miércoles, 13 de febrero de 2019

Penile Cancer Treatment (PDQ®)—Health Professional Version - National Cancer Institute

Penile Cancer Treatment (PDQ®)—Health Professional Version - National Cancer Institute



National Cancer Institute

Penile Cancer Treatment (PDQ®)–Health Professional Version

Go to Patient Version

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 2019:[1]
  • New cases: 2,080.
  • Deaths: 410.

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.[2-5] 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. 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 can be candidates for phase I and phase II clinical trials testing new drugs, biologicals, 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.
References
  1. American Cancer Society: Cancer Facts and Figures 2019. Atlanta, Ga: American Cancer Society, 2019. Available online. Last accessed January 23, 2019.
  2. Del Mistro A, Chieco Bianchi L: HPV-related neoplasias in HIV-infected individuals. Eur J Cancer 37 (10): 1227-35, 2001. [PUBMED Abstract]
  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. [PUBMED Abstract]
  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. [PUBMED Abstract]
  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. [PUBMED Abstract]
  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. [PUBMED Abstract]
  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. [PUBMED Abstract]
  8. Neonatal circumcision revisited. Fetus and Newborn Committee, Canadian Paediatric Society. CMAJ 154 (6): 769-80, 1996. [PUBMED Abstract]
  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. [PUBMED Abstract]
  10. Trabulsi DJ, Gomella LG: Cancer of the urethra and penis. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 1272-79.
  11. Chao KS, Perez CA: Penis and male urethra. In: Perez CA, Brady LW, eds.: Principles and Practice of Radiation Oncology. 3rd ed. Philadelphia, Pa: Lippincott-Raven Publishers, 1998, pp 1717-1732.

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.[3-5]
In addition, 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. [PUBMED Abstract]
  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. [PUBMED Abstract]
  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. [PUBMED Abstract]
  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. [PUBMED Abstract]
  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. [PUBMED Abstract]
  6. Vadmal MS, Steckel J, Teichberg S, et al.: Primary neuroendocrine carcinoma of the penile urethra. J Urol 157 (3): 956-7, 1997. [PUBMED Abstract]

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 0aa
StageTNMDescription
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.
0isTis, N0, M0Tis = Carcinoma in situ (PeIN).
N0 = cN0, no palpable or visibly enlarged inguinal lymph nodes; pN0, no lymph node metastasis.
M0 = No distant metastasis.
0aTa, N0, M0Ta = 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 Ia
StageTNMDescription
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.
IT1a, N0, M0T1a = 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 IIBa
StageTNMDescription
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.
IIAT1b, N0, M0T1b = 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, M0T2 = 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.
IIBT3, N0, M0T3 = 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 IIIBa
StageTNMDescription
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.
IIIAT1–3, N1, M0T1 = 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.
IIIBT1–3, N2, M0T1 = 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 IVa
StageTNMDescription
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.
IVT4, Any N, M0T4 = 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, M0TX = 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, M1TX = 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).
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. New York, NY: Springer, 2017, pp 701–14.

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: 3iiiDiv]
  2. Topical application of 5-fluorouracil cream has been reported to be effective in cases of erythroplasia of Queyrat [6] and Bowen disease.[7][Level of evidence: 3iiiDiv]
  3. Imiquimod 5% cream is a topical immune response modifier that has been reported to be effective with good cosmetic and functional results.[8-10][Level of evidence: 3iiiDiv]
  4. Laser therapy with Nd:YAG or CO2 lasers has also been reported to result in excellent cosmetic results.[11][Level of evidence: 3iiiDiv]
  5. Cryosurgery has been reported to result in good cosmetic results in patients with erythroplasia of Queyrat and verrucous penile carcinoma.[12,13][Level of evidence: 3iiiDiv]

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. New York, NY: 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. [PUBMED Abstract]
  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. [PUBMED Abstract]
  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. [PUBMED Abstract]
  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. [PUBMED Abstract]
  6. Goette DK, Carson TE: Erythroplasia of Queyrat: treatment with topical 5-fluorouracil. Cancer 38 (4): 1498-502, 1976. [PUBMED Abstract]
  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. [PUBMED Abstract]
  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. [PUBMED Abstract]
  9. Micali G, Nasca MR, Tedeschi A: Topical treatment of intraepithelial penile carcinoma with imiquimod. Clin Exp Dermatol 28 (Suppl 1): 4-6, 2003. [PUBMED Abstract]
  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. [PUBMED Abstract]
  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. [PUBMED Abstract]
  12. Michelman FA, Filho AC, Moraes AM: Verrucous carcinoma of the penis treated with cryosurgery. J Urol 168 (3): 1096-7, 2002. [PUBMED Abstract]
  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. [PUBMED Abstract]

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]
Standard 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]
Treatment options under clinical evaluation:
  • Nd:YAG laser therapy has offered excellent control/cure with preservation of cosmetic appearance and sexual function.[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.[9-12]

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. New York, NY: 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. Baltimore, Md: 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. Philadelphia: 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. Philadelphia, Pa: 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. [PUBMED Abstract]
  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. [PUBMED Abstract]
  7. Smith JA Jr.: Lasers in clinical urologic surgery. In: Dixon JA, ed.: Surgical Application of Lasers. 2nd ed. Chicago, Ill: 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. [PUBMED Abstract]
  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. [PUBMED Abstract]
  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. [PUBMED Abstract]
  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. [PUBMED Abstract]
  12. Young MJ, Reda DJ, Waters WB: Penile carcinoma: a twenty-five-year experience. Urology 38 (6): 529-32, 1991. [PUBMED Abstract]

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
Standard treatment options:
  • 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.[2-6]
Treatment options under clinical evaluation:
  • Nd:YAG laser therapy has been used to preserve the penis in selected patients with small lesions.[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.[8-11]
To reduce the morbidity associated with prophylactic lymphadenectomy, dynamic sentinel node biopsy is being 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. New York, NY: 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. Baltimore, Md: Williams and Wilkins, 1983, pp 581-597.
  3. Schellhammer PF, Spaulding JT: Carcinoma of the penis. In: Paulson DF, ed.: Genitourinary Surgery. Vol. 2. New York: 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. Philadelphia, Pa: 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. [PUBMED Abstract]
  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. [PUBMED Abstract]
  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. [PUBMED Abstract]
  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. [PUBMED Abstract]
  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. [PUBMED Abstract]
  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. [PUBMED Abstract]
  11. Young MJ, Reda DJ, Waters WB: Penile carcinoma: a twenty-five-year experience. Urology 38 (6): 529-32, 1991. [PUBMED Abstract]
  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. [PUBMED Abstract]

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.[2-5] Because many patients with positive lymph nodes are not cured, clinical trials may be appropriate.
Standard 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.
Treatment options under clinical evaluation:
  • 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 5-fluorouracil has also been shown to be effective.[6] Single-agent cisplatin (50 mg/m2) was tested in a large trial and was found to be 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 being 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. New York, NY: 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. Baltimore, Md: 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. [PUBMED Abstract]
  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. [PUBMED Abstract]
  5. Lynch DF, Pettaway CA: Tumors of the penis. In: Walsh PC, Retik AB, Vaughan ED, et al., eds.: Campbell's Urology. 8th ed. Philadelphia: 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. [PUBMED Abstract]
  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. [PUBMED Abstract]
  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. [PUBMED Abstract]
  10. Young MJ, Reda DJ, Waters WB: Penile carcinoma: a twenty-five-year experience. Urology 38 (6): 529-32, 1991. [PUBMED Abstract]
  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. [PUBMED Abstract]

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.
Standard 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.
Treatment options under clinical evaluation:
  • Clinical trials combining chemotherapy with palliative methods of local control are appropriate for such patients (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. New York, NY: 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. [PUBMED Abstract]

Recurrent Penile Cancer

Locally recurrent disease can be approached by surgery or radiation therapy. If the initial treatment of radiation therapy fails, patients are often salvaged by penile amputation. Patients with nodal recurrences that are not controllable by local measures are candidates for phase I and phase II clinical trials testing new biologicals and chemotherapeutic agents.[1-5]

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. [PUBMED Abstract]
  2. Ahmed T, Sklaroff R, Yagoda A: Sequential trials of methotrexate, cisplatin and bleomycin for penile cancer. J Urol 132 (3): 465-8, 1984. [PUBMED Abstract]
  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. [PUBMED Abstract]
  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. [PUBMED Abstract]

Changes to This Summary (02/06/2019)

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 2019 (cited American Cancer society as reference 1).
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® - NCI's Comprehensive Cancer Database 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 who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
  • be discussed at a meeting,
  • be cited with text, or
  • replace or update an existing article that is already cited.
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewer for Penile Cancer Treatment is:
  • Franco M. Muggia, MD (New York University Medical Center)
Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

Permission to Use This Summary

PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as “NCI’s PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary].”
The preferred citation for this PDQ summary is:
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]
Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.

Disclaimer

Based on the strength of the available evidence, treatment options may be described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page.

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  • Updated: February 6, 2019
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