PADRES: a phase 2 clinical trial of neoadjuvant axitinib for complex partial nephrectomy.

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

Role of neoadjuvant chemotherapy in patients with locally advanced and clinically positive nodes Upper Tract Urothelial Carcinoma treated with Nephroureterectomy: real-world data from the ROBUUST 2.0 Registry.

PURPOSE: To assess the impact of neoadjuvant and adjuvant chemotherapy on survival outcomes, within a large multicenter cohort of Upper tract urothelial carcinoma patients treated with Nephroureterectomy. METHODS: A multicenter retrospective analysis utilizing the Robotic surgery for Upper Tract Urothelial Cancer Study registry was performed. Baseline, preoperative, perioperative, and pathologic variables of three groups of patients receiving surgery only, neoadjuvant or adjuvant chemotherapy were compared. Categorical and continuous variables among the three subgroups were compared with Chi square and ANOVA tests. The impact of perioperative chemotherapy on survival outcomes was assessed with the Kaplan Meier method. Univariable and multivariable Cox regression analyses were performed to identify predictors of survival. RESULTS: Overall, 1,994 patients were included. Overall and Clavien grade ≥3 complications rates were comparable among the three subgroups (p = 0.65 and p = 0.92). At Kaplan Meier analysis, neoadjuvant chemotherapy significantly improved cancer-specific survival (p = 0.03) and overall survival (p = 0.03) probabilities of patients with cT ≥ 3 tumors and of those with positive cN (p = 0.03 and p = 0.02). On multivariable analysis, neoadjuvant chemotherapy was independently associated with an improvement of cancer-specific survival in cT ≥ 3 patients (HR 0.44; p = 0.04), and of both cancer-specific survival (HR 0.50; p = 0.03) and overall survival (HR 0.53; p = 0.02) probabilities in positive cN patients. CONCLUSIONS: This large multicenter retrospective analysis suggests significant survival benefit in Upper tract urothelial carcinoma patients with either locally advanced or clinically positive nodes disease receiving neoadjuvant chemotherapy. These findings can be regarded as "hypothesis generating", stimulating future trials focusing on such advanced stages.

Single-Port Robot assisted partial cystectomy for urachal adenocarcinoma.

OBJECTIVE: We present a novel technique to perform single-port (SP) robot-assisted partial cystectomy with excision of the urachal remnant and bilateral pelvic lymph node dissection for urachal adenocarcinoma (1-7). MATERIALS AND METHODS: A 41-year-old male presented to the clinic for multiple episodes of hematuria and mucousuria. Office cystoscopy revealed a small solitary tumor at the dome of the bladder, with a diagnostic bladder biopsy revealing a tubule-villous bladder adenoma. Cross-sectional imaging of the chest/abdomen/pelvis revealed a 4.5 cm cystic mass arising from the urachus without evidence of local invasion and metastatic spread. He underwent SP robotic-assisted partial cystectomy with excision of the urachal remnant and bilateral pelvic lymph node dissection. Surgical steps include: 1) peritoneal incision to release the urachus and drop bladder 2) identification of urachal tumor 3) intraoperative live cystoscopic identification of bladder mass and scoring of tumor margins using Toggle Pro feature 4) tumor excision with partial cystectomy 5) cystorrhaphy 6) bilateral pelvic lymph node dissection 7) peritoneal interposition flap to mitigate lymphocele formation. RESULTS: Surgery was successful, with no intraoperative complications, an operative time of 100 minutes, and estimated blood loss of 20 mL. The patient was discharged on post-op day one, and the Foley catheter removed one week after surgery. Final pathology revealed a 7.5 cm infiltrating urachal muscle-invasive adenocarcinoma of the bladder (pT2b). Negative surgical margins were achieved. CONCLUSIONS: Single-port robot-assisted partial cystectomy for urachal adenocarcinoma is safe and can achieve equivalent oncologic outcomes to the standard of care with minimally invasive and open techniques.

Pathological Outcomes of Patients With Advanced Renal Cell Carcinoma Who Receive Nephrectomy Following Immunotherapy.

BACKGROUND: Even though cytoreductive nephrectomy (CN) was once the standard of care for patients with advanced renal cell carcinoma (RCC), its role in treatment has not been well analyzed or defined in the era of immunotherapy (IO). MATERIALS AND METHODS: This study analyzed pathological outcomes in patients with advanced or metastatic RCC who received IO prior to CN. This was a multi-institutional, retrospective study of patients with advanced or metastatic RCC. Patients were required to receive IO monotherapy or combination therapy prior to radical or partial CN. The primary endpoint assessed surgical pathologic outcomes, including American Joint Committee on Cancer (AJCC) staging and frequency of downstaging, at the time of surgery. Pathologic outcomes were correlated to clinical variables using a Wald-chi squared test from Cox regression in a multi-variable analysis. Secondary outcomes included objective response rate (ORR) defined by response evaluation criteria in solid tumors (RECIST) version 1.1 and progression-free survival (PFS), which were estimated using the Kaplan-Meier method with reported 95% CIs. RESULTS: Fifty-two patients from 9 sites were included. Most patients were male (65%), 81% had clear cell histology, 11% had sarcomatoid differentiation. Overall, 44% of patients experienced pathologic downstaging, and 13% had a complete pathologic response. The ORR immediately prior to nephrectomy was stable disease in 29% of patients, partial response in 63%, progressive disease in 4%, and 4% unknown. Median follow-up for the entire cohort was 25.3 months and median PFS was 3.5 years (95% CI, 2.1-4.9). CONCLUSIONS: IO-based interventions prior to CN in patients with advanced or metastatic RCC demonstrates efficacy, with a small fraction of patients showing a complete response. Additional prospective studies are warranted to investigate the role of CN in the modern IO-era.

Impact of worsening surgically induced chronic kidney disease (CKD-S) in preoperative CKD-naïve patients on survival in renal cell carcinoma.

OBJECTIVES: To evaluate effects of worsening surgically induced chronic kidney disease (CKD-S) on oncological and non-oncological survival outcomes in renal cell carcinoma (RCC). PATIENTS AND METHODS: We performed a retrospective analysis of patients who underwent partial (PN) or radical nephrectomy (RN) and were free of preoperative CKD (estimated glomerular filtration rate [eGFR] ≥60 mL/min/1.73 m2 ). Patients were stratified by CKD stage at last follow-up: no CKD-S (eGFR ≥60 mL/min/1.73 m2 ), de novo CKD-S 3a (eGFR 45-59 mL/min/1.73 m2 ), CKD-S 3b (eGFR <45 and ≥30 mL/min/1.73 m2 ) and CKD-S 4 (eGFR <30 and ≥15 mL/min/1.73 m2 ). The primary outcome was all-cause mortality (ACM). Secondary outcomes included non-cancer mortality (NCM), cancer-specific mortality (CSM) and de novo CKD-S Stage 3/4. Multivariable analysis (MVA) was utilised to identify risk factors for outcomes. Kaplan-Meier analysis (KMA) was utilised to evaluate overall (OS), non-cancer (NCS), and cancer-specific survival with respect to CKD-S categories. RESULTS: We analysed 3239 patients. The mean preoperative and last-follow-up eGFRs were 87.4 and 69.5 mL/min/1.73 m2 , respectively. On last follow-up, 57.9% (n = 1876) had no CKD-S, 18.7% (n = 606) had CKD-S 3a, 15.1% (n = 489) had CKD-S 3b and 8.3% (n = 268) had CKD-S 4. On MVA, de novo CKD-S 3b and 4 were independently associated with ACM (hazard ratios [HRs] 1.3-2.1, P = 0.003-0.001) and NCM (HRs 1.5-2.8, P = 0.021-0.001), but not CSM (P = 0.219-0.909); de novo CKD-S 3a was not predictive for any mortality outcomes (P = 0.102-0.81). RN was independently associated with CKD-S 3-4 (HRs 1.78-1.99, P < 0.001-0.035). Comparing no CKD-S, CKD-S 3a, CKD-S 3b and CKD-S 4, KMA demonstrated worsening outcomes with progressive CKD-S stage: 5-year OS 84% vs 78% vs 71% vs 60% (P < 0.001) and 5-year NCS 93% vs 87% vs 83% vs 72% (P < 0.001). CONCLUSION: Development of CKD-S Stage 3b and 4, but not 3a, was associated with worsened ACM and NCM. The decision to proceed with nephron preservation via PN should be individualised based on oncological risk and risk of functional decline to CKD-S 3b or 4, and not CKD-S 3a.

Outcomes of Lymph Node Dissection in Nephroureterectomy in the Treatment of Upper Tract Urothelial Carcinoma: Analysis of the ROBUUST Registry.

PURPOSE: We sought to evaluate outcomes of lymph node dissection (LND) in patients with upper tract urothelial carcinoma. MATERIALS AND METHODS: We performed a multicenter retrospective analysis utilizing the ROBUUST (for RObotic surgery for Upper Tract Urothelial Cancer Study) registry for patients who did not undergo LND (pNx), LND with negative lymph nodes (pN0) and LND with positive nodes (pN+). Primary and secondary outcomes were overall survival (OS) and recurrence-free survival (RFS). Multivariable analyses evaluated predictors of outcomes and pathological node positivity. Kaplan-Meier analyses (KMAs) compared survival outcomes. RESULTS: A total of 877 patients were analyzed (LND performed in 358 [40.8%]/pN+ in 73 [8.3%]). Median nodes obtained were 10.2 for pN+ and 9.8 for pN0. Multivariable analyses noted increasing age (OR 1.1, p <0.001), pN+ (OR 3.1, p <0.001) and pathological stage pTis/3/4 (OR 3.4, p <0.001) as predictors for all-cause mortality. Clinical high-grade tumors (OR 11.74, p=0.015) and increasing tumor size (OR 1.14, p=0.001) were predictive for lymph node positivity. KMAs for pNx, pN0 and pN+ demonstrated 2-year OS of 80%, 86% and 42% (p <0.001) and 2-year RFS of 53%, 61% and 35% (p <0.001), respectively. KMAs comparing pNx, pN0 ≥10 nodes and pN0 <10 nodes showed no significant difference in 2-year OS (82% vs 85% vs 84%, p=0.6) but elicited significantly higher 2-year RFS in the pN0 ≥10 group (60% vs 74% vs 54%, p=0.043). CONCLUSIONS: LND during nephroureterectomy in patients with positive lymph nodes provides prognostic data, but is not associated with improved OS. LND yields ≥10 in patients with clinical node negative disease were associated with improved RFS. In high-grade and large tumors, lymphadenectomy should be considered.

Sun protection behaviors among people living with HIV.

People living with HIV (PLWH) are at increased risk for both melanoma and nonmelanoma skin cancers, but there is currently no data on sun protection behaviors among PLWH. We created a 28-question paper survey to collect information on patient demographics and sun protection behaviors among PLWH. We found that although 71.6% of respondents reported spending at least 30 minutes to two hours in the sun daily, only 29.7% reported consistent use of sunscreen. In addition, 41.9% rarely or never received sunscreen counseling by their healthcare providers. There is therefore a need for increased training for healthcare providers in sun protection behavior counseling for PLWH.

The development and validation of the AMPREDICT model for predicting mobility outcome after dysvascular lower extremity amputation.

OBJECTIVE: The objective of this study was the development of AMPREDICT-Mobility, a tool to predict the probability of independence in either basic or advanced (iBASIC or iADVANCED) mobility 1 year after dysvascular major lower extremity amputation. METHODS: Two prospective cohort studies during consecutive 4-year periods (2005-2009 and 2010-2014) were conducted at seven medical centers. Multiple demographic and biopsychosocial predictors were collected in the periamputation period among individuals undergoing their first major amputation because of complications of peripheral arterial disease or diabetes. The primary outcomes were iBASIC and iADVANCED mobility, as measured by the Locomotor Capabilities Index. Combined data from both studies were used for model development and internal validation. Backwards stepwise logistic regression was used to develop the final prediction models. The discrimination and calibration of each model were assessed. Internal validity of each model was assessed with bootstrap sampling. RESULTS: Twelve-month follow-up was reached by 157 of 200 (79%) participants. Among these, 54 (34%) did not achieve iBASIC mobility, 103 (66%) achieved at least iBASIC mobility, and 51 (32%) also achieved iADVANCED mobility. Predictive factors associated with reduced odds of achieving iBASIC mobility were increasing age, chronic obstructive pulmonary disease, dialysis, diabetes, prior history of treatment for depression or anxiety, and very poor to fair self-rated health. Those who were white, were married, and had at least a high-school degree had a higher probability of achieving iBASIC mobility. The odds of achieving iBASIC mobility increased with increasing body mass index up to 30 kg/m2 and decreased with increasing body mass index thereafter. The prediction model of iADVANCED mobility included the same predictors with the exception of diabetes, chronic obstructive pulmonary disease, and education level. Both models showed strong discrimination with C statistics of 0.85 and 0.82, respectively. The mean difference in predicted probabilities for those who did and did not achieve iBASIC and iADVANCED mobility was 33% and 29%, respectively. Tests for calibration and observed vs predicted plots suggested good fit for both models; however, the precision of the estimates of the predicted probabilities was modest. Internal validation through bootstrapping demonstrated some overoptimism of the original model development, with the optimism-adjusted C statistic for iBASIC and iADVANCED mobility being 0.74 and 0.71, respectively, and the discrimination slope 19% and 16%, respectively. CONCLUSIONS: AMPREDICT-Mobility is a user-friendly prediction tool that can inform the patient undergoing a dysvascular amputation and the patient's provider about the probability of independence in either basic or advanced mobility at each major lower extremity amputation level.

Suicidal ideation among individuals with dysvascular lower extremity amputation.

OBJECTIVE: To examine the estimated prevalence and correlates of suicidal ideation (SI) among individuals 1 year after a first lower extremity amputation (LEA). DESIGN: Cohort survey. SETTING: Four medical centers. PARTICIPANTS: A referred sample of patients (N=239), primarily men, undergoing their first LEA because of complications of diabetes mellitus or peripheral arterial disease, were screened for participation between 2005 and 2008. Of these patients, 136 (57%) met study criteria and 87 (64%) enrolled; 70 (80.5%) of the enrolled patients had complete data regarding SI at 12-month follow-up. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: SI, demographic/health information, depressive symptoms, mobility, independence in activities of daily living (ADL), satisfaction with mobility and ADL, medical comorbidities, social support, self-efficacy. RESULTS: At 12 months postamputation, 11 subjects (15.71%) reported SI; of these, 3 (27.3%) screened negative for depression. Lower mobility, lower satisfaction with mobility, greater impairment in ADL, lower satisfaction with ADL, lower self-efficacy, and depressive symptoms were all correlated with the presence of SI at a univariate level; of these, only depressive symptoms remained significantly associated with SI in a multivariable model. CONCLUSIONS: SI was common among those with recent LEA. Several aspects of an amputee's clinical presentation, such as physical functioning, satisfaction with functioning, and self-efficacy, were associated with SI, although depression severity was the best risk marker. A subset of the sample endorsed SI in the absence of a positive depression screen. Brief screening for depression that includes assessment of SI is recommended.

Changes in cognitive function from presurgery to 4 months postsurgery in individuals undergoing dysvascular amputation.

OBJECTIVE: To describe cognition among individuals with new amputations at 3 time points: presurgical, 6 weeks postamputation, and 4 months postamputation. DESIGN: Prospective cohort. SETTING: Medical centers. PARTICIPANTS: Referred sample Veterans who were primarily men (N=80) experiencing their first lower extremity amputation as a result of complications of diabetes mellitus or peripheral arterial disease. Patients were screened for the absence of gross cognitive impairment using the Short Portable Mental Status Questionnaire (SPMSQ). Of those 87 individuals who were eligible, 64% enrolled; 29 were enrolled presurgically and have cognitive data for all 3 time points, and 58 were enrolled postamputation. Eighty of the 87 individuals enrolled by 6 weeks remained enrolled at 4 months. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Demographic and general health information, general mental status (SPMSQ), and 4 brief, well-established neuropsychological measures. RESULTS: Most mean neuropsychological test scores fell in the low average or average range. For most participants, overall cognitive status improved from pre- to postsurgery and then remained stable between 6 weeks and 4 months. There were significant improvements between pre- and postsurgical test scores in verbal learning and memory, and these remained unchanged between 6 weeks and 4 months. Better 4 month cognitive performance was associated with higher perceived general health. CONCLUSIONS: Overall cognitive performance is poorest presurgically. Though there is improvement between pre- and postamputation, cognition appears generally stable between 6 weeks and 4 months.

Unraveling the BMI paradox in different renal cortical tumors: insights from the INMARC registry.

OBJECTIVE: To investigate impact of body mass index (BMI) on survival across different histologies and stages of renal cell carcinoma (RCC). METHODS: We conducted a retrospective multicenter analysis of clear cell (ccRCC) and non-ccRCC. Obesity was defined according to the WHO criteria (non-Asian BMI >30 Kg/m2, Asian BMI >27.5 Kg/m2). Multivariable analysis (MVA) via Cox regression model was conducted for all-cause (ACM), cancer-specific mortality (CSM) and recurrence. RESULTS: A total of 3,880 patients with a median follow-up of 31 (IQR 9-64) months were analyzed. Overall, 1,373 (35.3%) were obese; 2,895 (74.6%) were ccRCC and 985 (25.3%) were non-ccRCC (chRCC 246 [24.9%], pRCC 469 [47.6%] and vhRCC 270 [27.4%]). MVA in ccRCC revealed obesity associated with decreased risk of ACM, CSM and recurrence (hazard ratio [HR] 0.80, P = 0.044; HR 0.71, P = 0.039; HR 0.73, P = 0.012, respectively), while in non-ccRCC was not associated with decreased risk of ACM, CSM, and recurrence (P = 0.84, P = 0.53, P = 0.84, respectively). Subset analysis in stage IV ccRCC demonstrated obesity as associated with a decreased risk of ACM, CSM, and recurrence (HR 0.68, P = 0.04; HR 0.59, P = 0.01; HR 0.59, P = 0.01, respectively), while in stage I-III ccRCC was not (P = 0.21; P = 0.30; P = 0.19, respectively). CONCLUSION: Our findings refute a broad "obesity paradox" for RCC. Obesity was not associated with improved survival in non-ccRCC and in nonmetastatic ccRCC, while metastatic ccRCC patients with obesity had improved survival outcomes.

Association of Elevated C-Reactive Protein with Worsened Outcomes in Different Histologies of Renal Cortical Tumors: Analysis of the INMARC Registry.

BACKGROUND: To evaluate relationship between histological subtypes of renal cell carcinoma (RCC) and preoperative c-reactive protein (CRP). PATIENTS AND METHODS: We queried the International Marker Consortium for Renal Cancer database for patients affected by RCC. Patients were classified according to their histology: benign tumors, clear cell (cc) RCC, chromophobe (ch) RCC, papillary (p) RCC, and variant histology (vh) RCC; and according to CRP (mg/L): low CRP ≤5 and high CRP >5. Primary outcome was all-cause mortality (ACM). Secondary outcomes were cancer-specific mortality (CSM), recurrence and association between CRP and histology. Multivariable analysis (MVA) via Cox regression and multivariable logistic regression were fitted to elucidate predictors of outcomes. RESULTS: Total 3902 patients (high CRP n = 1266) were analyzed; median follow up 51 (IQR 20-91) months. On MVA elevated CRP was an independent risk factor associated with increased risk of ACM in benign tumors (HR 5.98, P < .001), ccRCC (HR 2.69, P < .001), chRCC (HR 3.99, P < .001), pRCC (HR 1.76, P = .009) and vhRCC (HR 2.97, P =.007). MVA for CSM showed CRP as risk factor in ccRCC (HR 2.77, P < .001), chRCC (HR 6.16, P = .003) and pRCC (HR 2.29, P = .011), while in vhRCC was not (P = .27). MVA for recurrence reported CRP as risk factor for ccRCC (HR 1.30, P = .013), while in chRCC (P = .33), pRCC (P = .34) and vhRCC (P = .52) was not. On multivariable logistic regression CRP was a predictor of pRCC (OR 1.003, P = .002), while decreasing CRP was associated with benign tumors (OR 0.994, P = .048). CONCLUSION: Elevated CRP was a robust predictor of worsened ACM in all renal cortical neoplasms. While most frequently observed in pRCC patients, elevated CRP was independently associated with worsened CSM in non-vhRCC. Conversely, elevated CRP was least likely to be noted in benign tumors, and elevation in this subgroup of patients should prompt further consideration for surveillance given increased risk of ACM. Further investigation is requisite.

NODESAFE Nomogram: A Novel Score System to Predict Lymph Node Involvement at the Time of Nephrectomy or Nodal Recurrence in Nonmetastatic Renal Cell Carcinoma.

OBJECTIVE: We sought to develop a preoperative nomogram called NODESAFE (NODE SAFEty) to predict nodal involvement (NI) at time of surgery or subsequent follow up in localized renal cell carcinoma (RCC), as the role of lymphadenectomy in localized RCC remains controversial. METHODS: We conducted a multicenter retrospective analysis of RCC patients who underwent primary surgical resection. Patients with clinical metastasis at presentation were excluded. NI was defined as presence of histological RCC with lymphadenectomy at time of surgery, or subsequent development histologically proven NI. The dataset was divided into training (70%) and testing subsets to facilitate model evaluation which was constructed through a stepwise multivariable logistic regression (MLR) model. Accuracy was tested with receiver operator characteristic estimated area under the curve (AUC). RESULTS: Total 3308 patients (2221 [67.1%] male) met inclusion criteria. During follow-up 25 patients (0.76 %) experienced nodal recurrence, and 22/25 were preoperatively classified as cN0. In our cohort, 112 (3.4%) patients had clinical lymphadenopathy preoperatively (cN1), and 34/112 were pN1. The following covariates were found to be statically significant on a MLR model: hypertension (Odds ratio [OR] 3.35, < .001), Charlson Comorbidity Index ≥ 5 (OR 1.93 P = .025), tumor size ≥ 6 cm (OR 2.63, P = .001), tumor necrosis at CT scan (OR 1.83, P = .036), cN1 (OR 5.59, P < .001) and CRP ≥ 8.5 mg/L (1.96, P = .018). Testing the prediction performance of the model in the validation set AUC of the model was 0.89. NODESAFE demonstrated a sensitivity of 83.9%, specificity of 86.1% and 99.1% negative predictive values using a 4% threshold probability. CONCLUSION: Combining clinical features, serum biomarkers and radiographic findings, we developed a model capable of predicting NI with high degree of accuracy. NODESAFE may refine clinical decision making with respect to the performance of lymphadenectomy at the time of surgery, postsurgical surveillance, and spur consideration for adjuvant therapy.

Survival Outcomes by Race Following Surgical Treatment for Upper Tract Urothelial Carcinoma.

OBJECTIVE: Discrepancies in survival outcomes of various genitourinary tract malignancies have been documented across different racial and ethnic groups. Here we sought to examine long-term survival outcomes of patients with upper tract urothelial carcinoma (UTUC) following radical nephroureterectomy (RNU) when stratified by race. METHODS: A multicenter retrospective analysis using the ROBUUST (ROBotic surgery for Upper tract Urothelial cancer Study) registry identified patients undergoing RNU for UTUC between 2015 and 2022 at 12 centers across the United States, Europe, and Asia. Patients were stratified by race (white, black, Hispanic, and Asian) and primary outcomes of interest-including recurrence-free survival (RFS), metastasis free survival (MFS) and overall survival (OS) - were assessed using univariate analysis, multivariate Cox regression modeling, and Kaplan-Meier analysis. RESULTS: 1446 patients (white n = 652, black n = 70, Hispanic n = 87, and Asian n = 637) who underwent RNU for treatment of the UTUC were included in our analysis. Cox regression modeling demonstrated pathologic nodal staging to be a significant predictor of RFS (HR 2.25; P = .0010), MFS (HR 2.50; P = .0028), and OS (HR 5.11; P < .0001). When using whites as the reference group, there were no significant differences in RFS, MFS, or OS across racial groups. CONCLUSIONS: Unlike other genitourinary tract malignancies, our study failed to demonstrate a survival disadvantage among minority racial groups with UTUC who underwent RNU. Furthermore, a significant difference in RFS, MFS, and OS was not identified across whites, blacks, Asians, or Hispanics with UTUC who underwent RNU.

Predictive factors for recurrence and outcomes in T1a renal cell carcinoma: Analysis of the INMARC (International Marker Consortium for Renal Cancer) database.

OBJECTIVE: Stage migration in renal cell carcinoma (RCC) has led to an increasing proportion of diagnosed small renal masses. Emerging knowledge regarding heterogeneity of RCC histologies and consequent impact on prognosis led us to further explore outcomes and predictive factors in surgically-treated T1a RCC. METHODS: The INMARC database was queried for T1aN0M0 RCC. Patients were stratified into groups based on recurrence. Primary outcome was overall survival (OS). Multivariable analyses (MVA) were performed for factors associated with recurrence, cancer-specific (CSM), and all-cause mortality (ACM). Kaplan-Meier analyses (KMA) assessed survival by histology and grade. Subset analysis for time to recurrence was conducted for grade and histologic groups and compared with recent AUA follow-up guidelines [low-risk (AUA-LR), intermediate-risk (AUA-IR), high-risk (AUA-HR), and very-high risk (AUA-VHR) groups]. RESULTS: We analyzed 1,878 patients (median follow-up 35.2 months); 101 (5.4%) developed recurrence. MVA for recurrence demonstrated increasing age (P = 0.026), male sex (P = 0.043), diabetes (P = 0.007), high/unclassified grade (P < 0.001-0.007), and variant histology (P = 0.017) as independent risk factors for increased risk, while papillary (P = 0.016) and chromophobe (P = 0.049) were associated with decreased risk. MVA identified high/unclassified grade (P = 0.003-0.004) and pT3a upstaging (P = 0.043) as predictive factors for worsened risk of CSM while papillary (P = 0.034) was associated with improved risk. MVA for ACM demonstrated increasing age (P < 0.001), non-white (P < 0.001), high-grade (P = 0.022), variant histology (P = 0.049), recurrence (P = 0.004), and eGFR<45 at last follow-up (P < 0.001) to be independent risk factors. KMA comparing clear cell, chromophobe, papillary, and variant RCC revealed significant differences for 5-year CSS (P = 0.018) and RFS (P < 0.001), but not OS (P = 0.34). Median time to recurrence was 23.8 months for low-grade (AUA-LR), 17.3 months for high-grade (AUA-IR), 18 months for pT3a upstaging (AUA-HR), and 12 months for variant histology (AUA-VHR; P < 0.001). CONCLUSION: We noted differential outcomes in T1a RCC based on histology and grade for recurrence and CSM, while renal functional decline in addition to pathological factors and recurrence were predictive for ACM. Our findings support recently promulgated AUA follow-up guidelines for low-grade and variant histology pT1a RCC, but call for consolidation of follow-up protocols for high-grade pT1a and pT3a upstaged patients, with intensification of frequency of imaging follow-up in pT1a high-grade RCC.

Age-Related Differences in Oncological Outcomes in Renal Cell Carcinoma: Impact of Functional Conservation as Measured by Postoperative eGFR.

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

Partial versus radical nephrectomy for complex renal mass: multicenter comparative analysis of functional outcomes (Rosula collaborative group).

BACKGROUND: Utility of partial nephrectomy (PN) for complex renal mass (CRM) is controversial. We determined the impact of surgical modality on postoperative renal functional outcomes for CRM. METHODS: We retrospectively analyzed a multicenter registry (ROSULA). CRM was defined as RENAL Score 10-12. The cohort was divided into PN and radical nephrectomy (RN) for analyses. Primary outcome was development of de-novo estimated glomerular filtration rate (eGFR)<45 mL/min/1.73 m2. Secondary outcomes were de-novo eGFR<60 and ΔeGFR between diagnosis and last follow-up. Cox proportional hazards was used to elucidate predictors for de-novo eGFR<60 and <45. Linear regression was utilized to analyze ΔeGFR. Kaplan-Meier Analysis (KMA) was performed to analyze 5-year freedom from de-novo eGFR<60 and <45. RESULTS: We analyzed 969 patients (RN=429/PN=540; median follow-up 24.0 months). RN patients had lower BMI (P<0.001) and larger tumor size (P<0.001). Overall postoperative complication rate was higher for PN (P<0.001), but there was no difference in major complications (Clavien III-IV; P=0.702). MVA demonstrated age (HR=1.05, P<0.001), tumor-size (HR=1.05, P=0.046), RN (HR=2.57, P<0.001), and BMI (HR=1.04, P=0.001) to be associated with risk for de-novo eGFR<60 mL/min/1.73 m2. Age (HR=1.03, P<0.001), BMI (HR=1.06, P<0.001), baseline eGFR (HR=0.99, P=0.002), tumor size (HR=1.07, P=0.007) and RN (HR=2.39, P<0.001) were risk factors for de-novo eGFR<45 mL/min/1.73 m2. RN (B=-10.89, P<0.001) was associated with greater ΔeGFR. KMA revealed worse 5-year freedom from de-novo eGFR<60 (71% vs. 33%, P<0.001) and de-novo eGFR<45 (79% vs. 65%, P<0.001) for RN. CONCLUSIONS: PN provides functional benefit in selected patients with CRM without significant increase in major complications compared to RN, and should be considered when technically feasible.

Outcomes of Consolidative Nephrectomy following Primary Immunotherapy in Advanced Renal Cell Carcinoma: A Multicenter Analysis.

BACKGROUND: To evaluate effect and outcomes of combination primary immunotherapy (IO) and nephrectomy for advanced renal cell carcinoma (RCC). METHODS: We conducted a multicenter, retrospective analysis of patients with advanced/metastatic RCC who received IO followed by nephrectomy. Primary outcome was Bifecta (negative surgical margins and no 30-day surgical complications). Secondary outcomes included progression-free survival (PFS) following surgery, reduction in tumor/thrombus size, RENAL score, and clinical/pathologic downstaging. Cox regression multivariable analysis was conducted for predictors of Bifecta and PFS. Kaplan-Meier analysis assessed PFS, comparing Bifecta and non-Bifecta groups. RESULTS: A total of 56 patients were analyzed (median age 63 years; median follow-up 22.5 months). A total of 40 (71.4%) patients were intermediate IMDC risk. Patients were treated with immunotherapy for median duration of 8.1 months. Immunotherapy resulted in reductions in tumor size (P < .001), thrombus size (P = .02), and RENAL score (P < .001); 38 (67.9%) patients were clinically downstaged on imaging (P < .001) and 25 (44.6%) patients were pathologically downstaged following surgery (P < .001). Bifecta was achieved in 38 (67.9%) patients. Predictors for bifecta achievement included decreasing tumor size (HR 1.08, P = .043) and pathological downstaging (HR 2.13, P = .047). Bifecta (HR 5.65, P = .009), pathologic downstaging (HR 5.15, P = .02), and increasing reduction in tumor size (HR 1.2, P = .007) were associated with improved PFS. Bifecta patients demonstrated improved 2-year PFS (84% vs. 71%, P = .019). CONCLUSIONS: Primary immunotherapy reduced tumor/thrombus size and complexity. Pathologically downstaged patients were more likely to achieve bifecta, and these patients displayed improved 2-year PFS. Our study supports further inquiry in the use of CRN following primary immunotherapy for advanced renal cancer.

Development of a novel score (RENSAFE) to determine probability of acute kidney injury and renal functional decline post surgery: A multicenter analysis.

OBJECTIVE: To create and validate 2 models called RENSAFE (RENalSAFEty) to predict postoperative acute kidney injury (AKI) and development of chronic kidney disease (CKD) stage 3b in patients undergoing partial (PN) or radical nephrectomy (RN) for kidney cancer. METHODS: Primary objective was to develop a predictive model for AKI (reduction >25% of preoperative eGFR) and de novo CKD≥3b (<45 ml/min/1.73m2), through stepwise logistic regression. Secondary outcomes include elucidation of the relationship between AKI and de novo CKD≥3a (<60 ml/min/1.73m2). Accuracy was tested with receiver operator characteristic area under the curve (AUC). RESULTS: AKI occurred in 452/1,517 patients (29.8%) and CKD≥3b in 116/903 patients (12.8%). Logistic regression demonstrated male sex (OR = 1.3, P = 0.02), ASA score (OR = 1.3, P < 0.01), hypertension (OR = 1.6, P < 0.001), R.E.N.A.L. score (OR = 1.2, P < 0.001), preoperative eGFR<60 (OR = 1.8, P = 0.009), and RN (OR = 10.4, P < 0.0001) as predictors for AKI. Age (OR 1.0, P < 0.001), diabetes mellitus (OR 2.5, P < 0.001), preoperative eGFR <60 (OR 3.6, P < 0.001) and RN (OR 2.2, P < 0.01) were predictors for CKD≥3b. AUC for RENSAFE AKI was 0.80 and 0.76 for CKD≥3b. AKI was predictive for CKD≥3a (OR = 2.2, P < 0.001), but not CKD≥3b (P = 0.1). Using 21% threshold probability for AKI achieved sensitivity: 80.3%, specificity: 61.7% and negative predictive value (NPV): 88.1%. Using 8% cutoff for CKD≥3b achieved sensitivity: 75%, specificity: 65.7%, and NPV: 96%. CONCLUSION: RENSAFE models utilizing perioperative variables that can predict AKI and CKD may help guide shared decision making. Impact of postsurgical AKI was limited to less severe CKD (eGFR<60 ml/min 71.73m2). Confirmatory studies are requisite.

The effect of rehabilitation in a comprehensive inpatient rehabilitation unit on mobility outcome after dysvascular lower extremity amputation.

OBJECTIVES: To (1) compare the total volume of rehabilitation therapy for patients ever attending a comprehensive inpatient rehabilitation unit (CIRU) versus never during the 12 months after amputation; (2) determine whether rehabilitation in a CIRU at any time in the first year after amputation results in greater mobility success compared with other types of rehabilitation environments of care; and (3) determine for those patients treated in a CIRU, which specific patient characteristics were associated with improved mobility outcome. DESIGN: Prospective cohort study. SETTING: Two Veterans Affairs medical centers. PARTICIPANTS: Patients (N=199) with peripheral vascular disease or diabetes undergoing a first unilateral major amputation were screened for participation between September 2005 and December 2008. Among these, 113 (57%) met study criteria; of these, 72 (64%) participated. INTERVENTION: Ever attending a CIRU versus never attending a CIRU in first 12 months after amputation. MAIN OUTCOME MEASURES: Number of rehabilitation therapy visits, Locomotor Capability Index scores, and mobility success. RESULTS: The mean number of all therapy visits for patients ever attending a CIRU was significantly greater than that for those never attending over a 12-month period (48.6 vs 22.6; P=.001). Mean total time per any rehabilitation visit was .83±.27 hours for those ever attending and .60±.20 hours for those never attending (P<.001). Patients who ever were treated in a CIRU were 17% more likely to achieve mobility success than those who were not, controlling for amputation level, major depressive episode, alcohol use, social support, total number of rehabilitation visits, and hospital site (risk difference=.17; 95% confidence interval, .09-.25; P<.001). CONCLUSIONS: Rehabilitation in a CIRU resulted in improved mobility success for veterans undergoing major lower extremity amputation secondary to peripheral vascular disease or diabetes. Among those admitted to a CIRU, younger patients with greater social support, healthy weight, and without chronic obstructive pulmonary disease had the greatest probability of mobility success.