Response of Primary Renal Cell Carcinoma to Systemic Therapy.

Background: Upfront cytoreductive nephrectomy (CRN) in renal cell carcinoma (RCC) has come into question in recent prospective clinical trials.

Objective: We investigated the effect of systemic therapies on primary tumor response in patients with metastatic RCC.

Design, Setting, And Participants: A pooled analysis of 12 phase II/III clinical trials of metastatic RCC patients treated with systemic therapy between 2003 and 2013 was performed. Patients with one target lesion in the kidney and no prior nephrectomy were identified as having their primary tumor in place.

Outcome Measurements And Statistical Analysis: The objective response rate (ORR) of the primary tumor was defined as per the Response Evaluation Criteria in Solid Tumors (RECIST). ORR was assessed in the overall population and patient subsets based on prior treatment and International Metastatic RCC Database Consortium (IMDC) risk group. Cox's models adjusting for baseline characteristics, treatment, line of therapy, and site of metastases were used for survival analyses.

Results And Limitations: In total, 4736 patients were identified, of whom 565 had their primary tumor in place: 461 (82%) were treatment naïve, 283 (50%) received first-line vascular endothelial growth factor (VEGF)-targeted therapy, and 222 (39%) were IMDC poor risk. The ORRs of the primary tumor were 19% (95% confidence interval 16-23) in patients treated with first-line therapy (any type), 28% (22-33) in those treated with first-line VEGF-targeted therapy, and 23% (19-28) in those treated with VEGF-targeted therapy (any line). The ORRs were 9% (5-13) and 20% (15-27) in IMDC poor- and intermediate-risk patients, respectively.

Conclusions: Systemic therapy reduces primary tumor size in patients with metastatic RCC. Responses in primary tumors treated with VEGF-targeted therapy were observed in upward of 28% of patients. Selection of patients for immediate CRN requires careful consideration of patient and disease characteristics.

Patient Summary: Antiangiogenic therapy meaningfully decreases the size of primary kidney tumor. Hence, for patients with metastatic disease who are not undergoing upfront cytoreductive nephrectomy, systemic therapy can palliate both primary tumor and metastases.