Survival Improved With Surgery/Targeted Therapy Combo in Renal Cell Carcinoma

Toni Choueiri, MD

Patients with renal cancer who underwent cytoreductive nephrectomy (CN) and targeted therapy (TT) had improved survival compared with patients who did not undergo the surgery, according to research from the Dana-Farber Cancer Institute and Brigham and Women’s Hospital.¹ Historically, only 3 in 10 such patients undergo the procedure.

The researchers reported that patients who underwent the procedure survived for a median period of 17.1 months compared with 7.7 months for those who didn’t receive the surgery. The finding corroborates the survival benefit of CN with TT in previously reported studies. The 1-, 2-, and 3-year overall survival (OS) rates were 62.7% (95% CI, 61.3%-64.1%), 39.1% (95% CI, 37.7%-40.6%), and 27.7% (95% CI, 26.3%- 29.1%) versus 34.7% (95% CI, 33.7%-35.8%), 17.1% (95% CI, 16.2%-17.9%), and 9.8% (95% CI, 9.1%-10.5%) for CN and non- CN patients, respectively.

“As we’ve learned about the molecular pathways that drive the disease, drugs that specifically target those pathways have come into wide use,” said the co-lead author, Toni Choueiri, MD, in a statement. “It hasn’t been clear whether this has led to a reduction in CN, whether the procedure improves survival in patients being treated with targeted therapy, and whether some categories of patients are more likely than others to receive the surgery,” continued Choueiri, clinical director of the Lank Center for Genitourinary Oncology and director of the Kidney Cancer Center at Dana-Farber Cancer Institute.

Most current guidelines call for CN to be performed in conjunction with TT for patients deemed to be good candidates for the procedure. Studies have shown that patients with poor survival outcomes or with rapidly advancing cancer are less likely to benefit from the surgery. In his study, Choueiri and his associates identified 15,390 patients with metastatic renal cell carcinoma (RCC) who had been treated with TTs between 2006 and 2013. Only 5374 of those patients, or about 35% of the total, underwent CN, the researchers found. The study is the largest sample size to date showing that CN has an OS benefit in patients treated with TT, while adjusting for other factors, according to the researchers. The investigators also found that patients who were younger, privately insured, treated at an academic medical center, and had smaller tumors were more likely to have the surgery performed.

In prior studies, Choueiri et al² showed that CN patients had improved OS compared with non-CN patients treated with vascular endothelial growth factor (VEGF) therapy (19.8 vs 9.4 months; HR, 0.44; P < .01). Heng et al³ showed that the median OS of patients with metastatic RCC treated with TT with CN versus without CN was 20.6 months vs 9.5 months, respectively (P < .001).

The reason why surgery provides a survival benefit for many patients is unclear, said the researchers, but they theorize that the primary tumor may be especially aggressive and drive metastatic growth elsewhere in the body. Removing it may therefore slow the spread of the disease.

Limitations of the study include its retrospective analyses and the National Cancer Database (NCDB) used for the study. The NCDB does not contain information on important preoperative laboratory variables that have been shown to be independent prognostic factors and does not list the exact TT used (eg, VEGF or mammalian target of rapamycin inhibitors), said the researchers. Future investigations will focus on identifying which patients are most likely to benefit from the surgery.

“The study underscores the importance of careful selection of patients who are good candidates for this surgery,” said Maxine Sun, PhD, the co-lead author of the study. “As we become better able to identify patients likely to derive the greatest benefit from surgery, survival rates may further improve.”

References

1. Hanna N, Sun M, Meyer CP, et al. Survival analyses of metastatic renal cancer patients treated with targeted therapy with or without cytoreductive nephrectomy: a national cancer data base study [ePub ahead of print]. J Clin Oncol. 2016.
2. Choueiri TK, Xie W, Kollmannsberger C, et al. The impact of cytoreductive nephrectomy on survival of patients with metastatic and renal cell carcinoma receiving vascular endothelial growth factor targeted therapy. J Urol. 2011;185(1):60-66.
3. Heng DYC, Wells JC, Rini BI, et al. Cytoreductive nephrectomy in patients with synchronous metastases from renal cell carcinoma: results from the International Metastatic Renal Cell Carcinoma Database Consortium. Eur Urol. 2014;66(4):704-710.