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OBJECTIVE: To report the results of PADRES (Prior Axitinib as a Determinant of Outcome of Renal Surgery, NCT03438708), a study investigating neoadjuvant axitinib for tumours of high complexity with imperative indication for partial nephrectomy (PN). METHODS: We conducted a single-arm phase II clinical trial of localized (cT1b-cT3M0) clear-cell renal cell carcinoma (RCC) patients with imperative indications for nephron preservation, where PN is a high-risk procedure due to complexity (RENAL score 10-12). Axitinib 5 mg was administered twice daily for 8 weeks with repeat imaging at completion, followed by surgery. The primary outcome was successful completion of planned PN following axitinib treatment. Secondary objectives included changes in tumour diameter, RENAL nephrometry score, renal function and Response Evaluation Criteria in Solid Tumours (RECIST) v1.1, and surgical complications. RESULTS: Twenty-seven patients were enrolled (median age 69 years). Prior to therapy, twenty patients (74.0%) had ≥ clinical T3a staged tumours. Axitinib resulted in reductions in tumour diameter (7.5 vs 6.2 cm; P < 0.001) and RENAL score (11 vs 10; P < 0.001). Nine patients (33.3%) had partial response based on RECIST and nine (33.3%) were clinically downstaged. PN was performed in twenty patients (74.0%); twenty-five patients (96.2%) had negative margins. Six patients (22.2%) had Clavien III-IV complications. The median change in estimated glomerular filtration rate (preoperative to last follow-up) was 8.5 mL/min/1.73 m2 . CONCLUSION: Neoadjuvant axitnib resulted in reductions in tumour size and complexity, enabling safe and feasible PN and functional preservation in patients with complex renal masses and imperative indication.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Anciano , Axitinib/uso terapéutico , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/cirugía , Neoplasias Renales/patología , Terapia Neoadyuvante , Resultado del Tratamiento , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/cirugía , Carcinoma de Células Renales/patología , Nefrectomía/métodos , Estudios RetrospectivosRESUMEN
Background and Objectives: to investigate the impact of age on renal function deterioration after robotic-assisted partial nephrectomy (RAPN) focusing on a decline to moderate and severe forms of chronic kidney disease (CKD). Materials and Methods: This is a single center prospective analysis of patients who underwent RAPN. The outcomes include the development of de novo CKD-S 3a [estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2)] and de novo CKD-S 3b (eGFR < 45 mL/min/1.73/m2). Multivariable analysis (MVA) via Cox regression identified predictors for CKD-S 3a/b. Kaplan -Meier Analyses (KMA) were fitted for survival assessment. Multivariable linear regression was utilized to identify the predictors of last-eGFR. Results: Overall, 258 patients were analyzed [low age (<50) n = 40 (15.5%); intermediate age (50-70) n = 164 (63.5%); high age (>70) n = 54 (20.9%)] with a median follow-up of 31 (IQR 20-42) months. MVA revealed an increasing RENAL score [Hazard Ratio (HR) 1.32, p = 0.009], age 50-70 (HR 6.21, p = 0.01), age ≥ 70 (HR 10.81, p = 0.001), increasing BMI (HR 1.11, p < 0.001) and preoperative CKD 2 (HR 2.43, p = 0.014) are independent risk factors associated with an increased risk of CKD-S 3a; conversely, post-surgical acute kidney injury was not (p = 0.83). MVA for CKD-S 3b revealed an increasing RENAL score (HR 1.51, p = 0.013) and age ≥ 70 (HR 2.73, p = 0.046) are associated with an increased risk of CKD-S 3b. Linear regression analysis revealed increasing age (Coeff. -0.76, p < 0.001), increasing tumor size (Coeff. -0.31, p = 0.03), and increasing BMI (Coeff. -0.64, p = 0.004) are associated with decreasing eGFR at last follow-up. We compare the survival distribution of our cohort stratified by age elderly patients experienced worsened CKD-S 3a/b disease-free survival (p < 0.001; p < 0.001, respectively). Conclusions: Age is independently associated with a greater risk of significant and ongoing decline in kidney function following RAPN. Recognizing the impact of aging on renal function post-surgery can guide better management practices. Further investigations are required.
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Neoplasias Renales , Insuficiencia Renal Crónica , Procedimientos Quirúrgicos Robotizados , Humanos , Anciano , Persona de Mediana Edad , Neoplasias Renales/cirugía , Procedimientos Quirúrgicos Robotizados/efectos adversos , Centros de Atención Terciaria , Resultado del Tratamiento , Estudios Retrospectivos , Riñón , Nefrectomía/efectos adversos , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/epidemiología , Tasa de Filtración GlomerularRESUMEN
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.
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Carcinoma de Células Renales , Neoplasias Renales , Insuficiencia Renal Crónica , Humanos , Carcinoma de Células Renales/complicaciones , Carcinoma de Células Renales/cirugía , Carcinoma de Células Renales/patología , Neoplasias Renales/complicaciones , Neoplasias Renales/cirugía , Neoplasias Renales/patología , Estudios Retrospectivos , Insuficiencia Renal Crónica/complicaciones , Nefrectomía/métodos , Tasa de Filtración GlomerularRESUMEN
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.
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Carcinoma de Células Renales , Neoplasias Renales , Procedimientos Quirúrgicos Robotizados , Humanos , Neoplasias Renales/patología , Carcinoma de Células Renales/patología , Procedimientos Quirúrgicos Robotizados/métodos , Resultado del Tratamiento , Nefrectomía/métodos , Estudios RetrospectivosRESUMEN
OBJECTIVE: To investigate association of preoperative C-reactive protein (CRP) and non-cancer mortality (NCM) in a cohort of patients undergoing surgery for localised renal cell carcinoma (RCC). PATIENTS AND METHODS: Retrospective multicentre analysis of patients surgically treated for clinical Stage 1-2 RCC from 2006 to 2017, excluding all cases of cancer-specific mortality. Descriptive analyses were obtained between the pre-treatment normal-CRP (≤5 mg/L) and elevated-CRP (>5 mg/L) groups. The primary outcome was NCM. The secondary outcomes included progression to de novo chronic kidney disease Stages 3-4 (estimated glomerular filtration rate [eGFR] of <60, <45, and <30 mL/min/1.73 m2 ). Multivariable analyses (MVA) were performed to assess for risk factors associated with functional decline and NCM, and Kaplan-Meier analysis was used to obtain survival estimates for outcomes. RESULTS: A total of 1987 patients who underwent radical or partial nephrectomy were analysed (normal-CRP group, n = 963; elevated-CRP group, n = 1024). Groups were similar in age (59 vs 60 years, P = 0.079). An elevated CRP was more frequent in males (36.8% vs 27.8%, P < 0.001), African-Americans (22.6% vs 2.9%, P < 0.001), and in those with a higher median body mass index (30 vs 25 kg/m2 , P < 0.001) and larger median tumour size (4.5 vs 3.3 cm, P < 0.001). On MVA, an elevated CRP was independently associated with development of de novo eGFR of <60 mL/min/1.73 m2 (hazard ratio [HR] 1.32, P = 0.015), <45 mL/min/1.73 m2 (HR 1.41, P = 0.023) and <30 mL/min/1.73 m2 (odds ratio 2.23, P < 0.001). The MVA for factors associated with NCM demonstrated increasing age (HR 1.06, P < 0.001), preoperative elevated CRP (HR 2.18, P < 0.001) and an eGFR of <45 mL/min/1.73 m2 (HR 1.16; P = 0.021) as independent risk factors. Kaplan-Meier analysis revealed significantly higher 5-year NCM in the elevated-CRP group vs the normal-CRP group (98% vs 80%, P < 0.001). CONCLUSIONS: Pre-treatment elevated CRP was independently associated with both progressive renal functional decline and NCM in patients undergoing surgery for Stage 1-2 RCC. Patients with elevated CRP and Stage 1 and 2 RCC may be considered as having indication for nephron-sparing strategies, which may be prioritised if oncologically appropriate.
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Proteína C-Reactiva/metabolismo , Carcinoma de Células Renales/cirugía , Neoplasias Renales/cirugía , Insuficiencia Renal/sangre , Factores de Edad , Anciano , Biomarcadores/sangre , Carcinoma de Células Renales/complicaciones , Carcinoma de Células Renales/patología , Progresión de la Enfermedad , Femenino , Tasa de Filtración Glomerular , Humanos , Estimación de Kaplan-Meier , Neoplasias Renales/complicaciones , Neoplasias Renales/patología , Masculino , Persona de Mediana Edad , Mortalidad , Nefrectomía/efectos adversos , Tratamientos Conservadores del Órgano , Selección de Paciente , Periodo Preoperatorio , Pronóstico , Insuficiencia Renal/etiología , Insuficiencia Renal/fisiopatología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
PURPOSE: To compare functional outcomes of partial nephrectomy (PN) and active surveillance (AS) in oncocytoma. METHODS: Multicenter retrospective analysis of patients with oncocytoma managed with PN or AS (biopsy-confirmed). Primary outcome development of de novo chronic kidney disease (CKD) (eGFR < 60 mL/min/1.73m2). Cox regression Multivariable analysis (MVA) was carried out for predictors of de novo CKD. Linear regression was carried out for factors associated with increasing deltaGFR. Kaplan-Meier Analysis (KMA) was performed to analyze 5-year CKD-free survival. RESULTS: 295 patients were analyzed (224 PN/71 AS, median follow-up 37.4 months). No differences were noted for clinical tumor size (AS 2.6 vs. PN 2.9 cm, p = 0.108), and baseline eGFR (AS 79.6 vs. PN 77, p = 0.9670). Median change in tumor diameter for AS was 0.42 cm. Compared to PN, AS had deltaGFR (-15.3 vs. -6.4 mL/min/1.73m2, p < 0.001) and de novo CKD (28.2% vs. 12.1%, p = 0.002). AS patients who developed CKD had higher RENAL score (p = 0.005) and lower baseline eGFR (73 vs. 91.2 mL/min/1.73m2, p < 0.001) than AS patients who did not. MVA demonstrated increasing age (OR = 1.03, p = 0.025), tumor size (HR = 1.26, p = 0.032) and AS (HR = 4.91, p < 0.001) to be predictive for de novo CKD. Linear regression demonstrated AS was associated with larger decrease in deltaGFR (B = -0.219, p < 0.001). KMA revealed 5-year CKD survival was higher in PN (87%) vs. AS (62%, p < 0.001). CONCLUSION: AS was associated with greater functional decline than PN in oncocytoma. PN may be considered to optimalize renal functional preservation in select circumstances. Further investigation into mechanisms of functional decline in oncocytoma is requisite.
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Adenoma Oxifílico/terapia , Neoplasias Renales/terapia , Nefrectomía/métodos , Espera Vigilante , Adenoma Oxifílico/cirugía , Anciano , Femenino , Humanos , Riñón/fisiología , Neoplasias Renales/cirugía , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
PURPOSE: To compare renal function and survival outcomes in patients with baseline chronic kidney disease (CKD) stage 2 undergoing partial (PN) or radical nephrectomy (RN), as nephron-sparing surgery is considered to be elective in this group. METHODS: Retrospective analysis of patients with CKD stage 2 and T1/T2 renal mass undergoing PN or RN from 2001 to 2015. Patients were stratified into substage CKD 2a or CKD 2b and analyzed between types of surgery. Primary outcome was overall survival (OS), eGFR < 45 at last follow-up was the secondary outcome. Multivariable analysis (MVA) was conducted for predictors of eGFR < 45 and OS. Kaplan-Meier analyses were conducted for freedom from eGFR < 45 and OS. RESULTS: 1213 patients analyzed (CKD 2a 609/CKD 2b 604) on MVA, RN (OR 3.68, p = 0.001) and CKD 2b (OR 3.3, p = 0.002) were independently associated with development of eGFR < 45 at last follow-up and RN (OR 3.76, p = 0.005) and eGFR < 45 (OR 2.51, p = 0.029) were associated with decreased OS. Kaplan-Meier analyses revealed that patients with CKD 2a/PN had the highest 5-year freedom from eGFR < 45 (94.3%) compared to CKD 2a/RN patients (91.5%), CKD2b/PN patients (87.6%) and CKD 2b/RN patients 82.0% (p < 0.001). Kaplan-Meier analyses for OS demonstrated that patients with CKD 2a/PN had significantly greater 5-year OS (97.6%) compared to CKD 2a/RN patients (95.2%), CKD 2b/PN patients (93.2%), and CKD 2b/RN patients (92.4%, p = 0.043). CONCLUSIONS: Patients with baseline CKD stage 2, particularly CKD 2b and undergoing RN, are at increased risk of GFR < 45, which was associated with decreased OS. In patients with CKD 2b, a nephron-sparing strategy is indicated and should be prioritized when feasible.
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Procedimientos Quirúrgicos Electivos , Nefrectomía/métodos , Insuficiencia Renal Crónica/mortalidad , Insuficiencia Renal Crónica/cirugía , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recuperación de la Función , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Systemic therapy strategies in the setting of localized and locally advanced renal cell carcinoma have continued to evolve in two directions: (i) as adjuvant therapy (to reduce the risk of recurrence or progression in high-risk localized groups); or (ii) as neoadjuvant therapy as a strategy to render primary renal tumors amenable to planned surgical resection in settings where radical resection or nephron-sparing surgery was not thought to be safe or feasible. In the realm of adjuvant therapy, the results of adjuvant therapy phase III randomized clinical trials have been mixed and contradictory; nevertheless, the findings of the landmark Sunitinib Treatment of Renal Adjuvant Cancer study have led to approval of sunitinib as an adjuvant agent in the USA. In the realm of neoadjuvant therapy, presurgical tumor reduction has been shown in a number of phase II studies utilizing targeted molecular agents and in a recently published small randomized double-blind placebo-controlled study, and an expanding body of literature suggests benefit in select patients. Thus, large randomized clinical trial data are not present to support this approach, and guidelines for use of presurgical therapy have not been promulgated. The advent of immunomodulation through checkpoint inhibition represents an exciting horizon for adjuvant and neoadjuvant strategies. The present article reviews the current status and future prospects of adjuvant and neoadjuvant therapy in localized and locally advanced renal cell carcinoma.
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Antineoplásicos/uso terapéutico , Carcinoma de Células Renales/terapia , Neoplasias Renales/terapia , Sunitinib/uso terapéutico , Carcinoma de Células Renales/patología , Quimioterapia Adyuvante , Humanos , Neoplasias Renales/patología , Terapia Neoadyuvante , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
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.
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Proteína C-Reactiva , Carcinoma de Células Renales , Neoplasias Renales , Sistema de Registros , Humanos , Proteína C-Reactiva/metabolismo , Neoplasias Renales/patología , Neoplasias Renales/cirugía , Neoplasias Renales/sangre , Masculino , Femenino , Persona de Mediana Edad , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/cirugía , Carcinoma de Células Renales/sangre , Carcinoma de Células Renales/metabolismo , Anciano , Sistema de Registros/estadística & datos numéricos , Recurrencia Local de Neoplasia , Pronóstico , Factores de Riesgo , Estudios Retrospectivos , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/metabolismoRESUMEN
OBJECTIVE: To evaluate predictive ability of a novel combined index, Charlson comorbidity index and C-reactive protein (CCI-CRP), for outcomes in renal cell carcinoma (RCC), and compare predictive outcomes with of CCI-CRP to its separate components and to the UCLA integrated staging system (UISS). PATIENTS AND METHODS: We retrospectively analyzed INMARC registry of RCC patients. Receiver Operator Characteristics (ROC) analysis was fitted to identify threshold defining low-CRP (LCRP) and high-CRP (HCRP). Patients were stratified according to CCI [low-CCI ≤ 3 (LCCI); intermediate-CCI 4-6 (ICCI); high-CCI > 6 (HCCI)] and CRP level. Kaplan-Meier analysis (KMA) was conducted for overall (OS) and cancer-specific survival (CSS). Based on survival analysis distribution we proposed a new stratification: CCI-CRP. Model performance was assessed with ROC/area under the curve (AUC) analysis and compared to CCI and CRP alone, and UISS. RESULTS: We analyzed 2,890 patients (median follow-up 30 months). ROC identified maximum product sensitivity and specificity for CRP at 3.5 mg/L. KMA revealed 5-year OS of 95.6% for LCRP/LCCI, 83% LCRP/ICCI, 73.3% LCRP/HCCI, 62.6% HCRP/LCCI, 51.6% HCRP/ICCI and 40.5% HCRP/HCCI (P < .001). From this distribution, new CCI-CRP is proposed: low CCI-CRP (LCRP/LCCI and LCRP/ICCI), intermediate CCI-CRP (LCRP/HCCI and HCRP/LCCI), and high CCI-CRP (HCRP/ICCI and HCRP/HCCI). AUC for CCI-CRP showed improved performance for predicting OS/CSS vs. CCI alone (0.73 vs. 0.63/0.77 vs. 0.60), CRP alone (0.73 vs. 0.71/0.77 vs. 0.74) and UISS (0.73 vs 0.67/0.77 vs 0.73). CONCLUSIONS: CCI-CRP, exhibits increased prognostic performance for survival outcomes in RCC compared to CCI and CRP alone, and UISS. Further investigation is requisite.
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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, Pâ¯=â¯0.044; HR 0.71, Pâ¯=â¯0.039; HR 0.73, Pâ¯=â¯0.012, respectively), while in non-ccRCC was not associated with decreased risk of ACM, CSM, and recurrence (Pâ¯=â¯0.84, Pâ¯=â¯0.53, Pâ¯=â¯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, Pâ¯=â¯0.04; HR 0.59, Pâ¯=â¯0.01; HR 0.59, Pâ¯=â¯0.01, respectively), while in stage I-III ccRCC was not (Pâ¯=â¯0.21; Pâ¯=â¯0.30; Pâ¯=â¯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.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/patología , Paradoja de la Obesidad , Neoplasias Renales/patología , Riñón/patología , Obesidad/complicaciones , Estudios Retrospectivos , NefrectomíaRESUMEN
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.
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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 (Pâ¯=â¯0.026), male sex (Pâ¯=â¯0.043), diabetes (Pâ¯=â¯0.007), high/unclassified grade (P < 0.001-0.007), and variant histology (Pâ¯=â¯0.017) as independent risk factors for increased risk, while papillary (Pâ¯=â¯0.016) and chromophobe (Pâ¯=â¯0.049) were associated with decreased risk. MVA identified high/unclassified grade (Pâ¯=â¯0.003-0.004) and pT3a upstaging (Pâ¯=â¯0.043) as predictive factors for worsened risk of CSM while papillary (Pâ¯=â¯0.034) was associated with improved risk. MVA for ACM demonstrated increasing age (P < 0.001), non-white (P < 0.001), high-grade (Pâ¯=â¯0.022), variant histology (Pâ¯=â¯0.049), recurrence (Pâ¯=â¯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 (Pâ¯=â¯0.018) and RFS (P < 0.001), but not OS (Pâ¯=â¯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.
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Carcinoma de Células Renales , Bases de Datos Factuales , Neoplasias Renales , Recurrencia Local de Neoplasia , Humanos , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/cirugía , Masculino , Femenino , Recurrencia Local de Neoplasia/patología , Neoplasias Renales/patología , Neoplasias Renales/mortalidad , Neoplasias Renales/cirugía , Persona de Mediana Edad , Anciano , Pronóstico , Factores de Riesgo , Estadificación de NeoplasiasRESUMEN
With the advent of new therapeutic modalities, management of metastatic castrate-sensitive prostate cancer (mCSPC) has been in flux. From androgen-deprivation therapy to docetaxel to androgen receptor-signaling inhibitors, each agent has heralded a new treatment paradigm. As such, the optimal first-line therapy for mCSPC remains incompletely defined. This review provides a narrative of recent advances to systemic therapy within the mCSPC treatment space, particularly with regard to expansion to triplet therapy.
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Purpose: To review the current status of surgical and procedural treatments for renal cell carcinoma (RCC), focusing on oncological and functional outcomes, and the use of techniques for advanced disease over the last 10 years. Findings: Partial nephrectomy (PN) has become the reference standard for most T1 and T2 masses. In cT2 RCC, PN exhibits oncological equivalence and improved functional outcomes compared to radical nephrectomy (RN). Additionally, emerging data suggest that PN may be used to treat cT3a RCC. The robot-assisted platform is increasingly used to treat locally advanced RCC. Studies suggest safety and feasibility of robotic RN and robotic inferior vena cava tumor thrombectomy. Additionally, single-port robot-assisted laparoscopic approaches are comparable to multiport approaches in select patients. Long-term data show that cryoablation, radiofrequency ablation, and microwave ablation are equipotent in management of small renal masses. Emerging data suggest that microwave may effectively treat cT1b masses.
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Purpose: To evaluate whether computer program-estimated urolith stone volume (SV) was a better predictor of spontaneous passage (SP) compared with program-estimated stone diameter (PD) or manually measured stone diameter (MD), and whether utilizing SV and MD together provided additional value in SP prediction compared with MD alone. Materials and Methods: Retrospective analysis of patients with acute renal colic and single renal/ureteral stone on CT from July 2017 to April 2020. Diameter obtained from radiology reports or manually measured when report not available. Semiautomated stone analysis software (qSAS) was used to estimate SV and PD. ROC analysis was performed to compare accuracy of SV vs MD vs PD in predicting SP by 2, 4, and 6 weeks. Subgroup analysis was performed by stone size (≥6 mm) and location (proximal/distal). Results: Among 172 patients analyzed, SP occurred in 71 (41%). Patient age (mean 53), gender (38%F), and stone history/side did not differ significantly by SP. Average MD, PD, and SV were significantly smaller among SP stones vs stones requiring surgery (MD 4.3 mm vs 8.0 mm, PD 5.5 mm vs 9.4 mm, and SV 40 mm3 vs 312 mm3; p < 0.001). ROC analysis showed significantly higher area under curve (AUC) for SV for predicting SP by 4 and 6 weeks compared with MD and PD (AUC 0.93 vs 0.86 vs 0.85 4 weeks, p < 0.001; 0.92 vs 0.85 vs 0.86 6 weeks, p < 0.003). AUC difference between SV vs MD was much greater among stones ≥6 mm or proximal stones. Utilizing SV and MD together yielded improved positive predictive value and negative predictive value for SP prediction. Conclusions: SV is a more accurate predictor of SP compared with linear stone dimensions, especially in the setting of larger and/or more proximal stones. Utilizing SV and diameter together yielded improved SP predictions compared with using either metric alone. Prospective studies are indicated to investigate the clinical utility of SV for SP prediction.
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Cálculos Renales , Cálculos Ureterales , Humanos , Estudios Retrospectivos , Estudios Prospectivos , Remisión Espontánea , Cálculos Ureterales/diagnóstico por imagen , Programas InformáticosRESUMEN
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.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Anciano , Carcinoma de Células Renales/patología , Estudios Retrospectivos , Nefrectomía , Neoplasias Renales/patología , Tasa de Filtración GlomerularRESUMEN
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 (ORâ¯=â¯1.3, Pâ¯=â¯0.02), ASA score (ORâ¯=â¯1.3, P < 0.01), hypertension (ORâ¯=â¯1.6, P < 0.001), R.E.N.A.L. score (ORâ¯=â¯1.2, P < 0.001), preoperative eGFR<60 (ORâ¯=â¯1.8, Pâ¯=â¯0.009), and RN (ORâ¯=â¯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 (ORâ¯=â¯2.2, P < 0.001), but not CKD≥3b (Pâ¯=â¯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.
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Lesión Renal Aguda , Neoplasias Renales , Insuficiencia Renal Crónica , Humanos , Masculino , Tasa de Filtración Glomerular , Neoplasias Renales/cirugía , Nefrectomía/efectos adversos , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/etiología , Insuficiencia Renal Crónica/etiología , Insuficiencia Renal Crónica/complicaciones , Factores de Riesgo , Estudios RetrospectivosRESUMEN
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.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Neoplasias Renales/patología , Carcinoma de Células Renales/patología , Estudios Retrospectivos , Nefrectomía/efectos adversos , Riñón/cirugía , Riñón/patologíaRESUMEN
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.