Variability in the multicentre National Registry in Active Surveillance; a questionnaire for urologists. / Variabilidad dentro del Registro Nacional multicéntrico en Vigilancia Activa; cuestionario a urólogos.

BACKGROUND: Our main objective was to report the current use of active surveillance in Spain and to identify areas for potential improvement. METHODS: A questionnaire generated by the Platform for Multicentre Studies of the Spanish Urology Association (AEU/PIEM/2014/0001, NCT02865330) was sent to all associate researchers from January to March 2016. The questionnaire included 7 domains covering various aspects of active surveillance. RESULTS: Thirty-three of the 41 associate researchers responded to the questionnaire. Active surveillance is mainly controlled by the urology departments (87.9%). There was considerable heterogeneity in the classical clinical-pathological variables as selection criteria. Only 36.4% of the associate researchers used prostate-specific antigen density (PSAd). Multiparametric magnetic resonance imaging (mpMRI) was clearly underused as initial staging (6%). Only 27.3% of the researchers stated that their radiology colleagues had a high level of experience in mpMRI. In terms of the confirmation biopsy, most of the centres used the transrectal pathway, and only 2 out of 33 used the transperineal pathway or fusion software. Half of the researchers interviewed applied active treatment when faced with disease progression to Gleason 7 (3+4). There was no consensus on when to transition to an observation strategy. CONCLUSIONS: The study showed the underutilisation of informed consent and quality-of-life questionnaires. PSAd was not included as a decisive element in the initial strategy for most researchers. There was a lack of confidence in the urologists' mpMRI experience and an underutilisation of the transperineal pathway. There was also no consensus on the follow-up protocols and active treatment criteria, confirming the need for prospective studies to analyse the role of mpMRI and biomarkers.

Preliminary results of the Spanish Association of Urology National Registry in Active Surveillance for prostate cancer.

OBJECTIVES: To present a National Registry of patients with prostate cancer as monitored through active surveillance, with the intention of testing the hypothesis that cancer-specific mortality in very low-risk and low-risk patients is less than 5% at 15 years. MATERIAL AND METHODS: A multicentre observational study (AEU-PIEM/2014/0001) sponsored by the Spanish Association of Urology was conducted using their platform for multicentre studies. The clinical-pathological inclusion criteria were as follows: cT1a-cT3a, PSA ≤ 20 ng/ml, initial minimum biopsy of 10 cores, number of affected cores ≤ 3, 1st Gleason score of 3 and 2nd Gleason score ≤ 4 and a known prostate volume (in cc). A unified follow-up was not established for all recruiting centres; however, a survey was conducted that reflects the follow-up characteristics based on a number of tangible parameters that allow for their comparison. With the same philosophy of flexibility, the use of certain biomarkers and multiparametric MRI was not considered necessary for inclusion. RESULTS: We describe the Registry's characteristics and possibilities, as well as the preliminary results from the 324 patients included in its first 5 months of operation in the 15 recruiting centres. We also report the clinical-pathological variables, biomarkers, radiodiagnosis technique and quality-of-life questionnaires considered for the database, as well as the possibilities for indefinite follow-up, remaining open to any active treatment recognized in clinical guidelines. CONCLUSIONS: The AEU-PIEM/2014/0001 represents an extremely useful tool for all Spanish urologists for multicentre clinical research. The registry will undoubtedly enable the dissemination of active surveillance of our patients in a more coordinated manner, thus maintaining the advantages of optimised opportunistic screening for prostate cancer without resulting in overtreatment.

Drug Cost Avoidance in Prostate Cancer Clinical Trials.

OBJECTIVES: Economic impact of prostate cancer is increasing in relation to its increased incidence and increased patient survival. Clinical trials are essential to evaluate the efficacy and safety of new treatments but may also result in economic benefits by avoiding the cost of the drug. Our objective is to determine the avoided cost in investigational drugs in clinical trials of prostate cancer conducted in a period of 18 years in a tertiary center. MATERIAL AND METHODS: We carried out an observational of prevalence study with retrospective collected data of clinical trials involving currently marketed drugs and cost avoidance during the study period (1996-2013) was calculated. RESULTS: We include in this review five clinical trials on prostate cancer that met selection criteria of 18 performed. All of them were phase III, multicenter, international and with current marketed drugs. 136 patients were included. Total cost avoidance of 696,002€ and an average cost avoidance by clinical trial of 139,200€ were obtained. Average cost avoidance per patient was 5,118€. CONCLUSION: Cost avoidance in investigational drugs is a tangible benefit of clinical trials, whose realization is a source of economic benefits for the hospital, not only by directly generated by each trial. Clinical trials are an exceptional framework for progress in clinical research and real savings for the health system.

Circulating MicroRNAs in blood of patients with prostate cancer.

INTRODUCTION: MicroRNAs (miRNAs) are small regulatory RNAs that do not code for proteins. Detection of circulating tumor cells (CTC) would provide diagnostic and prognostic information in prostate tumors (PT). Thus, miRNAs could constitute a promising new class of biomarkers for CTC detection. OBJECTIVES: To analyze circulating microRNAs in whole blood as non-invasive markers in patients with localized prostate cancer and healthy individuals. MATERIAL AND METHODS: A preliminary study including a population of 40 patients with mean age of 71 years and mean PSA of 18, 9 ng/ml (range). Regarding the risk group (RG): 33.3% had low risk, 30% intermediate risk and 36.7% high risk. A previous in silico study identified 92 candidates and was followed by another in vivo to verify the findings of the former using array technology by real-time PCR. RESULTS: Statistical analysis of the results revealed 10 microRNAs candidates with statistically significant differential expression between the different risk groups and healthy controls: hsa-miR-337-3p, hsa-miR-330-3p, hsa-miR-339-3p, hsa-miR-124, hsa-miR-218, hsa-miR-128, hsa-miR-10a, hsa-miR-199b-5p, hsa-miR-200b and hsa-miR-15b. CONCLUSIONS: Our data suggest that circulating microRNAs can act as biomarkers to identify risk groups in CaP.

Focal therapy for prostate cancer. Alternative treatment.

CONTEXT: The great controversy surrounding the treatment of localized prostate cancer is related with its possibilities of radical treatment or active surveillance. The objective of this paper is to analyze the rationale selection among current focal therapy modalities regarding tumor and patient selection. EVIDENCE ACQUISITION: Current articles about advantages and disadvantages on the treatment of localized prostate cancer as well as information about focal therapy regarding tumour selection, characteristics and indications cited in MEDLINE search were reviewed. SUMMARY OF EVIDENCE: Focal therapy standardized criteria must be: low risk tumors, PSA<10-15, Gleason score ≤ 6, and unilateral presentation all supported by image-guided biopsy and nuclear magnetic resonance (NMR). There are doubts about the suitability of focal therapy in cases of bilateralism or in those with Gleason score 3+4 or PSA>15. CONCLUSIONS: Focal therapy is an alternative for localized prostate cancer treatment. However, some aspects of their diagnosis and selection criteria should be defined by prospective studies which should provide knowledge about the indication for focal therapy.

Focal therapy for prostate cancer. Rationale, indications and selection.

CONTEXT: The great controversy surrounding the treatment of localized prostate cancer is related with its possibilities of radical treatment or active surveillance. The objective of this paper is to analyze the rationale selection among current focal therapy modalities regarding tumor and patient selection. EVIDENCE ACQUISITION: Current articles about advantages and disadvantages on the treatment of localized prostate cancer as well as information about focal therapy regarding tumour selection, characteristics and indications cited in MEDLINE search were reviewed. SUMMARY OF EVIDENCE: Focal therapy standardized criteria must be: low risk tumors, PSA<10-15, Gleason score ≤ 6, and unilateral presentation all supported by image-guided biopsy and nuclear magnetic resonance (NMR). There are doubts about the suitability of focal therapy in cases of bilateralism or in those with Gleason score 3+4 or PSA>15. CONCLUSIONS: Focal therapy is an alternative for localized prostate cancer treatment. However, some aspects of their diagnosis and selection criteria should be defined by prospective studies which should provide knowledge about the indication for focal therapy.

Advances in prevention and treatment of bone metastases in prostate cancer. Role of RANK/RANKL inhibition.

BACKGROUND: Bone metastases are a common complication of prostate cancer, so treatment and prevention are essential to slow the progression of the disease and the occurrence of skeletal related events (SREs), which have devastating consequences for the quality of life of patients. SUMMARY OF EVIDENCE: Bone metastases are characterized by increased bone turnover and altered balance between osteogenesis and osteolysis, with activation of the RANK and its ligand (RANKL). In patients with metastatic prostate cancer, bisphosphonates have been the bone-targeted agents most commonly used to date. Zoledronic acid has demonstrated efficacy in the reduction and delay of SREs in patients with bone metastases. Denosumab, a RANKL inhibitor, has been demonstrated to be superior to zoledronic acid in the prevention of SREs in castration-resistant prostate cancer (CRPC). Both agents are being considered, along with other new bone-targeted agents, for the prevention of bone metastases in patients with nonmetastatic CRPC, where denosumab has already demonstrated superiority over placebo. CONCLUSIONS: Denosumab and zoledronic acid prevent SREs in patients with prostate cancer and bone metastases. Denosumab also has a potential role in delaying bone metastases in nonmetastatic patients. Advances in the treatment of CRPC include an increasing focus on prevention of the progression of bone disease.

[Neprhon sparing surgery for renal tumours on kidney transplantation]. / Cirugía conservadora en el tratamiento de los tumores renales de novo en injertos de trasplante renal.

INTRODUCTION: Nowadays, nephron sparing surgery for renal carcinoma achieves good oncological results, similar to radical surgery, with the advantage of preserving renal function. Renal cell carcinomas appear de novo in 4.6% of post-transplant patients compared with 3% of tumors in the general population, affecting less than 10% to renal allograft. OBJECTIVE: The purpose is to analyze our experience and make a literature review about the role of nephron sparing surgery to treat de novo renal tumours in renal grafts. MATERIAL AND METHODS: A retrospective and descriptive analysis has been realized, finding four patients who presented with de novo renal tumours over renal graft after kidney transplantation and treated by nephron sparing surgery. A Medline review is done to search similar series published. Oncological and functional results were reviewed and analyzed. We worked with SPSS 12.0 software. RESULTS: Medium age at diagnosis was 46.5 y (42-62). Medium size was 2.4cm. (1.5-3.5) and final histology showed medium tumours size of 3.0cm. (1.7-3.5). Medium hospital stay was 6.0d. Medium time from transplantation to diagnosis was 92 months (42-192). NSS was done in all cases, in 3 cases tumorectomy and one partial nephrectomy. Transfusion was only needed in one case. All cases had pT1aN0M0 RCC histology exam. Renal function did not change from preoperative. All patients are free of progression with a medium follow-up of 46.5 months (15-58). CONCLUSIONS: NSS could be an option to treat graft tumours in selected cases, preserving renal function. In our experience, is a safe and efficient treatment in patients with small de novo renal tumours over renal graft.