eMedicine Specialties > Dermatology > Malignant Neoplasms

Penile Squamous Cell Carcinoma: Treatment & Medication

Author: Giuseppe Micali, MD, Head, Professor, Department of Dermatology, University of Catania School of Medicine, Italy
Coauthor(s): Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School; Maria R Nasca, MD, PhD, Assistant Professor, Department of Dermatology, University of Catania School of Medicine, Italy
Contributor Information and Disclosures

Updated: Mar 5, 2009

Treatment

Medical Care

The treatment of penile SCC varies according to the clinical stage. Treatment includes radiation therapy, medical therapy, and surgery (see Surgical Care), alone or in combination. However, because of the generally limited experience with SCC of the penis, considerable controversy exists as to the best form of treatment, specifically treatment for regional lymph nodes.5,85

  • Radiation therapy
    • Radiation therapy with external beams or mould techniques (cesium Cs 137, iridium Ir 192)86,87 may be an option to treat small, superficial, exophytic lesions in young individuals, allowing for the preservation of sexual function with a high cure rate. In case of relapse, salvage surgery may be required.88,89
    • Circumcision before therapy is recommended.
    • The advantage of radiation therapy over excision has not been definitively demonstrated,90,91 and major complications, such as urethral stenosis, fistulas, and penile necrosis, may occur.
    • Radiation therapy is not indicated in the treatment of verrucous carcinoma because it may result in anaplastic changes and metastases.92
    • Radiation therapy may also be used to treat advanced SCCs of lymph node metastases in patients with unresectable or recurrent lymph node disease or in patients in whom a surgical approach is not feasible.
    • Adjuvant inguinal radiation therapy may be performed after surgical resection of metastatic lymph nodes, whereas prophylactic groin irradiation should be avoided; in irradiated groins, detecting metastases is clinically more difficult, and a high rate of complications occurs after lymphadenectomy.
  • Medical treatment (local and systemic chemotherapy)
    • Early premalignant and in situ changes can be treated with topical chemotherapy (5-fluorouracil)93 or imiquimod.5,94,95
    • Systemic chemotherapy may be used according to the stage of the disease, with 3 distinct modalities,3,4 as follows:
      • Palliative chemotherapy is suggested for local recurrences and for metastases when other treatments fail. It is usually delivered systemically by means of intramuscular or intravenous injection (depending on the agent used), as monochemotherapy with bleomycin, methotrexate, or cisplatin alone or combined with other drugs for a synergistic effect. Drugs used in combination include vincristine, bleomycin, and methotrexate (VBM therapy); cisplatin and fluorouracil (PF therapy); and cisplatin, bleomycin, and methotrexate (CMB therapy). In 2008, the combination of cisplatin and fluorouracil with taxanes (paclitaxel) (TPF therapy) has been suggested.96 Generally, better results are obtained with combination chemotherapy than monotherapy.62
      • Adjuvant combined chemotherapy (VBM or CBM therapy) may be used to reduce the incidence of metastases in patients with involved nodes after surgical resection of the lymph nodes.97
      • Neoadjuvant combined chemotherapy may be attempted for locally invasive tumors (stages T3-T4) or for fixed regional node enlargement (stage N3) to reduce the neoplastic mass before surgical excision (down-staging). Surgery is recommended only for patients responding to chemotherapy. This approach may allow for a more conservative surgical procedure than what would otherwise be needed.98,99,100
    • Other medical treatments include the following:
      • Chemotherapy (bleomycin) and radiation therapy
      • Photodynamic therapy for Tis101
      • Regional intra-arterial chemotherapy (methotrexate and mitomycin C)
      • Systemic or intralesional interferon alfa either alone or combined with surgical shaving (for relapsing verrucous carcinoma)

Surgical Care

Surgical procedures consist of local excision, circumcision, glansectomy, partial penectomy, total penectomy, and demasculinization. The last 3 procedures may be performed in conjunction with lymph node dissection.5,102,103 104

  • Local excision: Small and superficial lesions on the glans or the shaft (<2 cm) may be treated with wide wedge resection, extending the surgical margin 2 cm beyond the proximal end of the lesion. Obtaining multiple deep and lateral biopsy samples at the time of surgery is strongly recommended. Glans skinning and resurfacing may represent an alternative option in selected cases.105
  • Circumcision: Small carcinomas of the distal foreskin without deep infiltration can be treated with wide circumcision with a 2-cm margin of clearance. Without adequate margins, the incidence of local recurrence is high (40%).
  • Mohs surgery: Local excision with Mohs micrographic surgery has been performed with good results for small and superficial invasive carcinomas located on the glans or near the preputial sulcus. It has the advantage of preserving large amounts of healthy tissue and normal functions. Careful follow up is essential because recurrence rates are high in some series.106
  • Laser therapy107
    • Destructive therapy can be administered with a carbon dioxide or a neodymium:yttrium-aluminum-garnet (Nd:YAG) laser, alone or in combination or with an argon and potassium-titanyl-phosphate (KTP) laser, although this last option is least common.108,109
    • Laser therapy has the advantage of providing a bloodless field,110 but it does not allow for histopathologic sampling and local recurrences can be frequent (>50%), especially with the carbon dioxide laser.
    • Better results are obtained with the Nd:YAG laser, which penetrates deeper and allows coagulation of larger vessels. For this reason, accurate preoperative staging of the tumor by means of multiple deep biopsies is recommended to establish the adequacy of the depth of laser destruction.62 This treatment should be reserved for Tis and T1 stage tumors only.111
  • Cryosurgery: The use of cryosurgery, either alone or combined with 5-fluorouracil, has been suggested for verrucous carcinoma.112
  • Glansectomy and penectomy
    • Glansectomy may be performed in verrucous carcinoma limited to the glans,113,114 whereas partial penectomy is the procedure of choice for tumors (SCC or verrucous carcinoma) at a low stage (stage I, T1-T2) that involves most of the glans or the distal third of the penis.83,115 Total penectomy is necessary when the lesion is in the proximal portion of the penis or when the tumor is at an advanced stage (stages II-III, T3-T4).83
    • Reconstruction techniques may help in preserving acceptable function and appearance of the penis.105,116,117,118 Conservative organ-sparing surgical techniques for penile SCC may reduce the emotional and functional impact of surgical treatments on patients without compromising oncological cure.119,120,121
  • Demasculinization
    • Penectomy plus scrotectomy and bilateral orchidectomy with wide en bloc excision of the involved abdominal wall and bilateral lymphadenectomy may be required for infiltrating masses at the base of shaft.83
    • In such patients with advanced penile cancer and metastatic disease, an aggressive palliative resection combined with vertical rectus abdominis flap reconstruction may improve the quality of life.122
  • Lymph node dissection
    • Because of the significant morbidity of inguinal and pelvic node dissection123 and because of the high incidence of reactive nodes, surgical dissection of the lymph nodes is necessary only if they are enlarged and do not regress after adequate antibiotic therapy.103 In general, if positive nodes are found during dissection of the superficial lymph nodes, bilateral dissection of the deep nodes is suggested. Bilateral pelvic lymphadenectomy should also be performed because approximately 30% of these nodes harbor tumor metastases when the inguinal lymph nodes are involved. However, pelvic lymph node dissection seems to be unnecessary in patients with 2 or fewer inguinal lymph nodes involved by a well differentiated tumor without extracapsular growth.124
    • As an alternative, some authors perform ipsilateral inguinal (superficial and deep) and pelvic lymphadenectomy with contralateral superficial inguinal node dissection to decrease the incidence of complications due to a radical approach.89 Extensive surgical dissection is not justified if the para-aortic lymph nodes are involved (stage N4) because improved survival is not likely.125 Surgical techniques to reduce the morbidity of inguinal node dissection, including the use of a spermatic cord patch and saphenous vein sparing, have been proposed.126,127
    • The timing and extension of lymph node dissection is controversial because histologic investigations have demonstrated that 10-20% of clinically normal nodes contain unsuspected metastases. The 5-year survival rate is as high as 84-88% in patients undergoing prophylactic inguinal lymphadenectomy, compared with 35-42% in patients undergoing therapeutic lymph node dissection.128,129 A disease-specific 3-year survival rate of 84% was reported in patients who underwent early lymph node resection, compared with 35% in those with positive lymph nodes detected during surveillance.129
    • Histopathologic variables considered to be strong predictors of inguinal metastases are vascular and perineural invasion, as well as the grade and stage of the primary tumor.59,60,89,130,131,132 Other factors that have been found to correlate with a higher risk of inguinal metastases are an infiltrating growth pattern of invasion,133  p53 immunoreactivity,134 a strong Ki67 labeling index,135,136 and a low E-cadherin expression137 of the primary tumor.
    • Watchful waiting is advised in patients who are not obese, those in whom accurate clinical assessment is possible, and those who are compliant and reliable for follow-up. Patients should also have impalpable lymph nodes and superficially invasive (<2 cm) tumors. Such patients may also be candidates for videoendoscopic inguinal lymphadenectomy, a new technique that may decrease postoperative morbidity without compromising oncological control.138,139,140 Patients with poorly differentiated and deep, invasive tumors (stage T2 or higher) are considered at high risk, especially if the tumor is proximal on the shaft and shows vascular invasion on histology; these patients are more likely than others to benefit from prophylactic dissection of the lymph nodes.62
    • Dynamic mapping of lymph nodes with technetium Tc 99m as a tracer plus blue dye followed by targeted biopsy has been introduced to restrict surgical dissection to sentinel nodes. The aim is to avoid the complications of unnecessary elective regional groin dissection, which can be reserved for patients with positive sentinel nodes.66,67,102,141,142,143 The Role of Sentinel Node Biopsy in Skin Cancer provides details on sentinel node biopsy.
      • Findings from 2007 suggest that the isolated gamma probe technique for sentinel node penile SCC has a very low sensitivity and a high false-negative rate. Therefore, use it in combination with other techniques, such as vital blue, lymphoscintigraphy, and/or ultrasonography.144
      • Preoperative ultrasonography with fine-needle aspiration cytology, groin exploration with intraoperative wound palpation, and serial sectioning with immunohistochemical staining have been suggested as adjunctive tools to increase the reliability of sentinel-node identification.98,125,145,146,147
      • Dynamic lymphotrophic nanoparticle-enhanced MRI with iron oxide is another technique that has been suggested in the evaluation of patients with palpable groin adenopathy148 in which standard sentinel node biopsy is considered of low value for the detection of lymphatic spread.69
      • Overall, the reliability of identifying sentinel nodes remains debatable, and superficial node dissection is still considered the criterion standard to detect micrometastases from penile SCC.149,150 The development of groin metastases after a negative result on sentinel node biopsy has been observed. Moreover, micrometastases may bypass the superficial nodes of the groin and drain directly into the deep groin or the iliac nodes.

Medication

Treatment for penile SCC includes medical and surgical procedures and radiation therapy. Medical therapy consists of local and systemic therapy.

Antineoplastic agents

These agents inhibit cell growth and proliferation.


Bleomycin (Blenoxane)

Composed of cytotoxic glycopeptide antibiotics, which appear to inhibit DNA synthesis with some evidence of RNA and protein synthesis inhibition; used to manage several neoplasms.

Adult

15-30 mg/m2/wk IV/IM

Pediatric

Not established

May decrease plasma levels of digoxin and phenytoin; cisplatin may increase toxicity when administered systemically

Documented hypersensitivity; significant renal function impairment; compromised pulmonary function

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Caution in renal impairment; possibly secreted in breast milk; may cause mutagenesis and pulmonary toxicity (10%); idiosyncratic reactions similar to anaphylaxis (1%) may occur; monitor for adverse effects during and after treatment; vaso-occlusive phenomenon with distal necrosis of digit; permanent damage to nail matrix may occur; adverse effects include pulmonary toxicity (progressive fibrosis), renal toxicity, cutaneous hyperpigmentation, and alopecia; check renal function


Methotrexate (Folex PFS, Rheumatrex)

Antiproliferative agent with anti-inflammatory and antineoplastic properties that inhibit purine and pyrimidine synthesis.

Adult

30-40 mg/m2 IV/IM

Pediatric

Not established

Oral aminoglycosides may decrease absorption and blood levels of concurrent oral methotrexate; charcoal lowers levels; coadministration with etretinate may increase hepatotoxicity; folic acid or its derivatives contained in some vitamins may decrease response; probenecid, NSAIDs, salicylates, procarbazine, and sulfonamides, including TMP-SMZ, can increase plasma levels; may decrease phenytoin plasma levels; may increase thiopurine plasma levels

Documented hypersensitivity; alcoholism; hepatic insufficiency; documented immunodeficiency syndromes; preexisting blood dyscrasias (eg, bone marrow hypoplasia, leukopenia, thrombocytopenia, significant anemia); renal insufficiency

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Monitor CBC counts monthly and liver and renal function q1-3mo during therapy (more frequently during initial dosing, dose adjustments, or with risk of elevated levels [eg, dehydration]); toxic effects on hematologic, renal, GI, pulmonary, and neurologic systems; discontinue if blood counts significantly decrease; fatal reactions reported when administered concurrently with NSAIDs; adverse effects include myelotoxicity, hepatotoxicity, nephrotoxicity, and alopecia; provide adequate water intake


Cisplatin (Platinol)

Kills cells at all steps of mitotic cycle by inhibiting DNA synthesis through cross-linking with guanine.

Adult

20 mg/m2/d IV for 5 d or 50-70 mg/m2 IV q3wk

Pediatric

Not established

Increases toxicity of bleomycin and ethacrynic acid

Documented hypersensitivity; preexisting renal insufficiency; myelosuppression; hearing impairment

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Adverse effects include nausea, emesis, myelotoxicity, ototoxicity, ophthalmic neuritis, hypomagnesemia, nephrotoxicity, and cerebral blindness; increase hydration to avoid risk of renal toxicity


Vincristine (Oncovin, Vincasar PFS)

Stops mitotic cycle by depolymerizing microtubules.

Adult

1.5 mg/m2 IV; not to exceed 2 mg/wk

Pediatric

Not established

Acute pulmonary reaction may occur with concurrent mitomycin-C; asparaginase, CYP450 3A4 inhibitors (eg, itraconazole, quinupristin/dalfopristin, sertraline, ritonavir), GM-CSF (eg, sargramostim, filgrastim), or nifedipine increase toxicity; CYP450 3A4 inducers (eg, carbamazepine, phenytoin, phenobarbital, rifampin) may decrease effects

Documented hypersensitivity; IT administration may cause death

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Adverse effects include peripheric paresthesia, abdominal pain, constipation, and myelotoxicity; caution in severe cardiopulmonary disease, hepatic impairment (adjust dose), or preexisting neuromuscular dysfunction


5-Fluorouracil (Adrucil)

Inhibits DNA synthesis after metabolic activation by altering thymine synthesis.

Adult

15 mg/kg/d IV for 5 d

Pediatric

Not established

Increased risk of bleeding with anticoagulants, NSAIDs, platelet inhibitors, and thrombolytic agents; enhanced bone marrow toxicity with other immunosuppressives

Documented hypersensitivity; bone marrow suppression; serious infection; topical administration contraindicated in pregnancy

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Nausea, oral and GI ulcers, depression of immune system, and hemopoietic failure (bone marrow suppression) may occur; adjust dose in renal impairment


Mitomycin C (Mutamycin)

Used for vesical and mammary neoplasms. Links to DNA with cross-linking after metabolic activation mediated by CYP450 reductase.

Adult

15-20 mg/m2 IV q6wk

Pediatric

Not established

May increase toxicity of vinca alkaloids and doxorubicin

Documented hypersensitivity; thrombocytopenia; platelet counts <75,000/µL, leukocyte counts <3,000/µL, or serum creatinine levels >1.7 mg/dL

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Closely monitor hemoglobin, BUN, creatinine, and hematocrit levels after therapy, especially after second and subsequent cycles; bone marrow suppression may contribute to development of secondary infections; may cause hemolytic uremic syndrome or pulmonary toxicity; use extravasation precautions

Interferons

These agents are naturally produced proteins with antiviral, antitumor, and immunomodulatory actions. Alpha, beta, and gamma interferons may be given topically, systemically, or intralesionally.


Interferon alfa-2a (Roferon-A), Interferon alfa-2b (Intron-A)

Glycoproteins with antiviral, immunomodulating, and antiproliferative activities. Both are recombinant alpha interferons with minor amino-acid differences but considered equivalent to treat chronic myeloid leukemia.
Roferon A in single-dose (3-, 9-, or 36-MIU strength) or multidose vial (9- or 18-MIU strength). Intron A in multidose pens of 18 (3 MIU/dose), 30 (5 MIU/dose), or 60 (10 MIU/dose) MIU; each pen has 6 doses. For elderly patients who cannot tolerate adverse effects of interferon alfa, may start at half the recommended starting dose.

Adult

3 million IU IM or intralesionally 3 times/wk

Pediatric

Not established

Theophylline may increase toxicity; cimetidine may increase antitumor effects; zidovudine and vinblastine may increase toxicity

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Adverse effects include nausea, lethargy, depression, obnubilation, myelotoxicity, hypotension and hypertension, nephrotoxicity, hepatotoxicity, and hyperglycemia; caution in brain metastases, severe hepatic or renal insufficiencies, seizure disorders, multiple sclerosis, or compromised CNS

More on Penile Squamous Cell Carcinoma

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References
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Further Reading

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Keywords

penile squamous cell carcinoma, penile SCC, SCC, penile cancer, genital cancer, penile tumor, epidermoid carcinoma of the penis, verrucous carcinoma, Buschke-Loewenstein tumor, penile malignant neoplasm, Bowen's disease, Bowen disease, erythroplasia of Queyrat, bowenoid papulosis, leukoplakia, HPV infection, human papillomavirus infection, penile lichen sclerosus, balanitis, PKMB

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Contributor Information and Disclosures

Author

Giuseppe Micali, MD, Head, Professor, Department of Dermatology, University of Catania School of Medicine, Italy
Giuseppe Micali, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

Coauthor(s)

Robert A Schwartz, MD, MPH, Professor and Head, Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, UMDNJ-New Jersey Medical School
Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American College of Physicians, and Sigma Xi
Disclosure: Nothing to disclose.

Maria R Nasca, MD, PhD, Assistant Professor, Department of Dermatology, University of Catania School of Medicine, Italy
Disclosure: Nothing to disclose.

Medical Editor

Alexa F Boer Kimball, MD, MPH, Associate Professor of Dermatology, Harvard University School of Medicine; Vice Chair, Department of Dermatology, Massachusetts General Hospital; Director of Clinical Unit for Research Trials in Skin (CURTIS), Department of Dermatology, Massachusetts General Hospital and Brigham and Women's Hospital
Alexa F Boer Kimball, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, and Society for Investigative Dermatology
Disclosure: Nothing to disclose.

Pharmacy Editor

David F Butler, MD, Professor of Dermatology, Texas A&M University College of Medicine; Chair, Department of Dermatology, Director, Dermatology Residency Training Program, Scott and White Clinic
David F Butler, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, American Society for Dermatologic Surgery, American Society for MOHS Surgery, Association of Military Dermatologists, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Managing Editor

Van Perry, MD, Assistant Professor, Department of Medicine, Division of Dermatology, University of Texas Health Science Center
Van Perry, MD is a member of the following medical societies: American Academy of Dermatology and American Society for Laser Medicine and Surgery
Disclosure: Nothing to disclose.

CME Editor

Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania
Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology
Disclosure: AMGEN Consulting fee Consulting; AMGEN Grant/research funds None; Genentech Consulting fee Consulting; Centocor Consulting fee Consulting; Centocor Grant/research funds None; Covance Consulting fee Consulting; Shire  Consulting

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
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