Penile%20cancer Treatment

• 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

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