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Background: Nephron-sparing approaches are preferred for renal mass in a solitary kidney (RMSK), with partial nephrectomy (PN) generally prioritized. Thermal ablation (TA) also is an option for small renal masses in this setting; however, comparative functional/survival outcomes are not well-defined., Methods: A retrospective study of 504 patients (1975-2022) with cT1 RMSK managed with PN (n = 409)/TA (n = 95) with necessary data for analysis was performed. Propensity score was used for matching patients, including age, preoperative glomerular filtration rate (GFR), tumor diameter, R.E.N.A.L. ((R)adius (tumor size as maximal diameter), (E)xophytic/endophytic properties of tumor, (N)earness of tumor deepest portion to collecting system or sinus, (A)nterior (a)/posterior (p) descriptor, and (L)ocation relative to polar lines), and comorbidities. Functional outcomes were compared, and Kaplan-Meier was used to analyze survival., Results: The matched cohort included 132 patients (TA = 66/PN = 66), with median tumor diameter of 2.4 cm, R.E.N.A.L. of 6, and preoperative GFR of 52 ml/min/1.73 m 2 . Acute kidney injury occurred in 11%/61% in the TA/PN cohorts, respectively (p < 0.01). After recovery, median GFR preserved was 89%/83% for TA/PN, respectively (p = 0.02), and 5-year dialysis-free survival was 96% in both cohorts. Median follow-up was 53 months. Five-year recurrence-free survival (RFS) was 62%/86% in the TA/PN cohorts, respectively (p < 0.01). Five-year local recurrence (LR)-free survival was 74%/95% in the TA/PN cohorts, respectively (p < 0.01). Five-year cancer-specific survival (CSS) was 96%/98% in the TA/PN cohorts, respectively (p = 0.7). Local recurrence was observed in nine of 36 (25%) and five of 30 (17%) patients managed with laparoscopic versus percutaneous TA, respectively. For TA with LR (n = 14), nine patients presented with multifocality and/or cT1b tumors. Twelve LR were managed with salvage TA, and seven remained cancer-free, while five developed systemic recurrence, three with concomitant LR., Conclusions: Functional outcomes for TA for RMSK were improved compared with PN. Local recurrence was more common after TA and often was associated with the laparoscopic approach, multifocality, and large tumor size. Improved patient selection and greater experience with TA should improve outcomes. Salvage of LR was not always possible. Partial nephrectomy remains the reference standard for RMSK., (© 2023. Society of Surgical Oncology.)

Background/aim: The safety and efficacy of anti-angiogenic agents in patients with cancer with proteinuria and a history of proteinuria are not well established. This systematic review aimed to answer these questions., Materials and Methods: We searched three electronic databases for articles published until June 18, 2021. The main outcomes used were "death", "renal impairment", and "proteinuria impairment"., Results: After screening 303 references in the PubMed, Cochrane Library, and ICHUSHI-web databases, this review included five studies on renal cell carcinoma (RCC). In patients with metastatic RCC, the hazard ratio of the presence of (or having) proteinuria (1+ or higher) at baseline was 0.82 (0.23-2.97); thus, proteinuria was not significantly associated with the outcome of death. No significant deterioration in kidney function was observed in patients with proteinuria. Although proteinuria at baseline was a significant risk factor for proteinuria progression during and after treatment, most patients maintained grade 1 or 2 proteinuria and continued treatment without dose reduction or discontinuation., Conclusion: While weak evidence suggests that proteinuria at the start of treatment with anti-angiogenic agents might be a risk factor for worsening proteinuria, it was not significantly associated with death or renal impairment., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objectives: Current prognostic models for metastatic renal cell carcinoma (mRCC) are likely inaccurate due to recent treatment advances and improved survival outcomes. The JEWEL study used a data set from patients who received tyrosine kinase inhibitors (TKIs) to explore the prognostic impact of the tumor immune environment in the absence of immune checkpoint inhibitor intervention., Methods: The primary analysis population comprised 569 of the 770 Japanese patients enrolled in the ARCHERY study who received first-line TKIs. Multivariable Cox proportional hazard models were used to identify factors associated with the primary (overall survival [OS]) and secondary outcomes (treatment duration) using 34 candidate explanatory variables., Results: Median OS was 34.1 months (95% CI, 30.4-37.6) in the primary analysis population. A considerable negative prognostic impact (descriptive p ≤ 0.0005) on OS was seen with lactate dehydrogenase (LDH) >1.5 × upper limit of normal (adjusted HR [aHR], 3.30; 95% CI, 2.19-4.98), Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 (aHR, 2.14; 95% CI, 1.56-2.94), World Health Organization (WHO)/International Society of Urological Pathology (ISUP) Grade 4 (aHR, 1.89; 95% CI, 1.43-2.51), C-reactive protein (CRP) level ≥0.3 (aHR, 1.78; 95% CI, 1.40-2.26), and age ≥75 years (aHR, 1.65; 95% CI, 1.24-2.18) in the multivariable analysis. PD-L1 and immunophenotype affected OS in univariable analyses but were not selected in the multivariable model as explanatory variables., Conclusions: JEWEL identified sex, age, ECOG PS, liver and bone metastases, CRP levels, WHO/ISUP grade, LDH, and albumin levels as key prognostic factors for OS after first-line TKI therapy for mRCC., (© 2023 The Authors. International Journal of Urology published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Urological Association.)

Introduction: We sought to determine whether loss of renal function increases risk of recurrence and metastases in renal cell carcinoma (RCC), and whether this impact was age-related., Materials and Methods: We performed a retrospective analysis of the International Marker Consortium for Renal Cancer (INMARC) registry. Patients were separated into younger (<65 years old) and elder (≥65 years old) age groups, and rates of de novo estimated glomerular filtration rate (eGFR<45 mL/min/1.73m2 [eGFR<45]) were calculated. Multivariable analysis (MVA) was conducted for predictors of progression-free survival (PFS) and all-cause mortality (ACM). Kaplan-Meier Analysis (KMA) was conducted for PFS and overall survival (OS) in younger and elder age groups stratified by functional status., Results: We analyzed 1805 patients (1113 age<65, 692 age≥65). On MVA in patients <65, de novo eGFR<45 was independently associated with greater risk for worsened progression (HR=1.61, P=.038) and ACM (HR=1.82, P=.018). For patients ≥65, de novo eGFR<45 was not independently associated with progression (P=.736), or ACM (P=.286). Comparing patients with de novo eGFR<45 vs. eGFR ≥45, KMA demonstrated worsened 5-year PFS and OS in patients <65 (PFS: 68% vs. 86%, P<.001; OS: 73% vs. 90%, P<.001), while in patients ≥65, only 5-year OS was worsened (77% vs. 81%, P<.021)., Conclusion: Development of de novo eGFR<45 was associated with more profound impact on patients <65 compared to patients ≥65, being an independent risk factor for PFS and ACM. The mechanisms of this phenomenon are unclear but underscore desirability for nephron preservation when safe and feasible in younger patients., (Copyright © 2022. Published by Elsevier Inc.)

Accurate prediction of new baseline GFR (NBGFR) after radical nephrectomy (RN) can inform clinical management and patient counseling whenever RN is a strong consideration. Preoperative global GFR, split renal function (SRF), and renal functional compensation (RFC) are fundamentally important for the accurate prediction of NBGFR post-RN. While SRF has traditionally been obtained from nuclear renal scans (NRS), differential parenchymal volume analysis (PVA) via software analysis may be more accurate. A simplified approach to estimate parenchymal volumes and SRF based on length/width/height measurements (LWH) has also been proposed. We compare the accuracies of these three methods for determining SRF, and, by extension, predicting NBGFR after RN. All 235 renal cancer patients managed with RN (2006-2021) with available preoperative CT/MRI and NRS, and relevant functional data were analyzed. PVA was performed on CT/MRI using semi-automated software, and LWH measurements were obtained from CT/MRI images. RFC was presumed to be 25%, and thus: Predicted NBGFR = 1.25 × Global GFR Pre-RN  × SRF Contralateral . Predictive accuracies were assessed by mean squared error (MSE) and correlation coefficients (r). The r values for the LWH/NRS/software-derived PVA approaches were 0.72/0.71/0.86, respectively (p < 0.05). The PVA-based approach also had the most favorable MSE, which were 120/126/65, respectively (p < 0.05). Our data show that software-derived PVA provides more accurate and precise SRF estimations and predictions of NBGFR post-RN than NRS/LWH methods. Furthermore, the LWH approach is equivalent to NRS, precluding the need for NRS in most patients., (© 2023. The Author(s).)

Background: A renal mass in a solitary kidney (RMSK) has traditionally been managed with partial nephrectomy (PN), although radical nephrectomy (RN) is occasionally required. Most RMSK studies have focused on patients for whom PN was achieved., Objective: To provide a comprehensive analysis of the management strategies/outcomes for an RMSK and address knowledge deficits regarding this challenging disorder., Design, Setting, and Participants: A total of 1024 patients diagnosed with an RMSK (1975-2022) were retrospectively evaluated. Baseline characteristics and pathologic/functional/survival outcomes were analyzed., Intervention: PN/RN/cryoablation (CA)/active surveillance (AS)., Outcome Measurements and Statistical Analysis: Functional outcomes, perioperative morbidity/mortality, and 5-yr recurrence-free survival (RFS) were evaluated. Kruskal-Wallis and chi-square tests were used to compare cohorts, and log-rank test and Cox proportional hazard model were used for survival analysis., Results and Limitations: Of 1024 patients, 842 underwent PN (82%), 102 CA (10%), 54 RN (5%), and 26 AS (3%). The median tumor size and RENAL([R]adius [tumor size as maximal diameter], [E]xophytic/endophytic properties of tumor, [N]earness of tumor deepest portion to collecting system or sinus, [A]nterior [a]/posterior [p] descriptor, and [L]ocation relative to polar lines) score were 3.7 cm and 8, respectively. The median follow-up was 53 mo. For PN, 95% were clamped, and the median warm and cold ischemia times were 22 and 45 min, respectively. For PN, the median preoperative glomerular filtration rate (GFR) was 57 ml/min/1.73 m 2 , and the median new baseline and 5-yr GFRs were 47 and 48 ml/min/1.73 m 2 , respectively. Dialysis-free survival for PN was 97% at 5 yr. Twenty-two (2.1%) patients with clear-cell renal cell carcinoma and RENAL score ≥10 (median = 11) received tyrosine kinase inhibitors (TKIs) to facilitate PN, leading to 57% median decrease of tumor volume; PN was accomplished in 20 (91%). Forty-one patients had planned RN (4.0%), most often due to severe pre-existing chronic kidney disease (CKD), and 13 were converted from PN to RN (1.5%). Clavien III-V perioperative complications were observed in 80 (8%) patients and 90-d mortality was 0.6%. Five-year RFS for PN, CA, and RN were 83%, 80%, and 72%, respectively (p = 0.03 for PN vs RN)., Conclusions: Nephron-sparing approaches are feasible and successful in most RMSK patients. PN for an RMSK is often challenging but can be facilitated by selective use of TKIs. RN is occasionally required due to severe CKD, over-riding oncologic concerns, or conversion from PN. This is the first large RMSK study to provide a comprehensive analysis of all management strategies/outcomes., Patient Summary: Kidney cancer in a solitary kidney is a major challenge for achieving cancer-free status and avoiding dialysis. Although partial nephrectomy is the principal treatment for a renal mass in a solitary kidney, other options are occasionally required to optimize outcomes., (Copyright © 2022 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Objectives: To evaluate effects of worsening surgically induced chronic kidney disease (CKD-S) on oncological and non-oncological survival outcomes in renal cell carcinoma (RCC)., Patients and Methods: We performed a retrospective analysis of patients who underwent partial (PN) or radical nephrectomy (RN) and were free of preoperative CKD (estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73 m 2 ). Patients were stratified by CKD stage at last follow-up: no CKD-S (eGFR ≥60 mL/min/1.73 m 2 ), de novo CKD-S 3a (eGFR 45-59 mL/min/1.73 m 2 ), CKD-S 3b (eGFR <45 and ≥30 mL/min/1.73 m 2 ) and CKD-S 4 (eGFR <30 and ≥15 mL/min/1.73 m 2 ). The primary outcome was all-cause mortality (ACM). Secondary outcomes included non-cancer mortality (NCM), cancer-specific mortality (CSM) and de novo CKD-S Stage 3/4. Multivariable analysis (MVA) was utilised to identify risk factors for outcomes. Kaplan-Meier analysis (KMA) was utilised to evaluate overall (OS), non-cancer (NCS), and cancer-specific survival with respect to CKD-S categories., Results: We analysed 3239 patients. The mean preoperative and last-follow-up eGFRs were 87.4 and 69.5 mL/min/1.73 m 2 , respectively. On last follow-up, 57.9% (n = 1876) had no CKD-S, 18.7% (n = 606) had CKD-S 3a, 15.1% (n = 489) had CKD-S 3b and 8.3% (n = 268) had CKD-S 4. On MVA, de novo CKD-S 3b and 4 were independently associated with ACM (hazard ratios [HRs] 1.3-2.1, P = 0.003-0.001) and NCM (HRs 1.5-2.8, P = 0.021-0.001), but not CSM (P = 0.219-0.909); de novo CKD-S 3a was not predictive for any mortality outcomes (P = 0.102-0.81). RN was independently associated with CKD-S 3-4 (HRs 1.78-1.99, P < 0.001-0.035). Comparing no CKD-S, CKD-S 3a, CKD-S 3b and CKD-S 4, KMA demonstrated worsening outcomes with progressive CKD-S stage: 5-year OS 84% vs 78% vs 71% vs 60% (P < 0.001) and 5-year NCS 93% vs 87% vs 83% vs 72% (P < 0.001)., Conclusion: Development of CKD-S Stage 3b and 4, but not 3a, was associated with worsened ACM and NCM. The decision to proceed with nephron preservation via PN should be individualised based on oncological risk and risk of functional decline to CKD-S 3b or 4, and not CKD-S 3a., (© 2022 BJU International.)

Studies have reported the relevance of immune phenotype, or presence of cluster of differentiation 8 (CD8)-positive tumour-infiltrating lymphocytes, to the anti-tumour efficacy of checkpoint inhibitors and to prognosis. The multicentre, retrospective ARCHERY study (UMIN000034131) collected tissue samples from Japanese patients with recurrent or metastatic renal cell carcinoma (RCC) who received systemic therapy between 2010 and 2015. In this exploratory analysis, the prognostic impact of immune phenotype and PD-L1 expression (separately and combined) was investigated using 770 surgical specimens and outcomes from patients enrolled in ARCHERY. A key objective was to determine overall survival (OS), defined as time from nephrectomy to death from any cause, by immune and PD-L1 subgroups. The median OS by immune phenotype was 28.8, 57.3, and 63.4 months in patients with inflamed, excluded, and desert tumours, respectively [hazard ratio (95% CI): inflamed 1.78 (1.27-2.49); excluded 1.08 (0.89-1.30); desert as reference]. PD-L1 positivity by SP142 showed a strong association with immune phenotype; 88.1%, 61.9%, and 8.7% of PD-L1-positive patients had inflamed, excluded, and desert phenotypes, respectively. PD-L1 positivity was also associated with worse OS in each phenotype, except for the inflamed phenotype (due to limited sample size in the PD-L1-negative immune inflamed subgroup; n=7). Additionally, the difference in OS by PD-L1 status was larger in the desert versus excluded phenotype [median OS in PD-L1 positive vs negative: 27.1 vs 67.2 months (desert), and 48.2 vs 78.1 months (excluded)]. Results show that PD-L1 expression was highly associated with immune phenotype, but both covariates should be evaluated when determining prognosis., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: The American-Urological-Association(AUA) Guidelines for renal cancer(2017) recommend consideration for radical-nephrectomy(RN) over partial(PN) whenever there is increased oncologic-risk; and RN should be prioritized if three other criteria are all also met: 1) increased tumor-complexity; 2) no preexisting chronic-kidney-disease/ proteinuria, and 3) normal contralateral kidney that will likely provide estimated glomerular-filtration-rate (eGFR) >45ml/min/1.73m 2 even if RN is performed. Our objective was to assess the complexity of decision-making about RN/PN and utility of AUA Guidelines statements regarding this issue., Patients and Methods: Retrospective review of 267 consecutive RN/PN from 2019(100-RN/167-PN). High tumor-complexity was defined as R.E.N.A.L.≥9. Increased oncologic-risk was defined as tumor >7cm, locally-advanced or infiltrative-features on imaging, or high-risk pathology on biopsy, if obtained. New-baseline GFR after RN was estimated using global-GFR, split-renal-function contralateral , and presuming 25% renal-functional-compensation., Results: 163 patients(61%) fit scenarios that are well-defined in the Guidelines. Of these, 34 had strong indications for RN, and all had RN. Twelve of 129 patients(9.3%) underwent RN despite Guidelines generally favoring PN. The remaining 104 patients(39%) did not fit within situations where the Guidelines provide specific recommendations. In these patients, RN was often performed despite functional-considerations favoring PN due to overriding concerns about oncologic-risk and/or tumor-complexity., Conclusion: Our data demonstrate complexity of decision-making about PN/RN as almost 40% of patients did not fit well-described AUA Guidelines descriptors. Compliance was generally strong although occasional overutilization of RN remains a concern in our series, and will be addressed with additional education. Further studies will be required to assess the generalizability of our findings in other institutions/settings., (Copyright © 2022. Published by Elsevier Inc.)

Introduction: Radical nephrectomy (RN) is an important consideration for the management of localized renal-cell-carcinoma (RCC) whenever the tumor appears aggressive, although reduced renal function is a concern. Split-renal-function (SRF) in the contralateral kidney and postoperative renal functional compensation (RFC) are fundamentally important for the accurate prediction of new baseline GFR (NBGFR) post-RN. SRF can be estimated either from nuclear renal scans (NRS) or from preoperative imaging using parenchymal-volume-analysis (PVA). We compare two SRF-based models for predicting NBGFR after RN with a subjective prediction of NBGFR by an experienced urologic-oncologist., Methods: 187 RCC patients managed with RN (2006-16) were included based on the availability of preoperative CT/MRI and NRS, and preoperative/postoperative eGFR. NBGFR was defined as the final GFR 3-12 months post-RN. For the SRF-based approaches, SRF was derived from either NRS or PVA, and RFC was estimated at 25% based on previous independent analyses. Thus, the formula (Global GFR Pre-RN  × SRF contralateral ) × 1.25 was used to predict NBGFR after RN. For subjective-assessment, a blinded, independent urologic oncologist provided NBGFR predictions based on preoperative eGFR, CT/MRI, and clinical/tumor characteristics. Predictive accuracies were assessed by correlation coefficients (r)., Results: The r values for subjective-assessment, NRS/SRF-based, and PVA/SRF-based approaches were 0.72/0.72/0.85, respectively (p < 0.05). The PVA/SRF-based model also demonstrated significant improvement across other performance parameters., Conclusions: The PVA/SRF-based model more accurately predicts NBGFR post-RN than NRS/SRF-based and Subjective Estimation. PVA software (Fujifilm-medical-systems) is readily available and affordable and provides accurate SRF estimations from routine preoperative imaging. This novel approach may inform clinical management regarding RN/PN for complex RCC cases., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Objectives: To evaluate the management, surgical outcomes, and pathological findings in patients with tumor in a horseshoe-kidney (HK). HK patients present unique challenges due to aberrant vascular anatomy and risk of renal insufficiency. We hypothesized that many tumors in this setting may be indolent or benign., Materials and Methods: Patients managed for renal mass in HK at our center (1999-2021) were reviewed. Baseline characteristics, surgical approach, complications, functional outcomes, pathology, and survival were analyzed., Results: Forty-three procedures were performed in 42 patients with HK including 24 nephron-sparing surgeries (NSS) and 19 radical nephrectomies (RN: splitting the isthmus and saving the contralateral moiety). NSS included 22 partial nephrectomy (PN) and 2 thermal ablations. Median tumor size was 4.3 cm. Eighteen cases (42%) were minimally-invasive, 17 open-midline, and 8 other open approaches. Ninety-day Clavien III-V complication rate was 12% with no mortalities. For PN, median warm/cold ischemia times were 26/31 minutes, respectively. On pathology, only 27 tumors (63%) were renal-cell-carcinoma (RCC), and 22 tumors (51%) were either benign (n = 10) or low grade, confined RCC (n = 12). Preoperative/new baseline/long-term eGFR were 82/83/78 mL/min/1.73 m 2 after NSS vs 75/48/57 mL/min/1.73 m 2 after RN, respectively. Long-term dialysis was required in 3 patients (7%). Median follow-up was 36 months. Five-year recurrence-free survival was 83% for NSS and 66% for RN., Conclusions: Management of renal masses in HK is challenging and requires versatility with multiple surgical approaches. Preservation of renal function was accomplished in most patients, with a functional advantage observed for NSS. RCC was less common than expected while benign and non-aggressive tumors were prevalent, suggesting consideration for preoperative renal-mass-biopsy when feasible., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: C-reactive protein is a useful biomarker for screening renal cell carcinoma (RCC); however, its significance in papillary RCC is unclear. We assessed the prognostic effect of serum C-reactive protein levels in patients with surgically treated non-metastatic papillary RCC., Patients and Methods: We established an international multi-institutional database (the INternational Marker Consortium for Renal Cancer) of 3799 patients with surgically treated RCC. Among these, data of 400 patients with non-metastatic papillary RCC were analyzed. An elevated pretreatment serum C-reactive protein level was defined as > 10 mg/L. Associations of clinical covariates with recurrence-free survival were investigated., Results: Among the patients, 174 were African Americans, 155 were European-Americans, 50 were Asians, and 21 were of other races. Pathological T stages were 1, 2, 3, and 4 in 313, 46, 32, and 3 patients, respectively. The median pretreatment C-reactive protein level was 1.0 mg/L; 48 patients exhibited an elevated C-reactive protein level. During follow-up (median 18 months), 30 patients presented recurrence. The 1-, 3-, and 5-year recurrence-free rates were 95%, 91%, and 87%, respectively. Multivariate analysis revealed a significant association of the elevated pretreatment C-reactive protein level with poor recurrence-free survival (hazard ratio 2.47, 95% confidence interval 1.03-5.48; P = .043). The 5-year recurrence-free survival was significantly worse for patients with elevated C-reactive protein levels (67% vs. 90%; P = .001)., Conclusions: C-reactive protein is a significant prognostic factor for patients with non-metastatic papillary RCC and can serve as a useful adjunct biomarker for screening patients with a high risk of recurrence., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To investigate association of African-American race and survival in Renal Cell Carcinoma (RCC)., Patients and Methods: We queried the International Marker Consortium for Renal Cancer database for patients who underwent partial or radical (RN) nephrectomy. The cohort was divided into African American (AA) and non-African American (NAA) patients. Primary outcome was all-cause mortality. Secondary outcome was cancer-specific mortality. Multivariable Analysis and Kaplan-Meier Analysis were used to elucidate predictive factors and survival outcomes., Results: Three thousand eight hundred and ninety-three patients were analyzed (AA, n = 564/NAA, n = 3329). AA had greater Stage I (73.8% vs 63.9%, P <.001) and papillary RCC (29.8% vs 8.5%, P <.001). Multivariable Analysis revealed increasing age (HR = 1.03, P <.001), AA (HR = 1.24, P = .027), higher stage (HR = 1.30-3.19, P <.001), RN (HR = 2.45, P <.001), clear cell (HR = 1.23, P <.001), positive margin (HR = 1.34, P .004), and high-grade (HR = 1.58, P <.001) to be associated with worsened all-cause mortality. Increasing age (HR = 1.02, P <.001), AA (HR = 1.48, P = .025), RN (HR = 2.98, P <.001), high-grade (HR = 3.11, P <.001), and higher stage (HR = 3.03-13.2, P <.001) were predictive for cancer-specific mortality. Kaplan-Meier Analysis revealed worsened 5-year overall survival for AA in stage I (80% vs 88%, P = .001), stage III (26% vs 70%, P = .001), and stage IV (23% vs 44%, P = .009). Five-year cancer-specific survival was worse for AA in stage III (36% vs 81%, P <.001) and stage IV (30% vs 49%, P = .007)., Conclusion: Despite presenting with more indolent histology and lower stage, African-Americans were at greater risk for diminished survival, faring worse in overall survival for all stages and cancer-specific survival in for stage III/IV RCC. Further investigation into factors associated with these disparities is warranted., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: To evaluate a conceptually simple model to predict new-baseline-glomerular-filtration-rate (NBGFR) after radical nephrectomy (RN) based on split-renal-function (SRF) and renal-functional-compensation (RFC), and to compare its predictive accuracy against a validated non-SRF-based model. RN should only be considered when the tumor has increased oncologic potential and/or when there is concern about perioperative morbidity with PN due to increased tumor complexity. In these circumstances, accurate prediction of NBGFR after RN can be important, with a threshold NBGFR > 45 ml/min/1.73m 2 correlating with improved overall survival., Methods: 236 RCC patients who underwent RN (2010-2012) with preoperative imaging (CT/MRI) and relevant functional data were included. NBGFR was defined as GFR 3-12 months post-RN. SRF was determined using semi-automated software that provides differential parenchymal-volume-analysis (PVA) from preoperative imaging. Our SRF-based model was: Predicted NBGFR = 1.24 (× Global GFR Pre-RN ) (× SRF Contralateral ), with 1.24 representing the mean RFC estimate from independent analyses. A non-SRF-based model was also assessed: Predicted NBGFR = 17 + preoperative GFR (× 0.65)-age (× 0.25) + 3 (if tumor > 7 cm)-2 (if diabetes). Alignment between predicted/observed NBGFR was assessed by comparing correlation coefficients and area-under-the-curve (AUC) analyses., Results: The correlation-coefficients (r) were 0.87/0.72 for SRF-based/non-SRF-based models, respectively (p = 0.005). For prediction of NBGFR > 45 ml/min/1.73m 2 , the SRF-based/non-SRF-based models provided AUC of 0.94/0.87, respectively (p = 0.044)., Conclusion: Previous non-SRF-based models to predict NBGFR post-RN are complex and omit two important parameters: SRF and RFC. Our proposed model prioritizes these parameters and provides a conceptually simple, accurate, and clinically implementable approach to predict NBGFR post-RN. SRF can be easily obtained using PVA software that is affordable, readily available (FUJIFILM-Medical-Systems), and more accurate than nuclear-renal-scans. The SRF-based model demonstrates greater predictive-accuracy than a non-SRF-based model, including the clinically-important predictive-threshold of NBGFR > 45 ml/min/1.73m 2 ., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To analyze predictors, extent and functional implications associated with renal parenchymal volume replacement (PVR) by renal cell carcinoma (RCC) prior to intervention. This phenomenon is well-recognized yet not adequately studied, and, if severe, can influence management., Materials and Methods: A retrospective review was performed of partial nephrectomy (PN) and radical nephrectomy (RN) patients with available preoperative nuclear-renal-scan and imaging demonstrating solitary RCC with normal contralateral kidney. Normal renal parenchymal volume of each kidney was measured by free-hand scripting from preoperative axial images. Primary endpoint was percent PVR which was estimated assuming that the contralateral-kidney serves as a control: PVR = (volume contralateral kidney - volume ipsilateral kidney) normalized by volume contralateral kidney. Multivariable linear-regression analysis assessed factors associated with preoperative PVR. Further analysis evaluated the functional effect of PVR prior to surgery., Results: 146 PN and 136 RN patients with necessary studies were analyzed. For RN, the median PVR was 15% and a quarter of patients had PVR ≥27%. In contrast, PVR was negligible in PN patients for whom median preoperative parenchymal volumes were nearly identical in the ipsilateral/contralateral kidneys (179/180cc, respectively). PVR inversely correlated with preoperative renal function in the ipsilateral kidney (P <.01). Tumor-size (P <.01), stage (P = .03), and endophytic properties (P = .03) associated with PVR on multivariable-analysis., Conclusion: Our data suggest that substantial replacement of normal parenchyma by RCC occurs in many patients selected for RN and can contribute to preexisting renal-insufficiency. PVR prior to intervention is mainly driven by tumor characteristics in RN patients, but is negligible in most PN patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: Locally advanced renal cell carcinoma is considered clinically aggressive, despite heterogeneity in survival outcomes. We investigated the clinical relevance and pathological implications of infiltrative tumor interface with normal renal parenchyma on preoperative imaging in locally advanced renal cell carcinoma., Methods: A total of 77 patients with locally advanced renal cell carcinoma (≥pT3a Nany M0) who underwent radical or partial nephrectomy (2008-2018) were analyzed. Preoperative dynamic computed tomography images were reviewed to assess radiological infiltrative features. A radiological infiltrative feature was defined as an ill-defined tumor interface with normal renal parenchyma. The tumor interfaces were analyzed histologically and compared with radiological findings., Results: The median tumor size was 6.4 cm. Lymphadenopathy was observed in four patients (5.2%). Clear cell renal cell carcinoma was diagnosed in 66 patients (86%) and Fuhrman grade was 3-4 in 38 patients (49%). A total of 30 patients (39%) showed radiological infiltrative features, which were significantly associated with larger tumor size and higher clinical T stage. The specificity and sensitivity of radiological infiltrative features in predicting pathological renal parenchymal infiltration were 90 and 64%, respectively. During a median follow-up period of 3.8 years, 27 patients (35%) developed cancer recurrences, and six patients (7.8%) died of renal cell carcinoma. Multivariable analysis showed that the presence of radiological infiltrative features was an independent risk factor for cancer recurrence. Cancer recurrence and cancer-specific mortality were significantly stratified by the presence or absence of radiological infiltrative features (P < 0.001 and P = 0.02, respectively)., Conclusions: Locally advanced renal cell carcinoma can show radiological infiltrative features preoperatively, which are significantly associated with unfavorable prognosis. Radiological infiltrative features on preoperative imaging correspond with a high specificity to pathological renal parenchymal infiltration., (© 2021 The Japanese Urological Association.)

Background: We sought to analyze the usefulness of pretreatment C-reactive protein (CRP) as a predictor of survival and oncological outcomes in patients with renal cell carcinoma (RCC)., Methods: Retrospective international analysis of patients with RCC with pretreatment CRP values from 2006 to 2017. A CRP of more than >5 mg/L was deemed elevated. The cohort was subdivided into 2 groups for analysis (normal CRP ≤5 mg/L; elevated CRP >5). Primary outcome was overall survival (OS) and secondary outcome was recurrence-free survival (RFS). Kaplan-Meier analyses (KMA) and multivariable analyses (MVA) were used to delineate survival outcomes and their predictors., Results: We analyzed 2445 patients (1641 male/804 female; normal CRP 1056/elevated CRP 1389; mean follow-up 36 months). Patients with elevated CRP had a higher incidence of hypertension (P = .001), higher body mass index (P < .001), and larger tumor size (6.0 cm vs 3.9 cm; P < .001). MVA for RFS demonstrated elevated CRP (hazard ratio [HR], 1.85; P = .005), tumor size (HR, 1.1; P < .001), and high tumor grade (HR, 3.1; P < .001) to be independent risk factors. For normal vs elevated CRP, KMA for RFS of stages 1-4 RCC revealed a 5-year RFS of 93% vs 88% (P = .001), 95% vs 83% (P = .163), 84% vs 62% (P = .001), and 58% vs 60% (P = .513), respectively. KMA MA KMA for OS of stages 1-4 RCC revealed a 5-year OS of 98% vs 81% (P = .001), 94% vs 80% (P = .103), 94% vs 65% (P = .001), and 99% vs 38% (P < .001), respectively., Conclusions: Pretreatment CRP was an independent predictor of RFS and OS in an international multicenter cohort of patients with RCC., (Copyright © 2021. Published by Elsevier Inc.)

Objective: To investigate association of preoperative C-reactive protein (CRP) and non-cancer mortality (NCM) in a cohort of patients undergoing surgery for localised renal cell carcinoma (RCC)., Patients and Methods: Retrospective multicentre analysis of patients surgically treated for clinical Stage 1-2 RCC from 2006 to 2017, excluding all cases of cancer-specific mortality. Descriptive analyses were obtained between the pre-treatment normal-CRP (≤5 mg/L) and elevated-CRP (>5 mg/L) groups. The primary outcome was NCM. The secondary outcomes included progression to de novo chronic kidney disease Stages 3-4 (estimated glomerular filtration rate [eGFR] of <60, <45, and <30 mL/min/1.73 m 2 ). Multivariable analyses (MVA) were performed to assess for risk factors associated with functional decline and NCM, and Kaplan-Meier analysis was used to obtain survival estimates for outcomes., Results: A total of 1987 patients who underwent radical or partial nephrectomy were analysed (normal-CRP group, n = 963; elevated-CRP group, n = 1024). Groups were similar in age (59 vs 60 years, P = 0.079). An elevated CRP was more frequent in males (36.8% vs 27.8%, P < 0.001), African-Americans (22.6% vs 2.9%, P < 0.001), and in those with a higher median body mass index (30 vs 25 kg/m 2 , P < 0.001) and larger median tumour size (4.5 vs 3.3 cm, P < 0.001). On MVA, an elevated CRP was independently associated with development of de novo eGFR of <60 mL/min/1.73 m 2 (hazard ratio [HR] 1.32, P = 0.015), <45 mL/min/1.73 m 2 (HR 1.41, P = 0.023) and <30 mL/min/1.73 m 2 (odds ratio 2.23, P < 0.001). The MVA for factors associated with NCM demonstrated increasing age (HR 1.06, P < 0.001), preoperative elevated CRP (HR 2.18, P < 0.001) and an eGFR of <45 mL/min/1.73 m 2 (HR 1.16; P = 0.021) as independent risk factors. Kaplan-Meier analysis revealed significantly higher 5-year NCM in the elevated-CRP group vs the normal-CRP group (98% vs 80%, P < 0.001)., Conclusions: Pre-treatment elevated CRP was independently associated with both progressive renal functional decline and NCM in patients undergoing surgery for Stage 1-2 RCC. Patients with elevated CRP and Stage 1 and 2 RCC may be considered as having indication for nephron-sparing strategies, which may be prioritised if oncologically appropriate., (© 2020 The Authors BJU International © 2020 BJU International Published by John Wiley & Sons Ltd.)

Background: The dynamic change in C-reactive protein (CRP) levels, CRP kinetics, is a prognostic factor for metastatic renal cell carcinoma (mRCC) in the tyrosine kinase inhibitor era. We investigated the impact of early CRP kinetics on the efficacy of nivolumab in patients with mRCC., Methods: We performed a retrospective analysis of 42 mRCC patients who were treated with nivolumab as a second-line or later therapy between 2016 and 2019. All patients had received previous TKI therapy. Patients were divided into three groups based on their early CRP kinetics: CRP levels increased to more than double compared with baseline within 1 month after initiation of nivolumab (flare) and then decreased to a lower value than baseline within 3 months (CRP flare-responders); CRP levels decreased by ≥30% within 3 months without "flare" (CRP responders); and the remaining patients (non-CRP responders). The maximum tumor shrinkage, objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were evaluated. The association of the early CRP kinetics and oncological outcomes was assessed., Results: The median follow-up period was 8 months. The median baseline CRP level was 23 mg/L. CRP flare-responders, CRP responders, and non-CRP responders included 11 (26%), 15 (36%), and 16 (38%) patients, respectively. Thirteen patients (31%) died of mRCC. The maximum changes in target lesions from baseline of CRP flare-responder, CRP-responder, and non-CRP responder groups were -38%, -13%, and 16%, on average, respectively (p<0.001). ORRs of these three groups were 73%, 27%, and 6%, respectively (p<0.001). The median PFS values of each group were not reached, 12 months, and 2.4 months (p=0.005), and the median OS values were not reached, not reached, and 12 months (p=0.048). In a multivariate analysis, early CRP kinetics was a significant independent factor for objective response, PFS, and OS (p<0.001, p=0.004, and p=0.006, respectively)., Conclusions: CRP flare-response was associated with significant tumor shrinkage and improved survival outcomes in patients with mRCC who were treated with nivolumab. Early CRP kinetics could be useful for evaluating nivolumab treatment efficacy., Competing Interests: Competing interests: YF received research grant from Ono Pharma (Osaka, Japan)., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There is no clear consensus regarding gender differences in the prognosis of patients with clear-cell renal cell carcinoma (ccRCC). In the present study, we investigated the prognostic value of gender in patients with non-metastatic ccRCC undergoing curative surgery using the inverse probability of treatment weighting (IPTW) method to balance the difference in baseline factors between females and males., Patients and Methods: We retrospectively reviewed the International Marker Consortium for Renal Cancer (INMARC) dataset and included 2055 patients with cT1-4N0M0 ccRCC who underwent partial or radical nephrectomy. The IPTW method was used to adjust for baseline characteristics between females and males (age, race, surgery type, and pT stage), and the association of gender with recurrence-free survival (RFS) was evaluated., Results: During the follow-up (median, 30 months), 162 (8%) patients had disease recurrence (5-year RFS rate, 88%). Female gender (n = 712; 35%) was significantly associated with a lower Fuhrman grade (unweighted, P = .022; IPTW-weighted, P < .001). Females had significantly better RFS compared with males (unweighted, 5-year RFS rate, 92% vs. 87%; P = .005; IPTW-weighted, 5-year RFS rate, 92% vs. 86%; P = .002). IPTW-weighted multivariate analysis showed that female gender was an independent predictor for better RFS (hazard ratio, 0.59; P = .005) along with lower pT stage and lower Fuhrman grade. The prognostic significance of female gender was also observed in the unweighted multivariate analysis., Conclusion: Female gender was significantly associated with a lower Fuhrman grade and better prognosis for patients with non-metastatic ccRCC undergoing curative surgery., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Pretreatment C-reactive protein (CRP) has been shown to be an independent prognostic factor for metastatic renal cell carcinoma (mRCC) treated with tyrosine kinase inhibitors (TKIs). We further evaluated the early response of CRP after the initiation of TKIs., Methods: A total of 103 patients (80 men and 23 women) were treated with TKIs for mRCC from 2008-2013. Patients were divided into three groups according to their early CRP kinetics-patients whose baseline CRP levels were <10 mg/L (non-elevated), patients whose baseline CRP levels were ≥10 mg/L and had decreased by >20% at 4 weeks after the initiation of TKIs (early CRP responder), and the remaining patients (non-early CRP responder). The endpoints were progression-free survival (PFS) and overall survival (OS)., Results: The median follow-up period was 21 (interquartile range 10-34) months. The numbers of patients classified as non-elevated, early CRP responder, and non-early CRP responder were 62, 19, and 22, respectively. The 1-year PFS rates of patients in the non-elevated, early CRP responder, and non-early CRP responder groups were 50, 23, and 9.7%, respectively (p < 0.001). The 1-year OS rates of patients in these three groups were 79, 62, and 36%, respectively (p < 0.001). In multivariate analysis, the early CRP kinetics assessment was a significant independent factor for PFS and OS., Conclusions: Early CRP response at 4 weeks is predictive of survival for patients with mRCC treated with TKI.

We herein report the case of a 61-year-old Japanese male with localized pleural metastases of renal cell carcinoma. The patient was admitted to our hospital because of dyspnea on exertion and left-sided pleural effusion. He had undergone right radical nephrectomy 10 years previously. Contrast-enhanced whole-body computed tomography revealed scattered nodular thickening of the left pleura with contrast enhancement and left-sided pleural effusion. Thoracoscopy performed under local anesthesia was applied to obtain a biopsy of the pleural nodules, and the specimen was consequently diagnosed as exhibiting pleural metastasis of renal cell carcinoma, clear cell type.

Background: Bisphosphonates play an indisputable role in preventing skeletal-related events (SREs) secondary to bone metastases, and also have a direct effect on tumor cells. However, it remains unclear whether bisphosphonates improve overall survival (OS) for renal cell carcinoma (RCC) patients with bone metastases., Methods: Between 1978 and 2010, a total of 45 patients who had RCC metastatic to bone and were classified as intermediate risk according to Memorial Sloan-Kettering Cancer Center criteria were included in this retrospective study. In this cohort, 23 patients received zoledronic acid (ZOL) treatment (ZOL-treated group) whereas the other 22 did not (non-ZOL-treated group). The primary endpoint was OS and the secondary endpoint was the SRE rate defined as the total number of SREs divided by the total years under study., Results: For the cohort of 45 patients, the median OS from diagnosis of bone metastases was 27.2 months. Multivariate analysis showed that lower serum calcium (p = 0.0083) and ZOL treatment (p = 0.0013) were independent factors predicting longer survival. The ZOL-treated group had significantly longer OS than the non-ZOL-treated group (p = 0.0034). Patients in the ZOL-treated group experienced a lower SRE rate than patients in the non-ZOL-treated group (p = 0.0453). In particular, none of the patients in the ZOL-treated group developed spinal compression whereas 6 (28%) in the non-ZOL-treated group did (p = 0.0479)., Conclusions: The current study indicates that ZOL not only reduces SREs but possibly improves OS in these patients.

Background: C-reactive protein (CRP) was an independent prognostic factor for metastatic renal cell carcinoma in the cytokine era. However, the impact of CRP on the survival of metastatic renal cell carcinoma patients treated with tyrosine kinase inhibitors has not yet been investigated. Therefore, we further evaluated the prognostic impact of CRP for patients with metastatic renal cell carcinoma treated with molecular-targeted agents of tyrosine kinase inhibitors., Methods: Fifty-two patients were treated with tyrosine kinase inhibitors for metastatic renal cell carcinoma at our institution. Overall, 31 and 21 patients were administered sunitinib and sorafenib, respectively. The prognostic value of all variables, including CRP, for overall survival was assessed using the Cox proportional hazards model., Results: The median baseline CRP level was 4.9 mg/l. In multivariate analysis, CRP was an independent predictor for overall survival as both continuous and categorical variable. The median overall survival times of patients with non-elevated CRP concentration (<8 mg/l) were not reached, compared with those of patients with elevated CRP concentration (8 mg/l or greater) of 15.9 months. There was a significant difference in overall survival rates between the two groups, with 1- and 3-year overall survival rates of 92.8 and 69.3% versus 50.2 and 22.9% for the non-elevated CRP group and the elevated CRP group (p = 0.003), respectively., Conclusions: CRP has a significant impact on overall survival of patients with metastatic renal cell carcinoma carcinoma treated with tyrosine kinase inhibitors.

Objective: The RENAL nephrometry scoring system characterizes tumors according to their size, growth pattern, location and nearness to the renal sinus or collecting system. The current study aims to evaluate the RENAL nephrometry scoring system in adopting nephron-sparing surgery (NSS) for cT1 renal cancer., Methods: Clinicopathological data of 200 consecutive patients who had undergone radical nephrectomy (RN) or NSS for clinical stage T1 renal cell cancer at our single institution during 2005-2009 were investigated retrospectively., Results: Of 200 patients, 103 were scheduled for RN, whereas 97 were planned to undergo NSS, 9 of whom actually underwent RN. Those who were planned to undergo NSS were younger and had smaller tumors (p < 0.001). The median RENAL score was significantly lower among those who were originally assigned to NSS (5, range 4-10) versus RN (8, range 4-11) (p < 0.001). Three months after surgery, the renal function of patients who had been scheduled for NSS was significantly better than in those treated by RN (p < 0.001)., Conclusions: This study suggests that the RENAL nephrometry scoring system is a useful tool in adopting NSS for cT1 renal cancer and that objective decision-making for NSS was possible., (Copyright © 2012 S. Karger AG, Basel.)