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Objective: To report the results of PADRES (Prior Axitinib as a Determinant of Outcome of Renal Surgery, NCT03438708), a study investigating neoadjuvant axitinib for tumours of high complexity with imperative indication for partial nephrectomy (PN). Methods: We conducted a single‐arm phase II clinical trial of localized (cT1b‐cT3M0) clear‐cell renal cell carcinoma (RCC) patients with imperative indications for nephron preservation, where PN is a high‐risk procedure due to complexity (RENAL score 10–12). Axitinib 5 mg was administered twice daily for 8 weeks with repeat imaging at completion, followed by surgery. The primary outcome was successful completion of planned PN following axitinib treatment. Secondary objectives included changes in tumour diameter, RENAL nephrometry score, renal function and Response Evaluation Criteria in Solid Tumours (RECIST) v1.1, and surgical complications. Results: Twenty‐seven patients were enrolled (median age 69 years). Prior to therapy, twenty patients (74.0%) had ≥ clinical T3a staged tumours. Axitinib resulted in reductions in tumour diameter (7.5 vs 6.2 cm; P < 0.001) and RENAL score (11 vs 10; P < 0.001). Nine patients (33.3%) had partial response based on RECIST and nine (33.3%) were clinically downstaged. PN was performed in twenty patients (74.0%); twenty‐five patients (96.2%) had negative margins. Six patients (22.2%) had Clavien III–IV complications. The median change in estimated glomerular filtration rate (preoperative to last follow‐up) was 8.5 mL/min/1.73 m2. Conclusion: Neoadjuvant axitnib resulted in reductions in tumour size and complexity, enabling safe and feasible PN and functional preservation in patients with complex renal masses and imperative indication. [ABSTRACT FROM AUTHOR]

Background and Objectives: to investigate the impact of age on renal function deterioration after robotic-assisted partial nephrectomy (RAPN) focusing on a decline to moderate and severe forms of chronic kidney disease (CKD). Materials and Methods: This is a single center prospective analysis of patients who underwent RAPN. The outcomes include the development of de novo CKD-S 3a [estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2)] and de novo CKD-S 3b (eGFR < 45 mL/min/1.73/m2). Multivariable analysis (MVA) via Cox regression identified predictors for CKD-S 3a/b. Kaplan –Meier Analyses (KMA) were fitted for survival assessment. Multivariable linear regression was utilized to identify the predictors of last-eGFR. Results: Overall, 258 patients were analyzed [low age (<50) n = 40 (15.5%); intermediate age (50–70) n = 164 (63.5%); high age (>70) n = 54 (20.9%)] with a median follow-up of 31 (IQR 20–42) months. MVA revealed an increasing RENAL score [Hazard Ratio (HR) 1.32, p = 0.009], age 50–70 (HR 6.21, p = 0.01), age ≥ 70 (HR 10.81, p = 0.001), increasing BMI (HR 1.11, p < 0.001) and preoperative CKD 2 (HR 2.43, p = 0.014) are independent risk factors associated with an increased risk of CKD-S 3a; conversely, post-surgical acute kidney injury was not (p = 0.83). MVA for CKD-S 3b revealed an increasing RENAL score (HR 1.51, p = 0.013) and age ≥ 70 (HR 2.73, p = 0.046) are associated with an increased risk of CKD-S 3b. Linear regression analysis revealed increasing age (Coeff. −0.76, p < 0.001), increasing tumor size (Coeff. −0.31, p = 0.03), and increasing BMI (Coeff. −0.64, p = 0.004) are associated with decreasing eGFR at last follow-up. We compare the survival distribution of our cohort stratified by age elderly patients experienced worsened CKD-S 3a/b disease-free survival (p < 0.001; p < 0.001, respectively). Conclusions: Age is independently associated with a greater risk of significant and ongoing decline in kidney function following RAPN. Recognizing the impact of aging on renal function post-surgery can guide better management practices. Further investigations are required. [ABSTRACT FROM AUTHOR]

With the advent of new therapeutic modalities, management of metastatic castrate-sensitive prostate cancer (mCSPC) has been in flux. From androgen-deprivation therapy to docetaxel to androgen receptor–signaling inhibitors, each agent has heralded a new treatment paradigm. As such, the optimal first-line therapy for mCSPC remains incompletely defined. This review provides a narrative of recent advances to systemic therapy within the mCSPC treatment space, particularly with regard to expansion to triplet therapy. [ABSTRACT FROM AUTHOR]

We sought to determine whether postnephrectomy loss of renal function increases risk of recurrence and mortality in renal cell carcinoma. Retrospective analysis of 1805 patients from the International Marker Consortium for Renal Cancer registry shows de novo eGFR < 45 mL/min/1.73m2 is independently associated with progression and worsened mortality in patients aged < 65 years, underscoring desirability for nephron preservation in younger patients. 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. [ABSTRACT FROM AUTHOR]

Purpose: We hypothesized that two-tier re-classification of the "M" (metastasis) domain of the Tumor-Node-Metastasis (TNM) staging of Renal Cell Carcinoma (RCC) may improve staging accuracy than the current monolithic classification, as advancements in the understanding of tumor biology have led to increased recognition of the heterogeneous potential of metastatic RCC (mRCC). Methods: Multicenter retrospective analysis of patients from the REMARCC (REgistry of MetAstatic RCC) database. Patients were stratified by number of metastases into two groups, M1 (=3, "Oligometastatic") and M2 (>3, "Polymetastatic"). Primary outcome was overall survival (OS). Secondary outcomes were cancer-specific survival (CSS). Cox-regression and Kaplan-Meier (KMA) analysis were utilized for outcomes, and receiver operating characteristic analysis (ROC) was utilized to assess diagnostic accuracy compared to current "M" staging. Results: 429 patients were stratified into proposed M1 and M2 groups (M1 = 286/M2 = 143; median follow-up 19.2 months). Cox-regression revealed M2 classification as an independent risk factor for worsened all-cause mortality (HR=1.67, p=0.001) and cancer-specific mortality (HR=1.74, p<0.001). Comparing M1-oligometastatic vs. M2-polymetastatic groups, KMA revealed significantly higher 5-year OS (36% vs. 21%, p<0.001) and 5-year CSS (39% vs. 17%, p<0.001). ROC analyses comparing OS and CSS, for M1/M2 reclassification versus unitary M designation currently in use demonstrated improved c-index for OS (M1/M2 0.635 vs. unitary M 0.500) and CSS (M1/M2 0.627 vs. unitary M 0.500). Conclusion: Subclassification of Stage "M" domain of mRCC into two clinical substage categories based on metastatic burden corresponds to distinctive tumor groups whose oncological potential varies significantly and result in improved predictive capability compared to current staging. [ABSTRACT FROM AUTHOR]

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 m2). Patients were stratified by CKD stage at last follow‐up: no CKD‐S (eGFR ≥60 mL/min/1.73 m2), de novo CKD‐S 3a (eGFR 45–59 mL/min/1.73 m2), CKD‐S 3b (eGFR <45 and ≥30 mL/min/1.73 m2) and CKD‐S 4 (eGFR <30 and ≥15 mL/min/1.73 m2). 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 m2, 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. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate whether computer program-estimated urolith stone volume (SV) was a better predictor of spontaneous passage (SP) compared with program-estimated stone diameter (PD) or manually measured stone diameter (MD), and whether utilizing SV and MD together provided additional value in SP prediction compared with MD alone. Materials and Methods: Retrospective analysis of patients with acute renal colic and single renal/ureteral stone on CT from July 2017 to April 2020. Diameter obtained from radiology reports or manually measured when report not available. Semiautomated stone analysis software (qSAS) was used to estimate SV and PD. ROC analysis was performed to compare accuracy of SV vs MD vs PD in predicting SP by 2, 4, and 6 weeks. Subgroup analysis was performed by stone size (

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. [ABSTRACT FROM AUTHOR]

The optimal management of bladder cancer with clinically positive regional lymph node (cN+) remains as a challenge. In analysis of patients with cN+ via the National Cancer Data Base bladder cancer, combined treatment with radical cystectomy (RC) and chemotherapy versus RC or chemotherapy alone was associated with a better overall survival outcome (Galsky et al. 2016).;However, despite advancement in multimodal approaches, the role of local definitive therapy in addition to systemic treatment in cN+ bladder cancer is yet to be determined. Herein, we sought to investigate the role of RC in management of patients with cN+ bladder cancer at US Veterans Health Administration Facilities. We identified patients diagnosed with non-metastatic cN+ bladder cancer between 2000-2017 using the Department of Veterans Affairs (VA) Informatics and Computing Infrastructure (VINCI). We used a combination of database/registry coded values and chart review to assemble tumor, treatment, comorbidity, and sociodemographic data.;Clinical nodal status was defined as the highest clinical N stage received within 90 days after diagnosis. To minimize mortality bias, we excluded patients who died within 90 days of diagnosis.;;We divided the cohort based on receiving RC to chemotherapy only group or RC group. The Propensity score matching was performed based on predictors of receipt of RC.;Multivariable Cox proportional hazards models and Kaplan-Meier survival curves were used to evaluate overall survival (OS). Of 475 patients with non-metastatic cN+ bladder cancer, 170 patients underwent RC with peri-operative chemotherapy. After propensity matching, 156 patients in each group were included in analysis. 84(54%) and 72(46%) patients in RC group received neoadjuvant and adjuvant chemotherapy, respectively. 66 patients (42%) in RC group and 62(40%) patients in chemotherapy group had clinical N1 disease (p=0.75).;;In multivariable logistic model, RC was associated with improved OS (HR 0.65, 95%CI 0.50-0.84, p=0.001). In subset analysis, RC was only associated with improved OS in patients with clinical N1 disease (0.54, 95%CI 0.33-0.87, p=0.01). There was no OS benefit from RC in patients with clinical N2/N3 bladder cancer (0.75, 95%CI 0.52-1.07, p=0.11). In sensitivity analysis, RC after neoadjuvant chemotherapy also improved OS (0.63, 95%CI 0.46-0.87, p=0.01). Kaplan-Meier survival curves were demonstrated in Figure1. Patients with bladder cancer and limited regional lymph node involvement (clinical N1), who underwent RC in addition to chemotherapy have an improved OS compared with patients who did not undergo RC. This study suggests RC should be considered, as part of multimodal treatment, in subset of patients with;clinically regional lymph node metastasis. More studies with focus of cancer specific outcomes are needed to validate these findings. [ABSTRACT FROM AUTHOR]

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 m2). 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/m2, 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 m2 (hazard ratio [HR] 1.32, P = 0.015), <45 mL/min/1.73 m2 (HR 1.41, P = 0.023) and <30 mL/min/1.73 m2 (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 m2 (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. [ABSTRACT FROM AUTHOR]

Systemic therapy strategies in the setting of localized and locally advanced renal cell carcinoma have continued to evolve in two directions: (i) as adjuvant therapy (to reduce the risk of recurrence or progression in high‐risk localized groups); or (ii) as neoadjuvant therapy as a strategy to render primary renal tumors amenable to planned surgical resection in settings where radical resection or nephron‐sparing surgery was not thought to be safe or feasible. In the realm of adjuvant therapy, the results of adjuvant therapy phase III randomized clinical trials have been mixed and contradictory; nevertheless, the findings of the landmark Sunitinib Treatment of Renal Adjuvant Cancer study have led to approval of sunitinib as an adjuvant agent in the USA. In the realm of neoadjuvant therapy, presurgical tumor reduction has been shown in a number of phase II studies utilizing targeted molecular agents and in a recently published small randomized double‐blind placebo‐controlled study, and an expanding body of literature suggests benefit in select patients. Thus, large randomized clinical trial data are not present to support this approach, and guidelines for use of presurgical therapy have not been promulgated. The advent of immunomodulation through checkpoint inhibition represents an exciting horizon for adjuvant and neoadjuvant strategies. The present article reviews the current status and future prospects of adjuvant and neoadjuvant therapy in localized and locally advanced renal cell carcinoma. [ABSTRACT FROM AUTHOR]

Introduction: Percutaneous renal mass biopsy has evolved over the last decade with improvements on previous pitfalls including low tissue yield, high non-diagnostic rates, and complications. As understanding of tumor biology and natural history of renal cortical neoplasms has improved, percutaneous renal mass biopsy is poised to have an expanding role in an area characterized by individualized management and refined risk stratification. Areas covered: This review summarizes the evolution of renal mass biopsy to its current state with respect to outcomes, indications, and clinical guidelines. Expert opinion: With improved understanding of differential biological potential of renal cortical neoplasms combined with technical improvements in diagnostic yield and accuracy, utilization of renal mass biopsy is becoming an important adjunct to patient care in a broad range of clinical scenarios, including active surveillance, thermal ablation, and use of primary systemic therapy in localized and advanced settings. [ABSTRACT FROM AUTHOR]