Does the Timing of Cytoreductive Nephrectomy Impact Outcomes? Analysis of REMARCC Registry Data for Patients Receiving Tyrosine Kinase Inhibitor Versus Immune Checkpoint Inhibitor Therapy.

Background and objective: The role of cytoreductive nephrectomy (CN) in the treatment of metastatic renal cell carcinoma (mRCC) has been called into question on the basis of clinical trial data from the tyrosine kinase inhibitor (TKI) era. Comparative analyses of CN for patients treated with immuno-oncology (IO) versus TKI agents are sparse. Our objective was to compare CN timing and outcomes among patients who received TKI versus IO therapy. Methods: This was a multicenter retrospective analysis of patients who underwent CN using data from the REMARCC (Registry of Metastatic RCC) database. The cohort was divided into TKI versus IO first-line therapy groups. The primary outcome was all-cause mortality (ACM). Secondary outcomes included cancer-specific mortality (CSM). Multivariable analysis was used to identify factors predictive for ACM and CSM. The Kaplan-Meier method was used to analyze 5-yr overall survival (OS) and cancer-specific survival (CSS) with stratification by primary systemic therapy and timing in relation to CN. Key findings and limitations: We analyzed data for 189 patients (148 TKI + CN, 41 IO +CN; median follow-up 23.2 mo). Multivariable analysis revealed that a greater number of metastases (hazard ratio [HR] 1.06; p = 0.015), greater primary tumor size (HR 1.10; p = 0.043), TKI receipt (HR 2.36; p = 0.015), and initiation of systemic therapy after CN (HR 1.49; p = 0.039) were associated with worse ACM. A greater number of metastases at diagnosis (HR 1.07; p = 0.011), greater primary tumor size (HR 1.12; p = 0.018), TKI receipt (HR 5.43; p = 0.004), and initiation of systemic therapy after CN (HR 2.04; p < 0.001) were associated with worse CSM. Kaplan-Meier analyses revealed greater 5-yr rates for OS (51% vs 27%; p < 0.001) and CSS (83% vs 30%; p < 0.001) for IO +CN versus TKI + CN. This difference persisted in a subgroup analysis for patients with intermediate or poor risk, with 5-yr OS rates of 50% for IO + CN versus 30% for TKI + CN (p < 0.001). A subanalysis stratified by CN timing revealed better 5-yr rates for OS (50% vs 30%; p = 0.042) and CSS (90% vs 30%, p = 0.019) for delayed CN after IO therapy, but not after TKI therapy. Conclusions and clinical implications: For patients who underwent CN, systemic therapy before CN was associated with better outcomes. In addition, IO therapy was associated with better survival outcomes in comparison to TKI therapy. Our findings question the applicability of clinical trial data from the TKI era to CN in the IO era for mRCC. Patient summary: For patients with metastatic kidney cancer treated with surgery, better survival outcomes were observed for those who also received immunotherapy in comparison to therapy targeting specific proteins in the body (tyrosine kinase inhibitors, TKIs). Immunotherapy or TKI treatment resulted in better outcomes if it was received before rather than after surgery.

Long-term effects of hypercalcemia in kidney transplant recipients with persistent hyperparathyroidism.

BACKGROUND: Hypercalcemia is highly prevalent in kidney transplant recipients with hyperparathyroidism. However, its long-term impact on graft function is uncertain. METHODS: We conducted a prospective cohort study investigating adverse graft outcomes associated with persistent hypercalcemia (free calcium > 5.2 mg/dL in ≥ 80% of measures) and inappropriately elevated intact parathyroid hormone (> 30 pg/mL) in kidney transplant recipients. Asymptomatic mild hypercalcemia was monitored unless complications developed. RESULTS: We included 385 kidney transplant recipients. During a 4-year (range 1-9) median follow-up time, 62% of kidney transplant recipients presented persistent hypercalcemia. Compared to kidney transplant recipients without hypercalcemia, there were no significant differences in graft dysfunction (10% vs. 12%, p = 0.61), symptomatic urolithiasis (5% vs. 3%, p = 0.43), biopsy-proven calcium deposits (6% vs. 5%, p = 1.0), fractures (6% vs. 4%, p = 0.64), and a composite outcome of urolithiasis, calcium deposits, fractures, and parathyroidectomy indication (16% vs. 13%, p = 0.55). In a subset of 76 kidney transplant recipients, subjects with persistent hypercalcemia had higher urinary calcium (median 84 [43-170] vs. 38 [24-64] mg/day, p = 0.03) and intact fibroblast growth factor 23 (median 36 [24-54] vs. 27 [19-40] pg/mL, p = 0.04), and lower 25-hydroxyvitamin D levels (11.3 ± 1.2 vs. 16.3 ± 1.4 ng/mL, p < 0.001). In multivariate analysis, pretransplant intact parathyroid hormone < 300 pg/mL was associated with a reduced risk of post-transplant hypercalcemia (OR 0.51, 95% CI 0.32-0.80). CONCLUSIONS: Long-term persistent mild hypercalcemia (tertiary hyperparathyroidism) was frequent in kidney transplant recipients in our series. This condition presented with lower phosphate and 25-hydroxyvitamin D, and higher urinary calcium and intact fibroblast growth factor 23 levels compared to kidney transplant recipients without hypercalcemia, resembling a mild form of primary hyperparathyroidism. Despite these metabolic derangements, the risk of adverse graft outcomes was low.

Proposal for a Two-Tier Re-classification of Stage IV/M1 domain of Renal Cell Carcinoma into M1 ("Oligometastatic") and M2 ("Polymetastatic") subdomains: Analysis of the Registry for Metastatic Renal Cell Carcinoma (REMARCC).

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.

Effect of Kidney transplantation on cyst growth in autosomal dominant polycystic kidney disease.

BACKGROUND: In patients with autosomal dominant polycystic kidney disease (ADPKD), there is limited evidence of the rate of cyst progression after kidney transplantation. AIMS: To compare the height-adjusted total kidney volume (Ht-TKV) before and after transplantation in kidney transplant recipients (KTR) with -ADPKD. MATERIALS AND METHODS: Retrospective cohort study. The estimate of Ht-TKV was calculated by the ellipsoid volume equation using measurements from CT or yearly MRI scans before and after transplantation. RESULTS: We included 30 patients with -ADPKD who underwent kidney transplantation (age 49 ± 10.1 years, 11 (37%) females, dialysis vintage 3 (1 - 6) years, and 4 (13%) underwent unilateral nephrectomy during the peritransplant period). The median follow-up time was 5 years (range 2 - 16 years). Transplantation was associated with a significant decrease in Ht-TKV after transplantation in 27 (90%) KTR. Median Ht-TKV decreased from 1,708 (IQR 1,100 - 2,350) mL/m to 710 (IQR 420 - 1,380) mL/m after 6 years of follow-up (p < 0.001), with a mean Ht-TKV change rate per year after transplantation of -1.4, -11.8, -9.7, -12.7, -7.0, and -9.4% after 1, 2, 3, 4, 5, and 6 years, respectively. Even in 2 (7%) KTR without regression, the annual growth was < 1.5% per year after transplantation. CONCLUSION: Kidney transplantation reduced Ht-TKV after the first 2 years of transplantation, and this decline was continuous for more than 6 years of follow-up.

Impact of Metastasectomy on Cancer Specific and Overall Survival in Metastatic Renal Cell Carcinoma: Analysis of the REMARCC Registry.

BACKGROUND: Treatment paradigms for management of metastatic renal cell carcinoma (mRCC) are evolving. We examined impact of surgical metastasectomy on survival across in mRCC stratified by risk-group. METHODS: Multicenter retrospective analysis from the Registry of Metastatic RCC database. The cohort was subdivided utilizing Motzer criteria (favorable-, intermediate-, high-risk). Primary outcome was all-cause mortality (ACM)/overall survival (OS); secondary outcome was cancer-specific mortality (CSM)/cancer-specific survival (CSS). Impact of metastasectomy was analyzed via Cox-Regression analysis adjusting for potential prognostic variables and Kaplan-Meier analysis (KMA) within each risk-group. RESULTS: Four hundred thirty-one patients (59 favorable-risk, 274 intermediate-risk, 98 high-risk; median follow-up 27.2 months) were analyzed. Metastasectomy was performed in 22 (37%), 66 (24%), and 32 (16%) of favorable-, intermediate- and high-risk groups (P = .012). Median number of metastases at diagnosis differed significantly (favorable-risk 2, intermediate-risk 3.4, high-risk 5.1, P < .001). On Cox-regression, high-risk (HR = 1.72, P = .002) was associated with worsened ACM, while metastasectomy was associated with improved ACM (HR = 0.56, P = .005). On KMA, median OS (months) was longer with metastasectomy in favorable- (92.7 vs. 25.8, P = .003) and intermediate-risk (26.3 vs. 20.1, P = .038), but not high-risk (P = .911) groups. Metastasectomy was associated with longer CSS in favorable- (76.1 vs. 32.8, P = .004) but not intermediate- (P = .06) and high-risk (P = .595) groups. CONCLUSIONS: Metastasectomy was independently associated with improved ACM and CSM, as well as improved CSS and OS in favorable- and intermediate-risk mRCC patients. Metastasectomy may be considered as component of multimodal management strategy in favorable and intermediate-risk subgroups. In high-risk patients, metastasectomy should be deferred except in select circumstances.

Development of a Novel Risk Score to Select the Optimal Candidate for Cytoreductive Nephrectomy Among Patients with Metastatic Renal Cell Carcinoma. Results from a Multi-institutional Registry (REMARCC).

BACKGROUND: Selection of patients for upfront cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC) has to be improved. OBJECTIVE: To evaluate a new scoring system for the prediction of overall mortality (OM) in mRCC patients undergoing CN. DESIGN, SETTING, AND PARTICIPANTS: We identified a total of 519 patients with synchronous mRCC undergoing CN between 2005 and 2019 from a multi-institutional registry (Registry for Metastatic RCC [REMARCC]). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cox proportional hazard regression was used to test the main predictors of OM. Restricted mean survival time was estimated as a measure of the average overall survival time up to 36 mo of follow-up. The concordance index (C-index) was used to determine the model's discrimination. Decision curve analyses were used to compare the net benefit from the REMARCC model with International mRCC Database Consortium (IMDC) or Memorial Sloan Kettering Cancer Center (MSKCC) risk scores. RESULTS AND LIMITATIONS: The median follow-up period was 18 mo (interquartile range: 5.9-39.7). Our models showed lower mortality rates in obese patients (p = 0.007). Higher OM rates were recorded in those with bone (p = 0.010), liver (p = 0.002), and lung metastases (p < 0.001). Those with poor performance status (<80%) and those with more than three metastases had also higher OM rates (p = 0.026 and 0.040, respectively). The C-index of the REMARCC model was higher than that of the MSKCC and IMDC models (66.4% vs 60.4% vs 60.3%). After stratification, 113 (22.0%) patients were classified to have a favorable (no risk factors), 202 (39.5%) an intermediate (one or two risk factors), and 197 (38.5%) a poor (more than two risk factors) prognosis. Moreover, 72 (17.2%) and 51 (13.9%) patients classified as having an intermediate and a poor prognosis according to MSKCC and IMDC categories, respectively, would be reclassified as having a good prognosis according to the REMARCC score. CONCLUSIONS: Our findings confirm the relevance of tumor and patient features for the risk stratification of mRCC patients and clinical decision-making regarding CN. Further prospective external validations are required for the scoring system proposed herein. PATIENT SUMMARY: Current stratification systems for selecting patients for kidney removal when metastatic disease is shown are controversial. We suggest a system that includes tumor and patient features besides the systems already in use, which are based on blood tests.

Oncological outcomes of salvage radical prostatectomy for recurrent prostate cancer in the contemporary era: A multicenter retrospective study.

BACKGROUND: Salvage radical prostatectomy (sRP) historically yields poor functional outcomes and high complication rates. However, recent reports on robotic sRP show improved results. Our objectives were to evaluate sRP oncological outcomes and predictors of positive margins and biochemical recurrence (BCR). METHODS: We retrospectively collected data of sRP for recurrent prostate cancer after local nonsurgical treatment at 18 tertiary referral centers in United States, Australia and Europe, from 2000 to 2016. SM and BCR were evaluated in a univariate and multivariable analysis. Overall and cancer-specific survival were also assessed. RESULTS: We included 414 cases, 63.5% of them performed after radiotherapy. Before sRP the majority of patients had biopsy Gleason score (GS) ≤7 (55.5%) and imaging negative or with prostatic bed involvement only (93.3%). Final pathology showed aggressive histology in 39.7% (GS ≥9 27.6%), with 52.9% having ≥pT3 disease and 16% pN+. SM was positive in 29.7%. Five years BCR-Free, cancer-specific survival and OS were 56.7%, 97.7% and 92.1%, respectively. On multivariable analysis pathological T (pT3a odds ratio [OR] 2.939, 95% confidence interval [CI] 1.469-5.879; ≥pT3b OR 2.428-95% CI 1.333-4.423) and N stage (pN1 OR 2.871, 95% CI 1.503-5.897) were independent predictors of positive margins. Pathological T stage ≥T3b (OR 2.348 95% CI 1.338-4.117) and GS (up to OR 7.183, 95% CI 1.906-27.068 for GS >8) were independent predictors for BCR. Limitations include the retrospective nature of the study and limited follow-up. CONCLUSIONS: In a contemporary series, sRP showed promising oncological control in the medium term despite aggressive pathological features. BCR risk increased in case of locally advanced disease and higher GS. Future studies are needed to confirm our findings.

Active surveillance for small renal masses in elderly patients does not increase overall mortality rates compared to primary intervention: a propensity score weighted analysis.

BACKGROUND: The aim of the study was to test the effect of active surveillance (AS) versus primary intervention (PI) on overall mortality (OM) in elderly patients diagnosed with SRM. METHODS: Elderly patients (75 years or older) diagnosed with SRMs (<4 cm) and treated with either PI (i.e. partial nephrectomy or kidney ablation) or AS between 2009 and 2018 were abstracted from the renal surgery in the elderly (RESURGE) and Delayed Intervention and Surveillance for small Renal Masses (DISSRM) datasets, respectively. OM rates were estimated among groups with Kaplan Meier method and Cox proportional hazards regression models after applying inverse probability of treatment weighting (IPTW). Multivariable logistic regression model was used to estimate IPTW. Covariates of interest were those unbalanced and/or significantly correlated with the treatment choice or with OM. RESULTS: A total of 483 patients were included; 121 (25.1%) underwent AS. Sixty patients (12.4%) died. Overall, 6.7% of all deaths were related to cancer. IPTW-Kaplan Meier curves showed a 5-year overall survival rates of 70.0±3.5% and 73.2±4.8% in AS and PI groups, respectively (IPTW-Log-rank P value=0.308). IPTW-Cox regression model did not show meaningfully increased OM rates in AS group (HR: 1.31, 95% CI: 0.69-2.49). CONCLUSIONS: AS represents an appealing treatment option for very elderly patients presenting with SRM, as it avoids the risks of a PI while not compromising the survival outcomes of these patients.

Outcomes of minimally invasive partial nephrectomy among very elderly patients: report from the RESURGE collaborative international database.

The aim of the study was to perform a comprehensive investigation of clinical outcomes of robot-assisted partial nephrectomy (RAPN) or laparoscopic partial nephrectomy (LPN) in elderly patients presenting with a renal mass. The REnal SURGery in Elderly (RESURGE) collaborative database was queried to identify patients aged 75 or older diagnosed with cT1-2 renal mass and treated with RAPN or LPN. Study outcomes were: overall complications (OC); warm ischemia time (WIT) and 6-month estimated glomerular filtration rate (eGFR); positive surgical margins (PSM), disease recurrence (REC), cancer-specific mortality (CSM) and other-cause mortality (OCM). Descriptive statistics, Kaplan-Meier, smoothed Poisson plots and logistic and linear regression models (MVA) were used. Overall, 216 patients were included in this analysis. OC rate was 34%, most of them being of low Clavien grade. Median WIT was 17 minutes and median 6-month eGFR was 54 ml/min/1.73 m2. PSM rate was 5%. After a median follow-up of 20 months, the 5-year rates of REC, CSM and OCM were 4, 4 and 5%, respectively. At MVA predicting perioperative morbidity, RAPN relative to LPN (odds ratio [OR] 0.33; p <0.0001) was associated with lower OC rate. At MVA predicting functional outcomes, RAPN relative to LPN was associated with shorter WIT (estimate [EST] -4.09; p <0.0001), and with higher 6-month eGFR (EST 6.03; p = 0.01). In appropriately selected patients with small renal masses, minimally-invasive PN is associated with acceptable perioperative outcomes. The use of a robotic approach over a standard laparoscopic approach can be advantageous with respect to clinically relevant outcomes, and it should be preferred when available.

Partial versus radical nephrectomy in very elderly patients: a propensity score analysis of surgical, functional and oncologic outcomes (RESURGE project).

PURPOSE: To compare the outcomes of PN to those of RN in very elderly patients treated for clinically localized renal tumor. PATIENTS AND METHODS: A purpose-built multi-institutional international database (RESURGE project) was used for this retrospective analysis. Patients over 75 years old and surgically treated for a suspicious of localized renal with either PN or RN were included in this database. Surgical, renal function and oncological outcomes were analyzed. Propensity scores for the predicted probability to receive PN in each patient were estimated by logistic regression models. Cox proportional hazard models were estimated to determine the relative change in hazard associated with PN vs RN on overall mortality (OM), cancer-specific mortality (CSM) and other-cause mortality (OCM). RESULTS: A total of 613 patients who underwent RN were successfully matched with 613 controls who underwent PN. Higher overall complication rate was recorded in the PN group (33% vs 25%; p = 0.01). Median follow-up for the entire cohort was 35 months (interquartile range [IQR] 13-63 months). There was a significant difference between RN and PN in median decline of eGFR (39% vs 17%; p < 0.01). PN was not correlated with OM (HR = 0.71; p = 0.56), OCM (HR = 0.74; p = 0.5), and showed a protective trend for CSM (HR = 0.19; p = 0.05). PN was found to be a protective factor for surgical CKD (HR = 0.28; p < 0.01) and worsening of eGFR in patients with baseline CKD. Retrospective design represents a limitation of this analysis. CONCLUSIONS: Adoption of PN in very elderly patients with localized renal tumor does not compromise oncological outcomes, and it allows better functional preservation at mid-term (3-year) follow-up, relative to RN. Whether this functional benefit translates into a survival benefit remains to be determined.

Trifecta Outcomes of Partial Nephrectomy in Patients Over 75 Years Old: Analysis of the REnal SURGery in Elderly (RESURGE) Group.

BACKGROUND: Partial nephrectomy (PN) in elderly patients is underutilized with concerns regarding risk of complications and potential for poor outcomes. OBJECTIVE: To evaluate quality and functional outcomes of PN in patients >75 yr using trifecta as a composite outcome of surgical quality. DESIGN, SETTING, AND PARTICIPANTS: Multicenter retrospective analysis of 653 patients aged >75 yr who underwent PN (REnal SURGery in Elderly [RESURGE] Group). INTERVENTION: PN. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary outcome was achievement of trifecta (negative margin, no major [Clavien ≥3] urological complications, and ≥90% estimated glomerular filtration rate [eGFR] recovery). Secondary outcomes included chronic kidney disease (CKD) stage III and CKD upstaging. Multivariable analysis (MVA) was used to assess variables for achieving trifecta and functional outcomes. Kaplan-Meier survival analysis (KMA) was used to calculate renal functional outcomes. RESULTS AND LIMITATIONS: We analyzed 653 patients (mean age 78.4 yr, median follow-up 33 mo; 382 open, 157 laparoscopic, and 114 robotic). Trifecta rate was 40.4% (n=264). Trifecta patients had less transfusion (p<0.001), lower intraoperative (5.3% vs 27%, p<0.001) and postoperative (25.4% vs 37.8%, p=0.001) complications, shorter hospital stay (p=0.045), and lower ΔeGFR (p <0.001). MVA for predictive factors for trifecta revealed decreasing RENAL nephrometry score (odds ratio [OR] 1.26, 95% confidence interval 1.07-1.51, p=0.007) as being associated with increased likelihood to achieve trifecta. Achievement of trifecta was associated with decreased risk of CKD upstaging (OR 0.47, 95% confidence interval 0.32-0.62, p<0.001). KMA showed that trifecta patients had improved 5-yr freedom from CKD stage 3 (93.5% vs 57.7%, p<0.001) and CKD upstaging (84.3% vs 8.2%, p<0.001). Limitations include retrospective design. CONCLUSIONS: PN in elderly patients can be performed with acceptable quality outcomes. Trifecta was associated with decreased tumor complexity and improved functional preservation. PATIENT SUMMARY: We looked at quality outcomes after partial nephrectomy in elderly patients. Acceptable quality outcomes were achieved, measured by a composite outcome called trifecta, whose achievement was associated with improved kidney functional preservation.

Salvage Radical Prostatectomy for Recurrent Prostate Cancer: Morbidity and Functional Outcomes from a Large Multicenter Series of Open versus Robotic Approaches.

PURPOSE: Salvage radical prostatectomy has historically yielded a poor functional outcome and a high complication rate. However, recent reports of robotic salvage radical prostatectomy have demonstrated improved results. In this study we assessed salvage radical prostatectomy functional outcomes and complications when comparing robotic and open approaches. MATERIALS AND METHODS: We retrospectively collected data on salvage radical prostatectomy for recurrent prostate cancer after local nonsurgical treatment at 18 tertiary referral centers from 2000 to 2016. The Clavien-Dindo classification was applied to classify complications. Complications and functional outcomes were evaluated by univariable and multivariable analysis. RESULTS: We included 395 salvage radical prostatectomies, of which 186 were open and 209 were robotic. Robotic salvage radical prostatectomy yielded lower blood loss and a shorter hospital stay (each p <0.0001). No significant difference emerged in the incidence of major and overall complications (10.1%, p=0.16, and 34.9%, p=0.67), including an overall low risk of rectal injury and fistula (1.58% and 2.02%, respectively). However, anastomotic stricture was more frequent for open salvage radical prostatectomy (16.57% vs 7.66%, p <0.01). Overall 24.6% of patients had had severe incontinence, defined as 3 or more pads per day, for 12 or 6 months. On multivariable analysis robotic salvage radical prostatectomy was an independent predictor of continence preservation (OR 0.411, 95% CI 0.232-0.727, p=0.022). Limitations include the retrospective nature of the study and the absence of a standardized surgical technique. CONCLUSIONS: In this contemporary series to our knowledge salvage radical prostatectomy showed a low risk of major complications and better functional outcomes than previously reported. Robotic salvage radical prostatectomy may reduce anastomotic stricture, blood loss and hospital stay, and improve continence outcomes.

Outcomes of Partial and Radical Nephrectomy in Octogenarians - A Multicenter International Study (Resurge).

OBJECTIVE: To analyze the outcomes of partial nephrectomy (PN) and radical nephrectomy (RN) in octogenarian patients. METHODS: The RESURGE (REnal SUrgery in the Eldely) multi-institutional database was queried to identify patients ≥80 years old who had undergone a PN or RN for a renal tumor. Multivariable binary logistic regression estimated the association between type of surgery and occurrence of complications. Multivariable Cox regression model assessed the association between type of surgery and All-Causes Mortality. RESULTS: The study analyzed 585 patients (median age 83 years, IQR 81-84), 364 of whom (62.2%) underwent RN and 221 (37.8%) PN. Patients undergoing RN were older (P = .0084), had larger tumor size (P < .0001) and higher clinical stage (P < .001). At multivariable analysis for complications, the only significant difference was found for lower risk of major postoperative complications for laparoscopic RN compared to open RN (OR: 0.42; P = .04). The rate of significant (>25%) decrease of eGFR in PN and RN was 18% versus 59% at 1 month, and 23% versus 65% at 6 months (P < .0001). After a median follow-up time of 39 months, 161 patients (31%) died, of whom 105 (20%) due to renal cancer. CONCLUSION: In this patient population both RN and PN carry a non-negligible risk of complications. When surgical removal is indicated, PN should be preferred, whenever technically feasible, as it can offer better preservation of renal function, without increasing the risk of complications. Moreover, a minimally invasive approach should be pursued, as it can translate into lower surgical morbidity.

[Kidney cancer stage pT3a: Fat invasion versus renal vein invasion.] / Cáncer renal pT3a: infiltración grasa versus infiltración de vena renal.

OBJECTIVE: We discuss the influence that involvement of fat (perirenal, sinus) and vascular structures (renal vein, segmental veins) have on cancer-specific mortality (CSM) rates in renal cancer. METHODS: We conducted a retrospective analysis of 140 stage pT3a kidney tumors (114 clear cell, 9 type I papillary, 6 type II papillary, 11 chromophobe) surgically treated between 1997 and 2015. We conducted a cancer-specific survival study (Kaplan Meier) and a univariate and multivariate analysis of the variables: perirenal fat invasion, sinus fat invasion, renal vein invasion, segmental vein invasion and Fuhrman grade. RESULTS: With a mean follow-up of 79 months, 47 deaths occurred overall (31.7%), 29 of which were due to the kidney tumor (CSM 20%). There were 50 cases of vascular invasion (35.7%), 40 cases with fat only invasion (28.6%) and 50 cases with invasion of both (35.7%). In the survival study, fat invasion had the least impact (17%), and invasion of both (fat and vascular structures) had the worst survival (48% of total mortality). Vascular invasion represents 35% of the mortality rate. In the multivariate study, Fuhrman grade 3-4 (HR 10.7), renal vein invasion (HR 9.2) and concomitant vascular and fat invasion (HR 5.6) are the factors with the greatest impact. CONCLUSIONS: Tumor fat invasion has a lower impact on the CSM of kidney cancer than vascular invasion.

Impact of Microscopic Wall Invasion of the Renal Vein or Inferior Vena Cava on Cancer-specific Survival in Patients with Renal Cell Carcinoma and Tumor Thrombus: A Multi-institutional Analysis from the International Renal Cell Carcinoma-Venous Thrombus Consortium.

BACKGROUND: Microscopic vein invasion (MVI), with local destruction and invasion of the endothelium by tumor, is of controversial predictive value in renal cell carcinoma (RCC). OBJECTIVE: To assess the impact of venous extension and wall invasion in RCC on survival. DESIGN, SETTING, AND PARTICIPANTS: Data for 1023 RCC patients with vena cava thrombus treated with radical nephrectomy and complete tumor thrombectomy were collected within a prospectively maintained international consortium (1995-2012). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The Kaplan-Meier method and univariable and multivariable Cox regression analyses were used to assess the impact of MVI on cancer-specific survival (CSS). The main two variables of interest were microscopic renal vein wall invasion (MRVI) and microscopic vena cava wall invasion (MVCI). RESULTS: MRVI was found in 725 cases (70.9%) and MVCI in 230 (22.5%). Patients with MRVI had larger tumors (p=0.005), longer hospital stay (p<0.001), higher clinical stage 0.039), higher Fuhrman grade (p=0.028), and more frequent fat invasion. Presence of MVCI was associated with larger tumors (p<0.001), longer hospital stay (p<0.001), higher clinical stage (p<0.001), lymph node involvement (p=0.045), higher Fuhrman grade (p<0.001), and higher thrombus level (p<0.001). With median follow-up of 52 mo, overall 5-yr CSS was 57.4%. Multivariable analysis showed that presence of MRVI was an independent factor related to CSS (hazard ratio 2.24, 95% confidence interval 1.24-3.59, p=0.006). The main limitation was the inability to report MVI percentages. CONCLUSIONS: Patients with MRVI experience significantly worse survival outcomes after radical nephrectomy and tumor thrombectomy. Consideration of MRVI at final pathology is appropriate to improve decision-making for risk-adapted follow-up. PATIENT SUMMARY: The behavior of locally advanced renal cell carcinoma (RCC) depends on clinical and pathologic factors. Analysis revealed that RCC patients with microscopic renal vein wall invasion experience significantly worse cancer-specific survival.

Cytoreductive nephrectomy in patients with metastatic renal cell carcinoma in the era of targeted therapy: a bibliographic review.

PURPOSE: To evaluate the role of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC), against a background of lack of evidence following the introduction of targeted therapy. METHODS: A literature review was performed in January 2017 using the MEDLINE/PubMed and EMBASE databases. The PRISMA guidelines were followed for conduct of the study. Two authors independently screened the 270 papers retrieved from the search, and the finally selected publications were identified by consensus between the two reviewers. A total of 55 studies were included in the present review. RESULTS: Globally, the indications for CN have decreased over recent years. Although current guidelines consider CN an adequate option in selected patients based on prospective studies in the cytokine era, evidence for CN in the era of targeted therapy is based on retrospective studies only. CONCLUSIONS: The results of ongoing prospective studies are still awaited. Retrospective data suggest that young male patients with oligometastatic disease and a good performance status can be considered suitable surgical candidates who may benefit from CN.

Impact of synchronous metastasis distribution on cancer specific survival in renal cell carcinoma after radical nephrectomy with tumor thrombectomy.

PURPOSE: Metastatic renal cell carcinoma can be clinically diverse in terms of the pattern of metastatic disease and response to treatment. We studied the impact of metastasis and location on cancer specific survival. MATERIALS AND METHODS: The records of 2,017 patients with renal cell cancer and tumor thrombus who underwent radical nephrectomy and tumor thrombectomy from 1971 to 2012 at 22 centers in the United States and Europe were analyzed. Number and location of synchronous metastases were compared with respect to patient cancer specific survival. Multivariable Cox regression models were used to quantify the impact of covariates. RESULTS: Lymph node metastasis (155) or distant metastasis (725) was present in 880 (44%) patients. Of the patients with distant disease 385 (53%) had an isolated metastasis. The 5-year cancer specific survival was 51.3% (95% CI 48.6-53.9) for the entire group. On univariable analysis patients with isolated lymph node metastasis had a significantly worse cancer specific survival than those with a solitary distant metastasis. The location of distant metastasis did not have any significant effect on cancer specific survival. On multivariable analysis the presence of lymph node metastasis, isolated distant metastasis and multiple distant metastases were independently associated with cancer specific survival. Moreover higher tumor thrombus level, papillary histology and the use of postoperative systemic therapy were independently associated with worse cancer specific survival. CONCLUSIONS: In our multi-institutional series of patients with renal cell cancer who underwent radical nephrectomy and tumor thrombectomy, almost half of the patients had synchronous lymph node or distant organ metastasis. Survival was superior in patients with solitary distant metastasis compared to isolated lymph node disease.

Lessons learned from the International Renal Cell Carcinoma-Venous Thrombus Consortium (IRCC-VTC).

Renal cell carcinoma (RCC) extension into the renal vein or the inferior vena cava occurs in 4%-10% of all kidney cancer cases. This entity shows a wide range of different clinical and surgical scenarios, making natural history and oncological outcomes variable and poorly characterized. Infrequency and variability make it necessary to share the experience from different institutions to properly analyze surgical outcomes in this setting. The International Renal Cell Carcinoma-Venous Tumor Thrombus Consortium was created to answer the questions generated by competing results from different retrospective studies in RCC with venous extension on current controversial topics. The aim of this article is to summarize the experience gained from the analysis of the world's largest cohort of patients in this unique setting to date.

[Sexual dysfunction secondary to urethral stricture and urethroplasty]. / Disfunciones sexuales secundarias a la estenosis uretral y a la uretroplastia.

OBJECTIVES: Urethral stenosis is a complex pathology that severely affects the quality of life of patients who suffer it. There are multiple therapeutic options, the main objective of which is to eliminate obstruction and improve symptoms, and consequently maintain or improve the quality of life of the patient. The objective of this article is to perform a systematic review of the literature with the aim to evaluate the results regarding the sexual sphere after urethral surgery. METHODS: We performed a bibliographic search in PubMed, identifying studies that analyzed the results in sexual function after various types of urethroplasties. Preference have been given to those articles evaluating sexual function both preoperative and postoperative, to determine the degree of involvement conditioned by surgery. Fourteen articles have been selected, including those making reference to sexual function (sexual desire, erectile and ejaculatory function). RESULTS: A total of 14 studies were selected to perform the analysis; they were divided into two groups depending of the perspective they have to evaluate results: Use of validated tests for data collection before and after surgery and a second group analyzing more qualitative features of the stenosis making the evaluation of results this way. Site of stenosis is not uniformly distributed in these articles, with predominance of those performing anterior urethra surgery. They have a comprehensive analysis of the various features that may affect directly or indirectly the result of the operation both in the short and long term. CONCLUSIONS: Most articles conclude that specific standardized tools are necessary for this type of pathology, with the aim of obtain results that are more adjusted to urethral surgery. Patient perception of the results of urethroplasty is a parameter that has gained great importance lately. Globally the results of postoperative sexual function are very satisfactory, mainly in young patients. It is important to globally analyze the results and surgical techniques currently in use with the aim to minimize deleterious effects on sexual function; moreover taking into account that the objective of surgery is to try to improve the patient's quality of life.