## 3 Discussion  
### RecIST Criteria  
Contemporary first-line therapies for mRCC can have different imaging responses (i.e., complete, or partial). [PERSON] et al. [22] questioned whether objective response at imaging is correlated with overall survival. Specifically, in this study they evaluated baseline characteristics, the type of first-line immuno-oncology combination therapy, and the relative objective imaging response in 899 mRCC patients [22]. Evaluation of response to immune checkpoint blockade (ICB) treatment on imaging was performed using the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 [23; 24; 25]. The use of RECIST has been of fundamental importance in the clinical development of therapies with ipilimumab-nivolumab (IOIO) and ICB therapy with VEGF receptor inhibitors (IOVE), and it is still used for the study of new therapeutic approaches for mRCC. The RECIST 1.1 criteria are based on the identification of the target lesions representative of the disease burden, and on the calculation of the largest diameter of all of the target lesions, taken as a reference through contrast-enhanced CT-based follow-up. Four scenarios can be observed for the assessment of response to therapy:  
* Complete response (CR): disappearance of all target lesions together with any pathological lymph nodes (target or non-target) with short axis < 10 mm (Figure 1). * Partial response (PR): \(\geq\)30% reduction in the sum of the target lesions' diameters. * Progressive disease (PD): \(\geq\)20% increase in the sum of the target lesions' diameters, with the lower sum considered as the reference, plus an absolute \(\geq\) 5 mm increment in the sum. * Stable disease (SD): there is not a sufficient reduction to be defined as a partial response, nor a sufficient increase to be defined as progressive disease, using the smallest sum of the target lesions' diameter as a reference (Figures 2 and 3) [23]. Figure 2: Contrast-enhanced CT axial scan during the venous phase of a 67-year-old female mRCC patient, showing a cystic renal cell carcinoma located at the upper pole of the left kidney (**a**). SD at follow-up with dimensional stability after ICI treatment (**b**). Regarding the best overall response of all patients, 4.1% had a CR, 38.3% a PR, 35% experienced SD, and 22.6% had PD; 73.1% of patients were treated with first line IOIO therapy, while the remaining 26.9% were treated with first-line IOVE therapy. In the adjusted logistic regression analysis, only cytocductive nephrectomy (odds ratio (OR), 1.59; 95% CI, 1.04-2.43; \(p=0.03\)), deferred nephrectomy--defined as nephrectomy performed after the receipt of systemic therapy (OR, 3.04; 95% CI, 1.03-8.97; \(p=0.04\)), lung metastases (OR, 1.49; 95% CI, 1.01-2.20; \(p=0.04\)), and favorable vs. poor IMDC risk group (OR, 1.93; 95% CI, 1.10-3.39; \(p=0.02\)) were significantly correlated with objective imaging response. Patients who received IOVE vs. IOIO were more likely to achieve an objective imaging response (OR, 1.89; 95% CI, 1.26-2.81; \(p=0.002\)). Considering intermediate and poor IMDC risk (n = 667), 34.1% of patients treated with IOIO vs. 51.8% treated with IOVE experienced a PR (\(p<0.001\)), while 27.5% of patients treated with IOIO vs. 12.2% treated with IOVE experienced PD (\(p<0.001\)). Patients with CR showed a non-estimable median overall survival (95% CI, 53.3 months to not estimable), patients with PR had a median OS of 55.9 months (95% CI, 44.1 months to not estimable), patients with SD had a median OS of 48.1 months (95% CI, 33.4 months to not estimable), and patients with PD had a median OS of 13.0 months (95% CI, 8.4-18.1 months), with log-rank \(p<0.001\)[22]. [PERSON] et al. [26] evaluated different organ responses to nivolumab in surgically treated mRCC by describing response patterns and discrepancies between the RECIST 1.1 and iRECIST criteria [26].