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Background: Identifying those of patients with metastatic renal cell carcinoma (mRCC) who are most likely to benefit from cytoreductive nephrectomy (CN) is challenging. We tested the association between preoperative value of Systemic Immune-Inflammation Index (SII) and overall survival (OS) as well as cancer-specific survival (CSS) in mRCC patients treated with CN., Methods: mRCC patients treated with CN at different institutions were included. After assessing for the optimal pretreatment SII cut‑off value, we found 710 to have the maximum Youden Index value. The overall population was therefore divided into two SII groups using this cut‑off (low, <710 vs. high, ≥710). Univariable and multivariable Cox regression analyses tested the association SII and OS as well as CSS. The discrimination of the model was evaluated with the Harrel's Concordance Index (C-Index). The clinical value of the SII was evaluated with decision curve analysis (DCA)., Results: Among 613 mRCC patients, 298 (49%) patients had a SII≥710. Median follow-up was 31 (IQR 16-58) months. On univariable analysis, high preoperative serum SII was significantly associated with worse OS (HR: 1.28, 95% CI: 1.07-1.54, P=0.01) and CSS (HR: 1.29, 95% CI: 1.08-1.55, P=0.01). On multivariable analysis, which adjusted for the effect of established clinicopathologic features, SII≥710 was associated with OS (HR: 1.25, 95% CI: 1.04-1.50, P=0.02) and CSS (HR: 1.26, 95% CI: 1.05-1.52, P=0.01). The addition of SII only slightly improved the discrimination of a base model that included established clinicopathologic features (C-index: 0.637 vs. 0.629). On DCA, the inclusion of SII did not improve the net-benefit of the prognostic model. On multivariable analyses, SII≥710 remained independently associated with the worse OS and CSS in IMDC intermediate risk group (both: HR: 1.31, 95% CI: 1.02-1.67, P=0.03). In the subgroup analyses based on the BMI, among patients with BMI ≥ 25, SII was significantly associated with OS (HR: 1.29, 95% CI: 1.04-1.61, P=0.02) and CSS (HR: 1.31, 95% CI: 1.05-1.63, P=0.02)., Conclusions: We found an independent association of high SII prior to CN with unfavorable clinical outcomes, particularly in patients with intermediate risk mRCC and patients with increased BMI. Despite these results, it does not seem to add any prognostic or clinical benefit beyond that obtained by currently available clinicopathologic characteristics as sole worker.

Purpose: Identifying which patients are likely to benefit from cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) is important. We tested the association between preoperative serum De Ritis ratio (DRR, Aspartate Aminotransferase/Alanine Aminotransferase) and overall survival (OS) as well as cancer-specific survival (CSS) in mRCC patients treated with CN., Material and Methods: mRCC patients treated with CN at different institutions were included. After assessing for the optimal pretreatment DRR cut-off value, we found 1.2 to have the maximum Youden index value. The overall population was therefore divided into 2 DRR groups using this cut-off (low, <1.2 vs. high, ≥1.2). Univariable and multivariable Cox regression analyses tested the association between DRR and OS as well as CSS. The discrimination of the model was evaluated with the Harrel's concordance index (C-index). The clinical value of the DRR was evaluated with decision curve analysis., Results: Among 613 mRCC patients, 239 (39%) patients had a DRR ≥1.2. Median follow-up was 31 (IQR 16-58) months. On univariable analysis, high DRR was significantly associated with OS (hazard ratios [HR]: 1.22, 95% confidence interval [CI]: 1.01-1.46, P = 0.04) and CSS (HR: 1.23, 95% CI: 1.02-1.47, P = 0.03). On multivariable analysis, which adjusted for the effect of established clinicopathologic features, high DRR remained significantly associated with both OS (HR: 1.26, 95% CI: 1.04-1.52, P = 0.02) and CSS (HR: 1.26, 95% CI: 1.05-1.53, P = 0.01). The addition of DRR only minimally improved the discrimination of a base model that included established clinicopathologic features (C-index = 0.633 vs. C-index = 0.629). On decision curve analysis, the inclusion of DRR did not improve the net-benefit beyond that obtained by established subgroup analyses stratified by IMDC risk groups, type of systemic therapy, body mass index and sarcomatoid features, did not reveal any prognostic value to DRR., Conclusion: Despite the statistically significant association between DRR and OS as well as CSS in mRCC patients treated with CN, DRR does not seem to add any further prognostic value beyond that obtained by currently available features., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Simple Summary: Upper tract urothelial carcinoma (UTUC) is a lethal cancer of the urinary tract. Radical nephroureterectomy with bladder cuff excision is the gold standard for the management of patients with UTUC. Nevertheless, less-invasive surgeries to preserve maximum kidney function, such as endoscopic ablation and segmental ureteral resection, have become the preferred options in select patients. In this paper, we reviewed the latest evidence on the kidney-sparing management of upper tract urothelial carcinoma. We showed that these approaches are acceptable for low- as well as select high-risk patients who are not eligible for radical treatments. The main advantages of such approaches include renal function preservation as well as decreased surgical morbidity associated with radical treatments. Purpose: To review the latest evidence on the modern techniques and outcomes of kidney-sparing surgeries (KSS) in patients with upper tract urothelial carcinoma (UTUC). Methods: A comprehensive literature search on the study topic was conducted before 30 April 2023 using electronic databases including PubMed, MEDLINE, and EMBASE. A narrative overview of the literature was then provided based on the extracted data and a qualitative synthesis of the findings. Results: KSS is recommended for low- as well as select high-risk UTUCs who are not eligible for radical treatments. Endoscopic ablation is a KSS option that is associated with similar oncological outcomes compared with radical treatments while preserving renal function in well-selected patients. The other option in this setting is distal ureterectomy, which has the advantage of providing a definitive pathological stage and grade. Data from retrospective studies support the superiority of this approach over radical treatment with similar oncological outcomes, albeit in select cases. Novel chemoablation agents have also been studied in the past few years, of which mitomycin gel has received FDA approval for use in low-risk UTUCs. Conclusion: KSSs are acceptable approaches for patients with low- and select high-risk UTUCs, which preserve renal function without compromising the oncological outcomes. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to determine the prognostic value of a panel of SIR-biomarkers, relative to standard clinicopathological variables, to improve mRCC patient selection for cytoreductive nephrectomy (CN). Material and methods: A panel of preoperative SIR-biomarkers, including the albumin–globulin ratio (AGR), De Ritis ratio (DRR), and systemic immune-inflammation index (SII), was assessed in 613 patients treated with CN for mRCC. Patients were randomly divided into training and testing cohorts (65/35%). A machine learning-based variable selection approach (LASSO regression) was used for the fitting of the most informative, yet parsimonious multivariable models with respect to prognosis of cancer-specific survival (CSS). The discriminatory ability of the model was quantified using the C-index. After validation and calibration of the model, a nomogram was created, and decision curve analysis (DCA) was used to evaluate the clinical net benefit. Results: SIR-biomarkers were selected by the machine-learning process to be of high discriminatory power during the fitting of the model. Low AGR remained significantly associated with CSS in both training (HR 1.40, 95% CI 1.07–1.82, p = 0.01) and testing (HR 1.78, 95% CI 1.26–2.51, p = 0.01) cohorts. High levels of SII (HR 1.51, 95% CI 1.10–2.08, p = 0.01) and DRR (HR 1.41, 95% CI 1.01–1.96, p = 0.04) were associated with CSS only in the testing cohort. The exclusion of the SIR-biomarkers for the prognosis of CSS did not result in a significant decrease in C-index (− 0.9%) for the training cohort, while the exclusion of SIR-biomarkers led to a reduction in C-index in the testing cohort (− 5.8%). However, SIR-biomarkers only marginally increased the discriminatory ability of the respective model in comparison to the standard model. Conclusion: Despite the high discriminatory ability during the fitting of the model with machine-learning approach, the panel of readily available blood-based SIR-biomarkers failed to add a clinical benefit beyond the standard model. [ABSTRACT FROM AUTHOR]

• The role of ICI-combination therapy as a first-line treatment for mRCC patients base on CN status was assessed. • A NMA was performed to indirectly compare available ICI treatment options in patients who have or have not undergone CN. • The effect of ICI combination therapy did not differ between mRCC patients undergoing and not undergoing CN. • Each ICI-combination therapy differs greatly in efficacy depending on whether or not the patients had undergone CN. Recently, immune checkpoint inhibitor (ICI)-combination therapies have radically altered the treatment landscape in metastatic renal cell carcinoma (mRCC). No phase 3 trials have assessed the impact of cytoreductive nephrectomy (CN) for efficacy in mRCC patients treated with ICI-combination therapy. We aimed to assess the role of ICI-combination therapy based on CN status. Multiple databases were searched for articles published until June 2021. Studies comparing overall and/or progression-free survival (OS/PFS) in mRCC patients treated with ICI combination-therapy were deemed eligible. Six studies met the eligibility criteria. ICI-combination therapy was associated with significantly better OS/PFS than sunitinib in patients who had undergone CN (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.59–0.77/HR, 0.57; 95% CI, 0.44–0.74, respectively; both P < 0.001), and in those who had not (HR, 0.69; 95% CI, 0.57–0.85/HR, 0.63; 95% CI, 0.52–0.77, respectively; both P < 0.001). Although the OS and PFS benefits of ICI-combination therapy were larger in those undergoing CN, the HR for OS and PFS indicated that ICI-combination therapy's treatment effect did not differ substantially with or without CN. In network meta -analyses, nivolumab plus cabozantinib was the most effective regimen in those undergoing CN, and pembrolizumab plus lenvatinib for those not undergoing CN. The effect of ICI combination therapy did not differ between mRCC patients undergoing and not undergoing CN. As each ICI combination regimen varied widely in its effect in patients undergoing and not undergoing CN, CN may contribute to better treatment decision-making for ICI-combination therapy recipients. [ABSTRACT FROM AUTHOR]