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Kidney transplantation offers a longer life expectancy and a better quality of life than dialysis to patients with end-stage kidney disease. Ischemia-reperfusion injury (IRI) is thought to be a cornerstone in delayed or reduced graft function and increases the risk of rejection by triggering the immunogenicity of the organ. IRI is an unavoidable event that happens when the blood supply is temporarily reduced and then restored to an organ. IRI is the result of several biological pathways, such as transcriptional reprogramming, apoptosis and necrosis, innate and adaptive immune responses, and endothelial dysfunction. Tubular cells mostly depend on fatty acid (FA) ß-oxidation for energy production since more ATP molecules are yielded per substrate molecule than glucose oxidation. Upon ischemia-reperfusion damage, the innate and adaptive immune system activates to achieve tissue clearance and repair. Several cells, cytokines, enzymes, receptors, and ligands are known to take part in these events. The complement cascade might start even before organ procurement in deceased donors. However, additional experimental and clinical data are required to better understand the pathogenic events that take place during this complex process.
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Trasplante de Riñón , Daño por Reperfusión , Humanos , Daño por Reperfusión/metabolismo , Trasplante de Riñón/efectos adversos , AnimalesRESUMEN
The authors describe their initial experience with robot-assisted buccal mucosal graft (BMG) ureteroplasty for the management of proximal ureteral strictures.
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Mucosa Bucal , Procedimientos Quirúrgicos Robotizados , Uréter , Obstrucción Ureteral , Procedimientos Quirúrgicos Urológicos , Humanos , Mucosa Bucal/trasplante , Procedimientos Quirúrgicos Robotizados/métodos , Obstrucción Ureteral/cirugía , Uréter/cirugía , Procedimientos Quirúrgicos Urológicos/métodos , Masculino , Constricción Patológica/cirugía , Persona de Mediana Edad , Femenino , AdultoRESUMEN
Mucins are a family of high-molecular-weight glycoproteins. MUC1 is widely studied for its role in distinct types of cancers. In many human epithelial malignancies, MUC1 is frequently overexpressed, and its intracellular activities are crucial for cell biology. MUC1 overexpression can enhance cancer cell proliferation by modulating cell metabolism. When epithelial cells lose their tight connections, due to the loss of polarity, the mucins become dispersed on both sides of the epithelial membrane, leading to an abnormal mucin interactome with the membrane. Tumor-related MUC1 exhibits certain features, such as loss of apical localization and aberrant glycosylation that might cause the formation of tumor-related antigen epitopes. Renal cell carcinoma (RCC) accounts for approximately 3% of adult malignancies and it is the most common kidney cancer. The exact role of MUC1 in this tumor is unknown. Evidence suggests that it may play a role in several oncogenic pathways, including proliferation, metabolic reprogramming, chemoresistance, and angiogenesis. The purpose of this review is to explore the role of MUC1 and the meaning of its overexpression in epithelial tumors and in particular in RCC.
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Carcinoma de Células Renales , Carcinoma , Neoplasias Renales , Adulto , Humanos , Carcinoma de Células Renales/genética , Mucina-1/genética , Mucinas , Antígenos de NeoplasiasRESUMEN
The crosstalk among the complement system, immune cells, and mediators of inflammation provides an efficient mechanism to protect the organism against infections and support the repair of damaged tissues. Alterations in this complex machinery play a role in the pathogenesis of different diseases. Core complement proteins C3 and C5, their activation fragments, their receptors, and their regulators have been shown to be active intracellularly as the complosome. The kidney is particularly vulnerable to complement-induced damage, and emerging findings have revealed the role of complement system dysregulation in a wide range of kidney disorders, including glomerulopathies and ischemia-reperfusion injury during kidney transplantation. Different studies have shown that activation of the complement system is an important component of tumorigenesis and its elements have been proved to be present in the TME of various human malignancies. The role of the complement system in renal cell carcinoma (RCC) has been recently explored. Clear cell and papillary RCC upregulate most of the complement genes relative to normal kidney tissue. The aim of this narrative review is to provide novel insights into the role of complement in kidney disorders.
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Carcinoma de Células Renales , Enfermedades Renales , Neoplasias Renales , Trasplante de Riñón , Daño por Reperfusión , Humanos , Trasplante de Riñón/efectos adversos , Carcinoma de Células Renales/patología , Riñón/metabolismo , Proteínas del Sistema Complemento/metabolismo , Enfermedades Renales/patología , Complemento C3/metabolismo , Daño por Reperfusión/patología , Neoplasias Renales/patología , Activación de ComplementoRESUMEN
The term "cancer stem cell" (CSC) refers to a cancer cell with the following features: clonogenic ability, the expression of stem cell markers, differentiation into cells of different lineages, growth in nonadhesive spheroids, and the in vivo ability to generate serially transplantable tumors that reflect the heterogeneity of primary cancers (tumorigenicity). According to this model, CSCs may arise from normal stem cells, progenitor cells, and/or differentiated cells because of striking genetic/epigenetic mutations or from the fusion of tissue-specific stem cells with circulating bone marrow stem cells (BMSCs). CSCs use signaling pathways similar to those controlling cell fate during early embryogenesis (Notch, Wnt, Hedgehog, bone morphogenetic proteins (BMPs), fibroblast growth factors, leukemia inhibitory factor, and transforming growth factor-ß). Recent studies identified a subpopulation of CD133+/CD24+ cells from ccRCC specimens that displayed self-renewal ability and clonogenic multipotency. The development of agents targeting CSC signaling-specific pathways and not only surface proteins may ultimately become of utmost importance for patients with RCC.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Células Madre Neoplásicas , Biomarcadores , Diferenciación CelularRESUMEN
Objective: Neuraxial anesthesia (NA) showed to reduce both morbidity and mortality in patients undergoing laparoscopic surgery. We aimed to investigate the use of NA in patients undergoing transperitoneal three-dimensional laparoscopic radical prostatectomy (t-3DLRP) and compare the intraoperative and postoperative outcomes with a control group of patients undergoing t-3DLRP under general anesthesia (GA). Methods: A prospective, double-center, double-surgeon study cohort of 84 consecutive patients undergoing t-3DLRP between June 2019 and June 2021 was analyzed. A study group of 42 patients undergoing t-3DLRP under NA was compared with a control group of 42 patients undergoing t-3DLRP under GA. Results: The two group were similar in all demographic, clinical, and pathological variables. Postoperative blood gas parameters were within physiologic limits in both groups. Muscle relaxation was adequate for surgery during both NA and GA. Median length of stay was 1 day shorter for NA group than GA group (5 days vs. 6 days, p=0.05). t-3DLRP under NA had a statistically lower rate of minor complications (4.8% vs. 19.0%, p=0.03) and less postoperative pain (median numeric rating scale 3 vs. 4, p=0.01) compared to GA. No major complications were observed in both groups. Significantly more patients were willing to undergo a similar intervention under NA than GA (p=0.04). Conclusion: t-3DLRP under NA is a feasible and safe procedure, with less postoperative pain and fewer minor complications than the same procedure under GA. NA allows the maintenance of muscle relaxation and respiratory excursions without interfering with surgery.
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Globally, clear-cell renal cell carcinoma (ccRCC) represents the most prevalent type of kidney cancer. Surgery plays a key role in the treatment of this cancer, although one third of patients are diagnosed with metastatic ccRCC and about 25% of patients will develop a recurrence after nephrectomy with curative intent. Molecular-target-based agents, such as tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs), are recommended for advanced cancers. In addition to cancer cells, the tumor microenvironment (TME) includes non-malignant cell types embedded in an altered extracellular matrix (ECM). The evidence confirms that interactions among cancer cells and TME elements exist and are thought to play crucial roles in the development of cancer, making them promising therapeutic targets. In the TME, an unfavorable pH, waste product accumulation, and competition for nutrients between cancer and immune cells may be regarded as further possible mechanisms of immune escape. To enhance immunotherapies and reduce resistance, it is crucial first to understand how the immune cells work and interact with cancer and other cancer-associated cells in such a complex tumor microenvironment.
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BACKGROUND: Ultra-minimally Invasive Surgical Techniques (uMISTs) play an increasingly significant role in treating benign prostatic obstruction (BPO) as an alternative to both medical therapy and surgery. Transperineal laser ablation of the prostate (TPLA) is an uMIST that has shown its efficacy in symptom relief and improvement of urodynamic parameters while sparing ejaculatory function and having a low risk of complications. This is the 3-year follow-up of a pilot study on TPLA. METHODS: TPLA was performed using the SoracteLite™ system. It consists of ablating prostate tissue through a diode laser, eventually causing prostate volume reduction. We recorded International Prostate Symptom Score (IPSS), uroflowmetry parameters, the Male Sexual Health Questionnaire (MSHQ-EjD), and prostate volume at baseline and after 3 years. The Wilcoxon Test was employed to compare continuous variables. RESULTS: Twenty men completed a 3-year follow-up after TPLA. The median prostate volume was 41.5 mL (IQR: 40.0-54.3). Preoperative median IPSS, Q
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Terapia por Láser , Hiperplasia Prostática , Humanos , Masculino , Próstata/diagnóstico por imagen , Próstata/cirugía , Hiperplasia Prostática/complicaciones , Proyectos Piloto , Eyaculación , Terapia por Láser/efectos adversos , Terapia por Láser/métodosRESUMEN
Renal cell carcinoma (RCC) is the seventh most common cancer in men and the ninth most common cancer in women worldwide. There is plenty of evidence about the role of the immune system in surveillance against tumors. Thanks to a better understanding of immunosurveillance mechanisms, immunotherapy has been introduced as a promising cancer treatment in recent years. Renal cell carcinoma (RCC) has long been thought chemoresistant but highly immunogenic. Considering that up to 30% of the patients present metastatic disease at diagnosis, and around 20-30% of patients undergoing surgery will suffer recurrence, we need to identify novel therapeutic targets. The introduction of immune checkpoint inhibitors (ICIs) in the clinical management of RCC has revolutionized the therapeutic approach against this tumor. Several clinical trials have shown that therapy with ICIs in combination or ICIs and the tyrosine kinase inhibitor has a very good response rate. In this review article we summarize the mechanisms of immunity modulation and immune checkpoints in RCC and discuss the potential therapeutic strategies in renal cancer treatment.
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Mucin1 (MUC1), a glycoprotein associated with an aggressive cancer phenotype and chemoresistance, is aberrantly overexpressed in a subset of clear cell renal cell carcinoma (ccRCC). Recent studies suggest that MUC1 plays a role in modulating cancer cell metabolism, but its role in regulating immunoflogosis in the tumor microenvironment remains poorly understood. In a previous study, we showed that pentraxin-3 (PTX3) can affect the immunoflogosis in the ccRCC microenvironment by activating the classical pathway of the complement system (C1q) and releasing proangiogenic factors (C3a, C5a). In this scenario, we evaluated the PTX3 expression and analyzed the potential role of complement system activation on tumor site and immune microenvironment modulation, stratifying samples in tumors with high (MUC1H) versus tumors with low MUC1 expression (MUC1L). We found that PTX3 tissue expression was significantly higher in MUC1H ccRCC. In addition, C1q deposition and the expressions of CD59, C3aR, and C5aR were extensively present in MUC1H ccRCC tissue samples and colocalized with PTX3. Finally, MUC1 expression was associated with an increased number of infiltrating mast cells, M2-macrophage, and IDO1+ cells, and a reduced number of CD8+ T cells. Taken together, our results suggest that expression of MUC1 can modulate the immunoflogosis in the ccRCC microenvironment by activating the classical pathway of the complement system and regulating the immune infiltrate, promoting an immune-silent microenvironment.
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Carcinoma de Células Renales , Neoplasias Renales , Mucina-1 , Microambiente Tumoral , Humanos , Carcinoma de Células Renales/inmunología , Carcinoma de Células Renales/patología , Activación de Complemento , Complemento C1q/metabolismo , Neoplasias Renales/inmunología , Neoplasias Renales/patología , Macrófagos/inmunología , Mucina-1/metabolismo , Microambiente Tumoral/inmunologíaRESUMEN
INTRODUCTION: Lipidomics focuses on the in-depth analysis of lipids, which are crucial macromolecules involved in a wide range of metabolic pathways. The increased intracellular accumulation of different classes of lipids in renal cell carcinoma (RCC) and prostate cancer (PCa) cells may be caused by elevated absorption or by increased de novo lipogenesis as a consequence of lipid metabolism reprogramming. The involvement of cholesterol metabolism in cancer's aberrant pathways has also been demonstrated. AREAS COVERED: This review provides an update on the most important lipidomics studies and applications in RCC and PCa, with a particular focus on how knowledge of aberrant lipid pathways may be used to identify biomarkers and novel therapeutic targets. In addition, the application of this methodologies have led to novel cancer subtypes identification and patient's risk stratification. Tracking tumor progression using specific biofluid metabolite profiles offers a huge translational opportunity for urological malignancies. EXPERT OPINION: Lipidomics is a promising branch of 'omics' approach and should include in next decade new standardized analysis methods and randomized clinical trials in order to reach the aim to use this high-throughput technique in patient-tailored therapy perspective.
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Carcinoma de Células Renales , Neoplasias Renales , Masculino , Humanos , Carcinoma de Células Renales/diagnóstico , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/metabolismo , Próstata/química , Próstata/metabolismo , Próstata/patología , Metabolismo de los Lípidos , Patología Molecular , Biomarcadores/metabolismo , Neoplasias Renales/diagnóstico , Neoplasias Renales/etiología , Neoplasias Renales/metabolismo , Lípidos/análisis , Metabolómica/métodosRESUMEN
Six food-grade tannins obtained from different woods were used as a source of polyphenolic compounds at two concentrations (0.5% and 1% w/w) in yogurt formulations and monitored during 3 weeks of storage. Yogurt containing tannins showed significantly higher total phenolic content (+200%), antioxidant activity (+400%), and syneresis (+100%) than control. These changes were higher with fortification at 1%. Tannin origin also significantly influenced the yogurt composition and yogurt obtained from a Turkish gall showed higher values of total phenolic content (4 mg GAE/g) and antioxidant activity (17 µM Trolox/g). Yogurt color was evaluated by CIELab parameters, and their values were influenced by tannin origin and concentration. The addition of tannins did not significantly affect the number of lactic acid bacteria. Yogurt with a lower amount of tannins (0.5% w/w) received higher consumer acceptability but significant differences in preferences were due to tannin origin. In particular, yogurt added with tannin obtained from Quebracho wood at 1% w/w showed higher consumer preference. The obtained results would provide an opportunity for dairy producers to develop a novel dairy food with high nutritional quality.
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Prostate cancer (PCa) is the most common male malignancy and the fifth leading cause of cancer death in men worldwide. Prostate cancer cells are characterized by a hybrid glycolytic/oxidative phosphorylation phenotype determined by androgen receptor signaling. An increased lipogenesis and cholesterogenesis have been described in PCa cells. Many studies have shown that enzymes involved in these pathways are overexpressed in PCa. Glutamine becomes an essential amino acid for PCa cells, and its metabolism is thought to become an attractive therapeutic target. A crosstalk between cancer and stromal cells occurs in the tumor microenvironment because of the release of different cytokines and growth factors and due to changes in the extracellular matrix. A deeper insight into the metabolic changes may be obtained by a multi-omic approach integrating genomics, transcriptomics, metabolomics, lipidomics, and radiomics data.
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Neoplasias de la Próstata , Humanos , Masculino , Neoplasias de la Próstata/metabolismo , Próstata/patología , Fosforilación Oxidativa , Transducción de Señal , Metabolómica , Receptores Androgénicos/genética , Receptores Androgénicos/metabolismo , Microambiente TumoralRESUMEN
We previously reported the novel finding that ß3-AR is functionally expressed in the renal tubule and shares its cellular localization with the vasopressin receptor AVPR2, whose physiological stimulation triggers antidiuresis by increasing the plasma membrane expression of the water channel AQP2 and the NKCC2 symporter in renal cells. We also showed that pharmacologic stimulation of ß3-AR is capable of triggering antidiuresis and correcting polyuria, in the knockout mice for the AVPR2 receptor, the animal model of human X-linked nephrogenic diabetes insipidus (XNDI), a rare genetic disease still missing a cure. Here, to demonstrate that the same response can be evoked in humans, we evaluated the effect of treatment with the ß3-AR agonist mirabegron on AQP2 and NKCC2 trafficking, by evaluating their urinary excretion in a cohort of patients with overactive bladder syndrome, for the treatment of which the drug is already approved. Compared to baseline, treatment with mirabegron significantly increased AQP2 and NKCC2 excretion for the 12 weeks of treatment. This data is a step forward in corroborating the hypothesis that in patients with XNDI, treatment with mirabegron could bypass the inactivation of AVPR2, trigger antidiuresis and correct the dramatic polyuria which is the main hallmark of this disease.
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Diabetes Insípida Nefrogénica , Diabetes Mellitus , Ratones , Animales , Humanos , Diabetes Insípida Nefrogénica/tratamiento farmacológico , Diabetes Insípida Nefrogénica/genética , Diabetes Insípida Nefrogénica/metabolismo , Acuaporina 2/genética , Acuaporina 2/metabolismo , Poliuria/tratamiento farmacológico , Agonistas Adrenérgicos betaRESUMEN
Clear cell renal cell carcinoma (ccRCC) is the most frequent histological kidney cancer subtype. Over the last decade, significant progress has been made in identifying the genetic and metabolic alterations driving ccRCC development. In particular, an integrated approach using transcriptomics, metabolomics, and lipidomics has led to a better understanding of ccRCC as a metabolic disease. The metabolic profiling of this cancer could help define and predict its behavior in terms of aggressiveness, prognosis, and therapeutic responsiveness, and would be an innovative strategy for choosing the optimal therapy for a specific patient. This review article describes the current state-of-the-art in research on ccRCC metabolic pathways and potential therapeutic applications. In addition, the clinical implication of pharmacometabolomic intervention is analyzed, which represents a new field for novel stage-related and patient-tailored strategies according to the specific susceptibility to new classes of drugs.
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Carcinoma de Células Renales , Neoplasias Renales , Enfermedades Metabólicas , Humanos , Carcinoma de Células Renales/tratamiento farmacológico , Carcinoma de Células Renales/genética , Neoplasias Renales/tratamiento farmacológico , Neoplasias Renales/genética , Biomarcadores , MetabolómicaRESUMEN
An altered metabolism is involved in the development of clear cell renal carcinoma (ccRCC). MUC1 overexpression has been found to be associated with advanced disease and poor prognosis. In this study, we evaluated the metabolomic profile of human ccRCC, according to MUC1 expression, and integrated it with transcriptomic data. Moreover, we analyzed the role of MUC1 in sustaining ccRCC aggressiveness and the prognostic value of its soluble form CA15-3. Integrated metabolomic and transcriptomic analysis showed that MUC1-expressing ccRCC was characterized by metabolic reprogramming involving the glucose and lipid metabolism pathway. In addition, primary renal cancer cells treated with a small interfering RNA targeting MUC1 (siMUC1) migrated and proliferated at a slower rate than untreated cancer cells. After cisplatin treatment, the death rate of cancer cells treated with siMUC1 was significantly greater than that of untreated cells. Kaplan-Meier curves showed significant differences in CSS and PFS among groups of patients with high versus low levels of CA15-3. In a multivariate analysis, CA15-3 was an independent adverse prognostic factor for cancer-specific and progression-free survival. In conclusion, MUC1 expressing ccRCC is characterized by a particular metabolic reprogramming. The inhibition of MUC1 expression decreases cell motility and viability and improves cisplatin susceptibility, suggesting that this pathway can regulate de novo chemotherapy resistance in ccRCC.
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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/genética , Cisplatino/farmacología , Cisplatino/uso terapéutico , Mucina-1/genética , Neoplasias Renales/genética , MetabolomaRESUMEN
Background: Delayed graft function (DGF) leads to a reduced graft survival. Donors' features have been always considered as key pathogenic factors in this setting. The aim of our study was to evaluate the recipients' characteristics in the development of DGF. Methods: We enrolled 932 kidney graft recipients from 466 donors; 226 recipients experienced DGF. In 290 donors, both recipients presented with early graft function (EGF, group A), in 50 both recipients experienced DGF (group B), and in 126 one recipient presented with DGF and the other with EGF (group C). In group C, we selected 7 couples of DGF/EGF recipients and we evaluated the transcriptomic profile by microarray on circulating mononuclear cells harvested before transplantation. Results were validated by qPCR in an independent group of 25 EGF/DGF couples. Findings: In the whole study group, DGF was associated with clinical characteristics related to both donors and recipient. In group C, DGF was significantly associated with body mass index, hemodialysis, and number of mismatches. In the same group, we identified 411 genes differently expressed before transplantation between recipients discordant for the transplant outcome. Those genes were involved in immune dysfunction and inflammation. In particular, we observed a significant increase in DGF patients in the expression of C-C chemokine receptor type 2 (CCR2), the monocyte chemoattractant protein-1 (MCP-1) receptor. CCR-2 upregulation was confirmed in an independent cohort of patients. Conclusions: Our results suggest that recipients' clinical/immunological features, potentially modulated by dialysis, are associated with the development of DGF independently of donors' features.
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Funcionamiento Retardado del Injerto , Trasplante de Riñón , Factor de Crecimiento Epidérmico , Humanos , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/métodos , Receptores de Quimiocina , Factores de RiesgoRESUMEN
Metabolomic analysis has proven to be a useful tool in biomarker discovery and the molecular classification of cancers. In order to find new biomarkers, and to better understand its pathological behavior, bladder cancer also has been studied using a metabolomics approach. In this article, we review the literature on metabolomic studies of bladder cancer, focusing on the different available samples (urine, blood, tissue samples) used to perform the studies and their relative findings. Moreover, the multi-omic approach in bladder cancer research has found novel insights into its metabolic behavior, providing excellent start-points for new diagnostic and therapeutic strategies. Metabolomics data analysis can lead to the discovery of a "signature pathway" associated with the progression of bladder cancer; this aspect could be potentially valuable in predictions of clinical outcomes and the introduction of new treatments. However, further studies are needed to give stronger evidence and to make these tools feasible for use in clinical practice.
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Neoplasias de la Vejiga Urinaria , Biomarcadores , Biomarcadores de Tumor/metabolismo , Femenino , Humanos , Masculino , Metabolómica/métodos , Enfermedades Raras , Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/metabolismoRESUMEN
Autophagy is a complex process involved in several cell activities, including tissue growth, differentiation, metabolic modulation, and cancer development. In prostate cancer, autophagy has a pivotal role in the regulation of apoptosis and disease progression. Several molecular pathways are involved, including PI3K/AKT/mTOR. However, depending on the cellular context, autophagy may play either a detrimental or a protective role in prostate cancer. For this purpose, current evidence has investigated how autophagy interacts within these complex interactions. In this article, we discuss novel findings about autophagic machinery in order to better understand the therapeutic response and the chemotherapy resistance of prostate cancer. Autophagic-modulation drugs have been employed in clinical trials to regulate autophagy, aiming to improve the response to chemotherapy or to anti-cancer treatments. Furthermore, the genetic signature of autophagy has been found to have a potential means to stratify prostate cancer aggressiveness. Unfortunately, stronger evidence is needed to better understand this field, and the application of these findings in clinical practice still remains poorly feasible.
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Fosfatidilinositol 3-Quinasas , Neoplasias de la Próstata , Apoptosis , Autofagia/genética , Línea Celular Tumoral , Humanos , Masculino , Fosfatidilinositol 3-Quinasas/metabolismo , Neoplasias de la Próstata/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismoRESUMEN
INTRODUCTION: The association between obesity and clinically significant prostate cancer (PCa) is still a matter of debate. In this study, we evaluated the effect of body mass index (BMI) on the prediction of pathological unfavorable disease (UD), positive surgical margins (PSMs), and biochemical recurrence (BCR) in patients with clinically localized (≤cT2c) International Society of Urological Pathology (ISUP) grade group 1 PCa at biopsy. METHODS: 427 patients with ISUP grade group 1 PCa who have undergone radical prostatectomy and BMI evaluation were included. The outcome of interest was the presence of UD (defined as ISUP grade group ≥3 and pT ≥3a), PSM, and BCR. RESULTS: Statistically significant differences resulted in comparing BMI with prostate-specific antigen (PSA) and serum testosterone levels (both p < 0.0001). Patients with UD and PSM had higher BMI values (p < 0.0001 and p = 0.006, respectively). BCR-free survival was significantly decreased in patients with higher BMI values (p < 0.0001). BMI was an independent risk factor for BCR and PSM. Receiver-operating characteristic analysis testing PSA accuracy in different BMI groups, showed that PSA had a reduced predictive value (area under the curve [AUC] = 0.535; 95% confidence interval [CI] = 0.422-0.646), in obese men compared to overweight (AUC = 0.664; 95% CI = 0.598-0.725) and normal weight patients (AUC = 0.721; 95% CI = 0.660-0.777). CONCLUSION: Our findings show that increased BMI is a significant predictor of UD and PSM at RP in patients with preoperative low-to intermediate-risk diseases, suggesting that BMI evaluation may be useful in a clinical setting to identify patients with favorable preoperative disease characteristics harboring high-risk PCa.