Ronald M. Bukowski, MD

Recent advances in the understanding of the biology of renal cell carcinoma (RCC) have been translated into clinical treatment options in metastatic disease.

Occult distant micrometastasis at the time of radical cystectomy leads predominantly to distant failures in patients with locally advanced muscle-invasive transitional cell carcinoma of the bladder. Cisplatin-based combination chemotherapy enhances survival in patients with metastatic urothelial cancer. Studies evaluating adjuvant chemotherapy have been limited by inadequate statistical power. However, randomized clinical trials have demonstrated a survival benefit for neoadjvuant cisplatin-based combination chemotherapy, which should be considered a standard of care. In addition, neoadjuvant therapy may assist in the rapid development of novel systemic therapy regimens, since pathologic complete remission appears to be a powerful prognostic factor for long-term outcomes. Patients who are either unfit for or refuse radical cystectomy may benefit from neoadjuvant chemotherapy with or without radiation to enable bladder preservation.

Paralleling the increasing use of multikinase inhibitors in the field of cancer therapy, patients and clinicians are confronted with frequently occurring cutaneous side effects associated with the use of these new drugs. Two such targeted agents, sunitinib (Sutent) and sorafenib (Nexavar), were recently approved by the US Food and Drug Administration to treat patients with metastatic renal cell cancer (RCC).

This report of a case of cytokine-refractory metastatic, clear-cell renal cell carcinoma (RCC) presents some current issues related to use of targeted therapy in the community. Due to the different mechanisms of cytostatic vs cytotoxic agents, traditional response assessments may not always apply in deciding when to either continue or stop treatment. While community physicians may increasingly focus more on duration of response, symptom relief, and how well patients tolerate treatment, there is a clear need for validated surrogate markers of biologic activity and response, as well as randomized trials that directly compare some of the targeted therapies being applied in advanced RCC.

Patients with metastatic renal cell carcinoma continue to present a therapeutic challenge. Current therapeutic approaches involve surgery and various types of immunotherapy. The rationale for this latter form of therapy