Unexpectedly we found no association of TVmets nor

Unexpectedly, we found no association of TVmets nor of the ratio TVmets-TVprimary with CN status, suggesting that neither metastatic volume nor its ratio to TVprimary was a factor in the decision for or against CN. This is contrary to our assumption that intermediate-risk patients with low metastatic volume would have been offered CN more often than patients with high metastatic volume or small primary tumour. However, the decision to remove the primary tumour substracted the substantial volume from the baseline TV. In the Cox regression analysis, only CN status was therefore significantly associated with survival in patients with intermediate-risk synchronous mRCC, who were treated with sunitinib. This is in line with previous trials in the cytokine era where the benefit of CN was proven [15,16]. However, taking the other parameters that were part of the regression analysis and which were each individually associated with a survival benefit into account (TBactual, IMDC 2 vs. 3 factors, and TVactual ) it is likely that CN status summarizes a favorable prognostic subgroup rather than being proof of a beneficial effect of debulking nephrectomy in the era of targeted therapy. Presently, only retrospective data are available that suggest that appropriately selected patients with mRCC benefit from Cyanine3.5 alkyne Supplier of CN with systemic targeted therapy [6,17–19]. Therefore, the results of the ongoing randomized controlled CARMENA trial that compares CN followed by sunitinib to sunitinib alone would have to be awaited to definitely settle this question.


Renal cell carcinoma (RCC) is the most common kidney cancer, accounting for about 80% to 90% of renal parenchymal neoplasms. Approximately 30% of patients have distant metastases at the time of diagnosis, and of those patients with RCC who undergo surgical resection, 20% to 40% have distant metastases. Once metastases occur, the 5-year survival rate of patients is only 0% to 20%. RCC is resistant to traditional chemotherapy drugs, and the response rate with immunotherapy regimens is only 5% to 20% [1]. Currently, tyrosine kinase inhibitors (TKIs) that target vascular endothelial growth factor receptors (VEGFRs) and platelet-derived growth factor receptors, such as sunitinib, sorafenib, and pazopanib, are the first-line options for the treatment of metastatic RCC (mRCC). In a study comparing the efficacy of sunitinib and interferon-α in treatment-naive patients with mRCC, the median overall survival (mOS) of patients who received sunitinib treatment was significantly longer than that of patients who received immunotherapy (26.4 vs. 21.8mo, respectively; P = 0.051) [2]. Another study of immunotherapy in patients with mRCC reported lower median survival times of 17.5 and 13 months, respectively, with high-dose intravenous interleukin-2 and subcutaneous interleukin-2 plus interferon-α [3].
A widely used prognostic model of mRCC is the Memorial Sloan-Kettering Cancer Center (MSKCC) model [4], which includes 5 principal adverse prognostic factors, Karnofsky score<80, serum lactate dehydrogenase (LDH) concentration>1.5×the upper limit of normal (ULN), low hemoglobin (<13g/l for males;<11.5g/l for females), serum calcium concentration>10mg/dl, and diagnosis to treatment time of<1 year. Based on these factors, patients can be segregated into 3 risk categories, favorable (no prognostic factors), intermediate (1 or 2 prognostic factors), and poor (3–5 prognostic factors). In the study of Motzer et al. [4], in which 463 patients with mRCC were treated with interferon-α, mOS times in the 3 prognostic groups were 28.6, 14.6, and 4.5 months, respectively. In another study in which 353 previously untreated patients with mRCC were evaluated on the basis of the MSKCC model, Mekhail et al. [5] concluded that prior radiotherapy and>1 metastatic site were also prognostic factors.
It should be noted that the MSKCC prognostic model was initially based on clinical trials of immunotherapeutic agents, but recently, a few retrospective studies have shown that the MSKCC prognostic model can also apply to mRCC treated with TKIs [6,7]. There is a need to explore additional prognostic factors for mRCCs treated with TKIs, and the role of the MSKCC prognostic model in East Asian, especially Chinese, populations still needs to be further confirmed. Thus, we retrospectively reviewed the data from 5 clinical trials of first-line TKI therapy in Chinese patients with mRCC.