Myopodin methylation is a prognostic biomarker and predicts antiangiogenic response in advanced kidney cancer.

Myopodin is a cytoskeleton protein that shuttles to the nucleus depending on the cellular differentiation and stress. It has shown tumor suppressor functions. Myopodin methylation status was useful for staging bladder and colon tumors and predicting clinical outcome. To our knowledge, myopodin has not been tested in kidney cancer to date. The purpose of this study was to evaluate whether myopodin methylation status could be clinically useful in renal cancer (1) as a prognostic biomarker and 2) as a predictive factor of response to antiangiogenic therapy in patients with metastatic disease. Methylation-specific polymerase chain reactions (MS-PCR) were used to evaluate myopodin methylation in 88 kidney tumors. These belonged to patients with localized disease and no evidence of disease during follow-up (n = 25) (group 1), and 63 patients under antiangiogenic therapy (sunitinib, sorafenib, pazopanib, and temsirolimus), from which group 2 had non-metastatic disease at diagnosis (n = 32), and group 3 showed metastatic disease at diagnosis (n = 31). Univariate and multivariate Cox analyses were utilized to assess outcome and response to antiangiogenic agents taking progression, disease-specific survival, and overall survival as clinical endpoints. Myopodin was methylated in 50 out of the 88 kidney tumors (56.8 %). Among the 88 cases analyzed, 10 of them recurred (11.4 %), 51 progressed (57.9 %), and 40 died of disease (45.4 %). Myopodin methylation status correlated to MSKCC Risk score (p = 0.050) and the presence of distant metastasis (p = 0.039). Taking all patients, an unmethylated myopodin identified patients with shorter progression-free survival, disease-specific survival, and overall survival. Using also in univariate and multivariate models, an unmethylated myopodin predicted response to antiangiogenic therapy (groups 2 and 3) using progression-free survival, disease-specific, and overall survival as clinical endpoints. Myopodin was revealed hypermethylated in kidney cancer. Myopodin methylation status identified which patients showed a more aggressive clinical behavior and predicted antiangiogenic response. These observations support the clinical utility of an unmethylated myopodin as a prognostic and predictive biomarker in kidney cancer.

Consensus document on the implications of standardization of BCG supply in the management of patients with non-muscle-invasive bladder cancer.

Patients with non-muscle-invasive bladder cancer (NMIBC) in the intermediate and high-risk groups must receive adjuvant treatment with intravesical Bacillus Calmette-Guérin (BCG) following transurethral resection (TUR), as it reduces the risk of recurrence and presumably the risk of progression as well. Optimization of BCG efficacy is achieved by administering maintenance therapy. However, since many immunological aspects of the mechanism of action of BCG in the bladder remain unknown, the implementation of the optimal dose, number of instillations, strains and adequate maintenance regimen over the last decades has been heterogeneous. Additionally, this has hindered the interpretation of efficacy in terms of oncologic outcomes. This, together with the shortages of BCG in recent years, have forced scientific societies to adapt their clinical practice guidelines and modify their protocols of adjuvant treatment with BCG. This includes changes to strains, doses, and maintenance during this period of time. This consensus document evaluates the current status of adjuvant BCG treatment and the implications of BCG supply availability in the treatment of patients with NMIBC. It also addresses the implementation of novel therapies that will improve cancer prognosis and the quality of life of patients with NMIBC in the future.

Biochemical markers of bone turnover and clinical outcome in patients with renal cell and bladder carcinoma with bone metastases following treatment with zoledronic acid: The TUGAMO study.

BACKGROUND: Levels of bone turnover markers (BTM) might be correlated with outcome in terms of skeletal-related events (SRE), disease progression, and death in patients with bladder cancer (BC) and renal cell carcinoma (RCC) with bone metastases (BM). We try to evaluate this possible correlation in patients who receive treatment with zoledronic acid (ZOL). METHODS: This observational, prospective, and multicenter study analysed BTM and clinical outcome in these patients. Serum levels of bone alkaline phosphatase (BALP), procollagen type I amino-terminal propeptide (PINP), and beta-isomer of carboxy-terminal telopeptide of type I collagen (ß-CTX) were analysed. RESULTS: Patients with RCC who died or progressed had higher baseline ß-CTX levels and those who experienced SRE during follow-up showed high baseline BALP levels. In BC, a poor rate of survival was related with high baseline ß-CTX and BALP levels, and new SRE with increased PINP levels. Cox univariate analysis showed that ß-CTX levels were associated with higher mortality and disease progression in RCC and higher mortality in BC. Bone alkaline phosphatase was associated with increased risk of premature SRE appearance in RCC and death in BC. CONCLUSION: Beta-isomer of carboxy-terminal telopeptide of type I collagen and BALP can be considered a complementary tool for prediction of clinical outcomes in patients with BC and RCC with BM treated with ZOL.

Usefulness of bone turnover markers as predictors of mortality risk, disease progression and skeletal-related events appearance in patients with prostate cancer with bone metastases following treatment with zoledronic acid: TUGAMO study.

BACKGROUND: Owing to the limited validity of clinical data on the treatment of prostate cancer (PCa) and bone metastases, biochemical markers are a promising tool for predicting survival, disease progression and skeletal-related events (SREs) in these patients. The aim of this study was to evaluate the predictive capacity of biochemical markers of bone turnover for mortality risk, disease progression and SREs in patients with PCa and bone metastases undergoing treatment with zoledronic acid (ZA). METHODS: This was an observational, prospective and multicenter study in which ninety-eight patients were included. Patients were treated with ZA (4 mg every 4 weeks for 18 months). Data were collected at baseline and 3, 6, 9, 12, 15 and 18 months after the beginning of treatment. Serum levels of bone alkaline phosphtase (BALP), aminoterminal propeptide of procollagen type I (P1NP) and beta-isomer of carboxiterminal telopeptide of collagen I (ß-CTX) were analysed at all points in the study. Data on disease progression, SREs development and survival were recorded. RESULTS: Cox regression models with clinical data and bone markers showed that the levels of the three markers studied were predictive of survival time, with ß-CTX being especially powerful, in which a lack of normalisation in visit 1 (3 months after the beginning of treatment) showed a 6.3-times more risk for death than in normalised patients. Levels of these markers were also predictive for SREs, although in this case BALP and P1NP proved to be better predictors. We did not find any relationship between bone markers and disease progression. CONCLUSION: In patients with PCa and bone metastases treated with ZA, ß-CTX and P1NP can be considered suitable predictors for mortality risk, while BALP and P1NP are appropriate for SREs. The levels of these biomarkers 3 months after the beginning of treatment are especially important.

Hormone sensitive protocol for metastatic prostate cancer, an update.

To review and update last protocols in hormone sensitive metastatic prostate cancer for improving clinical management in routine. Evidence analysis available about recent updates protocols in hormone sensitive metastatic prostate cancer according to expert panel of clinicians about this field. A nominal consensus group for unify and improve the recommendations to the management of sensitive metastatic prostate cancer patients is currently needed. This document unifies and improve the management of patients with hormone sensitive metastatic prostate cancer, with a methodology that combines data quantitative and qualitative and based on the participation of a broad scientific committee appointed by the Spanish Association of Urology.

A multidisciplinary consensus statement on the optimal pharmacological treatment for metastatic hormone-sensitive prostate cancer.

Androgen deprivation therapy (ADT) is the mainstay treatment for metastatic hormone-sensitive prostate cancer (mHSPC). The addition of docetaxel or new hormone therapies (abiraterone, apalutamide, or enzalutamide) improves overall survival and is currently the standard of care. However, the decision on the specific regimen to accompany ADT should be discussed with the patient, considering factors such as possible associated toxicities, duration of treatment, comorbidities, patient preferences, as there is no sufficient evidence to recommend one regimen over the other in most cases. This paper summarizes the evidence on the management of mHSPC and provides consensus recommendations on the optimal treatment in combination with ADT in mHSPC patients, with special attention to the patient's clinical profile.

Optimizing treatment for non muscle-invasive bladder cancer with an app.

OBJECTIVES: To evaluate overall and recurrence-progression rate-adjusted concordance of treatment prescription in non-muscle-invasive bladder cancer (NMIBC) of an app based on the best available scientific evidence and the urologist's opinion. METHODS: Development of an app (APPv) specifically designed for the treatment and follow-up of NMIBC and validation of the proposed APPv treatment endpoint by means of a prospective double-blind observational concordance study of related samples in 100 patients with initial or successive histological diagnosis of NMIBC. RESULTS: The treatment prescribed by the urologist agrees with that proposed by the APPv in 64% of cases (kappa index 0.55, P < 0.0001). Regarding low risk, the agreement is 77% (kappa 0.55, P = 0.002), 63% (kappa 0.52, P < 0.0001) for intermediate risk, 17% (kappa 0.143, P = 0.014) in high risk and 66% (kappa 0.71, P = 0.01) for very high risk. Of patients receiving adjuvant intravesical treatment according to APPv, 89.1% remain free of recurrence vs. 61.1% of those with disagreement (P = 0.0004), with a RR 0.46 (95%CI: 0.25-0.86) vs. RR 2.4 (95%CI: 1.5-3.8, P = 0.001). In the APPv-urologist agreement group, 100% of patients are free of progression and 88.9% in the disagreement group (P = 0.004) with a RR 1 vs. RR 1.125 (95%CI: 1-1.26, P = 0.004). CONCLUSIONS: APPv can improve adherence to treatment recommendations according to clinical practice guidelines and health outcomes at NMIBC.

Non-metastatic castration-resistant prostate cancer: management recommendations.

INTRODUCTION AND OBJECTIVE: Survival and quality of life (QoL) of patients with non-metastatic castration-resistant prostate cancer (nmCRPC) deteriorate significantly when they develop metastases. New generation antiandrogens (apalutamide, enzalutamide and darolutamide) can prolong metastasis-free survival (MFS) and overall survival (OS) in these patients, maintaining their QoL. MATERIAL AND METHODS: After the performance of a systematic review of the literature, a scientific committee reached a consensus on simple and practical recommendations to consolidate and improve the management of patients with nmCRPC in urology consultations. RESULTS: Recommendations are made on the frequency of PSA determination and imaging tests in patients with nmCRPC. The importance of co-morbidities in patients with nmCRPC is also highlighted, and recommendations are also made on functional and QoL assessment that can be carried out during urology consultations. The efficacy, safety, and effects on QoL of new generation antiandrogens are reviewed. CONCLUSIONS: To evaluate treatment of patients with nmCRPC, it is necessary to consider co-morbidities and QoL, in addition to age. New generation antiandrogens are a safe and effective treatment option for patients with nmCRPC. The recommendations of this review can be helpful in optimizing the management of nmCRPC patients in urology consultations.

Empiric therapy for idiopathic oligoasthenoteratozoospermia. / Tratamiento empírico de la oligoastenoteratozoospermia idiopática.

Male infertility accounts for 50% of the causes of infertile couples, being more than 30% of unknown etiology. In these cases, empiric treatment can be an option prior to the application of assisted reproduction techniques. Empiric treatment can be categorized as hormonal, such as gonadotropins, antiestrogens and aromatase inhibitors, and antioxidant, with vitamins, trace elements and carnitine, among others. Although scientifically acceptable evidence is limited due to the absence of large randomized and controlled clinical trials, recent systematic reviews and meta-analyses show that treatment with gonadotropins, antiestrogens and antioxidants increases pregnancy and live birth rates and improves seminal parameters. Empiric medical treatment for idiopathic infertility can be considered in specific cases in order to improve semen quality and spontaneous fertility.

Incidence of upper tract urothelial carcinoma in Spain. / Incidencia del carcinoma transicional del tracto urinario superior en España.

INTRODUCTION AND OBJECTIVES: The incidence of upper urinary tract tumors is currently unknown. The aim of this study is to determine the real incidence of upper tract urothelial carcinoma (UTUC) in Spain. MATERIAL AND METHODS: A descriptive, prospective and multicenter epidemiological study was conducted in 31 Spanish facilities by means of the Platform for Multicenter Studies of the Spanish Association of Urology. Recruitment was opened from May 1st, 2017 to April 30th, 2018. The original database was exported directly from the electronic Data Collection Logbook on December 15th, 2018, with a total of 404 cases registered (402 valid cases after depuration). Statistical analysis was performed using IBM SPSS software v 23 and EPIDAT v 3.4. RESULTS: The incidence adjusted to Spanish population from raw data was 3.27 cases per 100.000 inhabitants per year (2.93 - 3.61 95% CI) and 3,3 cases per 100.000 inhabitants per year (2.96-3.66 95%CI) when adjusted to European population by age. The mean age at diagnosis was 70 years, and 77% of patients were male. Thirty-four percent of patients had an incidental diagnosis. Tumors were most commonly located in the pyelocalyceal system (54%), followed by the distal ureter (22%). Prior ureteroscopy was performed in 114 patients: this technique modified the subsequent treatment indication in 58% of cases. Radical nephroureterectomy was performed in 311 patients. Kidney-sparing surgery was the elected treatment in 76 patients (20%). Complications were found in 69% of cases, most of them classified as Clavien 1 and 2 (86% of all complications). Postoperative mortality rate was 1.7%. CONCLUSIONS: UTUC adjusted incidence rate in Spain is 3.27 and 3.3 in Europe. Prior URS modified the treatment indication in 18% of patients. We found a 69% complication rate and a 1.7% mortality rate.

Postoperative pain and cosmetic results of minilaparoscopic nephrectomy compared to the conventional technique. / Dolor postoperatorio y resultados cosméticos de la nefrectomía minilaparoscópica frente a la técnica convencional.

INTRODUCTION: In recent years urology has been focussing on less invasive forms of laparoscopy with less impact on the abdominal wall. The minilaparoscopy (ML) is promising in this regard. Our objective is to compare the results of a series of patients who underwent minilaparoscopic nephrectomy with another series who underwent conventional laparoscopy (CL). MATERIAL AND METHODS: We chose 8 nephrectomies performed by mini-laparoscopy in a single hospital (NmL group) from a total of 110 patients included in multiple centres and compared them retrospectively with a contemporary series of 16 patients who underwent CL (NL group). From 1 to 3 3mm and 5mm trocars were used for the NmL and the NL, respectively, one 10mm trocar in the pararectal edge of a Pfannenstiel incision and another 11mm paraumbilical trocar for the optics. Age, BMI, ASA, complications, analgesic requirements in the postoperative period and cosmetic satisfaction were recorded using the Patient Scar Assessment Questionnaire (PSAQ), one month after the intervention. RESULTS: Both groups were comparable and there were no differences in terms of surgery time, number of ports used, hospital stay or intra-and postoperative complications. In only one patient from the NmL group, a 3mm trocar had to be replaced by a 5mm trocar and one patient in the NL group was converted to hand-assisted surgery due to severe adherences. The patients in the NmL group had less postoperative pain on the VAS (±0 vs. 4±25, P=.05) and were more satisfied with their appearance on the PSAQ (8.5±1.4 vs. 16.6±3.1, P=.05) compared to the NL group. CONCLUSIONS: The results obtained with the ML instrument were similar to those obtained by CL, but with the advantages of less postoperative pain and better cosmetic results.

Radium-223 for the treatment of metastatic castration-resistant prostate cancer: A window of opportunity. / Radio-223 en el tratamiento del cáncer de próstata resistente a la castración metastásico: una ventana de oportunidad.

CONTEXT: The elimination of bone metastases, restoration and/or preservation of bone morphology and prevention and/or delay of skeletal events are a fundamental objective in the management of metastatic castration-resistant prostate cancer (mCRPC). Radium-223 is the first targeted alpha therapy with effects on bone that has been shown to increase survival in these patients, besides providing other bone-related benefits. OBJECTIVE: To analyze the impact of bone metastasis on mCRPC, and the benefits and the window of opportunity provided by radium-223 in the treatment of patients with mCRPC in the current treatment era. EVIDENCE ACQUISITION: A bibliographic search of PubMed and Spanish and international congresses on radium-223 and other first-line treatments for mCRPC was performed. Recent guidelines and recommendations by experts were also consulted. SUMMARY OF THE EVIDENCE: Evidence for the mechanism of action of radium-223 widen its effects to the tumor bone environment. Survival of patients treated with radium-223 is higher in those with mild symptoms as opposed to those with moderate-severe symptoms. The presence of visceral metastases even in the early stages of mCRPC supports starting radium-223 therapy before the symptoms become clinically relevant. A 3-year study has confirmed its good safety profile. Changes in tALP and LDH may be useful markers for monitoring the treatment with radium-223, but they are not predictors of overall survival. CONCLUSION: Radium-223 is a valuable therapeutic alternative in the treatment of patients with mCRPC in early stages of the disease, with a good safety profile. Its benefits extend to the bone environment.

National recommendations document on the follow-up of patients with renal cell carcinoma. / Documento nacional de recomendaciones sobre el seguimiento del paciente con carcinoma de células renales.

OBJECTIVES: This document was developed to establish directives for the follow-up of patients with renal cell carcinoma (RCC) based on the best available scientific evidence and on expert opinions, which can help urologists in the decision-making process and standardise the criteria at the national level. MATERIAL AND METHODS: The methodology is based on the RAND/UCLA method. A panel of 9 experts on RCC participated in designing a thematic index, identifying and reading the available evidence, formulating recommendations and drafting the content. A validating group of 25 experts, who did not participate in the previous phases, assessed the recommendations through anonymous voting in a face-to-face consensus meeting. The recommendations that were agreed upon by 75% or more of the participants in this vote were accepted as consensus. The recommendations that did not achieve this consensus were rejected. RESULTS: A total of 25 recommendations were accepted as consensus. These recommendations cover the laboratory tests, clinical assessment tests and imaging tests that should be performed for patients with RCC. The presented recommendations have been adapted according to relapse risk. The current document also outlines the frequency and duration of follow-up for each patient profile. CONCLUSIONS: The current document enables standardisation of the follow-up criteria for patients with RCC treated in the Spanish healthcare setting, according to the patients' relapse risk.

Cognitive function in patients on androgen suppression: A prospective, multicentric study. / Función cognitiva en pacientes tratados con supresión androgénica: estudio prospectivo y multicéntrico.

OBJECTIVE: To assess the effect of androgen deprivation therapy (ADT) on cognitive performance (CP) in patients with prostate cancer (PCa) after 6 months of treatment with luteinizing hormone-releasing hormone (LHRH) analogues. MATERIAL AND METHODS: Prospective, observational, multicentre, open-label study of patients diagnosed with nonmetastatic or asymptomatic metastatic PCa scheduled to receive LHRH analogues for≥6 months. We assessed four CP domains at baseline and after 6 months of ADT: 1) Working memory: Wechsler Adult Intelligence Scale III (WAIS III) Digit Span Subtest (WAIS III-Digit); 2) Visual memory: ad hoc visual memory test; 3) Visuospatial ability: Judgement of Line Orientation (JLO) and Mental Rotation of Three-Dimensional Objects (3D-Rotation); and 4) Nonverbal analytical reasoning: WAIS III Matrix Reasoning Test (WAIS III-MRT). Changes outside the baseline 95% confidence intervals were considered significant. RESULTS: A total of 308 patients completed the study. Of these, 245 (79.6%) experienced no statistically significant changes on any test and 63 patients (20.4%) experienced significant changes in ≥1 test. Of these, most presented a change in only one test, distributed evenly between improvements (58 patients; 18.8%) and worsening (56 patients; 18.2%). For individual tests, most patients (87.8% to 91.8%) had no change from baseline; however, the significant changes (improvement vs. deterioration, respectively) were as follows: WAIS III-Digit (6.3% vs. 5.9%); visual memory (5.3% vs. 5.7%); JLO (5.3% vs. 4.5%); 3D-Rotation (4.1% vs. 4.1%); and WAIS III-MRT (4.8% vs. 5.8%). CONCLUSIONS: CP in patients with PCa does not appear to be adversely affected by 6 months of LHRH analogue administration.

Combination of extracorporeal lithotripsy and flexible ureterorenoscopy optimize renal lithiasis therapy. / La combinación de litotricia extracorpórea y ureterorrenoscopia flexible optimiza el tratamiento de litiasis renales.

OBJECTIVE: Describe our initial experience in the treatment of renal lithiasis with extracorporeal lithotripsy controlled by simultaneous flexible ureterorenoscopy and combined with holmium laser lithotripsy. MATERIAL AND METHODS: We performed this novel technique in a previously selected patient with left renal lithiasis, two in the superior calix, two in the medium calix and two in the inferior calix, the biggest of which was placed in medium calix and was 6mm long. We proceeded to an extracorporeal shock wave lithotripsy and a simultaneous flexible ureterorenoscopy for better controlling the fragmentation of the lithiasis with the use of a holmium laser. In the immediate post-operative, an ultrasound was performed and, one month later, a computerized tomography (CT) was done. RESULTS: The complete fragmentation of all the lithiasis was obtained and a double-J catheter was placed. After the assessment of the absence of stone fragments by CT the catheter was removed. No intra-operative or post-operative complications were described. CONCLUSIONS: The technique described is novel, safe and reproducible. The good result obtained through this combined technique increases our interest in continuing with its application and consider it as an option for the treatment of renal lithiasis in our patients.

The assessment of surgical skills as a complement to the training method. Revision.

CONTEXT AND OBJECTIVE: The acquisition and improvement of surgical skills constitute a fundamental element in the training of any practitioner. At present, however, the assessment of these skills is a scarcely developed area of research. The aim of this study was to analyse the peculiarities of the various assessment systems and establish the minimum criteria that a skills and knowledge assessment system should meet as a method for assessing surgical skills in urological surgery. ACQUISITION OF EVIDENCE: Scientific literature review aimed at the various currently available assessment systems for skills and competencies (technical and nontechnical), with a special focus on the systematic reviews and prospective studies. SUMMARY OF THE EVIDENCE: After conducting the review, we found that the various assessment systems for surgical competence have, in our opinion, a number of shortcomings. There is a certain degree of subjectivity in the assessment of surgeons by the evaluators. The assessment of nontechnical competencies is not formally recorded. There is no description of a follow-up assessment or any basic parameters associated with healthcare quality. There is no registration of associated competencies associated with the various surgical techniques. There is also no ranking of these competencies and the specific peculiarities for their application. CONCLUSIONS: We believe that the development of a new assessment system for surgical competencies (technical and nontechnical) aimed at assessing urologists in the various surgical techniques is necessary. To this end, our team has worked on developing the Evaluation System for Surgical Competencies on Laparoscopy, which is based on the definition, ranking and assessment of competencies demonstrated by surgeons.