Management Options for Stage III Renal Cancer?

Christopher W. Ryan, MD

Disclosures

May 13, 2004

Question

A 37-year-old man underwent radical nephrectomy for a left renal mass. Pathology showed a 4.5-cm moderately differentiated clear-cell carcinoma. Afferent lymphatics of 1 of 5 lymph nodes were positive for tumor. Inferior vena cava and renal veins were uninvolved, but a few small intrarenal veins had tumor cells. There was no invasion of the perinephric tissue or the renal fascia. Would you recommend adjuvant treatment?

Response from Christopher W. Ryan, MD

According to the AJCC staging system, this patient's kidney cancer is a T1b N1 Mx tumor, and based on the lymph node status, is classified as stage III, both by AJCC and the older Robson criteria. Stage III tumors < 5 cm in size showed a 55% 5-year survival in one retrospective study,[1] and this patient remains at a relatively high risk of relapse.

Unfortunately, there are no adjuvant therapies for renal cell carcinoma that have a proven survival benefit. Postoperative radiation therapy has not been shown to affect either relapse rate or survival.[2] Several randomized studies have investigated immunomodulatory agents such as interferon-alfa or interleukin-2 in the adjuvant setting, but none have demonstrated benefit.[3,4,5] A recently published, randomized study of an adjuvant autologous tumor vaccine showed a reduced risk in tumor progression in patients who received vaccination vs those randomized to no further treatment after nephrectomy.[6] However, overall survival -- the true benchmark of adjuvant therapy success -- was not an endpoint of this study. Additionally, only 3% of patients in this study had lymph node involvement, so the applicability of this strategy to the patient in question is unknown. A large, randomized, adjuvant study of an autologous tumor-derived heat-shock protein-peptide complex is currently accruing patients.[7]

Given our increasing understanding of kidney cancer biology -- most notably the link between von Hippel Lindau gene mutations and kidney cancer -- it is hoped that development of targeted agents for this disease will become a reality in the not-too-distant future. As novel agents are identified that have activity in the metastatic setting, investigation of their utility in the adjuvant setting will be warranted. Small molecules and antibody therapies that target pathways in production of vascular endothelial growth factor are one area of current interest.[8,9]

At this time, surveillance remains the standard management for stage III tumors after nephrectomy. If feasible, the patient should be offered referral to a clinical trial evaluating adjuvant therapies for renal cell carcinoma.

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