Penile cancer: current therapy and future directions

Abstract

Background Penile cancer (PC) is a rare cancer in western countries, but is more common in parts of the developing world. Due to its rarity and the consequent lack of randomized trials, current therapy is based on retrospective studies and small prospective trials. Design Studies of PC therapy were searched in PubMed and abstracts at major conferences. Results PC is generally an aggressive malignancy characterized by early locoregional lymph node (LN) spread and later metastases in distant sites. Given the strong predictive value of LN involvement for overall survival, evaluating regional LNs is critical. Advanced LN involvement is increasingly being treated with multimodality therapy incorporating chemotherapy and/or radiation. A single superior cisplatin-based regimen has not been defined. Further advances may occur with a better collaboration on an international scale and comprehensive understanding of tumor biology. To this end, the preventive role of circumcision and understanding of the oncogenic roles of Human Papilloma Virus-16, and smoking may yield advances. Preliminary data suggest a role for agents targeting epidermal growth factor receptor and angiogenesis. Conclusion Advances in therapy for PC will require efficient trial designs, synergistic collaboration, incentives to industry and the efforts of patient advocacy groups and venture philanthropists.

Figure 1.

Potential molecular pathways driving growth and resistance of penile cancer. Human Papilloma Virus (HPV) may play an initiating role, but no dominant molecular driver has emerged. The EGFR and Her3/Her4 family, signaling via Ras-Raf and PI3K-Akt, transcription factors (NF-kappa-B), tumor suppressor gene alterations (RB and p53), epigenetic factors (methylation), cell-cycling regulators (p16 and p21), pro-survival molecules (Bcl-2 family and telomerase), pro-inflammatory (COX-2) and pro-angiogenic molecules (VEGF axis) appear to play a role in subsets.

Figure 2.

Proposed strategy to manage local and locoregional invasive penile cancer. ^∞Consider LN biopsy to exclude false positive lymphadenopathy, *brachytherapy/external bean radiation/Mohs micrographic surgery/laser, ^†except for T1G1 where a role for surveillance exists, ^κpotential role for sentinel LN dissection followed by LN dissection if positive, ^πconsider pelvic LN dissection based on risk.