Clinical drivers for imaging testing in non-metastatic castration-resistant prostate cancer in clinical practice: Results of the IDENTIFICA study. / Factores clínicos determinantes para la realización de pruebas de imagen en cáncer de próstata resistente a la castración no metastásico en la práctica clínica: resultados del estudio IDENTIFICA.

INTRODUCTION: The aim of the study was to describe the clinical drivers that lead physicians to perform imaging tests in search of metastasis in non-metastasic castration prostate resistant cancer (nmCRPC) patients. METHODS: Observational, cross-sectional study conducted at the Departments of Urology of 38 Spanish hospitals. The study included 188 patients diagnosed with nmCRPC who underwent an imaging test for the assessment of metástasis. In one study visit, physicians were requested to specify the clinical factors that led them to perform these tests. The results of the imaging tests and the clinical characteristics of the patients since the time of prostate cancer (PC) diagnosis, were reported. Regression analyses were used to determine predictors of imaging test results. RESULTS: Prostate-specific antigen (PSA) level was the most important driver to order imaging tests (57.1%), followed by regular follow-up (16.5%) and PSA doubling time (PSADT) (12.0%). Although these drivers were not associated to detection of metastasis, patients with PSA levels ≥20 ng/mL had a greater risk of metastasis than patients with PSA levels <4ng/mL (P=.004) and CRPC patients diagnosed with metastasis (mCRPC) had higher median PSA levels (20.9; interquartile range [IQR]: 6.7-38.6) than nmCRPC (9.1; IQR: 5.0-18.0) (P=.005). Sixty-six percent of the patients did not undergo any imaging test after CRPC diagnosis until the study visit (10.6, IQR: 4.0-19.5 months). Curative-intent treatment at PC diagnosis and Gleason score predicted longer time from PC to CRPC diagnosis. CONCLUSIONS: Physicians based their decisions to order imaging tests for metastasis detection in nmCRPC patients mainly on PSA and PSA kinetics, including the regular follow-up stated by guideline recommendations.

Mortality prediction model for patients with bladder urothelial tumor after radical cystectomy. / Modelo predictivo de mortalidad en pacientes con tumor urotelial de vejiga tras cistectomía radical.

OBJECTIVE: Based on preoperative clinical and postoperative pathological variables, we aim to build a prediction model of cancer specific mortality (CSM) at 1, 3, and 5 years for patients with bladder transitional cell carcinoma treated with RC. MATERIAL AND METHODS: Retrospective analysis of 517 patients with diagnosis of cell carcinoma treated by RC (1986-2009). Demographic, clinical, surgical and pathological variables were collected, as well as complications and evolution after RC. Comparative analysis included Chi square test and ANOVA technique. Survival analysis was performed using Kaplan-Meier method and log-rank test. Univariate and multivariate analyses were performed using logistic regression to identify the independent predictors of CSM. The individual probability of CSM was calculated at 1, 3 and 5 years according to the general equation (logistic function). Calibration was obtained by the Hosmer-Lemeshow method and discrimination with the elaboration of a ROC curve (area under the curve). RESULTS: BC was the cause of death in 225 patients (45%). One, three and five-year CSM were 17%, 39.2% and 46.3%, respectively. The pT and pN stages were identified as independent prognostic variables of CSM at 1, 3 and 5 years. Three prediction models were built. The predictive capacity was 70.8% (CI 95% 65-77%, p=.000) for the 1st year, 73.9% (CI95% 69.2-78.6%, p=.000) for the third and 73.2% (CI% 68.5-77.9%, p=.000) for the 5th. CONCLUSIONS: The prediction model allows the estimation of CSM risk at 1, 3 and 5 years, with a reliability of 70.8, 73.9 and 73.2%, respectively.

Review of the experience and evidence of Pygeum africanum in urological practice. / Revisión sobre la experiencia y evidencias del Pygeum africanum en Urología.

CONTEXT: Pygeum africanum(P. africanum) is still being employed in urology practice for the treatment of lower urinary tract symptoms secondary to benign prostate hyperplasia. EVIDENCE ACQUISITION: A non-exhaustive review has been carried out about P. africanum, its mechanisms of action "in vitro" as well as "in vivo", clinical trials and routine clinical practice. EVIDENCE SYNTHESIS: The conclusions of the review and the reflections of the authors on the use of P. africanum are described. CONCLUSIONS: Although with an evidence level IV (based on expert opinion) the use of P. africanum seems to be an option in the urological therapeutic arsenal.

Effect of adjuvant chemotherapy in locally advanced urothelial carcinoma of the bladder treated with cystectomy. / Efecto de la quimioterapia adyuvante en el carcinoma urotelial de vejiga localmente avanzado tratado con cistectomía.

INTRODUCTION: Currently, the role of adjuvant chemotherapy (ADJ) in muscle invasive bladder tumor remains controversial. OBJECTIVE: To evaluate the effect of ADJ on cancer specific survival of muscle invasive bladder tumor after radical cystectomy (RC). MATERIAL AND METHODS: Retrospective analysis of 292 patients diagnosed with urothelial bladder tumor pT3-4pN0 / + cM0 stage, treated with RC between 1986-2009. Total cohort was divided in two groups: 185 (63.4%) patients treated with ADJ and 107 (36.6%) without ADJ. Median follow-up was 40.5 months (IQR 55-80.5). Comparative analysis was performed with Chi-square test and Student's t test /ANOVA. Survival analysis was carried out with the Kaplan-Meier method and log-rank test. Multivariate analysis (Cox regression) was made to identify independent predictors of cancer-specific mortality (CSM). RESULTS: 42.8% of the series presented lymph node involvement after RC. At the end of follow-up, 22.9% were BC-free and 54.8% had died due to this cause. The median cancer specific survival was 30 months. No significant differences were observed in cancer specific survival regarding the treatment with ADJ in pT3pN0 (p=.25) or pT4pN0 (p=.29) patients, but it was significant in pT3-4pN+ (p=.001). Multivariate analysis showed pathological stage (p=.0001) and treatment with ADJ (p=.007) as independent prognostic factors for CSM. ADJ reduced the risk of CSM (HR:0.59,95% CI 0.40-0.87, p=.007). CONCLUSIONS: pT and pN stages were identified as independent predictors of CSM after RC. The administration of ADJ in our series behaved as a protective factor reducing the risk of CSM, although only pN+ patients were benefited in the stage analysis.

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.

Safety and efficacy of various strains of bacille Calmette-Guérin in the treatment of bladder tumours in standard clinical practice. / Eficacia y seguridad de distintas cepas de BCG en el tratamiento del tumor vesical en práctica clínica habitual.

BACKGROUND: The natural progression of bladder tumours (nonmuscle-invasive bladder cancer [NMIBC]) is recurrence with a high rate of progression. Bacille Calmette-Guérin (BCG) has been shown effective in reducing these rates, but there are few comparative studies between strains. MATERIAL AND METHODS: An observational, prospective and multicentre registry studied 433 patients with a 12-month follow-up visit from 961 registered patients, assessing disease-free survival (DFS), progression-free survival (PFS) cancer-specific survival (CSS) and adverse effects. We studied the Tice, Russian, Tokyo, Connaught and RIVM strains. RESULTS: The sociodemographic data, NMIBC history, comorbidities, size, number, stage, grade, associated carcinoma in situ and transurethral resection were well balanced. DFS: There were 85 relapses (19.6%). The median DFS time was 20months. When comparing the various strains, we detected no statistically significant differences (log-rank test; P=.93). LPS: There were 33 cases of progression (7.62%). When comparing the various strains, we detected no statistically significant differences (log-rank test; P=.69). CSS: Seven patients died (1.68%). When comparing the various strains, we detected no statistically significant differences (log-rank test; P=.93). In terms of safety, 33.3% of the patients presented some type of adverse effect, mostly lower urinary symptoms (no urinary tract infections) <48h, >48h and haematuria. According to the Common Toxicity Criteria of the European Organisation for Research and Treatment of Cancer, 92.7% of the patients were grade1. There were no statistically significant differences between the strains. CONCLUSIONS: In this intermediate analysis, the risk of recurrence, progression, specific death and safety were independent of the BCG strain employed.

18F-Choline PET/CT scan in staging and biochemical recurrence in prostate cancer patients: Changes in classification and radiotherapy planning. / La PET/TC con 18F-Colina en la estadificación y recidiva bioquímica de pacientes con cáncer de próstata: cambios en la clasificación y planificación de radioterapia.

OBJECTIVE: To evaluate the role of the 18F-Choline PET/CT in prostate cancer management when detecting distant disease in planning radiotherapy and staging and to evaluate the therapy changes guided by PET/TC results. MATERIAL AND METHODS: A retrospective evaluation was performed on 18F-Choline PET/CT scans of patients with prostate cancer. Staging and planning radiotherapy scans were selected in patients with at least 9 months follow up. There was a total of 56 studies, 33 (58.93%) for staging, and 23 (41.07%) for planning radiotherapy. All scans were obtained using a hybrid PET/CT scanner. The PET/CT acquisition protocol consisted of a dual-phase procedure after the administration of an intravenous injection of 296-370MBq of 18F-Choline. RESULTS: There were 43 out of 56 (76.8%) scans considered as positive, and 13 (23.2%) were negative. The TNM staging was changed in 13 (23.2%) scans. The PET/CT findings ruled out distant disease in 4 out of 13 scans, and unknown distant disease was detected in 9 (69.3%) scans. CONCLUSIONS: 18F-Choline PET/CT is a useful technique for detecting unknown distant disease in prostate cancer when staging and planning radiotherapy. The inclusion of 18F-choline PET/CT should be considered in prostate cancer management protocols.

Role of taxanes in advanced prostate cancer.

Advanced prostate cancer is an androgen-dependent disease for which the initial treatment is an androgen deprivation maneuver. However, some primary resistances to hormonal treatment occur with increasing incidence throughout the evolution of the disease. The taxanes, docetaxel and cabazitaxel, exert their action at multiple levels at the tumor cell: besides inhibiting the mitosis and inducing the cell death, they induce the nuclear accumulation of FOXO1, a potent nuclear factor that acts against the activation of androgen receptor inhibiting the transcription of AR-V7 variant associated with the development of resistances to abiraterone and enzalutamide. Docetaxel, as first-line therapy, and cabazitaxel, as second-line therapy, have demonstrated to increase the survival in castration-resistant prostate cancer. The results from last studies either on high-risk localized disease or on androgen-sensitive tumors demonstrate the increasing role of taxanes at earlier states of prostate cancer.

Review of the pathophysiological aspects involved in urological disease associated with metabolic syndrome. / Aspectos fisiopatológicos implicados en la patología urologica asociada al síndrome metabólico. Revisión bibliográfica.

INTRODUCTION: Metabolic syndrome is a constellation of disorders that includes insulin resistance, central obesity, arterial hypertension and hyperlipidaemia. These disorders can have implications for the genitourinary apparatus. OBJECTIVES: To conduct a review on the pathophysiological aspects that explain the relationship between metabolic syndrome and sexual dysfunction, lower urinary tract syndrome, prostate cancer and stone disease. METHODS: We performed a qualitative, narrative literature review through a literature search on PubMed of articles published between 1997 and 2015, using the terms pathophysiology, metabolic syndrome, endothelial dysfunction, lipotoxicity, mitochondrial dysfunction, kidney stones, hypogonadism, erectile dysfunction, lower urinary tract syndrome and prostate cancer. SYNTHESIS OF THE EVIDENCE: Metabolic syndrome constitutes an established complex of symptoms, defined as the presence of insulin resistance, central obesity, hypertension and hyperlipidaemia. Endothelial dysfunction secondary to lipotoxicity generates an inflammatory state, which involves renal cell metabolism, vascularisation of the pelvis and androgen production. These facts explain the relationship between metabolic syndrome, nephrolithiasis, lower urinary tract syndrome, hypogonadism and erectile dysfunction in men. CONCLUSIONS: Strategies such as proper diet, regular exercise, insulin treatment, testosterone-replacement therapy, therapy with antioxidants and free-radical inhibitors and urological treatments classically used for lower urinary tract syndrome have shown promising results in this syndrome.

Comparative analysis of the incidence of bladder cancer in the communities of Andalusia, Catalonia and Madrid in 2011.

OBJECTIVES: To determine the incidence of bladder cancer (BC) in the autonomous communities that include the largest number of cases in the national hospital BC registry (Andalusia, Catalonia and Madrid) and report the clinical, pathological and diagnostic differences and similarities of BC in these regions. MATERIAL AND METHODS: An observational epidemiological study was performed in 2011 in 12 public hospitals with reference population areas according to the National Health System (Spain). Demographic and clinical variables were collected from new cases and relapses, with histopathologic confirmation of BC. The raw incidence rate was calculated using the number of diagnosed cases in all the participating centers compared with the aggregate total population assigned to each center. The raw rates by age and sex were obtained from the National Institute of Statistics (2011) by weighting the assigned population with the distribution by age and sex. RESULTS: The 3 autonomous communities recorded 51% of the 4285 cases included in the national registration, with relapses corresponding to 42.8% of these cases. The raw annual incidence rate for new episodes was 22.6 (95% CI: 20.7; 24.6) in Andalusia, 23.5 (95% CI: 20.9; 26.0) in Catalonia and 22.0 (95% CI: 19.9; 24.1) in Madrid. CONCLUSIONS: Except for the larger proportion of smokers and lower tumor grade of lesions in Andalusia, the 3 autonomous communities studied are similar in terms of clinical characteristics, comorbidities, patient symptoms and diagnostic processes for BC.

Factors that predict the development of bone metastases due to prostate cancer: Recommendations for follow-up and therapeutic options.

CONTEXT: Prostate cancer is a public health problem in Spain and in the Western world. Bone involvement, associated to significant morbidity, is practically constant in the advanced stages of the disease. This work aims to review the prognostic factors used in the usual clinical practice that predict the development of bone metastases and to analyze the follow-up and treatment option in these patient profiles. ACQUIRING OF EVIDENCE: We performed a review of the literature on the useful factors in the context of therapy with intention to cure. We included the classical clinical values in the diagnosis (PSA, clinical stage, Gleason score on the biopsy) pathological factors (pT stage, margins, bladder invasion, tumor volume, lymph node involvement) and PSA kinetics in their different contexts and the histological and molecular parameters. SYNTHESIS OF EVIDENCE: The tumor differentiation "Gleason" score and PSA are the most important predictive factors in the prediction of bone metastases in patients with intention to cure. Kinetic factors such as PSA doubling time (TDPSA) < 8 months or PSA > 10 ng/ml in the case of castration-resistant prostate cancer (CPRC), are predictive factors for the development of metastasis. Zoledronic acid and denosumab have demonstrated their effectiveness for the treatment of bone disease in randomized studies. CONCLUSIONS: There are predictive factors within the usual clinical practice that make it possible to recognize the "patient at risk" to develop bone metastatic disease. The currently available treatments, zoledronic acid or denosumab, can help us in the management of the patient at risk of developing metastasis or metastatic patient, increasing the quality of life and decreasing skeletal events.

Treatment of non muscle invasive bladder tumor related to the problem of bacillus Calmette-Guerin availability. Consensus of a Spanish expert's panel. Spanish Association of Urology.

CONTEXT: Since June 2012, the has been a worldwide lack of available of the Connaught strain. In December 2012, a group of experts met in the Spanish Association of Urology to analyze this situation and propose alternatives. OBJECTIVE: To present the work performed by said committee and the resulting recommendations. ACQUISITION OF EVIDENCE: An update has been made of the principal existing evidence in the treatment of middle and high risk tumors. Special mention has been made regarding the those related with the use of BCG and their possible alternative due to the different availability of BCG. EVIDENCE SYNTHESIS: In tumors with high risk of progression, immediate cystectomy should be considered when BCG is not available, with dose reduction or alternating with chemotherapy as methods to economize on the use of BCG when availability is reduced. In tumors having middle risk of progression, chemotherapy can be used, although when it is associated to a high risk of relapse, BCG would be indicated if available with the mentioned savings guidelines. BCG requires maintenance to maintain its effectiveness, it being necessary to optimize the application of endovesical chemotherapy and to use systems that increase its penetration into the bladder wall (EMDA) if they are available. CONCLUSIONS: Due to the scarcity of BCG, it has been necessary to agree on a series of recommendations that have been published on the web page of the Spanish Association of Urology.

[Effectiveness and tolerability of zoledronic acid in the treatment of metastatic prostate cancer]. / Efectividad y tolerabilidad del acido zoledrónico en el tratamiento del cancer de próstata metastásico.

OBJECTIVES: To assess the effectiveness and tolerability of zoledronic acid in prostate cancer patients with bone metastases at the hormone-sensitive (HS) and hormone-independent (HI) stages. MATERIALS AND METHODS: A nationwide, observational, prospective, open and multi-centre trial was devised, with a total of 218 male patients diagnosed with prostate cancer at the HS stage (36%) or HI stage (64%) who were administered zoledronic acid (4 mg/IV/month for 6 months) in addition to their specific oncological treatment. Effectiveness was assessed by the following means: 1) Assessment of the improvement in pain and mobility; 2) Incidence and time to onset of skeletal-related events (SREs) and 3) Analysis of bone markers. Tolerability was assessed by means of registering the number and type of adverse effects. A satisfaction survey was carried out amongst the patients after the end of the trial. RESULTS: Out of the 218 patients, 170 (78%) were evaluable for effectiveness. A decrease in pain ratings at rest and during movement was observed in all patients, whether in the HS or HI groups (p < 0.0001). Improved mobility was observed likewise (p = 0.005), as was quality of life. The global incidence of skeletal events was 11.2%, with a time to onset of SREs of 10.7 months. There were no significant differences observed between HS vs. HI patients. Osteolysis markers (N-telopeptide) decreased significantly with the treatment across both the HS and HI groups. For safety reasons. 212 patients were evaluable (97.2%). The incidence of adverse drug reactions was 16% (34/212) and was found to be significantly higher in HS patients (22.4%) compared with HI patients (11.9%). Overall, the tolerability of zoledronic acid was good, with no significant morbidity in either group (HS and HI). 66% of the patients reported feeling satisfied or very satisfied. CONCLUSIONS: Zoledronic acid proved effective in the relief of pain, improving mobility and quality of life as well as reducing or delaying the occurrence of skeletal-related events in prostate cancer patients presenting metastatic bone disease, regardless of the phase, whether HS or HI, they found themselves in. Tolerability and patient satisfaction were rates as good.

[Testicular carcinoid tumor associated with teratoma: with regard to a case]. / Tumor carcinoide testicular asociado a teratoma: a propósito de un caso.

We report a case of a carcinoid tumor originated in testicle associated with mature teratoma in a 31 years old male. Primary gonadal location of this tumor is unusual, moreover when associated with teratoma. Early diagnosis and treatment determine the prognostic of the patients affected of this neoplasm since the only curative potential treatment is surgery. Follow up must be extent for years due to the possibility of late relapse.

[Validity of tests for initial diagnosis and its concordance with final diagnosis in patients with suspected benign prostatic hyperplasia]. / Validez de las pruebas utilizadas en el diagnóstico inicial y su concordancia con el diagnóstico final en pacientes con sospecha de hiperplasia benigna de próstata.

OBJECTIVE: To assess the validity of diagnostic tools available at the primary care setting [medical history (MH), I-PSS questionnaire, digital rectal examination (DRE) and prostate specific antigen (PSA) evaluation] for the diagnosis of benign prostatic hyperplasia (BPH). SUBJECTS AND METHODS: 363 patients with suspected prostatic disease referred to urology outpatient clinics were included. For every subject initial BPH diagnosis was collected at each of the following sequential procedures: 1) MH; 2) I-PSS; 3) DRE; and 4) PSA. Each of these diagnostic decisions were compared to a final diagnosis (gold standard) reached after the addition of urinary sediment analysis, ultrasonographic assessment of residual volume and prostatic volume, and peak urinary flow measurement. A descriptive analysis was undertaken: validity and concordance between each diagnostic step and the gold standard was calculated. RESULTS: Sensitivity, specificity, positive predictive value, and negative predictive value of diagnosis based on MH+I-PSS+DRE+PSA with respect to the gold standard were 91%, 65%, 95% and 50%, respectively. The percentage of agreement and kappa index between both diagnostic strategies were 87.9% and 0.5, respectively. CONCLUSIONS: Concordance between BPH initial diagnosis based on MH+I-PSS+DRE+PSA and diagnosis based on a full range of tests was high, thus allowing recommending the use of this group of initial diagnostic procedures, which are available to the primary care physician, not only as a first diagnostic step in patients with suspected BPH, but also as a valid strategy to prevent unnecessary delay in its initial management and to facilitate appropriate referral from primary to specialized care.

[Gastric metastasis from renal cell carcinoma. Pathogenical hypothesis and literature revision]. / Metástasis gástrica de un adenocarcinoma renal. Hipótesis patogénica y revisión de la literatura.

Secondary gastric tumours are very uncommon clinical entities and even more so when the site for the primary tumour is the kidney. Only 11 cases of life diagnosis have been described up to now. Contribution of one case report: a female patient presenting with upper GI tract haemorrhage secondary to gastric metastasis from renal cell carcinoma four years after radical nephrectomy. A literature review is made on the cases described up to date in living patients and a pathogenic hypothesis established based on the theoretical dissemination routes for the cases of gastric location of the metastasis.