In this study, we established that pre-treatment PIV was an independent prognostic factor in patients with mRCC treated with nivolumab in the second line and beyond. To the best of our knowledge, this was the first study assessing the prognostic value of PIV in patients with mRCC treated with nivolumab.
In fact, the easy access to peripheral blood IIBs makes them more attractive for use as a prognostic biomarker. To date, many studies evaluated the prognostic value of NLR and SII in patients with mRCC.(Hizal et al. 2020; Rebuzzi et al. 2020; Teishima et al. 2020) However, a few studies assessed these biomarkers in patients with mRCC treated with ICIs. One of these studies showed that NLR was a prognostic factor for OS and PFS in patients with mRCC treated with nivolumab. However, a small sample size (n = 38) was an important limitation of this study.(Bilen et al. 2018) Similarly, in another study including a small number of patients (n = 42), Jeyakumar et al. showed that pre-treatment NLR was an independent prognostic factor for OS and PFS in patients with mRCC treated with ICIs.(Jeyakumar et al. 2017) On the other hand, Lalani et al. concluded that not only pre-treatment NLR but also change in NLR during the treatment period was associated with survival outcomes.(Lalani et al. 2018) In contrast to these studies, Nishiyama et al. established that baseline NLR was not associated with survival outcomes in patients with mRCC treated with nivolumab.(Nishiyama et al. 2020)
Composite biomarkers, such as NLR, PLR, and lymphocyte-to-monocyte (LMR), include only two parameters, while SII consists of three parameters (i.e., neutrophil, platelet, and lymphocyte). The conflicting results mentioned above may be associated with the parameters used to calculate peripheral blood IIBs. At that point, a question arises in terms of whether the effect of more parameters may increase the prognostic value of composite biomarkers. Interestingly, a study comparing the LMR and SII showed that SII was an independent prognostic factor, while LMR had no impact on survival outcomes after adjusting for confounding factors.(Rebuzzi et al. 2020) In another study, De Giorgi et al. showed that SII was superior to NLR in prognostic value.(De Giorgi et al. 2019) On the other hand, the pivotal study of PIV showed that PIV had a greater relative influence on OS and PFS than NLR and SII in patients with mCRC.(Fuca et al. 2020) Taken together, including four parameters (i.e., neutrophil, monocyte, platelet, and lymphocyte) of PIV might contribute to the prognostic value on patients with mRCC treated with nivolumab in the second line and beyond.
The IMDC risk score is a well-known prognostic tool in patients with mRCC. It is composed of six parameters, including two peripheral blood IIBs (i.e., neutrophil and platelet).(Heng et al. 2009) However, it was not an independent prognostic factor in multivariate analysis in our study. Similar to our results, a study of De Giorgi et al., which was evaluated the SII in patients with mRCC treated with nivolumab, established that the IMDC risk score was not an independent prognostic indicator, while SII was prognostic for survival outcomes in multivariate analysis.(De Giorgi et al. 2019) The IMDC risk score is used to stratify patients with mRCC before the initiation of the first line treatment.(National Comprehensive Cancer Network-Kidney Cancer 2021) Furthermore, studies showed that the IMDC risk score was a prognostic indicator in patients with mRCC treated with nivolumab in the second line.(Dudani et al. 2020; Yip et al. 2018) Interestingly, our study suggested that PIV might be a better option than the IMDC risk score to guide the prognosis in patients with mRCC treated with nivolumab in the second line and beyond.
In this study, we have several limitations. One of the most important limitations of our study was based on its retrospective nature. With this regard, PFS was not appropriately assessed by cross-sectional imaging in the prespecified intervals. Furthermore, we had to exclude patients with missing data because of the retrospective feature of our study. Additionally, our study was a multi-center study, and it might have led to variations in laboratory values and imaging methods. To mitigate the impact of variations on laboratory values, we included only laboratory data collected in the last week before the initiation of nivolumab.