penile%20cancer
PENILE CANCER

Penile cancer is a rare type of malignant growth that occurs on the skin or tissues of the penis.

It often presents as a palpable visible penile lesion w/ signs that may include pain, bleeding, discharge or a foul odor.

The lesion may be fungating, nodular or ulcerative and may be concealed by phimosis.


Principles of Therapy

  • Penile cancer is highly curable when diagnosed in its early stages, eg stages 0, I, & II; however, because of its rarity, specific clinical trials are infrequent & literature on the role of chemotherapy is limited
    • Stages III & IV can be included in phase I & II clinical trials that test biologicals, new drugs, or surgical procedures that will improve local control & distant metastases
  • There is no standard second-line systemic therapy as evidence to support its palliative use is limited
  • Choice of treatment depends on the invasiveness, location, size, & stage of the tumor
    • Includes an accurate histological diagnosis & staging of the primary tumor & regional nodes

Pharmacotherapy

Topical Chemotherapy

  • An effective 1st-line penile-preserving technique for carcinoma in situ, topical chemotherapy with 5-Fluorouracil (5-FU) or Imiquimod has low adverse effects & toxicity but with limited efficacy
    • Topical therapy should not be repeated if it fails
  • 5-FU cream has been reportedly effective in the treatment of erythroplasia of Queyrat & Bowen disease
  • Imiquimod cream, a topical immune response modifier, is also effective with good cosmetic & functional outcomes

Neoadjuvant Chemotherapy

  • Cytoreductive neoadjuvant chemotherapy induces a treatment response that facilitates local control through surgery or radiation therapy & should be considered if inguinal lymph nodes are >4 cm
    • Consolidation surgery after neoadjuvant chemotherapy results in remission in a number of patients
    • Radical surgery after neoadjuvant chemotherapy may be done in patients with unresectable or recurrent lymph node metastases
  • Patients unresponsive to neoadjuvant chemotherapy should be offered palliative treatment
  • Cisplatin is the cornerstone of combination therapies for ≥4 cm mobile or fixed inguinal lymph nodes positive for metastatic disease on fine-needle aspiration (FNA)
    • Four courses of Paclitaxel, Cisplatin & Ifosfamide (TIP) (preferred) chemotherapy were effective & well tolerated in patients with bulky regional disease (any T, N2 or N3) but without distant metastases
    • Other alternative regimens include Paclitaxel/Docetaxel, Cisplatin & 5-FU; Bleomycin,Methotrexate, & Cisplatin (BMP); Cisplatin & Irinotecan
    • Regimens that can be used in both neoadjuvant & adjuvant setting are Cisplatin & 5-FU (PF) (preferred); Bleomycin, Vincristine, & Methotrexate (BVM); Cisplatin, 5-FU, & Docetaxel (TPF)

Adjuvant Chemotherapy

  • Adjuvant chemotherapy is given in pN2-3 penile cancer patients or patients with high-risk features not previously treated with neoadjuvant chemotherapy with any of the following: >3 positive nodes, bilateral inguinal node involvement, extranodal extension, metastases to pelvic lymph nodes
    • Adjuvant chemotherapy in pN1 disease is recommended only in clinical trials

Clinical Trials

  • Whenever possible & if available, participation in clinical trials is encouraged
  • Clinical trials making use of radiosensitizers or cytotoxic drugs are suitable for stage III penile cancer
    • Radiosensitizing agents are used for radiation therapy with concurrent chemotherapy
      • Cisplatin alone or in combination with continuous-infusion 5-FU is preferred
      • Other alternate agents include Mitomycin C & 5-FU; Capecitabine for palliation;Bleomycin, Methotrexate & Vincristine combination therapy
  • Patients with stage IV penile cancer are given palliative therapy as there is no existing curative standard treatment; thus, clinical trials joining chemotherapy with palliative surgery or radiation therapy are suitable for stage IV penile cancer
    • Chemotherapeutic agents with demonstrable activity include Bleomycin, Cisplatin, Methotrexate & Vincristine

 Metastatic Disease

  • Presents a poor prognosis & palliative care should be considered early in the treatment
    • Overall survival is 0% at 5 years & <10% at 2 years
  • Patients are treated with systemic chemotherapy, radiation therapy, or radiation therapy with concurrent chemotherapy
    • Complete or partial responders or those with stable disease are given consolidation inguinal lymph node dissection (ILND)
    • Non-responders or those with disease progression may be treated with salvage systemic chemotherapy or consider radiation therapy for local control &/or best supportive care or clinical trial participation
  • Though active combination regimens are available, there is no preferred regimen for metastatic penile cancer treatment & selection of therapy should consider potential toxicities
    • A literature review found that Cisplatin-containing regimens were most active for metastatic disease; Bleomycin, though possessing a similar activity, is associated with severe adverse effects but can be safely given with Cisplatin in patients who are young, not heavy smokers, & without compromised lung function
  • For advanced disease, palliative chemotherapy with Cisplatin-based regimens had better results after adjustment for prognostic factors:
    • TIP may also be used as a reasonable 1st-line treatment in metastatic disease based on their activity with neoadjuvant usage
    • Cisplatin in combination with 5-FU or Irinotecan
      • Cisplatin & 5-FU can be considered an alternative option to TIP but toxicities may require dose reductions
    • Cisplatin & Gemcitabine had a sustained palliative response in patients with metastatic disease
    • Paclitaxel with Carboplatin is an alternative option for patients who cannot take Cisplatin
    • Paclitaxel as a single agent was effective in metastatic patients who previously were given Cisplatin combination regimens in the neoadjuvant or adjuvant setting
    • Other potentially active agents include Cetuximab, Panitumumab, Sorafenib, & Sunitinib
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