RCC: Urologists' role in the targeted therapy era

The treatment of metastatic renal cell carcinoma has undergone significant changes.

Key Points

Now, in the year 2007, all of that has changed. Patients with localized disease have a multitude of options, depending on tumor size, location, and clinical stage. These options include nephron-sparing, minimally invasive, and energy-ablative approaches that are surgically or radiographically guided. Even no therapy with active surveillance is a reasonable alternative in select patients. While the long-term outcomes of these approaches are awaited, the standard of care is shifting, and remains a moving target for the practicing urologist.

The treatment of metastatic renal cell carcinoma has also undergone significant changes. While nephrectomy in the setting of metastatic disease has been controversial in the past, we have seen confirmation of its value in select patients prior to the initiation of systemic immunotherapy through the completion of two independent, randomized phase III trials. The most significant advance has been the development of more effective systemic therapies for patients with metastatic disease.

New therapeutic options

With improved understanding of the biology of carcinogenesis and progression through the detailed analysis of hereditary or familial kidney cancer syndromes, investigators have identified specific molecular pathways that are important in renal cell carcinoma progression. This research naturally has evolved into the development of therapeutics that can disrupt the activity of these pathways.

Role of cytoreductive therapy

Proponents of cytoreductive nephrectomy in the setting of metastatic renal cell carcinoma argue that it can reduce local tumor morbidity, significantly reduce overall tumor burden, possibly enhance responses to systemic therapy, and improve survival. Rarely, if ever, does the primary tumor respond to systemic immunotherapy. Critics argue that cytoreductive nephrectomy in the metastatic setting is morbid surgery with great potential for complications, and that rapid disease progression or postoperative morbidity may preclude the patient from receiving systemic therapy after surgery.