Advanced penile carcinoma.
PURPOSE
In the United States penile carcinoma is an uncommon malignancy that represents only 0.4% of all male malignancies and 2% to 4% of genitourinary malignancies. Of penile cancer cases 30% are diagnosed with advanced disease. Improved understanding of the natural history, appropriate and accurate staging, and tailored, less morbid lymphadenectomy have led to improved survival and decreased the adverse effects of therapy. However, the management of advanced penile carcinoma remains a challenge to urological, medical and radiation oncologists. The rarity and paucity of well designed clinical studies of medical and/or surgical therapy for advanced penile cancer have hampered progress in the treatment of this disease. However, there is clear evidence that identifies active chemotherapy and radiation treatments. This review aims to provide the treating physician with an overview of available data for surgical, chemotherapeutic and radiation treatments, and provide guidelines for appropriate patient selection for these therapies.


MATERIALS AND METHODS
We performed a detailed review of the available literature regarding advanced penile carcinoma to include its etiology, epidemiology, natural history, staging classification and treatment.


RESULTS
Penile carcinoma typically spreads along an echelon of nodal pathways that permits fairly accurate staging. Prognosis correlates well with clinical nodal status and grade, and the TNM classification developed by the UICC should be uniformly used by clinicians. Treatment recommendations are tightly associated with disease stage. Although tailored lymphadenectomy as currently recommended has greatly decreased morbidity, improved staging accuracy and improved treatment results, controversies still exist regarding the need for lymphadenectomy in patients with impalpable lymph node (cN0) disease, and the role and timing of pelvic lymphadenectomy. There is evidence of modest activity for chemotherapy in advanced penile carcinoma. Active agents include cisplatin, bleomycin and methotrexate. Combination chemotherapy regimens with promising activity and toxicity profiles include cisplatin and 5-fluorouracil, and vincristine, bleomycin and methotrexate. Radiation in combination with surgery and/or chemotherapy in advanced disease have also demonstrated activity.


CONCLUSIONS
The natural history of penile carcinoma and its proclivity to spread via regional lymphatics has been well defined. This understanding has led to the development of effective locoregional treatment strategies. Penile carcinoma is sensitive to radiation and certain chemotherapeutic agents. A threshold volume of nodal metastases is associated with significant mortality. The optimal application of these strategies remains to be determined. Improvements in survival and quality of life likely require the incorporation of multiple modalities into the treatment of advanced penile carcinoma. A multi-institutional, international effort is essential to perform appropriately powered clinical trials to advance the standard of care in this rare disease.