Long-term functional outcomes in patients undergoing radical nephrectomy for renal cell carcinoma and tumor thrombus.

BACKGROUND: Up to 15% of patients with locally advanced renal cell carcinoma (RCC) harbors tumor thrombus (TT). In those cases, radical nephrectomy (RN) and thrombectomy represents the standard of care. We assessed the impact of TT on long-term functional and oncological outcomes in a large contemporary cohort. METHODS: Within a prospective maintained database, 1207 patients undergoing RN for non-metastatic RCC between 2000 and 2021 at a single tertiary centre were identified. Of these, 172 (14%) harbored TT. Multivariable logistic regression analyses evaluated the impact of TT on the risk of postoperative acute kidney injury (AKI). Multivariable Poisson regression analyses estimated the risk of long-term chronic kidney disease (CKD). Kaplan Meier plots estimated disease-free survival and cancer specific survival. Multivariable Cox regression models assessed the main predictors of clinical progression (CP) and cancer specific mortality (CSM). RESULTS: Patients with TT showed lower BMI (24 vs. 26 kg/m2) and preoperative Hb (11 vs. 14 g/mL; all-p < 0.05). Clinical tumor size was higher in patients with TT (9.6 vs. 6.5 cm; p < 0.001). After adjusting for potential confounders, the presence of TT was significantly associated with a higher risk of postoperative AKI (OR 2.03, 95% CI 1.49-3.6; p < 0.001) and long-term CKD (OR: 1.32, 95% CI 1.10-1.58; p < 0.01). Notably, patients with TT showed worse long-term oncological outcomes and TT was a predictor for CP (2.02, CI 95% 1.49-2.73, p < 0.001) and CSM (HR 1.61, CI 95% 1.04-2.49, p < 0.03). CONCLUSIONS: The presence of TT in RCC patients represents a key risk factor for worse perioperative, as well as long-term renal function. Specifically, patients with TT harbor a significant and early estimated glomerular filtration rate (eGFR) decrease. However, despite TT patients show a greater eGFR decline after surgery, they retain acceptable renal function, which remains stable over time.

Risks and benefits of partial nephrectomy performed with limited or with zero ischaemia time.

OBJECTIVE: To test the hypothesis that longer warm ischaemia time (WIT) might have a marginal impact on renal functional outcomes and might, in fact, reduce haemorrhagic risk intra-operatively. PATIENTS AND METHODS: Data from 1140 patients treated with elective partial nephrectomy (PN) for a cT1-2 cN0 cM0 renal mass were prospectively collected. WIT was defined as the duration of clamping of the main renal artery with no refrigeration and was tested as a continuous variable. The primary outcome of the study was evaluation of the effect of WIT on renal function (estimated glomerular filtration rate [eGFR]) postoperatively, at 6 months and in the long term (measured between 1 and 5 years after surgery). The secondary outcome of the study was haemorrhagic risk, defined as estimated blood loss (EBL) or peri-operative transfusions. Multivariable linear, logistic and Cox regression analyses, accounting for age, Charlson comorbidity index, clinical size, preoperative eGFR and year of surgery, were used and the potential nonlinear relationship between WIT and the study outcomes was modelled using restricted cubic splines. RESULTS: A total of 863 patients (76%) underwent PN with WIT and 277 (24%) without. The baseline median eGFR was 87.3 (68.8-99.2) mL/min/1.73m2 for the on-clamp population and 80.6 (63.2-95.2) mL/min/1.73m2  for the off-clamp population. The median duration of WIT was 17 (13-21) min. At multivariable analyses predicting renal function, longer WIT was associated with decreased postoperative eGFR (estimate: -0.21, 95% confidence interval [CI] -0.31; -0.11 [P < 0.001]). Conversely, no association between WIT and eGFR was recorded at 6-month or long-term follow-up (all P > 0.8). At multivariable analyses predicting haemorrhagic risk, clampless resection with no ischaemia time and PN with short WIT was associated with an increased EBL (estimate: -21.56, 95% CI -28.33; -14.79 [P < 0.001]) and peri-operative transfusion rate (estimate: -0.009, 95% CI -0.01; -0.003 [P = 0.002]). No association between WIT and positive surgical margin status was recorded (all P = 0.1). CONCLUSION: Patients and clinicians should be aware that performing PN with very limited or even with zero WIT might increase bleeding and the need for peri-operative transfusion while not improving long-term renal function outcomes.

Neglected lymph nodal metastases in patients with renal cancer: when to extend the anatomical template of lymph node dissection during nephrectomy.

BACKGROUND: The role of lymph node dissection (LND) in patients with renal cell carcinoma (RCC) is still controversial. However, detecting lymph node invasion (LNI) is key due to prognostic implications and to identify patients who might benefit from adjuvant therapies such as adjuvant pembrolizumab. MATERIALS AND METHODS: Out of 796 patients, 261 (33%) received eLND, of whom 62 (8%) for suspicious lymph node (LN) metastases at preoperative staging (cN1). eLND was divided in 3 anatomical areas: (1) hilar, (2) side-specific (pre-/para-aortic or pre-/para-caval) and (3) inter-aorto-caval nodes. Overall maximum LN diameter was measured by a dedicated radiologist for each patient. Multivariable logistic regression models (MVA) were tested for the effect of maximum LN diameter in predicting the presence of nodal metastases outside the anatomical area of cN1. RESULTS: LNI was confirmed in 50% of cN1, whilst only 13 out of 199 cN0 patients were pN1 at final histology (6.5%; p < 0.001). In a per-patient analysis, of 62 cN1 patients, 24% vs. 18% vs. 8% harboured pN1 disease only inside vs. in-outside vs. only outside the suspicious anatomical field of cN1 at preoperative CT/MRI scan. At MVA, increasing diameter of suspicious LNs was independently associated with risk of finding positive LNs outside the suspicious anatomical field (OR 1.05, 95%CI 1.02-1.11; p = 0.02). CONCLUSIONS: Roughly 50% of cN1 patients undergoing eLND will harbour LN metastases, also outside the suspicious radiological area, and maximum LNs diameter at preoperative imaging correlates with such risk. Thus, an eLND might be justified in patients with large suspicious LN metastases, to better stage this patient population and to improve postoperative treatment management.

How to optimize the use of adjuvant pembrolizumab in renal cell carcinoma: which patients benefit the most?

PURPOSE: The KEYNOTE-564 trial showed improved disease-free survival (DFS) for patients with high-risk renal cell carcinoma (RCC) receiving adjuvant pembrolizumab as compared to placebo. However, if systematically administered to all high-risk patients, it might lead to the overtreatment in a non-negligible proportion of patient. Therefore, we aimed to determine the optimal candidate for adjuvant pembrolizumab. METHODS: Within a prospectively maintained database we selected patients who fulfilled the inclusion criteria of the KEYNOTE-564. We compared baseline characteristics and oncologic outcomes in this cohort with those of the placebo arm of the KEYNOTE-564. Regression tree analyses was used to generate a risk stratification tool to predict 1-year DFS after surgery. RESULTS: In the off-trial setting, patients had worse tumor characteristics then in the KEYNOTE-564 placebo arm, i.e. there were more pT4 (5.4 vs. 2.7%, p = 0.046) and pN1 (15 vs. 6.3%, p < 0.001) cases. Median DFS was 29 (95% CI 21-35) months as compared to value not reached in KEYNOTE-564 and 1-year DFS was 64.2% (95% CI 59.6-69.2) as compared to 76.2% (95% CI 72.2-79.7), respectively. Patients with pN1 were at the highest risk of 1-year recurrence (1-year DFS 28.6% [95% CI 20.2-40.3]); patients without LNI, but necrosis were at intermediate risk (1-year DFS 62.5% [95% CI 56.9-68.8]); those without LNI and necrosis were at the lowest risk (1-year DFS 83.8% [95% CI 79.1-88.9]). LVI substratification furtherly improved the accuracy in the prediction of early recurrence. CONCLUSIONS: Patients potentially eligible for adjuvant pembrolizumab have worse characteristics and DFS in the off-trial setting as compared to the placebo arm of the KEYNOTE-564. Patients with either LNI or necrosis were at the highest risk of early-recurrence, which make them the ideal candidate to adjuvant pembrolizumab.

Acute Kidney Injury at Hospital Admission for SARS-CoV-2 Infection as a Marker of Poor Prognosis: Clinical Implications for Triage Risk Stratification.

BACKGROUND/AIMS: The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a wide spectrum of effects, including acute kidney injury (AKI) in up to 40% of hospitalized patients. Given the established relationship between AKI and poor prognosis, whether AKI might be a prognostic indicator for patients admitted to the hospital for SARS-CoV-2 infection would allow for a straightforward risk stratification of these patients. METHODS: We analyzed data of 623 patients admitted to San Raffaele Hospital (Milan, IT) between February 25 and April 19, 2020, for laboratory-confirmed SARS-CoV-2 infection. Incidence of AKI at hospital admission was calculated, with AKI defined according to the KDIGO criteria. Multivariable Cox regression models assessed the association between AKI and overall mortality and admission to the intensive care unit (ICU). RESULTS: Overall, 108 (17%) patients had AKI at hospital admission for SARS-CoV-2 infection. After a median follow-up for survivors of 14 days (interquartile range: 8, 23), 123 patients died, while 84 patients were admitted to the ICU. After adjusting for confounders, patients who had AKI at hospital admission were at increased risk of overall mortality compared to those who did not have AKI (hazards ratio [HR]: 2.00; p = 0.0004), whereas we did not find evidence of an association between AKI and ICU admission (HR: 0.95; p = 0.9). CONCLUSIONS: These data suggest that AKI might be an indicator of poor prognosis for patients with SARS-CoV-2 infection, and as such, given its readily availability, it might be used to improve risk stratification at hospital admission.

The role of 18F-FAZA PET/CT in detecting lymph node metastases in renal cell carcinoma patients: a prospective pilot trial.

BACKGROUND: The accurate detection of nodal invasion is an unmet need in the clinical staging of renal cancer. Positron emission tomography (PET) with 18F-fluoroazomycin arabinoside (18F-FAZA), a hypoxia specific tracer, is a non-invasive imaging method that detects tumour hypoxia. The aim of this work was to evaluate the role of 18F-FAZA PET/CT in the identification of lymph node metastases in renal cancer. METHODS: A proof-of-concept phase 2 study including 20 kidney cancer patients ( ClinicalTrials.gov Identifier: NCT03955393) was conducted. Inclusion criteria were one or more of the following three criteria: (1) clinical tumour size > 10 cm, (2) evidence of clinical lymphadenopathies at preoperative CT scan and (3) clinical T4 cancer. Before surgery, 18F-FAZA PET/CT was performed, 2 h after the intravenous injection of the radiotracer. An experienced nuclear medicine physician, aware of patient's history and of all available diagnostic imaging, performed a qualitative and semi-quantitative analysis on 18F-FAZA images. Histopathological analysis was obtained in all patients on surgical specimen. RESULTS: Fourteen/19 (74%) patients had a non-organ confined renal cell carcinoma (RCC) at final pathology (either pT3 or pT4). Median number of nodes removed was 12 (IQR 7-15). The rate of lymph node invasion was 16%. No patient with pN1 disease showed positive 18F-FAZA PET, thus suggesting the non-hypoxic behaviour of the lesions. In addition, neither primary tumour nor distant metastases presented a pathological 18F-FAZA uptake. No adverse events were recorded during the study. CONCLUSIONS: 18F-FAZA PET/CT scan did not detect RCC lymph neither nodal nor distant metastases and did not show any uptake in the primary renal tumour.

The impact of intraoperative bleeding on the risk of chronic kidney disease after nephron-sparing surgery.

PURPOSE: The current literature regarding the effect of blood loss (eBL) after nephron-sparing surgery (NSS) on long-term renal function is scarce. We tested the effect of eBL on the risk of developing chronic kidney disease (CKD) after NSS. METHODS: Within an institutional prospectively maintained database, we identified 215 patients treated with NSS for cT1N0M0 renal mass at one European high-volume center. Multivariable logistic regression models tested the effect of eBL on the risk of developing CKD, after accounting for surgical complexity, individual clinical characteristics, and surgical experience. Multivariable linear regression models identified predictors of eBL. RESULTS: After a median follow-up of 36 months, 55 (25.6%) patients experienced CKD after surgery. At multivariable analyses, eBL independently predicted higher risk of CKD after NSS (odds ratio [OR]: 1.16; 95% confidence intervals [CI] 1.04-1.30; p < 0.01). Specifically, the relationship between eBL and probability of CKD emerged as nonlinear, with a plateau from 0 to 500 mL of eBL and an increase afterward. When multivariable linear regression analyses investigated predictors of eBL, hypertension (Est: 127, 95% CI 12-242; p = 0.03), clinical size (Est: 47, 95% CI 7-87; p = 0.02), and PADUA score (Est: 42; 95% CI 4-80 p = 0.03) achieved independent predictor status for higher intraoperative eBL. Conversely, surgical experience was associated with lower eBL (p = 0.01). CONCLUSIONS: Intraoperative bleeding is independently associated with the risk of developing CKD after surgery, even after adjustment for well-known predictors of renal failure and tumor complexity. Hence, strategies aimed at maximally reducing such adverse events deserve special consideration.

Parenchymal biopsy in the management of patients with renal cancer.

PURPOSE: The role of non-tumour renal biopsy in predicting renal function after surgery for renal cell carcinoma (RCC) is poorly investigated. The aim of the study was to assess the impact of renal parenchymal histology on renal function after radical nephrectomy in a cohort of patients with RCC. METHODS: This cohort study included 171 patients with RCC submitted to radical nephrectomy between 2006 and 2018. Two biopsy samples from normal parenchyma were collected at nephrectomy and renal parenchyma damage (RPD) was scored on histologic samples according to validated methodology. The outcomes were eGFR after surgery and its reduction > 25% relative to baseline at maximum 12 months' follow-up. Linear and logistic multivariable regression were used, adjusting for age at surgery, presence of hypertension, diabetes, clinical tumour size, time from surgery and basal eGFR. RESULTS: 171 patients were enrolled and RPD was demonstrated in 64 (37%). Patients with RPD had more comorbidities (CCI > 2 in 25 vs. 9%, p < 0.001), in particular hypertension (70 vs. 53%; p = 0.03), diabetes with (5% vs. 0%, p = 0.007) or without (31 vs. 18%; p = 0.007) organ damage, cerebrovascular disease (19 vs. 5%; p = 0.006) and nephropathy (20 vs. 3%; p = 0.0004). At multivariable analyses, RPD was associated with lower eGFR (Est. - 5.48; 95% CI - 9.27: - 1.7; p = 0.005) and with clinically significant reduction of eGFR after surgery (OR 3.06; 95% CI 1.17: 8.49; p = 0.026). CONCLUSIONS: Presence of RPD in non-tumour renal tissue is an independent predictor of functional impairment in patients with RCC. Such preliminary finding supports the use of parenchyma biopsy during clinical decision making.

Postoperative complications increase the risk of long-term chronic kidney disease after nephron-sparing surgery in patients with renal cancer and normal preoperative renal function.

OBJECTIVES: To investigate whether postoperative complications affect long-term functional outcomes of renal patients treated with nephron-sparing surgery (NSS). MATERIALS AND METHODS: We performed an observational study, enrolling 596 patients with preoperative normal renal function treated with NSS for clinical T1abN0M0 renal masses. Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for chronic kidney disease (CKD) including as covariates age, comorbidity (scored according to the Charlson comorbidity index), hypertension, tumour size, preoperative estimated glomerular filtration rate (eGFR), eGFR < 60 mL/min/1.73 m2 at discharge, and ischaemia time. RESULTS: A total of 137 patients (23%) developed postoperative complications. At a median (interquartile range) follow-up of 53 (26-91) months, CKD risk was 19% for patients with postoperative complications and 11% for those without complications. Patients experiencing postoperative complications (HR 1.90, 95% CI 1.26-2.86) were at increased risk of developing CKD during the follow-up at multivariable analysis, after accounting for confounders. CONCLUSIONS: Our data outline how postoperative complications might have a detrimental impact on postoperative renal function in patients submitted to NSS. Improper patient selection, increasing the risk of postoperative complications, could limit the benefit in terms of renal function brought by NSS.

Nomogram for predicting the likelihood of postoperative surgical complications in patients treated with partial nephrectomy: a prospective multicentre observational study (the RECORd 2 project).

OBJECTIVE: To identify meaningful predictors and to develop a nomogram of postoperative surgical complications in patients treated with partial nephrectomy (PN). PATIENTS AND METHODS: We prospectively evaluated 4308 consecutive patients who had surgical treatment for renal tumours, between 2013 and 2016, at 26 Italian urological centres (RECORd 2 project). A multivariable logistic regression for surgical complications was performed. A nomogram was created from the multivariable model. Internal validation processes were performed using bootstrapping with 1000 repetitions. RESULTS: Overall, 2584 patients who underwent PN were evaluated for the final analyses. The median (interquartile [IQR]) American Society of Anesthesiologists (ASA) score was 2 (2-3). In all, 72.4% of patients had clinical T1a (cT1a) stage tumours. The median (IQR) Preoperative Aspects and Dimensions Used for an Anatomical (PADUA) score was 7 (6-8). Overall, 34.3%, 27.7%, 38% of patients underwent open PN (OPN), laparoscopic PN (LPN), and robot-assisted PN (RAPN). Overall and major postoperative surgical complications were recorded in 10.2% and 2.5% of patients, respectively. At multivariable analysis, age, ASA score, cT2 vs cT1a stage, PADUA score, preoperative anaemia, OPN and LPN vs RAPN, were significant predictive factors of postoperative surgical complications. We used these variables to construct a nomogram for predicting the risk of postoperative surgical complications. At decision curve analysis, the nomogram led to superior outcomes for any decision associated with a threshold probability of >5%. CONCLUSION: Several clinical predictors have been associated with postoperative surgical complications after PN. We used this information to develop and internally validate a nomogram to predict such risk.

The side and the location of the primary tumor does not affect the probability of lymph node invasion in patients with renal cell carcinoma.

PURPOSE: To evaluate the role of side and location of the primary renal cell carcinoma (RCC) on the risk of lymph node invasion (LNI) and/or nodal progression (NP) during follow-up. MATERIALS AND METHODS: We evaluated 2485 patients with unilateral RCC, surgically treated in a single tertiary care referral center. Outcomes were LNI at surgery and/or NP during follow-up. We studied if RCC side (left vs. right) and location (upper vs. middle vs. hilar vs. lower area vs. more than one area) affected the probability of LNI and/or NP at follow-up. RESULTS: Overall, 43 and 15% of patients underwent lymph node dissection and had LNI at surgery, respectively. During follow-up, 2.2% of patients had NP. Higher rates of LNI and NP were observed for patients with primary tumor located in more than one anatomical kidney area relative to patients with tumor in a single area (upper 11% vs. middle 10% vs. hilar 0%, vs. lower 12% vs. more than one area 26%, p < 0.01). cM1, cN1, pT2/pT3/pT4 disease and Fuhrman grade 3/4 were independent predictors of the study outcome (all p ≤ 0.01). Neither the RCC side nor the location reached the independent predictor status (all p > 0.1). CONCLUSIONS: Patients with single-side and more than one anatomical kidney area affected by RCC have higher rate of LNI at surgery and/or NP at follow-up. Neither side nor location of primary RCC tumor is related to the risk of harboring LNI at surgery and/or developing NP at follow-up.

Predictive and prognostic effect of inflammatory lymphadenopathies in renal cell carcinoma.

PURPOSE: A significant proportion of patients affected by renal cell carcinoma (RCC) shows a suspicious lymph node involvement (LNI) at preoperative imaging. We sought to evaluate the effect of lymphadenopathies (cN1) on survival in surgical RCC patients with no evidence of LNI at final pathology (pN0). METHODS: 719 patients underwent either radical or partial nephrectomy and lymph node dissection at a single tertiary care referral centre between 1987 and 2015. All patients had pathologically no LNI (pN0). Outcomes of the study were cancer-specific mortality (CSM) and other-cause mortality. Multivariable competing-risks regression models assessed the impact of inflammatory lymphadenopathies (cN1pN0) on mortality rates, after adjustment for clinical and pathological confounders. RESULTS: 114 (16%) and 605 (84%) patients (16%) were cN1pN0 and cN0pN0, respectively. cN1pN0 patients were more frequently diagnosed with larger tumours (8.4 vs. 6.5 cm), higher pathological tumour stage (pT3-4 in 71 vs. 36%), higher Fuhrman grade (G3-G4 in 64 vs. 31%), more frequently with necrosis (75 vs. 44%), and distant metastases (33 vs. 10%) (all p < 0.0001). At univariable analysis, inflammatory lymphadenopathies resulted associated with worse CSM (HR 2.45; p < 0.0001). However, at multivariable analysis, inflammatory lymphadenopathies were not an independent predictor of CSM (HR 0.81; p = 0.4). The presence of metastases at diagnosis was the most important factor affecting CSM (HR 6.54; p < 0.0001). This study is limited by its retrospective nature. CONCLUSIONS: In RCC patients, inflammatory lymphadenopathies (cN1pN0) are associated with unfavourable clinical and pathological characteristics. However, the presence of inflammatory lymphadenopathies does not affect RCC-specific mortality.

On-clamp versus off-clamp partial nephrectomy: Propensity score-matched comparison of long-term functional outcomes.

OBJECTIVES: To compare long-term functional outcomes of off-clamp or on-clamp partial nephrectomy patients of two high-volume centers with cT1-2/N0 M0 renal tumors and baseline estimated glomerular filtration rate >60 mL/min. METHODS: A 3:1 propensity score-matched analysis was used to select two homogeneous cohorts to compare off-clamp versus on-clamp partial nephrectomy. Joinpoint regression analysis was used to compare the 2-8-year probabilities of estimated glomerular filtration rate modifications in both selected cohorts. The Kaplan-Meier method assessed the risk of developing a stage ≥3b chronic kidney disease during follow up. Multivariable analyses aimed to identify predictors of renal function deterioration. Perioperative complications and oncological outcomes were compared. RESULTS: Overall, 1073 patients were included (588 on-clamp and 485 off-clamp). After applying the propensity score-matched analysis, the two cohorts of 157 on-clamp and 472 off-clamp patients did not differ for all covariates, except for warm ischemia time and last estimated glomerular filtration rate. At joinpoint analysis, the off-clamp group showed higher probabilities of maintaining an unmodified estimated glomerular filtration rate (P = 0.02). The probability of developing a stage ≥3b chronic kidney disease was significantly higher (P < 0.001) in the on-clamp cohort. At multivariable analysis, estimated glomerular filtration rate at discharge and off-clamp approach were independent predictors of improved functional outcomes. Perioperative complications were comparable among the two cohorts (P = 0.67). There were not any statistically significant differences in terms of cancer-specific survival (P = 0.26) and overall survival (P = 0.18). CONCLUSIONS: Off-clamp partial nephrectomy seems to offer a higher probability of maintaining 100% estimated glomerular filtration rate after surgery. In our cohort, patients undergoing on-clamp partial nephrectomy presented a 7.3-fold increased risk of developing a severe chronic kidney disease during follow up.

Risk Based Surveillance after Surgical Treatment of Renal Cell Carcinoma.

PURPOSE: We assessed the accuracy of the UISS (UCLA Integrated Staging System) to predict the postoperative recurrence of renal cell carcinoma. We also evaluated whether including patient age and tumor histology would improve clinical decision making. MATERIALS AND METHODS: We analyzed the records of 1,630 patients treated with nephrectomy at a single academic center. The accuracy of the UISS model to predict early (12 months or less) and late (more than 60 months) recurrence after surgery was compared with a new model including patient age and disease histology. RESULTS: The new model and the UISS model showed high accuracy to predict early recurrence after surgery (AUC 0.84, 95% CI 0.81-0.88 and 0.83, 95% CI 0.80-0.87, respectively). In patients diagnosed with low risk tumor types (eg papillary type 1 and chromophobe lesions) the average risk of early recurrence significantly decreased in each UISS risk category when tumor histology was added to the predictive model (low risk 1.6% vs 0.6%, intermediate risk 5.5% vs 1.9% and high risk 45% vs 22%). Kaplan-Meier analysis showed no difference in the risk of late recurrence among the UISS risk categories. CONCLUSIONS: The UISS model should be applied to tailor the early followup protocol after nephrectomy. Patients with low risk histology deserve less stringent followup regardless of the UISS risk category. Our results do not support a risk stratification model to design a surveillance protocol after 5 years postoperatively.

Radical Nephrectomy with or without Lymph Node Dissection for High Risk Nonmetastatic Renal Cell Carcinoma: A Multi-Institutional Analysis.

PURPOSE: Lymph node dissection may benefit patients at increased risk for lymph node metastases from renal cell carcinoma. Therefore, we evaluated the association of lymph node dissection with survival in patients at high risk undergoing radical nephrectomy for renal cell carcinoma. MATERIALS AND METHODS: We identified 2,722 patients with M0 renal cell carcinoma who underwent radical nephrectomy with or without lymph node dissection at 2 international centers from 1990 to 2010. The associations of lymph node dissection with the development of distant metastases, and cancer specific and all cause mortality were evaluated using propensity score techniques and traditional multivariable Cox regression. Subset analyses were done to examine patients at increased risk of lymph node metastases. RESULTS: Overall 171 patients (6.3%) had pN1 disease. Median followup was 9.6 years. Clinicopathological features were well balanced after propensity score adjustment. Lymph node dissection was not significantly associated with a reduced risk of distant metastases, or cancer specific or all cause mortality in the overall cohort, among patients with preoperative radiographic lymphadenopathy (cN1), or across an increasing probability of pN1 disease from 0.10 or greater to 0.50 or greater. Neither extended lymph node dissection nor the extent of lymph node dissection was associated with improved oncologic outcomes. CONCLUSIONS: The current analysis of a large, international cohort indicates that lymph node dissection is not associated with improved oncologic outcomes among patients at high risk who undergo radical nephrectomy for M0 renal cell carcinoma. This includes patients with radiographic lymphadenopathy (cN1) and across increasing probability thresholds of pN1 disease.

When to perform preoperative chest computed tomography for renal cancer staging.

OBJECTIVES: To provide objective criteria for preoperative staging chest computed tomography (CT) in patients diagnosed with renal cell carcinoma (RCC) because, in the absence of established indications, the decision for preoperative chest CT remains subjective. PATIENTS AND METHODS: A total of 1 946 patients undergoing surgical treatment of RCC, whose data were collected in a prospective institutional database, were assessed. The outcome of the study was presence of pulmonary metastases at staging chest CT. A multivariable logistic regression model predicting positive chest CT was fitted. Predictors consisted of preoperative clinical tumour (cT) and nodal (cN) stage, presence of systemic symptoms and platelet count (PLT)/haemoglobin (Hb) ratio. RESULTS: The rate of positive chest CT was 6% (n = 119). At multivariable logistic regression, ≥cT1b, cN1, systemic symptoms and Hb/PLT ratio were all associated with higher risk of positive chest CT (all P < 0.001). After 2000-sample bootstrap validation, the concordance index was found to be 0.88. At decision-curve analysis, the net benefit of the proposed strategy was superior to the select-all and select-none strategies. Accordingly, if chest CT had been performed when the risk of a positive result was >1%, a negative chest CT would have been spared in 37% of the population and a positive chest CT would have been missed in 0.2% of the population only. CONCLUSIONS: The proposed strategy estimates the risk of positive chest CT at RCC staging with optimum accuracy and the results were statistically and clinically relevant. The findings of the present study support a recommendation for chest CT in patients with ≥cT1b, cN1, systemic symptoms or anaemia and thrombocythemia. Conversely, in patients with cT1a, cN0 without systemic symptoms, anaemia and thrombocythemia, chest CT could be omitted.

MicroRNA 193b-3p as a predictive biomarker of chronic kidney disease in patients undergoing radical nephrectomy for renal cell carcinoma.

BACKGROUND: A significant proportion of patients undergoing radical nephrectomy (RN) for clear-cell renal cell carcinoma (RCC) develop chronic kidney disease (CKD) within a few years following surgery. Chronic kidney disease has important health, social and economic impact and no predictive biomarkers are currently available. MicroRNAs (miRs) are small non-coding RNAs implicated in several pathological processes. METHODS: Primary objective of our study was to define miRs whose deregulation is predictive of CKD in patients treated with RN. Ribonucleic acid from formalin-fixed paraffin embedded renal parenchyma (cortex and medulla isolated separately) situated >3 cm from the matching RCC was tested for miR expression using nCounter NanoString technology in 71 consecutive patients treated with RN for RCC. Validation was performed by RT-PCR and in situ hybridisation. End point was post-RN CKD measured 12 months post-operatively. Multivariable logistic regression and decision curve analysis were used to test the statistical and clinical impact of predictors of CKD. RESULTS: The overexpression of miR-193b-3p was associated with high risk of developing CKD in patients undergoing RN for RCC and emerged as an independent predictor of CKD. The addition of miR-193b-3p to a predictive model based on clinical variables (including sex and estimated glomerular filtration rate) increased the sensitivity of the predictive model from 81 to 88%. In situ hybridisation showed that miR-193b-3p overexpression was associated with tubule-interstitial inflammation and fibrosis in patients with no clinical or biochemical evidence of pre-RN nephropathy. CONCLUSIONS: miR-193b-3p might represent a useful biomarker to tailor and implement surveillance strategies for patients at high risk of developing CKD following RN.

Elective Nephron Sparing Surgery Decreases Other Cause Mortality Relative to Radical Nephrectomy Only in Specific Subgroups of Patients with Renal Cell Carcinoma.

PURPOSE: There is no consensus regarding a protective effect on mortality due to a cause other than cancer in patients treated with elective nephron sparing surgery relative to their radical nephrectomy counterparts. We test whether the protective effect of nephron sparing surgery relative to radical nephrectomy is universal or present in specific subgroups of patients. MATERIALS AND METHODS: A collaborative database of 5 institutions was queried to evaluate 1,783 patients without chronic kidney disease diagnosed with a clinical T1 renal mass that was treated with nephron sparing surgery or radical nephrectomy. Multivariable Cox regression analysis was done to assess the impact of surgery type (nephron sparing surgery vs radical nephrectomy) on other cause mortality after adjustment for patient and cancer characteristics. Interaction terms were used to test the hypothesis that the impact of surgery type varies according to specific subcohorts of patients. RESULTS: Ten-year other cause mortality-free survival rates were 90% and 88% after nephron sparing surgery and radical nephrectomy, respectively. In the overall population radical nephrectomy was not associated with an increased risk of other cause mortality on multivariable analysis compared to nephron sparing surgery (HR 0.91, 95% CI 0.6-1.38, p = 0.6). However, radical nephrectomy increased the risk of other cause mortality according to the increasing baseline Charlson comorbidity index (interaction test p = 0.0008). For example, in a patient with a Charlson comorbidity index of 4 the probability of 10-year other cause mortality-free survival was 86% after nephron sparing surgery and 60% after radical nephrectomy. CONCLUSIONS: Elective nephron sparing surgery does not improve other cause survival relative to radical nephrectomy consistently in all patients with kidney cancer. Patients who are more ill with relevant comorbidities are those who benefit the most from nephron sparing surgery in terms of other cause mortality.

Lymphadenopathies in patients with renal cell carcinoma: clinical and pathological predictors of pathologically confirmed lymph node invasion.

INTRODUCTION: In renal cell carcinoma (RCC), lymph node status at preoperative imaging is affected by a non-negligible false-positive rate. We aimed to investigate which factors are related to a concordance between clinical suspicion and pathological confirmation of lymph node invasion (LNI). METHODS: At a single tertiary care institution, 2954 RCC patients underwent either partial or radical nephrectomy. For the aim of the study, only clinically positive lymph node cases were included (cN1). Statistical analyses assessed the concordance between preoperative and pathological nodal status. RESULTS: Preoperative axial CT scans revealed 424 (14.4 %) patients showing at least one enlarged lymph node suspected for LNI (cN1). All lymphadenopathies were removed at surgery, and LNI was pathologically confirmed (pN1) in 122 patients (28.8 %). When focusing the analyses on clinical characteristics (variables known before surgery), metastases at diagnosis [OR 3.0 (95 %1.9-4.8), p < 0.001] and tumor size [OR 1.1 (95 % 1.1-1.2), p < 0.001] were the two most informative predictors of concordance between clinical and pathological nodal status. Concordance was also more likely in patients with papillary type II tumors (55.6 %) relative to papillary type I (38.1 %), clear cell (27.7 %) and chromophobe (8.3 %) tumors. At multivariable analyses, none of the considered blood markers resulted to be independently associated with LNI. CONCLUSIONS: Roughly 70 % of patients showing a suspected lymph node preoperatively do not show LNI at the final pathological report. Among patients with clinically positive nodes, clinical tumor size and metastases at diagnosis represent the most informative and independent predictors of confirmed LNI at final pathology.