McLean M, Akl AM, Warde P, et al.: The results of primary radiation therapy in the management of squamous cell carcinoma of the penis. Int J Radiat Oncol Biol Phys 25 (4): 623-8, 1993.
6. Mohs FE, Snow SN, Messing EM, et al.: Microscopically controlled surgery in the treatment of carcinoma of the penis. J Urol 133 (6): 961-6, 1985.
7. Smith JA Jr.: Lasers in clinical urologic surgery. In: Dixon JA, ed.: Surgical Application of Lasers. 2nd ed. Year Book Medical Publishers, Inc., 1987, pp 218-237.
8. Horenblas S, van Tinteren H, Delemarre JF, et al.: Squamous cell carcinoma of the penis. II. Treatment of the primary tumor. J Urol 147 (6): 1533-8, 1992.
9. Theodorescu D, Russo P, Zhang ZF, et al.: Outcomes of initial surveillance of invasive squamous cell carcinoma of the penis and negative nodes. J Urol 155 (5): 1626-31, 1996.
10. Lindegaard JC, Nielsen OS, Lundbeck FA, et al.: A retrospective analysis of 82 cases of cancer of the penis. Br J Urol 77 (6): 883-90, 1996.
11. Ornellas AA, Seixas AL, Marota A, et al.: Surgical treatment of invasive squamous cell carcinoma of the penis: retrospective analysis of 350 cases. J Urol 151 (5): 1244-9, 1994.
12. Young MJ, Reda DJ, Waters WB: Penile carcinoma: a twenty-five-year experience. Urology 38 (6): 529-32, 1991.

Treatment of Stage II Penile Cancer

Stage II penile cancer is defined by the following TNM classifications:[1]

• T1b, N0, M0
• T2, N0, M0
• T3, N0, M0

Treatment options:

1. Stage II penile cancer is most frequently managed by penile amputation for local control. Whether the amputation is partial, total, or radical will depend on the extent and location of the neoplasm. External-beam radiation therapy and brachytherapy with surgical salvage are alternative approaches.[2,3,4,5,6]
2. Nd:YAG laser therapy has been used to preserve the penis in selected patients with small lesions (under clinical evaluation).[7]

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.[8,9,10,11]

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]

Current Clinical Trials

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.

References:

1. Penis. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. Springer; 2017, pp 701–14.
2. Harty JI, Catalona WJ: Carcinoma of the penis. In: Javadpour N, ed.: Principles and Management of Urologic Cancer. 2nd ed. Williams and Wilkins, 1983, pp 581-597.
3. Schellhammer PF, Spaulding JT: Carcinoma of the penis. In: Paulson DF, ed.: Genitourinary Surgery. Vol. 2. Churchill Livingston, 1984, pp 629-654.
4. Johnson DE, Lo RK: Tumors of the penis, urethra, and scrotum. In: deKernion JB, Paulson DF, eds.: Genitourinary Cancer Management. Lea and Febiger, 1987, pp 219-258.
5. McLean M, Akl AM, Warde P, et al.: The results of primary radiation therapy in the management of squamous cell carcinoma of the penis. Int J Radiat Oncol Biol Phys 25 (4): 623-8, 1993.
6. Crook JM, Jezioranski J, Grimard L, et al.: Penile brachytherapy: results for 49 patients. Int J Radiat Oncol Biol Phys 62 (2): 460-7, 2005.
7. Horenblas S, van Tinteren H, Delemarre JF, et al.: Squamous cell carcinoma of the penis. II. Treatment of the primary tumor. J Urol 147 (6): 1533-8, 1992.
8. Theodorescu D, Russo P, Zhang ZF, et al.: Outcomes of initial surveillance of invasive squamous cell carcinoma of the penis and negative nodes. J Urol 155 (5): 1626-31, 1996.
9. Lindegaard JC, Nielsen OS, Lundbeck FA, et al.: A retrospective analysis of 82 cases of cancer of the penis. Br J Urol 77 (6): 883-90, 1996.
10. Ornellas AA, Seixas AL, Marota A, et al.: Surgical treatment of invasive squamous cell carcinoma of the penis: retrospective analysis of 350 cases. J Urol 151 (5): 1244-9, 1994.
11. Young MJ, Reda DJ, Waters WB: Penile carcinoma: a twenty-five-year experience. Urology 38 (6): 529-32, 1991.
12. Perdonà S, Autorino R, De Sio M, et al.: Dynamic sentinel node biopsy in clinically node-negative penile cancer versus radical inguinal lymphadenectomy: a comparative study. Urology 66 (6): 1282-6, 2005.

Treatment of Stage III Penile Cancer

Stage III penile cancer is defined by the following TNM classifications:[1]

• T1–3, N1, M0
• T1–3, N2, M0

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.[2,3,4,5] Because many patients with positive lymph nodes are not cured, clinical trials may be appropriate.

Treatment options:

1. Clinically evident regional lymph node metastasis without evidence of distant spread is an indication for bilateral ilioinguinal lymph node dissection after penile amputation.[6]
2. Radiation therapy may be considered as an alternative to lymph node dissection in patients who are not surgical candidates.
3. Postoperative radiation therapy may decrease incidence of inguinal recurrences.
4. Clinical trials using radiosensitizers or cytotoxic drugs are appropriate. A combination of vincristine, bleomycin, and methotrexate has been effective as both neoadjuvant and adjuvant therapy.[7] Cisplatin (100 mg/m²) as neoadjuvant therapy plus continuous-infusion fluorouracil has also been effective.[6] Single-agent cisplatin (50 mg/m²) was tested in a large trial and was ineffective.[8]

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]

Current Clinical Trials

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.

References:

1. Penis. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. Springer; 2017, pp 701–14.
2. Harty JI, Catalona WJ: Carcinoma of the penis. In: Javadpour N, ed.: Principles and Management of Urologic Cancer. 2nd ed. Williams and Wilkins, 1983, pp 581-597.
3. Theodorescu D, Russo P, Zhang ZF, et al.: Outcomes of initial surveillance of invasive squamous cell carcinoma of the penis and negative nodes. J Urol 155 (5): 1626-31, 1996.
4. Lindegaard JC, Nielsen OS, Lundbeck FA, et al.: A retrospective analysis of 82 cases of cancer of the penis. Br J Urol 77 (6): 883-90, 1996.
5. Lynch DF, Pettaway CA: Tumors of the penis. In: Walsh PC, Retik AB, Vaughan ED, et al., eds.: Campbell's Urology. 8th ed. Saunders, 2002, pp 2945-2947.
6. Fisher HA, Barada JH, Horton J, et al.: Neoadjuvant therapy with cisplatin and 5-fluorouracil for stage III squamous cell carcinoma of the penis. [Abstract] J Urol 143(4 Suppl): A-653, 352A, 1990.
7. Pizzocaro G, Piva L: Adjuvant and neoadjuvant vincristine, bleomycin, and methotrexate for inguinal metastases from squamous cell carcinoma of the penis. Acta Oncol 27 (6b): 823-4, 1988.
8. Gagliano RG, Blumenstein BA, Crawford ED, et al.: cis-Diamminedichloroplatinum in the treatment of advanced epidermoid carcinoma of the penis: a Southwest Oncology Group Study. J Urol 141 (1): 66-7, 1989.
9. Ornellas AA, Seixas AL, Marota A, et al.: Surgical treatment of invasive squamous cell carcinoma of the penis: retrospective analysis of 350 cases. J Urol 151 (5): 1244-9, 1994.
10. Young MJ, Reda DJ, Waters WB: Penile carcinoma: a twenty-five-year experience. Urology 38 (6): 529-32, 1991.
11. Perdonà S, Autorino R, De Sio M, et al.: Dynamic sentinel node biopsy in clinically node-negative penile cancer versus radical inguinal lymphadenectomy: a comparative study. Urology 66 (6): 1282-6, 2005.

Treatment of Stage IV Penile Cancer

Stage IV penile cancer is defined by the following TNM classifications:[1]

• T4, Any N, M0
• Any T, N3, M0
• Any T, Any N, M1

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:

1. Palliative surgery may be considered for control of the local penile lesion and even for the prevention of the necrosis, infection, and hemorrhage that can result from neglected regional adenopathy.
2. Radiation therapy may be palliative for the primary tumor, regional adenopathy, and bone metastases.
3. Clinical trials combining chemotherapy with palliative methods of local control are appropriate. Tested chemotherapeutic drugs with some efficacy include vincristine, cisplatin, methotrexate, and bleomycin. The combination of vincristine, bleomycin, and methotrexate has been effective both as adjuvant and neoadjuvant therapy.[2]

Current Clinical Trials

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.

References:

1. Penis. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. Springer; 2017, pp 701–14.
2. Pizzocaro G, Piva L: Adjuvant and neoadjuvant vincristine, bleomycin, and methotrexate for inguinal metastases from squamous cell carcinoma of the penis. Acta Oncol 27 (6b): 823-4, 1988.

Treatment of Recurrent Penile Cancer

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.[1,2,3,4,5]

Current Clinical Trials

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.

References:

1. Pizzocaro G, Piva L: Adjuvant and neoadjuvant vincristine, bleomycin, and methotrexate for inguinal metastases from squamous cell carcinoma of the penis. Acta Oncol 27 (6b): 823-4, 1988.
2. Ahmed T, Sklaroff R, Yagoda A: Sequential trials of methotrexate, cisplatin and bleomycin for penile cancer. J Urol 132 (3): 465-8, 1984.
3. Dexeus FH, Logothetis CJ, Sella A, et al.: Combination chemotherapy with methotrexate, bleomycin and cisplatin for advanced squamous cell carcinoma of the male genital tract. J Urol 146 (5): 1284-7, 1991.
4. Fisher HA, Barada JH, Horton J, et al.: Neoadjuvant therapy with cisplatin and 5-fluorouracil for stage III squamous cell carcinoma of the penis. [Abstract] J Urol 143(4 Suppl): A-653, 352A, 1990.
5. Hussein AM, Benedetto P, Sridhar KS: Chemotherapy with cisplatin and 5-fluorouracil for penile and urethral squamous cell carcinomas. Cancer 65 (3): 433-8, 1990.

Latest Updates to This Summary (02 / 02 / 2024)

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.

About This PDQ Summary

Purpose of This Summary

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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Last Revised: 2024-02-02