In order to successfully cure patients with prostate cancer (PCa), it is important to detect the disease at an early stage. The existing clinical biomarkers for PCa are not ideal, since they cannot specifically differentiate between those patients who should be treated immediately and those who should avoid over-treatment. Current screening techniques lack specificity, and a decisive diagnosis of PCa is based on prostate biopsy. Although PCa screening is widely utilized nowadays, two thirds of the biopsies performed are still unnecessary. Thus the discovery of non-invasive PCa biomarkers remains urgent. In recent years, the utilization of urine has emerged as an attractive option for the non-invasive detection of PCa. Moreover, a great improvement in high-throughput “omic” techniques has presented considerable opportunities for the identification of new biomarkers. Herein, we will review the most significant urine biomarkers described in recent years, as well as some future prospects in that field.

The term castrate resistant prostate cancer (CRPC) was initially proposed by the Prostate Cancer Working Group 2 in 2008 to define the state of clinical and/or biochemical progression of prostate cancer (PCa) in an environment with very low serum testosterone concentration. Clinical progression is based on the radiological imaging proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) adapted to PCa. Biochemical progression is defined as an over 25% increase in serum prostate-specific antigen within two consecutive measurements separated by at least one week, and an absolute value above 2.0 ng/mL. Finally, the castrate environment is usually defined as a serum testosterone concentration maintained below 50 ng/dL or 1.7 nmol/dL. This definition does not incorporate the new and more accurate imaging modalities to assess clinical progression and the capability of the new biochemical measurements to assess the true castration environment. Ga-68-PSMA-11 PET CT/MRI and whole-body MRI are the new imaging modalities that should replace the classic thoracic CT scan, abdomino-pelvic CT scan, and technetium 99-m bone scintigraphy. In addition, Ga-68-PSMA-11 PET is the current basis for the new therapies targeting metastatic sites. Moreover, the current methods for measuring the very low serum testosterone concentrations in clinical laboratories are the widespread chemiluminescent assays, which are inappropriate, while LC-MSMS is the only method recommended to assess the castrate environment. In addition, recent research shows that serum luteinising hormone concentration associates better than serum testosterone with the castration environment, even when it is measured with LC-MSMS. In summary, the current definition of CRPC seems outdated. An extensive update to diagnose true CRPC is also needed to differentiate CRPC men with M0 (non-metastatic) from those with M1 (metastatic) CRPC. WC: 277.

A new and externally validated MRI-PM for csPCa was developed in the metropolitan area of Barcelona, and a web-RC designed with the new option of selecting the csPCa probability threshold. The development cohort comprised 1486 men scheduled to undergo a 3-tesla multiparametric MRI (mpMRI) and guided and/or systematic biopsies in one academic institution of Barcelona. The external validation cohort comprised 946 men in whom the same diagnostic approach was carried out as in the development cohort, in two other academic institutions of the same metropolitan area. CsPCa was detected in 36.9% of men in the development cohort and 40.8% in the external validation cohort (p = 0.054). The area under the curve of mpMRI increased from 0.842 to 0.897 in the developed MRI-PM (p < 0.001), and from 0.743 to 0.858 in the external validation cohort (p < 0.001). A selected 15% threshold avoided 40.1% of prostate biopsies and missed 5.4% of the 36.9% csPCa detected in the development cohort. In men with PI-RADS <3, 4.3% would be biopsied and 32.3% of all existing 4.2% of csPCa would be detected. In men with PI-RADS 3, 62% of prostate biopsies would be avoided and 28% of all existing 12.4% of csPCa would be undetected. In men with PI-RADS 4, 4% of prostate biopsies would be avoided and 0.6% of all existing 43.1% of csPCa would be undetected. In men with PI-RADS 5, 0.6% of prostate biopsies would be avoided and none of the existing 42.0% of csPCa would be undetected. The Barcelona MRI-PM presented good performance on the overall population; however, its clinical usefulness varied regarding the PI-RADS category. The selection of csPCa probability thresholds in the designed RC may facilitate external validation and outperformance of MRI-PMs in specific PI-RADS categories.

OBJECTIVE: To evaluate changes in bone mass and fracture risk in patients with prostate cancer on androgen‐deprivation therapy (ADT) and with a basal T‐score of >−2.0, who were treated with an oral bisphosphonate, as such patients treated with ADT are at increased risk of bone loss and bone fracture. PATIENTS AND METHODS: We selected 61 patients with prostate cancer treated with ADT; 31 were treated with oral alendronate 70 mg once‐weekly and a control group of 30 were not. At baseline and 12 months we measured bone mineral density (BMD) of the lumbar spine, femoral neck and total hip by dual‐energy X‐ray absorptiometry. All patients had severe osteopenia or osteoporosis at baseline. The risk of femoral neck fracture was calculated at baseline and 12 months (Z‐score 2.7). RESULTS: Patients treated with alendronate had a significant increase in BMD at the lumbar spine and femoral neck after 1 year of follow‐up, with mean ( sd ) values of 1.06 (0.26) vs 1.01 (0.21) g/cm ² at baseline ( P < 0.001), and 0.75 (0.07) vs 0.73 (0.07) g/cm ² ( P = 0.03), respectively, while the control group had a significant loss of BMD at the total hip of 0.79 (0.14) vs 0.81 (0.13) g/cm ² ( P = 0.03). BMD was significantly improved at the three locations in patients treated with alendronate compared with the control group, with differences at the lumbar spine, femoral neck and total hip of 0.05 (0.07) vs 0.01 (0.10) ( P = 0.001), 0.01 (0.04) vs −0.002 (0.03) ( P = 0.04) and 0.01 (0.04) vs −0.01 (0.02) g/cm ² , respectively ( P = 0.001). Patients treated with alendronate had a significant decrease in the fracture risk at the femoral neck, by −0.54 (1.29) ( P = 0.04) after 1 year of follow‐up. CONCLUSIONS: Treatment with once‐weekly 70 mg alendronate significantly improved the BMD at the lumbar spine and femoral neck in patients with prostate cancer with severe osteopenia or osteoporosis and on ADT, and significantly decreased the risk of femoral neck fracture.

MRI can identify suspicious lesions, providing the semi-quantitative risk of csPCa through the Prostate Imaging-Report and Data System (PI-RADS). Predictive models of clinical variables that individualise the risk of csPCa have been developed by adding PI-RADS score (MRI-PMs). Our objective is to analyse the current developed MRI-PMs and define their clinical usefulness. A systematic review was performed after a literature search performed by two independent investigators in PubMed, Cochrane, and Web of Science databases, with the Medical Subjects Headings (MESH): predictive model, nomogram, risk model, magnetic resonance imaging, PI-RADS, prostate cancer, and prostate biopsy. This review was made following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) criteria and studied eligibility based on the Participants, Intervention, Comparator, and Outcomes (PICO) strategy. Among 723 initial identified registers, 18 studies were finally selected. Warp analysis of selected studies was performed with the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Clinical predictors in addition to the PI-RADS score in developed MRI-PMs were age, PCa family history, digital rectal examination, biopsy status (initial vs. repeat), ethnicity, serum PSA, prostate volume measured by MRI, or calculated PSA density. All MRI-PMs improved the prediction of csPCa made by clinical predictors or imaging alone and achieved most areas under the curve between 0.78 and 0.92. Among 18 developed MRI-PMs, 7 had any external validation, and two RCs were available. The updated PI-RADS version 2 was exclusively used in 11 MRI-PMs. The performance of MRI-PMs according to PI-RADS was only analysed in a single study. We conclude that MRI-PMs improve the selection of candidates for prostate biopsy beyond the PI-RADS category. However, few developed MRI-PMs meet the appropriate requirements in routine clinical practice.