Multimodal Approaches in the Management of Locally Advanced and Metastatic Renal Cell Carcinoma: Combining Surgery and Systemic Therapies to Improve Patient Outcome

Abstract

Patients with locally advanced renal cell carcinoma are at high risk of metastatic relapse following surgery. Patients with metastatic disease have a poor prognosis and few systemic therapy options. Radiation, chemotherapy, hormonal therapy, vaccines, and immunotherapy have all been tested as adjuvant therapy without benefit. Neoadjuvant therapy in the metastatic setting holds promise as a new treatment paradigm. It can serve as a litmus test to allow proper patient selection for aggressive surgical intervention and may provide limited downstaging of primary tumors in selected cases. It can also provide a histologic assessment of the effect of targeted therapy. Application of this paradigm may have merit in the locally advanced setting as well. Effective adjuvant therapy for renal cell carcinoma remains elusive. The benefit of new targeted therapies has yet to be tested in this setting. Neoadjuvant strategies that integrate aggressive surgical intervention with systemic therapy may hold promise as a treatment paradigm. Development of an Effective Adjuvant Strategy for Locally Advanced Renal Cell Carcinoma at High Risk of Relapse following SurgeryRenal cell carcinoma remains one of the most lethal of urologic malignancies despite recent inroads into the biology of progression and metastases that have translated into the development of novel therapies. Despite this, effective adjuvant therapy for patients with renal cell carcinoma at high risk of relapse following surgery remains elusive in 2006. The ideal adjuvant is nontoxic, is administrable in the outpatient setting, has shown activity in metastatic disease, has demonstrable efficacy against the standard of care (observation) in phase 3 randomized trials, and can be applied in patient populations most likely to benefit from adjuvant therapy, those with highrisk disease.

Successful Treatment of T4 Renal Cell Carcinoma After a Neoadjuvant Targeted Therapy Using Sunitinib: Report of a Case

“…Currently, several phase II trials are ongoing to determine appropriate patient selection and timing of cytoreductive nephrectomy in patients with metastatic RCC treated with sunitinib or other targeted drugs [12]. Our observations support the suggestion that sunitinib could prove useful in the neoadjuvant setting by facilitating surgical procedures.…”

Sunitinib for Treatment of Advanced Renal Cell Cancer: Primary Tumor Response

“…Whether this is beneficial for patient outcome cannot be answered on the basis of these three cases. Prospective randomized phase III clinical trials in patients presenting with mRCC are warranted to define which patients treated with sunitinib will benefit from nephrectomy, to analyze whether nephrectomy has an effect on survival, and to determine the optimal timing of a nephrectomy (28). Such trials will lead to new guidelines on the role of nephrectomy in mRCC patients in the sunitinib era.…”

Tratamiento de los tumores renales localmente avanzados

“…El tratamiento adyuvante en los pacientes de alto riesgo de progresión puede actuar sobre las células tumorales presentes tras la cirugía y responsables de la aparición de las metástasis, mejorando así la supervivencia de estos pacientes. Ninguno de los agentes estudiados hasta el momento (radioterapia, tratamiento hormonal, inmunoterapia) ha conseguido confirmar la afirmación anterior 4,5,42,43 . Los inhibidores de la angiogénesis tienen el reto de modificar la evolución del la historia natural del carcinoma renal en este grupo de pacientes con alto riesgo de progresión.…”