VII Rising Stars in Urology

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1 VII Rising Stars in Urology Sesión: Poster Session I - Group B Moderadores: M. Ruibal y T. Pereira Sala: Salón Árabe; Día: 25 de febrero de 2016; Hora: 10:30-12:00 P-7: Urinary Biomarkers for Detection of Prostate Cáncer in Patients with High- Grade Prostatic Intraepithelial Neoplasia (HGPIN) Regís, L; Bastaros, JM; Sequeiros, T; Sánchez, M; Rigau, M; Placer, J; Planas, J; De Torres, I; Raventos, J; Doll, A; Morote, J Hospital General Universitario Vall d'hebron P-8: Stereotactic radiotherapy as treatment of oligometastatic prostate cancer. Our initial experience. Sobrón Bustamante M.; Pastor Peidró J.; Juan Escudero J.; Hernández Manchacoses A.; Marqués Vidal E.; López Torrecillas J. Consorcio Hospital General Universitario de Valencia P-9: Clinical Significance of Proliferative Inflammatory Atrophy in Negative Prostatic Biopsies Servián Vives, P.; Celma Domènech, A.; Planas Morin, J.; Placer Santos, J.; de Torres Ramirez, I.M.; Morote Robles, J. Hospital Vall d'hebrón P-10: Papillary Renal Cell Carcinoma. Identification and prognosis by mirna profiling. Arrebola Pajares A.; Villacampa Aubá F.; Sopeña Sutil R.; Alonso Isa M.; Duarte Ojeda J.M.; Gámez A.; Fresno J.A.; García Muñóz H.; Castellano Gauna D.; De la Rosa Kehrmann F.; Passas Martínez J. UroOncology Unit, Urology Service, Hospital Universitario 12 de Octubre. - IdiPaz P-11: Results of therapy with inhibitor growth factors as treatment for the advanced renal carcinoma. Rodezno, D; Pieras, E; Garcías de España, C; Martínez, A; Alcojor, I; Moncada, O; Soriano, T; Guimera, J; Sabate, A; Pizá, P Hospital Universitario Son Espases P-12: Urinary exosomes as potential biomarkers in bladder cancer Otta Oshiro, R.J.; Acosta Reveles, M.A.; Andreu Martínez, Z.; Yañez-Mó, M.; Redruello, A.; Olivier Gómez, C. Hospital Universitario de La Princesa

2 P-7 Urinary Biomarkers for Detection of Prostate Cáncer in Patients with High-Grade Prostatic Intraepithelial Neoplasia (HGPIN) Regís, L; Bastaros, JM; Sequeiros, T; Sánchez, M; Rigau, M; Placer, J; Planas, J; De Torres, I; Raventos, J; Doll, A; Morote, J Hospital General Universitario Vall d'hebron Introduction & Objectives Men with suspicion of prostate cancer (PCa) are referred for prostatic biopsy (PB), and some of them will present HGPIN (a commonly accepted precursor of PCa) in this first PB. Because of the impossibility to predict whether a HGPIN lesion will evolve to PCa, those patients frequently face several years of active surveillance including repeat PBs. Previously, our research group showed that PCA3 and PSGR gene expression in urine sediment could be useful biomarkers for the detection of PCa in benign prostatic hyperplasia cases. Although with a lower efficacy, we also observed that PCA3 was able to detect PCa in those patients with a previous diagnosis of HGPIN.The aim of this study is to identify urinary biomarkers that could differentiate between indolent HGPIN cases and those who actually present PCa. Material & Methods From a cohort of 114 patients with diagnosis of HGPIN (in a first PB recommended due to increased serum PSA levels (>4ng/mL) and/or an abnormal diagnostic DRE), urine sediment samples were obtained, after DRE within days before a repeat biopsy after a posterior follow up of at least two years. Reverse-transcriptase PCR (RTqPCR) of extracted RNA was conducted to determine expression of 6 endogenous genes and 17 target genes, all of them putative PCa biomarkers. Univariate tests and univariate and multivariate logistic regressions were used to examine associations between PCa diagnostic status and testing genes. All possible models were created using combinations of the most significant genes obtained in the univariate analysis and multivariate logistic regression was applied to them. The number of PBs potentially avoided by the use of the proposed biomarkers was calculated. Results By univariate statistical analysis of the obtained data, it was found that PSMA, PCA3, PSGR, GOLM, KLK3 and CDH1 were significant predictors of PCa in repeat PB. Multiplex models that use the PCa biomarkers KLK3, PSMA, PSGR, GOLM1 and CDH1 (AUC= ) outperform all the assayed genes, including PCA3 (AUC=0.70), when used individually. With a fixed sensitivity of 95%, the specificity of the models was of 41-58%, compared to the 30% of PCA3. Applying these models, it would be possible to save from 33% and up to 47% of the repeat biopsies practiced. Conclusions A multiplexed RTqPCR assay on urine sediments from patients presenting for a repeat PB due to a diagnosis of HGPIN can significantly improve the predictive ability when compared to PCA3 or any other assayed gene when used alone. Further evaluation and validation of these biomarkers in larger and independent cohorts is highly desirable, in order to confirm these results.

3 P-8 Stereotactic radiotherapy as treatment of oligometastatic prostate cancer. Our initial experience. Sobrón Bustamante M.; Pastor Peidró J.; Juan Escudero J.; Hernández Manchacoses A.; Marqués Vidal E.; López Torrecillas J. Consorcio Hospital General Universitario de Valencia Introduction The Oligometastatic state would represent an intermediate stage between localized and diseminated disease, being amenable for treatment 1. Agressive treatment of this oligometastatic state (local therapy) have demonstrated a long-term disease control as well as an impact on survival 2. Stereotactic radiotherapy (SBRT) is a treatment modality which deliver high doses of radiation with high precision, enabling aggressive treatment of the injury. Objective To report our preliminary clinical experience regarding SBRT as treatment of oligometastatic disease in patients with prostate cancer (CaP-O). Methodology We analyze a prospective cohort of 11 patients (23 lesions) with CaP-O treated with SBRT between October 2010 and November Treatment plans were designed using the Pinnacle (Philips) software with daily image guidance using TrueBeam linac. Treatment sites included bone (n = 7) and lymph nodes (n = 16). In each case fractionation schemes and doses prescribed per sesion were individualized. Response to treatment was assessed with PSA levels and imaging techniques (RECIST/PERCIST criteria) and toxicity was assessed with RTOG/EORTC score. Results The mean age was 66.6 years (SD ± 13.5) with a median follow up of 11.7 months (range 1,5-50,5). One patient was treated twice. All patients received primary treatment prior development of distant metastatic disease [Hormonetherapy (n = 11), Radical Radiation Therapy (n = 11), surgery (n = 7), chemotherapy (n = 1)]. During follow-up, 7 patients (63,6%) achieved a complete response, 4 patients (36.4%) achieved a stable disease, with no patient showing local progression. Only 2 patients (18,1%) show posterior progression out of treatment field. No acute or late toxicity (G0) was observed in any of the patients during all follow-up. Conclusions These preliminary results suggest that SBRT would be an effective treatment showing a safe profile for patients with prostate cancer and oligometastatic disease. References 1. Hellman S, Weichselbaum RR: Oligometastases. J Clin Oncol 1995, 13: Weichselbaum RR, Hellman S: Oligometastases revisited. Nat Rev Clin Oncol 2011, 8:

4 P-9 Clinical Significance of Proliferative Inflammatory Atrophy in Negative Prostatic Biopsies Servián Vives, P.; Celma Domènech, A.; Planas Morin, J.; Placer Santos, J.; de Torres Ramirez, I.M.; Morote Robles, J. Hospital Vall d'hebrón Proliferative inflammatory atrophy (PIA) has been involved in prostatic carcinogenesis through the development of high-grade prostatic intraepithelial neoplasia (HGPIN). However, little is known about the clinical significance of PIA finding in men with negative prostatic biopsies (PBs). Objective: To analyze the association between PIA finding in negative PBs and future detection of prostate cancer (PCa) and its aggressiveness in men subjected to repeat PB, due to persistent suspicion of PCa. Design, Setting and Participants: Prospective and observational study of 474 men scheduled to repeated PBs in an academic institution. Intervention: Assessment of PIA and its extension in previous PBs. Outcome Measurements and Statistical Analysis: PCa detection rate and tumor aggressiveness. Age, serum total PSA, free PSA, percent free PSA (%fpsa), digital rectal exam (DRE), prostate volume (PV), PSA density (PSAD), PSA kinetics (PSAV and PSADT) findings of PIA and HGPIN and number of affected cores in previous PBs were included in the univariate and multivariate analysis. Aggressive tumors were considered when any Gleason pattern 4 was found. Results: PCa was detected in 133 men (28.1%). Age, serum total PSA, %fpsa, PV, PSAD, PSAV, PSADT and PIA finding were significantly associated to PCa detection. However, only age, OR: 1.061(95%CI: ), p=0.001; DRE, OR: 1.755(95%CI: ), p=0.031; %fpsa, OR: 0.963(95%CI: ), p=0.028; PV, OR: 0.983(95%CI: ) and PIA finding, OR: 0.491(95%CI: ), p=0.008, were independent predictors of PCa detection. PCa was found in 18% of 159 men with previous PIA finding while in 33% of 315 men without previous PIA (p=0.001). None of the studied parameters including PIA in previous PB were related with subsequent PCa aggressiveness. Conclusions: PIA finding in negative PBs decreases the risk of PCa detection in men with persistent suspicion of PCa. The aggressiveness of future detected tumors was not associated with previous PIA finding.

5 P-10 Papillary Renal Cell Carcinoma. Identification and prognosis by mirna profiling. Arrebola Pajares A.; Villacampa Aubá F.; Sopeña Sutil R.; Alonso Isa M.; Duarte Ojeda J.M.; Gámez A.; Fresno J.A.; García Muñóz H.; Castellano Gauna D.; De la Rosa Kehrmann F.; Passas Martínez J. UroOncology Unit, Urology Service, Hospital Universitario 12 de Octubre. - IdiPaz Background and Objective: Papillary Renal Cell Carcinoma (prcc) is the second most common renal malignancy. They can be divided into two distinct subtypes (I, II), with very different prognosis. Although this is clinically relevant, only few reports address the problem of differentiating them at the molecular level. Our objective is to find a "mirna signature" that can identify the different types of prcc and their prognosis. Material and Methods: Patients with prcc which have had previous nephrectomy at our institution from 2001 to 2010 were included. Formalin-fixed and paraffin embedded samples were anonymized and molecular analysis was performed blinded to clinical data. RNA was extracted (RecoverAll Kit) and mirna expression profiles were obtained using Affymetrix mirna 4.1 strip arrays, and compared to clinicopathological information. Results: 46 patients were found, but clinical data was available from 36 patients: 16 prcc type I, 8 prcc type II and 12 prcc indeterminate. With a mean follow-up of 71 months, 93% type I and indeterminate were free of recurrence, but only 62% type II showed no relapse. From the mirna standpoint, 812 had detectable signal in at least 75% of one group of samples, and 4 of them (mir-16-5p, mir-193b-3p, mir-451a, mir-650) are able to differentiate between I and II. We have also identified a 5 mirna "signature" (mirna-378d, mir-99a-5p, mir4776-5p, mir , mir a) with prognostic value independently of the prcc subtype. Using this signature, 5 year Disease Free Survival for high and low risk patients is 62% and 100% respectively. Conclusions: To our Knowledge, this is the largest prcc series to be studied for mirna profile. In our series, 4 mirna are differentially expressed among prcc subtypes. Also, we have found a 5 mirna signature that can predict accurately the risk of relapse, although it must be validated in other series.

6 P-11 Results of therapy with inhibitor growth factors as treatment for the advanced renal carcinoma. Rodezno, D; Pieras, E; Garcías de España, C; Martínez, A; Alcojor, I; Moncada, O; Soriano, T; Guimera, J; Sabate, A; Pizá, P Hospital Universitario Son Espases The advances in many fields of medicine in the recent years have reached an important development that can be translated in an increment of the global survival of the human being. In the case of renal cancer specifically, molecular biology has opened a new different options for the treatment for the metastatic cases. In this presentation we pretend to share our experience with a group of patients fallowed since January 2010 till November of 2015, treated with inhibitor growth factors for the advanced renal carcinoma (Patients at stage IV), emphasizing in the most important aspects as indications, global survival, survival without progression and secondary effects of the treatments. We can conclude in our work, that even if the treatment with inhibitor growth factors its far away from a total curative results, it has opened a new brand of options for different kind of therapies that can delay the disease progression.

7 P-12 Urinary exosomes as potential biomarkers in bladder cancer Otta Oshiro, R.J.; Acosta Reveles, M.A.; Andreu Martínez, Z.; Yañez-Mó, M.; Redruello, A.; Olivier Gómez, C. Hospital Universitario de La Princesa INTRODUCTION AND OBJECTIVES: Exosomes represent a kind of extracellular vesicles (Evs) that are released by many different cell types. Exosomes containing specific proteins, lipids, mrnas and mirnas have emerged as potent intercellular communicators. In a tumoral milieu these Evs can alter the extracellular matrix promoting tumoral progression and represent a source of potent non-invasive biomarkers since they can be isolated from different kind of fluids (urine, blood, bronchoalveolar lavage, cerebrospinal fluid, etc). Our objective was to determine possible markers of tumor aggressiveness in patients with urothelial carcinoma of the bladder by extracting mirnas from exosomes isolated from urine samples. METHODS: Exosomes were isolated from urine of patients with urothelial bladder cancer. Patients with low grade urothelial carcinoma (n=20). Patients with high grade urothelial carcinoma (n=20) and healthy donors (n=5). We performed mass spectrometry and mirna arrays in order to find differences in the tumor profile, namely, mirna expression. The results were tested with Western blot and Polymerase chain reaction. RESULTS: We found that mirna 375 was down expressed in high grade urothelial carcinoma when compared to low grade urothelial carcinoma or healthy donors. We also found that the mirna 146 profile is significantly affected in low grade urothelial carcinoma when compared to high grade urothelial carcinoma or healthy donors. CONCLUSIONS: Bladder cancer is a complex and heterogeneous tumor. The study of urinary exosomes is a promising field of research in order to understand tumor behavior, hence tumor progression. The study of mirna 375 and mirna 146 could help us differentiate aggressive tumors.