Exposure to environmental pollutants and genetic variants related to oxidative stress and xenobiotic metabolism - Association with prostate cancer.

This study assessed whether genetic variants coding for certain enzymes involved in xenobiotic detoxification, antioxidant defences and DNA repair, along with exposure to environmental chemicals, were associated with an increased prostate cancer (PCa) risk. The study population consisted of 300 men (150 PCa cases and 150 controls) which underwent prostate biopsy as their serum prostate specific antigen (PSA) levels were greater than 4ng/ml. Genetic variants in GSTM1, GSTP1, SOD2, CAT, GPX1, XRCC1 were determined and data for chemical exposures was obtained through a structured questionnaire and by biomonitoring in a subsample of cases and controls. High serum PSA levels were associated with a greater risk of PCa, while physical exercise appears to exert a protective effect against its development. In addition, elevated urinary levels of certain organic pollutants, such as benzo(a)pyrene (BaP), bisphenol A (BPA), and ethyl-paraben (EPB), were associated with an increased risk of PCa.

Genetic variants of antioxidant and xenobiotic metabolizing enzymes and their association with prostate cancer: A meta-analysis and functional in silico analysis.

The development and progression of prostate cancer (PCa) depends on complex interactions between genetic, environmental and dietary factors that modulate the carcinogenesis process. Interactions between chemical exposures and genetic polymorphisms in genes encoding xenobiotic metabolizing enzymes (XME), antioxidant enzymes and DNA repair enzymes have been reported as the main drivers of cancer. Thus, a better understanding of the causal risk factors for PCa will provide avenues to identify men at increased risk and will contribute to develop effective detection and prevention methods. We performed a meta-analysis on 17,518 cases and 42,507 controls obtained from 42 studies to determine whether seven SNPs and one CNV pertaining to oxidative stress, xenobiotic detoxification and DNA repair enzymes are associated with the risk of PCa (GPX1 (rs1050450), XRCC1 (rs25487), PON1 (rs662), SOD2 (rs4880), CAT (rs1001179), GSTP1 (rs1695) and CNV GSTM1). A significant increased risk of PCa was found for SOD2 (rs4880) ORGG+GA vs. AA 1.08; 95%CI 1.01-1.15, CAT (rs1001179) ORTT vs. TC+CC 1.39; 95%CI 1.17-1.66, PON1 (rs662) ORCT vs. CC+TT 1.17; 95%CI 1.01-1.35, GSTP1 (rs1695) ORGG vs. GA+AA 1.20; 95%CI 1.05-1.38 and GSTM1 (dual null vs. functional genotype) ORN vs. NN1+NN2 1.34; 95%CI 1.10-1.64. The meta-analysis showed that the CNV GSTM1, and the SNPs GSTP1 (rs1695) and CAT (rs1001179) are strongly associated with a greater risk of PCa and, to a lesser extent, the genetic variants SOD2 (rs4880) and PON1 (rs662). Although several antioxidant enzymes and XME play an important role in the PCa development, other risk factors such as chemical exposures should also be considered to gain insight on PCa risk. The functional in silico analysis showed that the genetic variants studied had no clinical implication regarding malignancy, except for GPX1 (rs1050450) SNP.

Ejaculation Frequency and Prostate Cancer: CAPLIFE Study.

PURPOSE: To evaluate the association between ejaculation frequency (EF) during four stages of life and prostate cancer (PCa) according to tumor aggressiveness, PCa stage, and urinary symptomatology. MATERIALS AND METHODS: A total of 456 incident PCa cases histologically confirmed, and 427 controls aged 40-80 years from the CAPLIFE study were analyzed. This study is a population-based case-control study carried out in the south of Spain. Average EF was measured for: (1) 20s, (2) 30s, (3) 40s, and (4) one year before the interview. EF was categorized into: (1) 0-3, (2) 4, and (3) >4 ejaculations/month. Sociodemographic, lifestyle, and medical information were also collected. To estimate the association between EF and PCa, adjusted ORs (aORs) and 95% CIs were calculated by logistic regression models. RESULTS: A year before the interview, PCa cases ejaculated less frequently than the controls. An inverse association was observed between the EF a year before and PCa, aOR=1.64 (95% CI 1.03-2.61) for men with 4 ejaculations/month, and aOR=2.38 (95% CI 1.57-3.60) for men with 0-3 ejaculations/month, compared to men with >4. The association was higher for cases with ISUP 3-5 (aOR=2.76 [95% CI 1.34-5.67] for men with 0-3 ejaculations/month) or with a locally advanced-metastatic tumor (aOR=4.70 [95% CI 1.55-14.29]). Moreover, men with moderate urinary symptoms and 0-3 ejaculations/month had the highest risk, aOR=3.83 (95% CI 1.84-7.95). CONCLUSIONS: A low EF could be associated with a higher risk of PCa, especially for cases with ISUP 3-5 or with a locally advanced-metastatic tumor.

Dietary Patterns and Prostate Cancer: CAPLIFE Study.

The etiology of prostate cancer (PCa) remains uncertain, and the role of diet is unclear. We aimed to evaluate the role of diet, through dietary patterns, on PCa, considering tumor aggressiveness and extension. The CAPLIFE study is a population-based case-control study including a total of 428 incident PCa cases and 393 controls aged 40-80 years. Dietary information was collected through a validated food frequency questionnaire. Three dietary patterns were identified through principal component analysis: "Mediterranean," "Western," and "Unhealthy," which were categorized into tertiles according to the control group cutoff points. Tumor aggressiveness and extension was determined. Logistic regression models were used to assess the association between dietary patterns and PCa. High adherence to an unhealthy dietary pattern was associated with higher odds of PCa, ORT3vsT1 = 1.52 (95% CI 1.02-2.27), especially for cases with ISUP 1-2 and localized PCa tumors. This association was not observed with a Western or Mediterranean pattern. In conclusion, adherence to an unhealthy diet appears to be associated with higher odds of PCa, especially for cases with ISUP 1-2 and localized PCa tumors.

Follow-Up Biomarkers in the Evolution of Prostate Cancer, Levels of S100A4 as a Detector in Plasma.

The management and screening of prostate cancer (PC) is still the main problem in clinical practice. In this study, we investigated the role of aggressiveness genetic markers for PC stratification. We analyzed 201 plasma samples from PC patients and controls by digital PCR. For selection and validation, 26 formalin-fixed paraffin-embedded tissues, 12 fresh tissues, and 24 plasma samples were characterized by RNA-Seq, immunochemistry, immunofluorescence, Western blot, and extracellular-vesicles analyses. We identified three novel non-invasive biomarkers; all with an increased expression pattern in patients (PCA3: p = 0.002, S100A4: p ≤ 0.0001 and MRC2: p = 0.005). S100A4 presents the most informative AUC (area under the curve) (0.735). Combination of S100A4, MRC2, and PCA3 increases the discriminatory power between patients and controls and between different more and less aggressive stages (AUC = 0.761, p ≤ 0.0001). However, although a sensitivity of 97.47% in PCA3 and a specificity of 90.32% in S100A4 was reached, the detection signal level could be variable in some analyses owing to tumor heterogeneity. This is the first time that the role of S100A4 and MRC2 has been described in PC aggressiveness. Moreover, the combination of S100A4, MRC2, and PCA3 has never been described as a non-invasive biomarker for PC screening and aggressiveness.

Salivary Melatonin Rhythm and Prostate Cancer: CAPLIFE Study.

PURPOSE: We analyzed the association between salivary melatonin rhythm and prostate cancer (PCa). MATERIALS AND METHODS: A total of 40 PCa cases and 41 controls from the CAPLIFE study were analyzed to determine the salivary melatonin rhythm through 6 saliva samples. Amplitude (maximum melatonin peak) was categorized as low or high using the cutoff point median of the controls. Acrophase (time of maximum melatonin peak) was classified as early or late using the same criteria. In addition, the following data were collected: characteristics related to sleep habits, and clinical and sociodemographic information. Melatonin rhythms were represented for cases and controls and analyzed according to urinary symptoms, tumor aggressiveness and tumor extension. Variations in melatonin levels were estimated using generalized estimating equations on the ln-transformed values. To estimate the association between amplitude, acrophase and PCa, adjusted odds ratio (aOR) and 95% CI were calculated using logistic regression models. RESULTS: The mean age was 67.0 years (SD 7.3) for cases and 67.5 (SD 5.5) for controls. Melatonin levels were always lower in PCa cases than in controls. On average, melatonin levels in cases were -64.0% (95% CI -73.4, -51.4) than controls. PCa cases had lower amplitude, 26.0 pg/ml (SD 27.8) vs 46.3 pg/ml (SD 28.2; p <0.001). A high amplitude was associated with a decreased risk of PCa, aOR=0.31 (95% CI 0.11, 0.86), while a late acrophase could be increased risk of PCa, aOR=2.36 (95% CI 0.88, 6.27). CONCLUSIONS: Patients with PCa always had lower melatonin levels than men without PCa, independent of urinary symptomatology or extension and aggressiveness of the tumor.

Identification of MicroRNAs as Viable Aggressiveness Biomarkers for Prostate Cancer.

MiRNAs play a relevant role in PC (prostate cancer) by the regulation in the expression of several pathways' AR (androgen receptor), cellular cycle, apoptosis, MET (mesenchymal epithelium transition), or metastasis. Here, we report the role of several miRNAs' expression patterns, such as miR-93-5p, miR-23c, miR-210-3p, miR-221-3p, miR-592, miR-141, miR-375, and miR-130b, with relevance in processes like cell proliferation and MET. Using Trizol® extraction protocol and TaqMan™ specific probes for amplification, we performed miRNAs' analysis of 159 PC fresh tissues and 60 plasmas from peripheral blood samples. We had clinical data from all samples including PSA, Gleason, TNM, and D'Amico risk. Moreover, a bioinformatic analysis in TCGA (The Cancer Genome Atlas) was included to analyze the effect of the most relevant miRNAs according to aggressiveness in an extensive cohort (n = 531). We found that miR-210-3p, miR-23c, miR-592, and miR-93-5p are the most suitable biomarkers for PC aggressiveness and diagnosis, respectively. In fact, according with our results, miR-93-5p seems the most promising non-invasive biomarker for PC. To sum up, miR-210-3p, miR-23c, miR-592, and miR-93-5p miRNAs are suggested to be potential biomarkers for PC risk stratification that could be included in non-invasive strategies such as liquid biopsy in precision medicine for PC management.

Determination of Exosome Mitochondrial DNA as a Biomarker of Renal Cancer Aggressiveness.

Here, the role of non-invasive biomarkers in liquid biopsy was evaluated, mainly in exosomes and mitochondrial DNA (mtDNA) as promising, novel, and stable biomarkers for renal cell carcinoma (RCC). A total of 140 fractions (named from B to F) obtained by ultracentrifugations of whole blood samples from 28 individuals (13 patients and 15 controls) were included. Nanoparticle Tracking Analysis (NTA) was conducted to characterized exosomal fraction. Subsequently, an analysis of digital PCR (dPCR) using the QuantStudio™ 3D Digital PCR platform was performed and the quantification of mtDNA copy number by QuantStudioTM 12K Flex Real-Time PCR System (qPCR) was developed. Moreover, Next Generation Sequencing (NGS) analyses were included using MiSeq system (Illumina, San Diego, CA, USA). An F fraction, which contains all exosome data and all mitochondrial markers, was identified in dPCR and qPCR with statistically significant power (adjusted p values ≤ 0.03) when comparing cases and controls. Moreover, present analysis in mtDNA showed a relevant significance in RCC aggressiveness. To sum up, this is the first time a relation between exosomal mtDNA markers and clinical management of RCC is analyzed. We suggest a promising strategy for future liquid biopsy RCC analysis, although more analysis should be performed prior to application in routine clinical practice.

Night Shift Work, Chronotype, Sleep Duration, and Prostate Cancer Risk: CAPLIFE Study.

To analyze the association between prostate cancer (PCa) risk and night shift work, chronotype, and sleep duration in the context of a population-based case-control study of incident prostate cancer in Spain, a total of 465 PCa cases and 410 controls were analyzed. Selection criteria were: (i) age 40-80 years, and (ii) residence in the coverage area of the reference hospitals for ≥6 months before recruitment. Exposure variables were: (i) night shift work (permanent or rotating); (ii) chronotype: morning, neither, or evening (Munich ChronoType Questionnaire) and (iii) sleep duration according to the recommendations of the American National Sleep Foundation. PCa aggressiveness was determined according to the International Society of Urology Pathology classification. Adjusted odds ratios (aOR) and 95% confidence intervals (95% CI) were estimated using logistic regression models. Night shift work was associated with PCa, aOR = 1.47 (95% CI 1.02-2.11), especially for rotating night shifts, aOR = 1.73 (95% CI 1.09-2.75). The magnitude of the association between ever night work and PCa was higher in evening subjects with aOR = 3.14 (95% CI 0.91-10.76) than in morning chronotypes with an aOR = 1.25 (95% CI 0.78-2.00). Working night shifts, especially rotating night shifts, could increase PCa risk. This risk may be higher in people with an evening chronotype.

Dietary Diversity and Prostate Cancer in a Spanish Adult Population: CAPLIFE Study.

Dietary diversity (DD) is a key component of a high-quality diet, providing the adequate nutrient requirements. However, the role of DD on prostate cancer (PCa) is still uncertain. The aim of this study was to evaluate the relationship between DD, adequate nutrient intake and PCa, according to the aggressiveness of the tumor. The CAPLIFE (CAP: prostate cancer; LIFE: lifestyles) study is a population-based case-control study including a total of 402 incident PCa cases and 302 controls. The DD score (DDS), adjusted by total energy intake, was collected through a validated food frequency questionnaire. Nutrient adequacy was defined according to European Dietary Recommendation Intake for men. The aggressiveness of PCa was determined according to the International Society of Urology Pathology classification. The association between DDS, nutrient intake and PCa was assessed by logistic regression models with adjustment for potential confounding factors. DDS was similar for PCa cases and controls, independent of PCa aggressiveness. According to each food group DDS, the protein group showed the highest mean score in all the subgroups analyzed. However, no differences were observed for each of the DDS components. The DDS, the variety of the group's food intake, and the adequate nutrient intake, were not associated with PCa.

[Emergency surgery during COVID-19 pandemia.] / Cirugía de urgencia en urología durante la pandemia Covid-19.

INTRODUCTION: The crisis in the SARSCoV-2 coronavirus causing COVID-19 is putting health systems around the world to the test. In a great effort to standardize the management and treatment guidelines, the different health authorities and scientific associations have tried to issue recommendations on how to act in this new and complex scenario. OBJECTIVE: To synthesize the existing evidence and recommendations about urological emergency surgery during the COVID-19 pandemic situation. Furthermore, we propose a general action protocol for these patients. MATERIAL AND METHODS: The document is based ont he scarce evidence on SARS / Cov-2 and the experience of the authors in the management of COVID-19 in their institutions, including specialists from Andalusia, Cantabria, Madrid and the Basque Country. A web and PubMed search was performed using the keywords "SARS-CoV-2", "COVID19",  "COVID Urology", "COVID19 surgery" and "emergency care". A narrative review of the literature was carried out until April 30, 2020, including only articles and documents written in Spanish and English. After the nominal group technique modified due to the extraordinary restrictions, a first draft was made to unify criteria. Finally, a definitive version was made, agreed by all the authors on May 12, 2020. RESULTS: General principles of action are set out, as well as specific recommendations for the most frequent urgent urological procedures. CONCLUSIONS: Given the exceptional nature of the situation, there is a lack of evidence regarding the optimal management of the patient with urgent urological pathology. The information is changing, as the epidemiological knowledge of the disease advances. The establishment of multidisciplinary surgical committees that develop and implement action protocols appropriate to the different resources and particular situations of each center is recommended. Likewise, these committees must individually assess each possible urological surgical emergency situation and ensure compliance with protective measures for the patient and other healthcare personnel.

INTRODUCCIÓN: La crisis del coronavirus SARS-CoV-2 causante del COVID-19 está poniendoa prueba los sistemas sanitarios de todo el mundo. En un gran esfuerzo por estandarizar las pautas de manejo y tratamiento, las distintas autoridades sanitarias y asociaciones científicas han tratado de dictar unas recomendaciones sobre como actuar en este nuevo y complejo escenario.OBJETIVO: Sintetizar la evidencia y recomendaciones existentes acerca de la cirugía de urgencia urológica durante la situación de pandemia COVID-19. Además, proponemos un protocolo de actuación general para estos pacientes. MATERIAL Y MÉTODOS: El documento se basa en la escasa evidencia sobre SARS/Cov-2 y la experiencia de los autores en el manejo de COVID-19 en sus instituciones incluyendo especialistas de Andalucía, Cantabria, Madrid y País Vasco. Se realizó una búsqueda web y en PubMed utilizando las palabras clave "SARSCoV-2", "COVID19", "COVID Urology", "COVID19 surgery" y "emergency care". Se realizó una revisión narrativa de la literatura hasta el día 30 de Abril de2020 incluyendo solo artículos y documentos escritos en lengua española e inglesa. Tras técnica de grupo nominal modificada debido a las restricciones extraordinarias se realizó un primer borrador para unificar criterios. Finalmente, se realizó una versión definitiva, consensuada por todos los autores el 12 Mayo 2020. RESULTADOS: Se exponen unos principios generales de actuación, así como unas recomendaciones específicas para los procedimientos urológicos urgentes más frecuentes.CONCLUSIONES: Dado el carácter excepcional de la situación, existe un déficit de evidencia respecto al óptimo manejo del paciente con patología urológica urgente. La información es cambiante, según avanza el conocimiento epidemiológico de la enfermedad. Es recomendable el establecimiento de comités multidisciplinares quirúrgicos que desarrollen e implementen protocolos de actuación adecuados a los distintos recursos y situaciones particulares de cada centro. Del mismo modo, estos comités deben evaluar de forma individualizada cada posible situación de urgencia quirúrgica urológica y velar por el cumplimiento de las medidas de protección para el paciente y resto del personal sanitario.

Cirugía de urgencia en urología durante la pandemia Covid-19 / Emergency surgery during COVID-19 pandemia

INTRODUCCIÓN: La crisis del coronavirus SARS-CoV-2 causante del COVID-19 está poniendoa prueba los sistemas sanitarios de todo el mundo. En un gran esfuerzo por estandarizar las pautas de manejo y tratamiento, las distintas autoridades sanitarias y asociaciones científicas han tratado de dictar unas recomendaciones sobre como actuar en este nuevo y complejo escenario. OBJETIVO: Sintetizar la evidencia y recomendaciones existentes acerca de la cirugía de urgencia urológica durante la situación de pandemia COVID-19. Además, proponemos un protocolo de actuación general para estos pacientes. MATERIAL Y MÉTODOS: El documento se basa en la escasa evidencia sobre SARS/Cov-2 y la experiencia de los autores en el manejo de COVID-19 en sus instituciones incluyendo especialistas de Andalucía, Cantabria, Madrid y País Vasco. Se realizó una búsqueda web y en PubMed utilizando las palabras clave "SARSCoV-2", "COVID19", "COVID Urology", "COVID19 surgery" y "emergency care". Se realizó una revisión narrativa de la literatura hasta el día 30 de Abril de2020 incluyendo solo artículos y documentos escritos en lengua española e inglesa. Tras técnica de grupo nominal modificada debido a las restricciones extraordinarias se realizó un primer borrador para unificar criterios. Finalmente, se realizó una versión definitiva, consensuada por todos los autores el 12 Mayo 2020. RESULTADOS: Se exponen unos principios generales de actuación, así como unas recomendaciones específicas para los procedimientos urológicos urgentes más frecuentes. CONCLUSIONES: Dado el carácter excepcional de la situación, existe un déficit de evidencia respecto al óptimo manejo del paciente con patología urológica urgente. La información es cambiante, según avanza el conocimiento epidemiológico de la enfermedad. Es recomendable el establecimiento de comités multidisciplinares quirúrgicos que desarrollen e implementen protocolos de actuación adecuados a los distintos recursos y situaciones particulares de cada centro. Del mismo modo, estos comités deben evaluar de forma individualizada cada posible situación de urgencia quirúrgica urológica y velar por el cumplimiento de las medidas de protección para el paciente y resto del personal sanitario

INTRODUCTION: The crisis in the SARSCoV-2 coronavirus causing COVID-19 is putting health systems around the world to the test. In a great effort to standardize the management and treatment guidelines, the different health authorities and scientific associations have tried to issue recommendations on how to act in this new and complex scenario. OBJECTIVE: To synthesize the existing evidence and recommendations about urological emergency surgery during the COVID-19 pandemic situation. Furthermore, we propose a general action protocol for these patients. MATERIAL AND METHODS: The document is based on the scarce evidence on SARS/Cov-2 and the experience of the authors in the management of COVID-19 in their institutions, including specialists from Andalusia, Cantabria, Madrid and the Basque Country. A web and PubMed search was performed using the keywords "SARS-CoV-2", "COVID19", "COVID Urology", "COVID19 surgery" and "emergency care". A narrative review of the literature was carried out until April 30, 2020, including only articles and documents written in Spanish and English. After the nominal group technique modified due to the extraordinary restrictions, a first draft was made to unify criteria. Finally, a definitive version was made, agreed by all the authors on May 12, 2020. RESULTS: General principles of action are set out, as well as specific recommendations for the most frequent urgent urological procedures. CONCLUSIONS: Given the exceptional nature of the situation, there is a lack of evidence regarding the optimal management of the patient with urgent urological pathology. The information is changing, as the epidemiological knowledge of the disease advances. The establishment of multidisciplinary surgical committees that develop and implement action protocols appropriate to the different resources and particular situations of each center is recommended. Likewise, these committees must individually assess each possible urological surgical emergency situation and ensure compliance with rotective measures for the patient and other healthcare personnel

Recent clinical relevance of mono-genital colonization/infection by Ureaplasma parvum.

Ureaplasma parvum is the most prevalent genital mycoplasma in women of childbearing age. There is debate around the relevance of its presence in male or female genitals for disease development and as a cofactor. The objective of this study was to determine the prevalence of colonization/infection by U. parvum and its possible relationship with reproductive tract infections. We retrospectively analyzed the presence of U. parvum in patients referred by specialist clinicians for suspicion of genitourinary tract infection. U. parvum was detected in 23.8% of samples, significantly more frequently in females (39.9%) than in males (6%). Among the males, U. parvum was found alone in 68.4% of episodes, with Ct < 30. Among the females, U. parvum was detected in 88.6% of cases, with Ct < 30, including 22 cases with premature rupture of membranes and 6 cases with threat of preterm labor. Co-infection was significantly more frequent in females (62.6%) than in males (31.6%). Given the high prevalence of U. parvum as sole isolate in males and females with genitourinary symptoms, it should be considered in the diagnosis and treatment of genital infections, although its pathogenic role in some diseases has not been fully elucidated.

Compliance with the 2018 World Cancer Research Fund/American Institute for Cancer Research Cancer Prevention Recommendations and Prostate Cancer.

The etiology of prostate cancer (PCa) remains largely unknown. Compliance with the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRC/AICR) cancer prevention recommendations and its relationship to PCa was evaluated. A total of 398 incident PCa cases and 302 controls were included. The selection criteria for both cases and controls were: (i) age between 40-80 years; and (ii) residence in the coverage area of the reference hospitals for 6 months or more prior to recruitment. A score to measure the compliance with the recommendations of 2018 WCRC/AICR criteria was built. The level of compliance was used as a continuous variable and categorized in terciles. The aggressiveness of PCa was determined according to the ISUP classification. Adjusted odds ratios (aOR) and their 95% confidence intervals (95% CI) were estimated using multivariable logistic regression models. A slight protective tendency was observed between the level of compliance with the preventive recommendations and PCa risk, aOR = 0.81 (95% CI 0.69-0.96) for the total cases of PCa. This association also was observed when the aggressiveness was considered. In addition, limiting consumption of "fast foods", sugar-sweetened drinks, and alcohol were independently associated with lower risk of PCa.

[Axitinib in real life, analysis of our results.] / Axitinib en el tratamiento del cáncer renal metastásico en la vida real, análisis de nuestros resultados.

OBJECTIVE: Following first-line treatment progression in metastatic renal carcinoma, different options for second-line treatment are available, with axitinib being one of them. The objective of this article is to evaluate the results of Axitinib in a real practice setting. METHODS: From December 2011 to October 2016, we treated 19 patients with CCRM with Axitinib, 3 patients in third line and 16 patients in second line after progression on Sunitinib or Pazopanib. We performed a retrospective study of the last 16 patients, analyzing the effectiveness and safety of the drug. RESULTS: The median progression-free survival (PFS) was 9 months and the median overall survival with 8 dead patients was 59 months. Overall, toxicity by Axitinib was very common, diarrhea 87.5%, asthenia 75%, dysphonia 56.25%, hypertension 37.5% and anorexia 37.5%, although most are grade 1-2 toxicities controlled with hygiene-diet measures and treatment recommendations. CONCLUSIONS: Axitinib is a drug that has been shown to increase PFS after 1st line progression, with a tolerable toxic profile. With the approval of nivolumab and cabozantinib, the place of Axitinib in sequential therapy is yet to be defined.

OBJETIVO: Tras progresión de primera línea de tratamiento en el carcinoma renal metastásico hay disponibles distintas opciones de tratamiento de segunda línea, siendo Axitinib una de ellas. MÉTODOS: Desde diciembre de 2011 hasta octubre de 2016, hemos tratado a 19 pacientes con CCRm con Axitinib, 3 pacientes en tercera línea y 16 en segunda línea tras progresión de Sunitinib o Pazopanib. Realizamos un estudio retrospectivo de los últimos 16 pacientes, analizando efectividad y seguridad del fármaco. RESULTADOS: La mediana de la supervivencia libre de progresión (SLP) fue de 9 meses y la mediana de supervivencia global con 8 pacientes fallecidos fue de 59 meses. La toxicidad global por Axitinib fue muy frecuente, diarrea 87,5%, astenia 75%, disfonía 56,25%, HTA 37,5% y anorexia 37,5%, aunque en su mayoría fueron toxicidades grado 1-2 controlados con medidas higiénico dietéticas y recomendaciones de tratamiento. CONCLUSIONES: Axitinib es un fármaco que ha demostrado aumentar la SLP tras progresión de 1ª línea, con un perfil toxico tolerable. Con la aprobación de nivolumab y cabozantinib, el lugar de Axitinib en la terapia secuencial está por definir.

Axitinib en el tratamiento del cáncer renal metastásico en la vida real, análisis de nuestros resultados / Axitinib in real life, analysis of our results

Objetivo: Tras progresión de primera línea de tratamiento en el carcinoma renal metastásico hay disponibles distintas opciones de tratamiento de segunda línea, siendo Axitinib una de ellas. Métodos: Desde diciembre de 2011 hasta octubre de 2016, hemos tratado a 19 pacientes con CCRm con Axitinib, 3 pacientes en tercera línea y 16 en segunda línea tras progresión de Sunitinib o Pazopanib. Realizamos un estudio retrospectivo de los últimos 16 pacientes, analizando efectividad y seguridad del fármaco. Resultados: La mediana de la supervivencia libre de progresión (SLP) fue de 9 meses y la mediana de supervivencia global con 8 pacientes fallecidos fue de 59 meses. La toxicidad global por Axitinib fue muy frecuente, diarrea 87,5%, astenia 75%, disfonía 56,25%, HTA 37,5% y anorexia 37,5%, aunque en su mayoría fueron toxicidades grado 1-2 controlados con medidas higiénico dietéticas y recomendaciones de tratamiento. Conclusiones: Axitinib es un fármaco que ha demostrado aumentar la SLP tras progresión de 1 línea, con un perfil toxico tolerable. Con la aprobación de nivolumab y cabozantinib, el lugar de Axitinib en la terapia secuencial está por definir

Objective: Following first-line treatment progression in metastatic renal carcinoma, different options for second-line treatment are available, with axitinib being one of them. The objective of this article is to evaluate the results of Axitinib in a real practice setting. Methods: From December 2011 to October 2016, we treated 19 patients with CCRM with Axitinib, 3 patients in third line and 16 patients in second line after progression on Sunitinib or Pazopanib. We performed a retrospective study of the last 16 patients, analyzing the effectiveness and safety of the drug. Results: The median progression-free survival (PFS) was 9 months and the median overall survival with 8 dead patients was 59 months. Overall, toxicity by Axitinib was very common, diarrhea 87.5%, asthenia 75%, dysphonia 56.25%, hypertension 37.5% and anorexia 37.5%, although most are grade 1-2 toxicities controlled with hygiene-diet measures and treatment recommendations. Conclusions: Axitinib is a drug that has been shown to increase PFS after 1st line progression, with a tolerable toxic profile. With the approval of nivolumab and cabozantinib, the place of Axitinib in sequential therapy is yet to be defined

[Recommendations for follow up in castration resistant prostate cancer.] / Recomendaciones para el seguimiento del cáncer de próstata resistente a la castración.

OBJECTIVES: There is no broad consensus about what diagnostic tests use for CRPC follow up as well as their frequency. Our objective is to review and analyze the most important CRPC follow up patterns described in the literature to date. METHODS: We performed a critical analysis of the recommendations for follow up most universally employed (PCWG3, RADAR, St Gallen consensus, NCCN guidelines, EAU guidelines) RESULTS: CT scan and bone scan are the routine recommended diagnostic tests, in front of other techniques such as PET/CT or MRI, that may improve the diagnostic efficacy but they have the problem of availability and lack of internal validity for follow up. CONCLUSIONS: Follow up is different for non metastatic and metastatic CRPC. For nm CRPC, it is recommended to perform monitoring that includes PSA and imaging tests, without consensus about periodicity. For mCRPC, it is recommendable to do follow up with periodic PSA and imaging tests, since it is possible to have radiological progression without PSA progression.

Variantes agresivas de cáncer de próstata resistente a la castracion (CPRC): cáncer de próstata neuroendocrino / Aggressive variants of castration resistant prostate cancer (crpc): neuroendocrine prostate cancer

OBJETIVO: No existe un consenso amplio sobre qué pruebas diagnósticas emplear en el seguimiento del CPRC, así como la periodicidad de las mismas. Nuestro objetivo es revisar y analizar las pautas de seguimiento en el CPRC más importantes descritas hasta la fecha en la literatura. MÉTODOS: Se realiza un análisis crítico de las recomendaciones de seguimiento más universalmente empleadas (PCWG3, RADAR, consenso de St Gallen, guías NCCN, Guías Europeas de Urología). RESULTADO: El TC y la gammagrafía ósea son las técnicas diagnósticas recomendadas rutinariamente, por delante de otras técnicas como el PET/TC o la RM, las cuales pueden mejorar la eficacia diagnóstica pero tienen el problema de la disponibilidad y la falta de validez interna para el seguimiento. CONCLUSIONES: El seguimiento es diferente entre CPRC no metastásico (nm) y metastásico(m). En el CPRCnm, se recomienda realizar una monitorización que incluya PSA y pruebas de imagen, no existiendo consenso en la periodicidad. En el CPRCm, es recomendable realizar el seguimiento con PSA y con pruebas de imagen periódicas, pues se puede dar una progresión radiológica sin progresión por PSA

OBJECTIVES: There is no broad consensus about what diagnostic tests use for CRPC follow up as well as their frequency. Our objective is to review and analyze the most important CRPC follow up patterns described in the literature to date. METHODS: We performed a critical analysis of the recommendations for follow up most universally employed (PCWG3, RADAR, St Gallen consensus, NCCN guidelines, EAU guidelines) RESULTS: CT scan and bone scan are the routine recommended diagnostic tests, in front of other techniques such as PET/CT or MRI, that may improve the diagnostic efficacy but they have the problem of availability and lack of internal validity for follow up. CONCLUSIONS: Follow up is different for non metastatic and metastatic CRPC. For nm CRPC, it is recommended to perform monitoring that includes PSA and imaging tests, without consensus about periodicity. For mCRPC, it is recommendable to do follow up with periodic PSA and imaging tests, since it is possible to have radiological progression without PSA progression

[New therapeutic schedules of Sunitinib: Current evidence regarding the 2:1 scheme.] / Nuevos esquemas terapéuticos con Sunitinib: evidencia actual en torno a la pauta 2:1.

INTRODUCTION: In 2006, sunitinib approval by the FDA was a real revolution for the treatment of metastatic renal cell carcinoma (mRCC). However, considerable rates of dose reductions and therapeutic suppressions with the standard regimen (4:2) have forced the search for new schedule proposals in order to optimize the balance between side effects and oncologic efficacy. Among these new proposals, the 2:1 scheme is the one that has generated more expectations. OBJECTIVE: The objective of this paper is to make a review and critical discussion of current evidence about the new schedules of treatment with sunitinib. METHODS: Unstructured review of the literature on the various therapeutic regimens with sunitinib, making a comparison in terms of progression-free survival (PFS), overall survival (OS) and toxicity. RESULTS: We summarize the data from all relevant studies published to date comparing the standard 4:2 schedule versus the new 2:1. Most patients treated with 2:1 scheme are grouped in three retrospective observational studies and mostly correspond to patients who were initially treated with a 4:2 scheme and then moved to 2:1. A phase II randomized clinical trial comparing 4:2 and 2:1 schemes from the beginning has also been conducted. None of these studies found significant differences between the two regimens in terms of PFS or OS. Regarding the toxicity profile, the 2:1 scheme has proved to be more advantageous than the 4:2. CONCLUSIONS: Despite the still limited amount of data, current evidence supports the use of a 2:1 schedule, as it provides patients substantial advantages because of its better tolerability profile, without a loss in oncological efficacy. Currently, the 2:1 scheme is an appropriate alternative therapeutic strategy, especially in patients with poor tolerance to the standard 4:2 regimen.