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PURPOSE: To examine associations between ablative therapy (AT) and partial nephrectomy (PN) and the occurrence of local recurrence (LR), distant metastatic recurrence (DMR) and all-cause mortality in a nation-wide real-world population-based cohort of patients with nonmetastatic renal cell carcinoma (nmRCC). METHODS: Data on 2751 AT- or PN-treated nmRCC tumours diagnosed during 2005-2018, representing 2701 unique patients, were obtained from the National Swedish Kidney Cancer Register. Time to LR/DMR or death with/without LR/DMR was analysed using Cox regression models. RESULTS: During a mean of 4.8 years follow-up, LR was observed for 111 (4.0%) tumours, DMR for 108 (3.9%) tumours, and death without LR/DMR for 206 (7.5%) tumours. AT-treated tumours had a 4.31 times higher risk of LR (P < 0.001) and a 1.91 times higher risk of DMR (P = 0.018) than PN-treated, with no significant differences in risk of death without LR/DMR. During a mean of 3.2 and 2.5 years of follow-up after LR/DMR, respectively, 24 (21.6%) of the LR cases and 56 (51.9%) of the DMR cases died, compared to 7.5% in patients without LR/DMR. There were no significant differences between AT- and PN-treated regarding risks of early death after occurrence of LR or DMR. CONCLUSION: AT treatment of patients with nmRCC implied significantly higher risks of LR and DMR compared with PN treatment. To minimize the risks of LR and DMR, these results suggest that PN is preferred over AT as primary treatment, supporting the EAU guidelines to recommended AT mainly to frail and/or comorbid patients.
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Carcinoma de Células Renales , Neoplasias Renales , Recurrencia Local de Neoplasia , Nefrectomía , Nefronas , Humanos , Carcinoma de Células Renales/cirugía , Carcinoma de Células Renales/terapia , Neoplasias Renales/patología , Neoplasias Renales/cirugía , Neoplasias Renales/terapia , Masculino , Femenino , Anciano , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Nefrectomía/métodos , Medición de Riesgo , Tratamientos Conservadores del Órgano , Técnicas de Ablación/métodos , Suecia/epidemiologíaRESUMEN
OBJECTIVE: Several risk factors for end-stage renal disease (ESRD), in patients undergoing surgical treatment for renal cell carcinoma (RCC), have been suggested by others. This study aimed to investigate such risk factors and disclose the effect of developing ESRD, postoperatively, on overall survival. The risk of developing ESRD after RCC diagnosis was also evaluated. MATERIAL AND METHODS: The data of 16,220 patients with RCC and 162,199 controls were extracted from the Renal Cell Cancer Database Sweden, with linkages across multiple national registers between 2005 and 2020. Cox proportional hazards regression, Kaplan-Meier curves and cumulative incidence were used for statistical analysis. RESULTS: The 5-year cumulative incidence of ESRD following RCC diagnosis was 2.4% (95% confidence interval [CI] 2.1-2.6) and 0.4% (95% CI 0.3-0.4) for the patients with RCC and controls, respectively. Age, chronic kidney disease, higher T-stage and radical nephrectomy (RN) were significant risk factors for ESRD within 1-year of surgery. A total of 104 and 12,152 patients with and without ESRD, respectively, survived 1-year postoperatively. The 5-year overall survival rates of patients with ESRD and those with RCC only were 50% (95% CI 0.40-0.60) and 80% (95% CI 0.80-0.81), respectively. CONCLUSIONS: Patients who developed ESRD following renal cancer surgery had significantly poorer survival outcomes. Advanced age, comorbidities, higher-stage tumours and RN were identified as risk factors for developing ESRD. Surgical decisions are crucial. Efforts to spare renal function, including nephron-sparing surgery and active surveillance in appropriate cases, are highly relevant to reduce the development of severe kidney dysfunction.
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Carcinoma de Células Renales , Fallo Renal Crónico , Neoplasias Renales , Nefrectomía , Humanos , Neoplasias Renales/cirugía , Neoplasias Renales/mortalidad , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/complicaciones , Masculino , Femenino , Factores de Riesgo , Persona de Mediana Edad , Anciano , Carcinoma de Células Renales/cirugía , Carcinoma de Células Renales/mortalidad , Tasa de Supervivencia , Complicaciones Posoperatorias/epidemiología , Suecia/epidemiología , Incidencia , Adulto , Anciano de 80 o más AñosRESUMEN
Objectives: This study aimed to assess the cellular localization and expression levels of hypoxia-inducible factor (HIF) -α proteins (specifically HIF-1α, HIF-2α, and HIF-3α) that play a role in the hypoxia pathway and to determine their correlation with clinicopathological parameters and patient survival in renal cell carcinoma (RCC). Materials and methods: Tissue microarray (TMA) with cores from 150 clear cell RCCs and 31 non-ccRCC samples. HIF-1α, HIF-2α, and HIF-3α antibodies were used for immunohistochemistry (IHC) of TMA to evaluate the cellular localization and expression levels of HIF-α proteins, specifically in relation to the hypoxia pathway. Results: The expression levels of the HIF-α proteins were higher in the nucleus than in the cytoplasm. Furthermore, the nuclear expression levels of all HIF-α proteins were significantly higher in clear cell RCC (ccRCC) than in non-ccRCC. Cytoplasmic HIF-3α expression was also higher in ccRCC than in non-ccRCC, whereas cytoplasmic HIF-1α and HIF-2α expression levels were similar between the different RCC types. In ccRCC, nuclear HIF-1α expression levels correlated with both nuclear HIF-2α and HIF-3α levels, whereas cytoplasmic HIF-3α expression levels were associated with HIF-1α only.In non-ccRCC, there was a positive correlation observed between nuclear HIF-1α and HIF-3α expression, but no correlation was found with HIF-2α. In patients with ccRCC, the nuclear expressions of HIF-1α and HIF-3α was significantly associated with cancer-specific survival (CSS) in univariate analysis. This association was no longer evident in multivariate analysis. Notably, there was no correlation observed between nuclear HIF-2α expression and CSS in these patients. In contrast, cytoplasmic expression levels showed no association with CSS. Conclusion: The expression levels of the three primary HIF-α proteins were found to be higher in the nucleus than in the cytoplasm. Furthermore, the results indicated that HIF-3α and HIF-1α expression levels were significant univariate factors associated with CSS in patients with clear cell RCC. These results highlight the critical role that HIF-3α and HIF-1α play in the hypoxia pathway.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/análisis , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/metabolismo , Inmunohistoquímica , Hipoxia , Subunidad alfa del Factor 1 Inducible por HipoxiaRESUMEN
BACKGROUND: Primary tumor removal by cytoreductive nephrectomy in synchronous metastatic renal cell carcinoma patients has been investigated in the context of various treatment regimens. Two randomized controlled trials investigated the role and timing of cytoreductive nephrectomy in the era of targeted therapy and demonstrated that upfront nephrectomy should no longer be performed when patients require systemic therapy. Superiority of checkpoint immunotherapy agents has led to a paradigm change from targeted therapies to immunotherapy-based first-line treatment in patients with primary metastatic disease; thus, deferred cytoreductive nephrectomy needs to be verified in the immunotherapy setting. Furthermore, a need exists for personalizing treatment choices for the individual patient to avoid unnecessary overtreatment. METHODS/DESIGN: To explore the impact of cytoreductive nephrectomy in this patient group receiving checkpoint immunotherapy, we initiated a randomized, controlled trial comparing deferred cytoreductive nephrectomy with no surgery. The trial integrates a comprehensive translational research program with specimen sampling for biomarker analysis. DISCUSSION: The trial aims to show that deferred cytoreductive nephrectomy improves overall survival in patients with synchronous metastatic renal cell carcinoma, and furthermore, to identify relevant biomarkers for personalized renal cancer management. TRIAL REGISTRATION: ClinicalTrials.gov NCT03977571 June 6, 2019.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/cirugía , Terapia Combinada , Procedimientos Quirúrgicos de Citorreducción , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/cirugía , NefrectomíaRESUMEN
BACKGROUND: Surgical strategy in renal cell carcinoma (RCC) is considered based on the renal function. Partial nephrectomy (PN) preserves kidney function better than radical nephrectomy (RN), lowering risk of chronic kidney disease (CKD). The aim was to evaluate whether renal function and other clinical variables were important for surgical treatment selection. METHODS: Patients with RCC, surgically treated between 1994 and 2018 were included. There were 663 patients in all stages, 265 women and 398 men, mean age 66 years. CLINICAL DATA: estimated glomerular filtration rate (eGFR), WHO performance status (WHO-PS), Charlson comorbidity index (CCI), surgery, T-stage, M-stage, RCC type, tumor size, age, and gender were extracted from the medical records. Statistical analysis included Mann-Whitney U, X2-test, and logistic regression analysis. RESULTS: Of 663 patients, 455 were treated with RN and 208 with PN. In all patients, preoperative eGFR was significantly higher in PN (80.8) than in RN (77.1, p = 0.015). Using logistic regression tumor size (odds ratio [OR]: 0.96; 95% confidence interval [CI]: 0.95-0.98, T-stage (OR: 0.46; 95% CI: 0.33-0.65), WHO-PS (OR: 0.39; 95% CI: 0.04-0.57), and CCI (OR: 1.23; 95% CI: 1.05-1.44), associated to treatment selection, while eGFR, M-stage, age, and gender did not. In cTa subgroup, eGFR was also higher in PN (84.6) than in RN (75.0, p = 0.007). Using logistic regression, tumor size (OR: 0.93; 95% CI: 0.83-0.98) and WHO-PS (OR: 0.36; 95% CI: 0.20-0.66) associated to treatment selection, while eGFR, CCI, age, and gender did not. CONCLUSION: Tumor size, CCI scores, T-stage, and WHO-PS, all had an impact on the surgical strategy for all RCC patients. In patients with T1a RCC, tumor size and WHO-PS associated independently with treatment decision. After adjusted analysis, renal function lost its independent association with the treatment strategy in RCC patients.
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Carcinoma de Células Renales , Neoplasias Renales , Insuficiencia Renal Crónica , Masculino , Humanos , Femenino , Anciano , Carcinoma de Células Renales/cirugía , Carcinoma de Células Renales/patología , Neoplasias Renales/patología , Nefrectomía/efectos adversos , Tasa de Filtración Glomerular , Toma de Decisiones , Estudios RetrospectivosRESUMEN
OBJECTIVE: Nationwide register data provide unique opportunities for real-world assessment of complications from different surgical methods. This study aimed to assess incidence of, and predictors for, post-operative complications and to evaluate 90-day mortality following different surgical procedures and thermal ablation for renal cell carcinoma (RCC). MATERIAL AND METHODS: All patients undergoing surgical treatment and thermal ablation for RCC in Sweden during 2015-2019 were identified from the National Swedish Kidney Cancer Register. Frequencies and types of post-operative complications were analysed. Logistic regression models were used to identify predictors for 90-day major (Clavien-Dindo grades III-V) complications, including death. RESULTS: The overall complication rate was 24% (1295/5505), of which 495 (8.7%) were major complications. Most complications occurred following open surgery, of which bleeding and infection were the most common. Twice as many complications were observed in patients undergoing open surgery compared to minimally invasive surgery (20% vs. 10%, P < 0.001). Statistically significant predictors for major complications irrespective of surgical category and technique were American society of anesthiologists (ASA) score, tumour diameter and serum creatinine. Separating radical and partial nephrectomy, surgical technique remained a significant risk factor for major complications. Most complications occurred within the first 20 days. The overall 90-day readmission rate was 6.2%, and 30- and 90-day mortality rates were 0.47% and 1.5%, respectively. CONCLUSIONS: In conclusion, bleeding and infection were the most common major complications after RCC surgery. Twice as many patients undergoing open surgery suffer a major post-operative complication as compared to patients subjected to minimally invasive surgery. General predictors for major complications were ASA score, tumour size, kidney function and surgical technique.
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Carcinoma de Células Renales , Neoplasias Renales , Complicaciones Posoperatorias , Humanos , Carcinoma de Células Renales/cirugía , Riñón , Neoplasias Renales/cirugía , Nefrectomía/efectos adversos , Complicaciones Posoperatorias/epidemiología , IncidenciaRESUMEN
BACKGROUND & AIMS: Diet may play an essential role in the aetiology of bladder cancer (BC). Vitamin D is involved in various biological functions which have the potential to prevent BC development. Besides, vitamin D also influences the uptake of calcium and phosphorus, thereby possibly indirectly influencing the risk of BC. The aim of the present study was to investigate the relation between vitamin D intake and BC risk. METHODS: Individual dietary data were pooled from ten cohort studies. Food item intake was converted to daily intakes of vitamin D, calcium and phosphorus. Pooled multivariate hazard ratios (HRs), with corresponding 95% confidence intervals (CIs) were obtained using Cox-regression models. Analyses were adjusted for gender, age and smoking status (Model 1), and additionally for the food groups fruit, vegetables and meat (Model 2). Dose-response relationships (Model 1) were examined using a nonparametric test for trend. RESULTS: In total, 1994 cases and 518,002 non-cases were included in the analyses. The present study showed no significant associations between individual nutrient intake and BC risk. A significant decreased BC risk was observed for high vitamin D intake with moderate calcium and low phosphorus intake (Model 2: HRhigh vitD, mod Ca, low P: 0.77, 95% CI: 0.59-1.00). No significant dose-response analyses were observed. CONCLUSION: The present study showed a decreased BC risk for high dietary vitamin D intake in combination with low calcium intake and moderate phosphorus intake. The study highlights the importance of examining the effect of a nutrient in combination with complementary nutrients for risk assessment. Future research should focus on nutrients in a wider context and in nutritional patterns.
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Fósforo Dietético , Neoplasias de la Vejiga Urinaria , Humanos , Calcio , Estudios Prospectivos , Dieta , Vitamina D , Vitaminas , Calcio de la Dieta , Neoplasias de la Vejiga Urinaria/epidemiología , Neoplasias de la Vejiga Urinaria/prevención & control , Neoplasias de la Vejiga Urinaria/etiología , Estudios de Cohortes , Fósforo , Factores de RiesgoRESUMEN
BACKGROUND: Renal cell carcinoma (RCC) is twice as common among men compared with women, and hormonal factors have been suggested to partially explain this difference. There is currently little evidence on the roles of reproductive and hormonal risk factors in RCC aetiology. MATERIALS & METHODS: We investigated associations of age at menarche and age at menopause, pregnancy-related factors, hysterectomy and ovariectomy and exogenous hormone use with RCC risk among 298,042 women in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. RESULTS: During 15 years of follow-up, 438 RCC cases were identified. Parous women had higher rates of RCC compared with nulliparous women (HR = 1.71, 95% CI 1.18, 2.46), and women who were older at age of first pregnancy had lower rates of RCC (30 years + vs. <20 years HR = 0.53, 95% CI 0.34, 0.82). Additionally, we identified a positive association for hysterectomy (HR = 1.43 95% CI 1.09, 1.86) and bilateral ovariectomy (HR = 1.67, 95% CI 1.13, 2.47), but not unilateral ovariectomy (HR = 0.99, 95% CI 0.61, 1.62) with RCC risk. No clear associations were found for age at menarche, age at menopause or exogenous hormone use. CONCLUSION: Our results suggest that parity and reproductive organ surgeries may play a role in RCC aetiology.
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Carcinoma de Células Renales , Neoplasias Renales , Embarazo , Masculino , Femenino , Humanos , Adulto , Carcinoma de Células Renales/epidemiología , Carcinoma de Células Renales/etiología , Estudios Prospectivos , Historia Reproductiva , Paridad , Menopausia , Neoplasias Renales/epidemiología , Neoplasias Renales/etiología , Hormonas , Factores de RiesgoRESUMEN
Prognostic tools are an essential component of the clinical management of patients with renal cell carcinoma (RCC). Although tumour stage and grade can provide important information, they fail to consider patient- and tumour-specific biology. In this study, we set out to find a novel molecular marker of RCC by using hepatocyte nuclear factor 4A (HNF4A), a transcription factor implicated in RCC progression and malignancy, as a blueprint. Through transcriptomic analyses, we show that the nuclear factor I A (NFIA)-driven transcription network is active in primary RCC and that higher levels of NFIA confer a survival benefit. We validate our findings using immunohistochemical staining and analysis of a 363-patient tissue microarray (TMA), showing for the first time that NFIA can independently predict poor cancer-specific survival in clear cell RCC (ccRCC) patients (hazard ratio = 0.46, 95% CI = 0.24-0.85, p value = 0.014). Furthermore, we confirm the association of HNF4A with higher grades and stages in ccRCC in our TMA cohort. We present novel data that show HNF4A protein expression does not confer favourable prognosis in papillary RCC, confirming our survival analysis with publicly available HNF4A RNA expression data. Further work is required to elucidate the functional role of NFIA in RCC as well as the testing of these markers on patient material from diverse multi-centre cohorts, to establish their value for the prognostication of RCC.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/patología , Neoplasias Renales/patología , Pronóstico , Análisis de Supervivencia , Núcleo Celular/patología , Factores de Transcripción NFI/genéticaRESUMEN
Background: Retrospective comparative studies suggest a survival benefit after complete local treatment of recurrence (LTR) in renal cell carcinoma (RCC), which may be largely due to an indication bias. Objective: To determine the role of LTR in a homogeneous population characterised by limited and potentially resectable recurrence. Design setting and participants: RECUR is a protocol-based multicentre European registry capturing patient and tumour characteristics, risk of recurrence (RoR), recurrence patterns, and survival of those curatively treated for nonmetastatic RCC from 2006 to 2011. Per-protocol resectable disease (RD) recurrence was defined as (1) solitary metastases, (2) oligometastases, or (3) renal fossa or renal recurrence after radical or partial nephrectomy, respectively. Intervention: Local treatment of recurrence. Outcome measurements and statistical analysis: Overall survival (OS) and cancer-specific survival was compared in the RD population that underwent LTR versus no LTR. We constructed a multivariate model to predict risk factors for overall mortality and analysed the effect of LTR across RoR groups. Results and limitations: Of 3039 patients with localised RCC treated with curative intent, 505 presented with recurrence, including 176 with RD. Of these patients, 97 underwent LTR and 79 no LTR. Patients in the LTR group were younger (64.3 [40-80] vs 69.2 [45-87] yr; p = 0.001). The median OS was 70.3 mo (95% confidence interval [CI] 58-82.6) versus 27.4 mo (95% CI 23.6-31.15) in the LTR versus no-LTR group (p < 0.001). After a multivariate analysis, having LTR (hazard ratio [HR] 0.37 [95% CI 0.2-0.6]), having low- versus high-risk RoR (HR 0.42 [95% CI [0.20-0.83]), and not having extra-abdominal/thoracic metastasis (HR 1.96 [95% CI 1.02-3.77]) were prognostic factors of longer OS. The LTR effect on survival was consistent across risk groups. OS HR for high, intermediate, and low risks were 0.36 (0.2-0.64), 0.27 (0.11-0.65), and 0.26 (0.08-0.8), respectively. Limitations include retrospective design. Conclusions: This is the first study assessing the effectiveness of LTR in RCC in a comparable population with RD. This study supports the role of LTR across all RoR groups. Patient summary: We assessed the effectiveness of local treatment of resectable recurrent renal cell carcinoma after surgical treatment of the primary kidney tumour. Local treatment of recurrence was associated with longer survival across groups with a risk of recurrence.
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Carcinoma de Células Renales , Neoplasias Renales , Urología , Humanos , Estadificación de Neoplasias , PacientesRESUMEN
OBJECTIVE: Patients with clinical T1 renal cell carcinoma (cT1RCC) have risks for recurrence and reduced overall survival despite being in the best prognostic group. This study aimed to evaluate the association of different treatments on disease recurrence and overall survival using clinical and pathological characteristics in a nation-wide cT1RCC cohort. MATERIALS AND METHODS: A total of 4,965 patients, registered in the National Swedish Kidney Cancer Register (NSKCR) between 2005 and 2014, with ≥ 5-years follow-up were identified: 3,040 males and 1,925 females, mean age 65 years. Times to recurrence and overall survival were analyzed with Kaplan-Meier curves, log-rank test, and Cox regression models. RESULTS: Age, TNM-stage, tumor size, RCC-type, and performed treatment were all associated with disease recurrence. Patients selected for ablative treatments had increased risk for recurrent disease: hazard ratio (HR) = 3.79 [95% confidence interval (CI) = 2.69-5.32]. In multivariate analyses, age, gender, tumor size, RCC-type, N-stage, recurrence and performed treatment were all independently associated with overall survival. Patients with chRCC had a 41% better overall survival (HR = 0.59, 95% CI = 0.44-0.78; p < 0.001) than ccRCC. Patients treated with partial nephrectomy (PN) had an 18% better overall survival (HR = 0.83, 95% CI = 0.71-0.95, p < 0.001) than patients treated with radical nephrectomy. CONCLUSIONS: Age, gender, T-stage, tumor size, RCC type and treatment modality are all associated with risk of recurrence. Furthermore, age, male gender, tumor size, N-stage and recurrence are associated with reduced overall survival. Patients with chRCC, compared with ccRCC and pRCC patients, and PN compared with RN treated patients, had an advantageous overall survival, indicating a possible survival advantage of nephron sparing treatment.
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Carcinoma de Células Renales , Neoplasias Renales , Femenino , Humanos , Masculino , Anciano , Carcinoma de Células Renales/cirugía , Suecia , Neoplasias Renales/cirugía , Pronóstico , Modelos de Riesgos Proporcionales , Nefrectomía/efectos adversos , Estadificación de Neoplasias , Estudios RetrospectivosRESUMEN
The fifth edition of the World Health Organization (WHO) classification of urogenital tumours published in 2022 will be implemented in the European Association of Urology guidelines on renal cell carcinoma for 2023. Here we provide an update summarising changes in the new WHO classification of renal tumours from a clinician perspective.
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Carcinoma de Células Renales , Neoplasias Renales , Urología , Humanos , Carcinoma de Células Renales/patología , Urólogos , Neoplasias Renales/patología , Organización Mundial de la SaludRESUMEN
In KEYNOTE-564, adjuvant pembrolizumab, a PD-1 antibody, significantly improved disease-free survival (DFS) in localised clear-cell renal cell carcinoma (ccRCC) with a high risk of relapse. In 2021, the European Association of Urology RCC Guidelines Panel issued a weak recommendation for adjuvant pembrolizumab for high-risk ccRCC as defined by the trial until final overall survival data and results from other trials were available. Meanwhile, the primary DFS endpoints were not met for adjuvant atezolizumab (PD-L1 inhibitor; IMmotion010), adjuvant nivolumab plus ipilimumab (CheckMate 914), or perioperative nivolumab (PROSPER). Owing to heterogeneity, a meta-analysis is not recommended. Pembrolizumab remains the only immune checkpoint inhibitor currently recommended in this setting. Overall survival data are immature and biomarkers to predict outcome are lacking. Uncertainty exists and overtreatment is occurring. Treatment decisions should be made with caution and with the involvement of each patient. PATIENT SUMMARY: New results from three trials of immunotherapy after surgery for kidney cancer to reduce the risk of recurrence showed no improvement with these treatments. These results are in contrast to an earlier study that showed that the antibody pembrolizumab did extend the time before kidney cancer recurrence, even though it is not yet clear if overall survival is longer. Thus, we cautiously recommend pembrolizumab as additional treatment in high-risk kidney cancer after surgery, but patient preference should be carefully considered and the risk of overtreatment should be discussed.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/terapia , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Recurrencia Local de Neoplasia , Neoplasias Renales/patología , Nivolumab/uso terapéuticoRESUMEN
Over the past decade, only minor changes have been introduced in the TNM staging system for renal cancer. Conversely, many milestones and modifications in management of the disease have been achieved, especially for patients with locally advanced and metastatic cancers. The European Association of Urology guidelines panel proposes a new TNM classification scheme for staging of renal cell carcinoma to reflect these breakthrough clinical improvements.
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Carcinoma de Células Renales , Neoplasias Renales , Urología , Humanos , Carcinoma de Células Renales/patología , Estadificación de Neoplasias , Neoplasias Renales/patologíaRESUMEN
Background: Prostate cancer has a multifaceted treatment pattern. Evidence is lacking for optimal treatment sequences for metastatic castration-resistant prostate cancer (mCRPC). Objective: To increase the understanding of real-world treatment pathways and outcomes in patients with mCRPC. Design setting and participants: A prospective, noninterventional, real-world analysis of 3003 patients with mCRPC in the Prostate Cancer Registry (PCR; NCT02236637) from June 14, 2013 to July 9, 2018 was conducted. Intervention: Patients received first- and second-line hormonal treatment and chemotherapy as follows: abiraterone acetate plus prednisone (abiraterone)-docetaxel (ABI-DOCE), abiraterone-enzalutamide (ABI-ENZA), abiraterone-radium-223 (ABI-RAD), docetaxel-abiraterone (DOCE-ABI), docetaxel-cabazitaxel (DOCE-CABA), docetaxel-enzalutamide (DOCE-ENZA), and enzalutamide-docetaxel (ENZA-DOCE). Outcome measurements and statistical analysis: Baseline patient characteristics, quality of life, mCRPC treatments, and efficacy outcomes (progression and survival) were presented descriptively. Results and limitations: Data from 727 patients were eligible for the analysis (ABI-DOCE nâ¯=â¯178, ABI-ENZA nâ¯=â¯99, ABI-RAD nâ¯=â¯27, DOCE-ABI nâ¯=â¯191, DOCE-CABA nâ¯=â¯74, DOCE-ENZA nâ¯=â¯116, and ENZA-DOCE nâ¯=â¯42). Demographics and disease characteristics among patients between different sequences varied greatly. Most patients who started on abiraterone or enzalutamide stopped therapy because of disease progression. No randomisation to allow treatment/sequence comparisons limited this observational study. Conclusions: The real-world PCR data complement clinical trial data, reflecting more highly selected patient populations than seen in routine clinical practice. Baseline characteristics play a role in mCRPC first-line treatment selection, but other factors, such as treatment availability, have an impact. Efficacy observations are limited and should be interpreted with caution. Patient summary: Baseline characteristics appear to have a role in the first-line treatment selection of metastatic castration-resistant prostate cancer in the real-world setting. First-line abiraterone acetate plus prednisone seems to be the preferred treatment option for older patients and those with lower Gleason scores, first-line docetaxel for younger patients and those with more advanced disease, and first-line enzalutamide for patients with fewer metastases and more favourable performance status. The benefit to patients from these observations remains unknown.
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INTRODUCTION: The impact of open versus minimally invasive surgery on recurrence pattern in the management of localized renal cell carcinoma (RCC) remains uncertain. We thus aimed to determine the impact of surgical approach on survival and recurrence pattern. MATERIAL AND METHODS: This is a multi-institutional, matched cohort study on patients with pT1-3aN0M0 RCC from the RECUR database. After propensity score matching between open and minimally invasive surgery, disease-free (DFS) survival and risk of first recurrence according to recurrence site, namely local recurrence, abdominal/retroperitoneal, thoracic/mediastinal or uncommon site metastases were investigated with Cox regression analysis. Overall (OS) and Cancer Specific Survival (CSS) were also assessed. RESULTS: After matching, 1,019 patients who underwent open and 1,019 who underwent minimally invasive surgery were included (of which 70 robot-assisted). At 5.2 years of median follow-up, 130 patients in open and 125 in minimally invasive group experienced disease progression. A higher risk of local recurrence (HR 2.06; 95% CI 1.18-3.58, P-valueâ¯=â¯0.01) and uncommon site metastases (HR 1.09; 95% CI 1.01-1.16; P-valueâ¯=â¯.04) was found for minimally invasive surgery relative to open surgery, while no difference was found in terms of DFS (HR 0.83; 95% CI 0.64-1.06; P-valueâ¯=â¯.14). No differences were found in terms of OS and CSS. Main limitation is the retrospective nature of the study. CONCLUSIONS: The risk for local recurrence and uncommon site metastases was higher for minimally invasive surgery compared to open surgery, although no differences were found for OS, CSS, and DFS.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/patología , Estudios de Cohortes , Supervivencia sin Enfermedad , Neoplasias Renales/patología , Estudios Retrospectivos , RecurrenciaRESUMEN
OBJECTIVES: Early mobilisation and effective pain management after open nephrectomy for renal cell carcinoma often include epidural analgesia (EDA), requiring an infusion pump and a urinary catheter, thus impeding mobilisation. Spinal anaesthesia (SpA) may be an alternative. This randomised clinical trial evaluated whether SpA improves analgesia and facilitates mobilisation over EDA and which factors influence mobilisation and length of stay (LOS). METHODS: Between 2012 and 2015, 135 patients were randomised and stratified by surgical method to either SpA with clonidine or EDA. Mobility index score (MobIs), pain scale, patient satisfaction questionnaire, and LOS were the main outcome measures. RESULTS: SpA patients exhibited an increase in MobIs significantly earlier than EDA patients. Among SpA patients >50% reached MobIs ≥13 by postoperative day 3, while 29% of EDA patients never reached MobIs ≥13 before discharge. SpA patients had higher maximum pain scores on postoperative days 1 and 2, but both groups had similar patient satisfaction. One day before discharge, 36/64 SpA versus 22/67 EDA patients (56% and 33%, respectively) were opioid-free. SpA patients were discharged significantly earlier than EDA patients. CONCLUSIONS: SpA facilitates postoperative pain management and is associated with faster mobilisation and shorter LOS.The trial was registered at ClinicalTrials.org (ID-NCT02030717).
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Analgesia Epidural , Anestesia Raquidea , Neoplasias Renales , Analgesia Epidural/métodos , Clonidina/uso terapéutico , Ambulación Precoz , Humanos , Nefrectomía/efectos adversos , Manejo del Dolor/métodos , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/etiologíaAsunto(s)
Neoplasias Renales , Medicina de Precisión , Humanos , Neoplasias Renales/terapia , Nefrectomía , BiopsiaRESUMEN
BACKGROUND: Mycotoxins have been suggested to contribute to a spectrum of adverse health effects in humans, including at low concentrations. The recognition of these food contaminants being carcinogenic, as co-occurring rather than as singularly present, has emerged from recent research. The aim of this study was to assess the potential associations of single and multiple mycotoxin exposures with renal cell carcinoma risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS: Food questionnaire data from the EPIC cohort were matched to mycotoxin food occurrence data compiled by the European Food Safety Authority (EFSA) from European Member States to assess long-term dietary mycotoxin exposures, and to associate these with the risk of renal cell carcinoma (RCC, n = 911 cases) in 450,112 EPIC participants. Potential confounding factors were taken into account. Analyses were conducted using Cox's proportional hazards regression models to compute hazard ratios (HRs) and 95% confidence intervals (95% CIs) with mycotoxin exposures expressed as µg/kg body weight/day. RESULTS: Demographic characteristics differed between the RCC cases and non-cases for body mass index, age, alcohol intake at recruitment, and other dietary factors. In addition, the mycotoxin exposure distributions showed that a large proportion of the EPIC population was exposed to some of the main mycotoxins present in European foods such as deoxynivalenol (DON) and derivatives, fumonisins, Fusarium toxins, Alternaria toxins, and total mycotoxins. Nevertheless, no statistically significant associations were observed between the studied mycotoxins and mycotoxin groups, and the risk of RCC development. CONCLUSIONS: These results show an absence of statistically significant associations between long-term dietary mycotoxin exposures and RCC risk. However, these results need to be validated in other cohorts and preferably using repeated dietary exposure measurements. In addition, more occurrence data of, e.g., citrinin and fumonisins in different food commodities and countries in the EFSA database are a prerequisite to establish a greater degree of certainty.