Delphi consensus on stereotactic ablative radiotherapy for oligometastatic and oligoprogressive renal cell carcinoma-a European Society for Radiotherapy and Oncology study endorsed by the European Association of Urology.

The purpose of this European Society for Radiotherapy and Oncology (ESTRO) project, endorsed by the European Association of Urology, is to explore expert opinion on the management of patients with oligometastatic and oligoprogressive renal cell carcinoma by means of stereotactic ablative radiotherapy (SABR) on extracranial metastases, with the aim of developing consensus recommendations for patient selection, treatment doses, and concurrent systemic therapy. A questionnaire on SABR in oligometastatic renal cell carcinoma was prepared by a core group and reviewed by a panel of ten prominent experts in the field. The Delphi consensus methodology was applied, sending three rounds of questionnaires to clinicians identified as key opinion leaders in the field. At the end of the third round, participants were able to find consensus on eight of the 37 questions. Specifically, panellists agreed to apply no restrictions regarding age (25 [100%) of 25) and primary renal cell carcinoma histology (23 [92%] of 25) for SABR candidates, on the upper threshold of three lesions to offer ablative treatment in patients with oligoprogression, and on the concomitant administration of immune checkpoint inhibitor. SABR was indicated as the treatment modality of choice for renal cell carcinoma bone oligometatasis (20 [80%] of 25) and for adrenal oligometastases 22 (88%). No consensus or major agreement was reached regarding the appropriate schedule, but the majority of the poll (54%-58%) retained the every-other-day schedule as the optimal choice for all the investigated sites. The current ESTRO Delphi consensus might provide useful direction for the application of SABR in oligometastatic renal cell carcinoma and highlight the key areas of ongoing debate, perhaps directing future research efforts to close knowledge gaps.

Pulmonary lesion after surgery for renal cancer: progression or new primary?

PURPOSE: To investigate clinical and radiological differences between kidney metastases to the lung (RCCM +) and metachronous lung cancer (LC) detected during follow-up in patients surgically treated for Renal Cell Carcinoma (RCC). METHODS: cM0 surgically-treated RCC who harbored a pulmonary mass during follow-up were retrospectively scrutinized. Univariate logistic regression assessed predictive features for differentiating between LC and RCCM + . Multivariable analyses (MVA) were fitted to predict factors that could influence time between detection and histological diagnosis of the pulmonary mass, and how this interval could impact on survivals. RESULTS: 87% had RCCM + and 13% had LC. LC were more likely to have smoking history (75% vs. 29%, p < 0.001) and less aggressive RCC features (cT1-2: 94% vs. 65%, p = 0.01; pT1-2: 88% vs. 41%, p = 0.02; G1-2: 88% vs. 37%, p < 0.001). The median interval between RCC surgery and lung mass detection was longer between LC (55 months [32.8-107.2] vs. 20 months [9.0-45.0], p = 0.01). RCCM + had a higher likelihood of multiple (3[1-4] vs. 1[1-1], p < 0.001) and bilateral (51% vs. 6%, p = 0.002) pulmonary nodules, whereas LC usually presented with a solitary pulmonary nodule, less than 20 mm. Univariate analyses revealed that smoking history (OR:0.79; 95% CI 0.70-0.89; p < 0.001) and interval between RCC surgery and lung mass detection (OR:0.99; 95% CI 0.97-1.00; p = 0.002) predicted a higher risk of LC. Conversely, size (OR:1.02; 95% CI 1.01-1.04; p = 0.003), clinical stage (OR:1.14; 95% CI 1.06-1.23; p < 0.001), pathological stage (OR:1.14; 95% CI 1.07-1.22; p < 0.001), grade (OR:1.15; 95% CI 1.07-1.23; p < 0.001), presence of necrosis (OR:1.17; 95% CI 1.04-1.32; p = 0.01), and lymphovascular invasion (OR:1.18; 95% CI 1.01-1.37; p = 0.03) of primary RCC predicted a higher risk of RCCM + . Furthermore, number (OR:1.08; 95% CI 1.04-1.12; p < 0.001) and bilaterality (OR:1.23; 95% CI 1.09-1.38; p < 0.001) of pulmonary lesions predicted a higher risk of RCCM + . Survival analysis showed a median second PFS of 10.9 years (95% CI 3.3-not reached) for LC and a 3.8 years (95% CI 3.2-8.4) for RCCM + . The median OS time was 6.5 years (95% CI 4.4-not reached) for LC and 6 years (95% CI 4.3-11.6) for RCCM + . CONCLUSIONS: Smoking history, primary grade and stage of RCC, interval between RCC surgery and lung mass detection, and number of pulmonary lesions appear to be the most valuable predictors for differentiating new primary lung cancer from RCC progression.

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.

Cancer-specific Mortality After Cryoablation vs Heat-based Thermal Ablation in T1a Renal Cell Carcinoma.

PURPOSE: Guidelines suggest less favorable cancer control outcomes for local tumor destruction in T1a renal cell carcinoma patients with tumor size 3.1-4 cm. We compared cancer-specific mortality between cryoablation vs heat-based thermal ablation in patients with tumor size 3.1-4 cm, as well as in patients with tumor size ≤3 cm. MATERIALS AND METHODS: Within the Surveillance, Epidemiology, and End Results database (2004-2018), we identified patients with clinical T1a stage renal cell carcinoma treated with cryoablation or heat-based thermal ablation. After up to 2:1 ratio propensity score matching between patients treated with cryoablation vs heat-based thermal ablation, we addressed cancer-specific mortality relying on competing risks regression models, adjusted for other-cause mortality and other covariates (age, tumor size, tumor grade, and histological subtype). RESULTS: Of 1,468 assessable patients with tumor size 3.1-4 cm, 1,080 vs 388 were treated with cryoablation vs heat-based thermal ablation, respectively. After up to 2:1 propensity score matching that resulted in 757 cryoablations vs 388 heat-based thermal ablations, in multivariable competing risks regression models, heat-based thermal ablation was associated with higher cancer-specific mortality (HR:2.02, P < .001), relative to cryoablation. Of 4,468 assessable patients with tumor size ≤3 cm, 3,354 vs 1,114 were treated with cryoablation vs heat-based thermal ablation, respectively. After up to 2:1 propensity score matching that resulted in 2,217 cryoablations vs 1,114 heat-based thermal ablations, in multivariable competing risks regression models, heat-based thermal ablation was not associated with higher cancer-specific mortality (HR:1.13, P = .5) relative to cryoablation. CONCLUSIONS: Our findings corroborated that in cT1a patients with tumor size 3.1-4 cm, cancer-specific mortality is twofold higher after heat-based thermal ablation vs cryoablation. Conversely, in patients with tumor size ≤3 cm either ablation technique is equally valid. These findings should be considered at clinical decision making and informed consent.

Diabetes, Obesity, and Pathological Upstaging in Renal Cell Carcinoma: Results From a Large Multi-institutional Consortium.

PURPOSE: We sought to determine whether clinical risk factors and morphometric features on preoperative imaging can be utilized to identify those patients with cT1 tumors who are at higher risk of upstaging (pT3a). MATERIALS AND METHODS: We performed a retrospective international case-control study of consecutive patients treated surgically with radical or partial nephrectomy for nonmetastatic renal cell carcinoma (cT1 N0) conducted between January 2010 and December 2018. Multivariable logistic regression models were used to study associations of preoperative risk factors on pT3a pathological upstaging among all patients, as well as subsets with those with preoperative tumors ≤4 cm, renal nephrometry scores, tumors ≤4 cm with nephrometry scores, and clear cell histology. We also examined association with pT3a subsets (renal vein, sinus fat, perinephric fat). RESULTS: Among the 4,092 partial nephrectomy and 2,056 radical nephrectomy patients, pathological upstaging occurred in 4.9% and 23.3%, respectively. Among each group independent factors associated with pT3a upstaging were increasing preoperative tumor size, increasing age, and the presence of diabetes. Specifically, among partial nephrectomy subjects diabetes (OR=1.65; 95% CI 1.17, 2.29), male sex (OR=1.62; 95% CI 1.14, 2.33), and increasing BMI (OR=1.03; 95% CI 1.00, 1.05 per 1 unit BMI) were statistically associated with upstaging. Subset analyses identified hilar tumors as more likely to be upstaged (partial nephrectomy OR=1.91; 95% CI 1.12, 3.16; radical nephrectomy OR=2.16; 95% CI 1.44, 3.25). CONCLUSIONS: Diabetes and higher BMI were associated with pathological upstaging, as were preoperative tumor size, increased age, and male sex. Similarly, hilar tumors were frequently upstaged.

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.

Partial or radical nephrectomy for complex renal mass: a comparative analysis of oncological outcomes and complications from the ROSULA (Robotic Surgery for Large Renal Mass) Collaborative Group.

PURPOSE: To compare outcomes of robotic-assisted partial nephrectomy (RAPN) and minimally invasive radical nephrectomy (MIS-RN) for complex renal masses (CRM). METHODS: We conducted a retrospective multicenter analysis of CRM patients who underwent MIS-RN and RAPN. CRM was defined as RENAL score 10-12. Primary outcome was overall survival (OS). Secondary outcomes were cancer-specific survival (CSS), recurrence, and complications. Multivariable analysis (MVA) and Kaplan-Meier Analysis (KMA) were used to analyze functional and survival outcomes for RN vs. PN by pathological stage. RESULTS: 926 patients were analyzed (MIS-RN = 437/RAPN = 489; median follow-up 24.0 months). MVA demonstrated lack of transfusion (HR = 1.63, p = 0.005), low-grade (HR = 1.18, p = 0.018) and smaller tumor size (HR = 1.05, p < 0.001) were associated with OS. Younger age (HR = 1.01, p = 0.017), high-grade (HR = 1.18, p = 0.017), smaller tumor size (HR = 1.05, p < 0.001), and lack of transfusion (HR = 1.39, p = 0.038) were associated with CSS. Increasing tumor size (HR = 1.18, p < 0.001), high-grade (HR = 3.21, p < 0.001), and increasing age (HR = 1.02, p = 0.009) were independent risk factors for recurrence. Type of surgery was not associated with major complications (p = 0.094). For KMA of MIS-RN vs. RAPN for pT1, pT2 and pT3, 5-year OS was 85% vs. 88% (p = 0.078); 82% vs. 80% (p = 0.442) and 84% vs. 83% (p = 0.863), respectively. 5-year CSS was 98% for both procedures (p = 0.473); 94% vs. 92% (p = 0.735) and 91% vs. 90% (p = 0.581). 5-year non-CSS was 87% vs. 93% (p = 0.107); 87% for pT2 (p = 0.485) and 92% for pT3 for both procedures (p = 0.403). CONCLUSION: RAPN in CRM is not associated with increased risk of complications or worsened oncological outcomes when compared to MIS-RN and may be preferred when clinically indicated.

External validation of yonsei nomogram predicting chronic kidney disease development after partial nephrectomy: An international, multicenter study.

OBJECTIVE: To externally validate Yonsei nomogram. METHODS: From 2000 through 2018, 3526 consecutive patients underwent on-clamp PN for cT1 renal masses at 23 centers were included. All patients had two kidneys, preoperative eGFR ≥60 ml/min/1.73 m2, and a minimum follow-up of 12 months. New-onset CKD was defined as upgrading from CKD stage I or II into CKD stage ≥III. We obtained the CKD-free progression probabilities at 1, 3, 5, and 10 years for all patients by applying the nomogram found at https://eservices.ksmc.med.sa/ckd/. Thereafter, external validation of Yonsei nomogram for estimating new-onset CKD stage ≥III was assessed by calibration and discrimination analysis. RESULTS AND LIMITATION: Median values of patients' age, tumor size, eGFR and follow-up period were 47 years (IQR: 47-62), 3.3 cm (IQR: 2.5-4.2), 90.5 ml/min/1.73 m2 (IQR: 82.8-98), and 47 months (IQR: 27-65), respectively. A total of 683 patients (19.4%) developed new-onset CKD. The 5-year CKD-free progression rate was 77.9%. Yonsei nomogram demonstrated an AUC of 0.69, 0.72, 0.77, and 0.78 for the prediction of CKD stage ≥III at 1, 3, 5, and 10 years, respectively. The calibration plots at 1, 3, 5, and 10 years showed that the model was well calibrated with calibration slope values of 0.77, 0.83, 0.76, and 0.75, respectively. Retrospective database collection is a limitation of our study. CONCLUSIONS: The largest external validation of Yonsei nomogram showed good calibration properties. The nomogram can provide an accurate estimate of the individual risk of CKD-free progression on long-term follow-up.

External validation of the Palacios' equation: a simple and accurate tool to estimate the new baseline renal function after renal cancer surgery.

PURPOSE: To externally validate the Palacios' equation estimating the new baseline glomerular filtration rate (NB-GFR) after partial or radical-nephrectomy (PN, RN) for Renal cancer carcinoma (RCC). MATERIALS AND METHODS: Our research group recently published two studies that investigated the association between renal function and cancer-specific survival in RCC. The first one included 3457 patients undergone RN or PN for a cT1-2 RCC coming from five high-volume centers; the second one considered 1767 patients undergone RN or PN for a cT1-4 RCC in a single high-volume center. From such datasets, available complete patients' data were used to calculate the predicted NB-GFR through the Palacios' equation: predicted NB-GFR = 35.03 + 0.65 ∙ preoperative GFR - 18.19 ∙ (if radical nephrectomy) - 0.25 ∙ age + 2.83 ∙ (if tumor size > 7 cm) - 2.09 ∙ (if diabetes). The observed NB-GFR was calculated by the CKD-EPI equation on serum creatinine at 3-12 months after surgery. Concordance between observed and predicted NB-GFR was evaluated by Lin's concordance correlation coefficient and Bland-Altman analysis. RESULTS: 2419 patients were included (1210, cohort #1; 1219, cohort #2). The median observed NB-GFR value in cohorts #1 and #2 was 73.0 ml/min/1.73 m2 (IQR 56.1-90.1) and 64.2 ml/min/1.73 m2 (IQR 49.6-83); the median predicted NB-GFR was 71.1 ml/min/1.73 m2 (IQR 58-81.5) and 62.6 ml/min/1.73m2 (IQR 47.9-75.9). The concordance line showed a slope of 0.80 and 0.86, and an intercept at 11.02 and 5.41 ml/min/1.73 m2 in the cohort#1 and #2, respectively. The Palacio's equation moderately over-estimated and under-estimated NB-GFR, for values below and above the cut-off of 50 ml/min/1.73 m2 and 35 ml/min/1.73m2 in cohort#1 and #2. The Lin's concordance correlation coefficient was 0.79 (95% CI 0.77-0.81) and 0.83 (95% CI 0.82-0.85). CONCLUSIONS: We confirm the predictive performances of Palacios' equation, supporting its utilization in clinical practice.

Radical nephroureterectomy for UTUC conferred survival benefits irrespective of age and comorbidities.

PURPOSE: We investigated the effects of age, American Society of Anesthesiologists Physical Status Classification (ASA) grading and Charlson Comorbidity Index (CCI) on the survival outcomes of upper tract urothelial carcinoma (UTUC). METHODS: The CROES-UTUC registry was an international, multicenter study on patients with UTUC. Primary outcomes were overall survival (OS) and disease-free survival (DFS). Kaplan-Meier and multivariate Cox regression analyses were performed by stratifying patients according to their age (≤ 70 and > 70 years old) and ASA grade (I-II and III-V)/CCI (0-1 and ≥ 2). RESULTS: A total of 2352 patients were included in this study. Patients aged ≤ 70 years with ASA grading of I-II (p = 0.002), and patients aged ≤ 70 years with a CCI of 0-1 (p = 0.002) had the best OS. Upon multivariate analysis, both in patients aged ≤ 70 and > 70 years, ASA grading and CCI were not significantly associated with OS. Patients aged ≤ 70 years with ASA grading of III-IV (p = 0.024) had the best DFS. When stratified according to age and CCI, no significant difference in DFS was noted. Upon multivariate analysis, radical nephroureterectomy (RNU) was significantly associated with better DFS in patients aged ≤ 70 and > 70 years; CCI of ≥ 3 was significantly associated with worse DFS in patients ≤ 70 years; ASA grading was not associated with DFS in patients aged ≤ 70 and > 70 years. CONCLUSIONS: A high ASA grading and CCI should not be considered contraindications for RNU. RNU should be considered even in elderly patients when it is deemed feasible and achievable after a geriatric assessment.

Pancreatic metastases after surgery for renal cell carcinoma: survival and pathways of progression.

PURPOSE: Metastatic ccRCC has peculiar tropism in the pancreas. We describe the characteristics and pathways of progression of patients with PM in a large multi-institutional consortium and compare them to patients with metastases from ccRCC at other sites. METHODS: Detailed clinical and histopathological data were collected. To account for differences in baseline characteristics between the two groups, IPTW was used to compare the two groups in terms of PFS and OS. RESULTS: Of the 182 patients, 33 (18%) had pancreatic, 94 (52%) pulmonary, 30 (16%) bone, 13 (7%) hepatic, and 12 (7%) brain metastases. Patients with PM had less aggressive ccRCC at baseline compared to those with progression at other sites in terms of tumour stage and grade. Median time from ccRCC surgery to PM was 8 (95%CI 5-10) vs. 1 year (95%CI 1-2) for progression to other sites (p < 0.001). Median IPTW-weighted time to second progression was 4.3 years (95%CI 2.4-not reached) for patients with PM vs 1.1 year (95%CI 0.8-2.3) for those with progression in other sites (p < 0.001). The most frequent second progression sites were pancreas (24%) and liver (15%) in patients with PM, while progression to the pancreas was rare (4%) in those with a different first progression site. Surgery alone (55%) or in combination with medical therapy (30%) was more frequent in the PM group than in other sites (p < 0.001). Median IPTW-OS time was longer for patients with PM [8.8 years (95%CI 6.5-not reached)] compared to those with first progression in other sites [2.8 years (95%CI 1.9-4.3), p < 0.001]. CONCLUSION: Pancreatic tropism is typical of ccRCC tumours with more indolent behaviour than those progressing to other sites. A long follow-up period is necessary to distinguish PM from ccRCC.

Contemporary vs historical survival rates in metastatic clear cell renal carcinoma according to race/ethnicity.

PURPOSE: Systemic therapies (ST) improved contemporary survival rates, relative to historical in clear cell metastatic renal carcinoma (ccmRCC) patients. The magnitude of this improvement is unknown according to race/ethnicity. METHODS: Within the SEER registry (2000-2017), ccmRCC patients were stratified according to race/ethnicity (Caucasian, Hispanic, African American, Asian) and historical (2000-2009) vs contemporary (2010-2017) years of diagnosis. Competing risks regression (CRR) with adjustment for other-cause mortality and Poisson smoothed cumulative incidence plots addressed cancer-specific mortality (CSM). RESULTS: Of 10,141 mRCC patients, 4316 (43%) vs 5825 (57%) were diagnosed in historical vs contemporary era. Of 4316 historical patients, 3203 (74%) vs 593 (14%) vs 293 (7%) vs 227 (5%) were Caucasian, Hispanic, African American and Asian. Of 5825 contemporary patients, 4124 (71%) vs 977 (17%) vs 362 (6%) vs 362 (6%) were Caucasian, Hispanic, African American and Asian. Between 2000 and 2017, ST rates ranged from 12 to 57% in Caucasians, 2 to 57% in Hispanics, 33 to 50% in African Americans, 17 to 70% in Asians and universally increased toward a plateau in 2010. In Caucasians, CSM decreased from 80 to 74% vs 79 to 74% in Hispanics vs 79 to 77% in African Americans, but not in Asians (67-73%). Nonetheless, these rates translated into independent predictor status of contemporary years of diagnosis in all race/ethnicity groups: CSM hazard ratios of 0.75, 0.75, 0.73 and 0.80 in, respectively, Caucasian, Hispanic, African American and Asian. CONCLUSIONS: In all race/ethnicity groups, contemporary ST rates increased and improved CSM rates have also been recorded.

Perioperative outcomes following robot-assisted partial nephrectomy in elderly patients.

OBJECTIVE: To compare perioperative outcomes following robot-assisted partial nephrectomy (RAPN) in patients with age ≥ 70 years to age < 70 years. METHODS: Using Vattikuti Collective quality initiative (VCQI) database for RAPN we compared perioperative outcomes following RAPN between the two age groups. Primary outcome of the study was to compare trifecta outcomes between the two groups. Propensity matching using nearest neighbourhood method was performed with trifecta as primary outcome for sex, body mass index (BMI), solitary kidney, tumor size and Renal nephrometery score (RNS). RESULTS: Group A (age ≥ 70 years) included 461 patients whereas group B included 1932 patients. Before matching the two groups were statistically different for RNS and solitary kidney rates. After propensity matching, the two groups were comparable for baselines characteristics such as BMI, tumor size, clinical symptoms, tumor side, face of tumor, solitary kidney and tumor complexity. Among the perioperative outcome parameters there was no difference between two groups for operative time, blood loss, intraoperative transfusion, intraoperative complications, need for radical nephrectomy, positive margins and trifecta rates. Warm ischemia time was significantly longer in the younger age group (18.1 min vs. 16.3 min, p = 0.003). Perioperative complications were significantly higher in the older age group (11.8% vs. 7.7%, p = 0.041). However, there was no difference between the two groups for major complications. CONCLUSION: RAPN in well-selected elderly patients is associated with comparable trifecta outcomes with acceptable perioperative morbidity.

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.

Comparison of perioperative outcomes following transperitoneal versus retroperitoneal robot-assisted partial nephrectomy: a propensity-matched analysis of VCQI database.

OBJECTIVE: To compare perioperative outcomes following retroperitoneal robot-assisted partial nephrectomy (RPRAPN) and transperitoneal robot-assisted partial nephrectomy (TPRAPN). METHODS: With this Vattikuti Collective Quality Initiative (VCQI) database, study propensity scores were calculated according to the surgical access (TPRAPN and RPRAPN) for the following independent variables, i.e., age, sex, side of the surgery, RENAL nephrometry scores (RNS), estimated glomerular filtration rate (eGFR) and serum creatinine. The study's primary outcome was the comparison of trifecta between the two groups. RESULTS: In this study, 309 patients who underwent RPRAPN were matched with 309 patients who underwent TPRAPN. The two groups matched well for age, sex, tumor side, polar location of the tumor, RNS, preoperative creatinine and eGFR. Operative time and warm ischemia time were significantly shorter with RPRAPN. Intraoperative blood loss and need for blood transfusion were lower with RPRAPN. There was a significantly higher number of intraoperative complications with RPRAPN. However, there was no difference in the two groups for postoperative complications. Trifecta outcomes were better with RPRAPN (70.2% vs. 53%, p < 0.0001) compared to TPRAPN. We noted no significant change in overall results when controlled for tumor location (anteriorly or posteriorly). The surgical approach, tumor size and RNS were identified as independent predictors of trifecta on multivariate analysis. CONCLUSION: RPRAPN is associated with superior perioperative outcomes in well-selected patients compared to TPRAPN. However, the data for the retroperitoneal approach were contributed by a few centers with greater experience with this technique, thus limiting the generalizability of the results of this study.

Von Hippel-Lindau disease-associated renal cell carcinoma: a call to action.

PURPOSE OF REVIEW: While the molecular and genetic bases of Von Hippel-Lindau (VHL) disease have been extensively investigated, limited evidence is available to guide diagnosis, local or systemic therapy, and follow-up. The aim of the current review is to summarize the ongoing trials both in preclinical and clinical setting regarding VHL disease management. RECENT FINDINGS: Although genotype/phenotype correlations have been described, there is considerable inter and intra-familiar heterogeneity in VHL disease. Genetic anticipation has been reported in VHL disease. From a clinical point of view, expert-opinion-based protocols suggest testing those patients with any blood relative of an individual diagnosed with VHL disease, those with at least 1 or more suggestive neoplasms or patients presenting with clear cell renal cell carcinoma (ccRCC) diagnosed at a less than 40 years old, and/or multiple ccRCC. Clinical research is focused on safety and efficacy of systemic agents for patients with VHL-related ccRCC, with the aim to possibly preserve kidney function and improve patient survival. SUMMARY: To date, preclinical and clinical research on the topic is scarce and clinical guidelines are not supported by strong validation studies.

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.

Prediction of significant renal function decline after open, laparoscopic, and robotic partial nephrectomy: External validation of the Martini's nomogram on the RECORD2 project cohort.

OBJECTIVES: Martini et al. developed a nomogram to predict significant (>25%) renal function loss after robot-assisted partial nephrectomy and identified four risk categories. We aimed to externally validate Martini's nomogram on a large, national, multi-institutional data set including open, laparoscopic, and robot-assisted partial nephrectomy. METHODS: Data of 2584 patients treated with partial nephrectomy for renal masses at 26 urological Italian centers (RECORD2 project) were collected. Renal function was assessed at baseline, on third postoperative day, and then at 6, 12, 24, and 48 months postoperatively. Multivariable models accounting for variables included in the Martini's nomogram were applied to each approach predicting renal function loss at all the specific timeframes. RESULTS: Multivariable models showed high area under the curve for robot-assisted partial nephrectomy at 6- and 12-month (87.3% and 83.6%) and for laparoscopic partial nephrectomy (83.2% and 75.4%), whereas area under the curves were lower in open partial nephrectomy (78.4% and 75.2%). The predictive ability of the model decreased in all the surgical approaches at 48 months from surgery. Each Martini risk group showed an increasing percentage of patients developing a significant renal function reduction in the open, laparoscopic and robot-assisted partial nephrectomy group, as well as an increased probability to develop a significant estimated glomerular filtration rate reduction in the considered time cutoffs, although the predictive ability of the classes was <70% at 48 months of follow-up. CONCLUSIONS: Martini's nomogram is a valid tool for predicting the decline in renal function at 6 and 12 months after robot-assisted partial nephrectomy and laparoscopic partial nephrectomy, whereas it showed a lower performance at longer follow-up and in patients treated with open approach at all these time cutoffs.

Perioperative outcomes following robot-assisted partial nephrectomy for complex renal masses: A Vattikuti Collective Quality Initiative database study.

Introduction: Outcomes of robot-assisted partial nephrectomy (RAPN) depend on tumor complexity, surgeon experience and patient profile among other variables. We aimed to study the perioperative outcomes of RAPN for patients with complex renal masses using the Vattikuti Collective Quality Initiative (VCQI) database that allowed evaluation of multinational data. Methods: From the VCQI, we extracted data for all the patients who underwent RAPN with preoperative aspects and dimensions used for an anatomical (PADUA) score of ≥10. Multivariate logistic regression was conducted to ascertain predictors of trifecta (absence of complications, negative surgical margins, and warm ischemia times [WIT] <25 min or zero ischemia) outcomes. Results: Of 3,801 patients, 514 with PADUA scores ≥10 were included. The median operative time, WIT, and blood loss were 173 (range 45-546) min, 21 (range 0-55) min, and 150 (range 50-3500) ml, respectively. Intraoperative complications and blood transfusions were reported in 2.1% and 6%, respectively. In 8.8% of the patients, postoperative complications were noted, and surgical margins were positive in 10.3% of the patients. Trifecta could be achieved in 60.7% of patients. Clinical tumor size, duration of surgery, WIT, and complication rates were significantly higher in the group with a high (12 or 13) PADUA score while the trifecta was significantly lower in this group (48.4%). On multivariate analysis, surgical approach (retroperitoneal vs. transperitoneal) and high PADUA score (12/13) were identified as predictors of the trifecta outcomes. Conclusion: RAPN may be a reasonable surgical option for patients with complex renal masses with acceptable perioperative outcomes.