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Item does not contain fulltext Introduction: The use of fluoroscopy during percutaneous nephrolithotomy (PCNL) may lead to an overestimation of stone-free rates. The objective of this study is to demonstrate the feasibility of intraoperative CT-guided PCNL compared with standard of care (SoC) PCNL. Patients and Methods: A prospective feasibility study (20 patients undergoing PCNL with an intraoperative CT scan between June 2017 and February 2020) and a retrospective study of a historical cohort (20 consecutive patients undergoing SoC PCNL between September 2015 and September 2016) were conducted. All procedures were performed by an expert endourologist in a tertiary referral hospital. Follow-up was performed at 6 weeks postoperatively. The primary goal is to investigate the practicality and potential benefits and harms of intraoperative CT scanning during PCNL. Secondary outcomes are a stone-free rate after the 6-week follow-up, perioperative radiation exposure, the need for postoperative imaging, and peri- and postoperative complications. Statistical significance was considered at p < 0.05. Results: The initial stone-free rate in the CT scan group was 65% (n = 13). In 25% (n = 5) of patients, residual stone fragments were removed after the perioperative CT scan. In the SoC group, 85% (n = 17) of patients were thought to be stone free perioperatively. At the 6-week follow-up, 80% (n = 16) in the CT scan group vs 50% in the SoC group (n = 10) were found to be stone free. Radiation exposure, perioperatively, was higher in the CT scan group. Complications were comparable between groups. Limitations of the study are the nonrandomized design of the study and nonstandardized follow-up imaging. Conclusions: Intraoperative CT scanning during PCNL is feasible and gives a better estimate of any remaining stone fragments compared with fluoroscopy only.

SamenvattingDe TURP (transurethrale resectie van de prostaat) is nog steeds de gouden standaard bij chirurgische desobstructie bij benigne prostaathyperplasie (BPH). Toch zijn er significante risico’s aan de operatie verbonden, zoals nabloeding, blaashalssclerose, urethrastrictuur en seksuele disfunctie, ondanks de intrede van bipolaire en vaporiserende technieken. Er zijn dan ook meerdere ontwikkelingen binnen de minimaal-invasieve urologie die zich richten op het verminderen van de kans op complicaties en seksuele bijwerkingen, maar die net zo effectief pogen te zijn als de TURP.

Objective To assess urological function, sexual function, and quality of life in patients with exstrophy or epispadias. Little is known regarding these outcomes in adult patients; our aim is to determine where improvements are needed for long-term management. Methods The study population comprised adult (>18 years) patients. Demographic data were gathered and patients were asked to fill out 4 validated questionnaires: (1) International Consultation on Incontinence Questionnaire urinary incontinence form (ICIQ-UI) regarding continence; (2) International Prostate Symptom Score (IPSS) for men and International Consultation on Incontinence Questionnaire-Female Lower Urinary Tract Symptoms (ICIQ-FLUTS) for women regarding lower urinary tract symptoms; (3) 12-Item Short Form Health Survey regarding quality of life; (4) International Index of Erectile Function for men and Female Sexual Function Index for women regarding sexual function. Results Seventeen patients were included (9 men and 8 women) with a median age of 36 years (range 19-73). Median score on ICIQ-UI was 5/21. Median IPSS score was 7/35 and median quality of life score was 1 (=pleased). Median scores per domain within ICIQ-FLUTS were 7 for storage, 0 for voiding, and 6 for urinary incontinence with bother scores of 4, 0, and 2.8, respectively. Scores for 12-Item Short Form Health Survey in the study population were comparable with those of the Dutch population, except for Physical Component Summary in women. For sexual function, no difference was found between those in the general population and our participants except for the domain "pain" in Female Sexual Function Index. Conclusion Adult patients with exstrophy or epispadias have a high rate of incontinence and lower urinary tract symptoms with relatively low to some degree of bother. When compared with the general population, quality of life, and sexual function of our patients were more or less similar.

Trimethylamine N-oxide (TMAO) leads to the development of cardiovascular and chronic kidney diseases, but there are currently no potent drugs that inhibit the production or toxicity of TMAO. In this study, high-fat diet-fed ApoE-/- mice were treated with finasteride, ranitidine, and andrioe. Subsequently, the distribution and quantity of gut microbiota in the faeces of the mice in each group were analysed using 16S rRNA sequencing of the V3+V4 regions. Pathological examination confirmed that both ranitidine and finasteride reduced atherosclerosis and renal damage in mice. HPLC analysis also indicated that ranitidine and finasteride significantly reduced the synthesis of TMAO and the TMAO precursor delta-Valerobetaine in their livers. The 16S rRNA sequencing showed that all 3 drugs significantly increased the richness and diversity of gut microbiota in the model mice. Bioinformatic analysis revealed that the faeces of mice treated with ranitidine and finasteride, had significant increases in the number of microbes in the families g_Helicobacter, f_Desulfovibrionaceae, Mucispirillum_schaedleri_ASF457, and g_Blautia, whereas the relative abundances of microbes in the families Enterobacter_sp._IPC1-8 and g_Bacteroides were significantly reduced. The microbiota metabolic pathways, such as nucleotide and cofactor and vitamin metabolism were also significantly increased, whereas the activities of metabolic signalling pathways related to glycan biosynthesis and metabolism and cardiovascular diseases were significantly reduced. Therefore, our study indicates that in addition to their known pharmacological effects, ranitidine and finasteride also exhibit potential cardiovascular and renal protective effects. They inhibit the synthesis and metabolism of TMAO and delay the deposition of lipids and endotoxins through improving the composition of the gut microbiota.

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BACKGROUND We hypothesized that the levels of red cell distribution width (RDW) would correlate with lupus nephritis (LN) disease activity, therapeutic response after induction therapy, and its rise would be associated with future renal relapse in patients who had achieved clinical remission. METHODS The associations of RDW and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), renal response, and renal relapse after induction therapy were examined in 172 biopsy-proven LN patients at the Division of Nephrology, Huashan Hospital Fudan University between 2007 and 2017. RESULTS The median RDW of LN patients was significantly higher than that of healthy individuals (p < 0.001). Baseline RDW demonstrated positive correlation with baseline SLEDAI (r = 0.239, p = 0.004). Overall RDW after induction treatment was significantly decreased (p = 0.005), especially in the complete remission (CR) group (p = 0.02), and the partial remission (PR) group had a decreasing trend (p = 0.09), while the change of RDW in the no response (NR) group was not statistically significant (p = 0.70). Among the 153 patients who achieved remission after induction therapies, 37 (24.2%) patients developed 42 episodes of subsequent renal flare during a median follow-up of 36.0 (IQR, 20 - 66) months. The median time from remission to renal flare was 18.0 (IQR, 7.0 - 45.0) months. The overall renal flare rate was 0.065 relapse per patient-year. During follow up, 54 RDW rises (defined as more than 0.5% increase in RDW) were identified. There were 33 episodes (61.1%) of renal flares in patients with RDW rises, while there were only 9 renal flares (8.65%) in 104 patients without RDW rise (p < 0.001). Survival analysis showed that RDW rise was associated with a significantly higher risk of future renal relapse (adjusted HR, 14.03; 95% CI, 5.29 to 37.20; p < 0.001). CONCLUSIONS In addition to correlating with disease activity and therapeutic response to induction therapy in patients with LN, RDW rise is a significant predictor of future renal relapse in patients who achieve remission.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:. To assess the effects of en-bloc resection compared with conventional transurethral resection for the best approach of bladder cancer in patients with non-muscle-invasive bladder cancer.

Although phosphorus (P) is a limiting nutrient for plant growth in subtropical forests, the effects of forest succession on soil P dynamics, which in turn influences P availability, are unclear. The objective was to access the impacts of forest succession on P fractions of different availability (Hedley sequential fractionation) in highly weathered subtropical soils. We compared the P dynamics and availability under the chronosequence of forest succession from four stages: i) Cunninghamia lanceolata plantation, ii) through mixed broadleaf-conifer, iii) deciduous broadleaved, and finally iv) evergreen broadleaved forest. The soil P was dominated by stable P fractions (69–76%) in all successional stages. Forest succession increased total P content from plantation (199 mg kg−1) to evergreen broadleaved forest (253 mg kg−1), whereas P reached the peak in deciduous broadleaved forest and then remains stable due to balance between input with litter and litter decomposition and tree uptake. Stable P (non-available P) increased for 31–39% with forest succession because soil acidification led to more Fe and Al (oxyhydr)oxides strongly bounding P. Moderately labile P (moderately available P) contents under deciduous and evergreen broadleaved forests were higher than under plantation and mixed forest due to organic matter accumulation. However, labile (easily available) P content was reduced 35–50% by succession because of P removal by plant uptake. Available P content reached the peak under deciduous broadleaved forest (64–81 mg kg−1) and decreased again, indicating that forest ecosystem transit from P acquiring to P recycling system (litter input and plant uptake of mineralized P). Fine root biomass was the primary driver that controlled total, moderately labile and stable P contents during forest succession. Available P increased with soil organic carbon (SOC), suggesting that organic matter is crucial to maintain P availability. The C/P ratio of litter was the primary driver decreasing available P because litter decomposition released P is the main source determining P availability in soil. The increase of moderately labile P following forest succession played a crucial role for accumulation of available P. These results suggest that forest succession increases soil P availability until deciduous broadleaved forest. Therefore, strong measures to facilitate succession to the deciduous broadleaved forest stage should be a key approach to increase long-term soil P availability in subtropics.

Previously, we found that mild tubulointerstitial injury sensitizes glomeruli to subsequent injury. Here, we evaluated whether stabilization of hypoxia-inducible factor-α (HIF-α), a key regulator of tissue response to hypoxia, ameliorates tubulointerstitial injury and impact on subsequent glomerular injury. Nep25 mice, which express the human CD25 receptor on podocytes under control of the nephrin promotor and develop glomerulosclerosis when a specific toxin is administered were used. Tubulointerstitial injury, evident by week two, was induced by folic acid, and mice were treated with an HIF stabilizer, dimethyloxalylglycine or vehicle from week three to six. Uninephrectomy at week six assessed tubulointerstitial fibrosis. Glomerular injury was induced by podocyte toxin at week seven, and mice were sacrificed ten days later. At week six tubular injury markers normalized but with patchy collagen I and interstitial fibrosis. Pimonidazole staining, a hypoxia marker, was increased by folic acid treatment compared to vehicle while dimethyloxalylglycine stimulated HIF-2α expression and attenuated tubulointerstitial hypoxia. The hematocrit was increased by dimethyloxalylglycine along with downstream effectors of HIF. Tubular epithelial cell injury, inflammation and interstitial fibrosis were improved after dimethyloxalylglycine, with further reduced mortality, interstitial fibrosis, and glomerulosclerosis induced by specific podocyte injury. Thus, our findings indicate that hypoxia contributes to tubular injury and consequent sensitization of glomeruli to injury. Hence, restoring HIFs may blunt this adverse crosstalk of tubules to glomeruli.

The rapid development of graphics hardware has spawned a large number of GPU-based direct volume rendering methods. However, fast volume rendering for out-of-core datasets faces specific challenges, and many in-core-based methods cannot be applied to the volume rendering of out-of-core datasets. Although volume rendering algorithms based on partitioning strategies can effectively overcome these problems, the current partition-based techniques do not achieve a good balance between the partitioning method and the sub-block drawing method. In this paper, we propose an efficient out-of-core volume rendering method for datasets consisting of non-uniform size sub-blocks. The proposed method examines the parallel rendering possibilities between sub-blocks to accelerate the rendering process. Experimental comparisons with several volume rendering algorithms show that our method is faster than the current state-of-the-art approaches.

OBJECTIVE: To develop an evidence-based recommendation concerning the use of α-blockers for uncomplicated ureteric stones based on an up-to-date Cochrane review, as the role of medical expulsive therapy for uncomplicated ureteric stones remains controversial in the light of new contradictory trial evidence. METHODS: We applied the Rapid Recommendations approach to guideline development, which represents an innovative approach by an international collaborative network of clinicians, researchers, methodologists and patient representatives seeking to rapidly respond to new, potentially practice-changing evidence with recommendations developed according to standards for trustworthy guidelines. RESULTS: The panel suggests the use of α-blockers in addition to standard care over standard care alone in patients with uncomplicated ureteric stones (weak recommendation based on low-quality evidence). The panel judged that the net benefit of α-blockers was small and that there was considerable uncertainty about patients' values and preferences. This means that the panel expects that most patients would choose treatment with α-blockers but that a substantial proportion would not. This recommendation applies to both patients in whom the presence of ureteric stones is confirmed by imaging, as well as patients in whom the diagnosis is made based on clinical grounds only. CONCLUSION: The Rapid Recommendations panel suggests the use of α-blockers for patients with ureteric stones. Shared decision-making is emphasised in making the final choice between the treatment options. ispartof: Bju International vol:122 issue:6 pages:924-931 ispartof: location:England status: published

Strain BEY10T was isolated from an old fermentation pit, which had been used for the production of Chinese strong-flavoured liquor for over 20 years. The strain was strictly anaerobic, Gram-stain positive, rod-shaped, non-motile and spore-forming. Strain BEY10T grew at temperatures of 22–47 °C (optimum 37 °C), at pH 5.5–9.0 (optimum pH 7.5–8.5) and with NaCl concentrations of 0–4 % (w/v) (optimum 0 %). The isolate was able to utilize glucose, mannitol, lactose, xylose, maltose, glycerol, cellobiose and trehalose as carbon sources for growth. The major end-products from glucose fermentation were ethanol and butyric acid. The polar lipids consisted of phosphatidylglycerol, phosphatidylethanolamine, phospholipids, a glycolipid and an aminolipid. The predominant fatty acids (>10 %) were C20 : 0, C18 : 0, C16 : 0, C12 : 0 and C14 : 0. The DNA G+C content was 34.4 mol%. Sequence analysis of the 16S rRNA gene indicated that strain BEY10T belongs to the genus Clostridium in the family Clostridiaceae. The closest phylogenetic neighbour is Clostridium lundense DSM 17049T, showing 97.6 % 16S rRNA gene sequence similarity with strain BEY10T. DNA–DNA relatedness values of strain BEY10T with Clostridium lundense DSM 17049T, Clostridium tetanomorphum DSM 4474T and Clostridium pascui DSM 10365T were 58.8 %, 57.9 % and 42.2 %, respectively. This characterization based on phylogenetic, phenotypic and chemotaxonomic evidence demonstrated that strain BEY10T represents a novel species of the genus Clostridium, for which the name Clostridium liquoris sp. nov. is proposed. The type strain is BEY10T ( = ACCC 00785T = DSM 100320T).

Pulsed low-dose cyclophosphamide (CTX) therapy has become a very effective approach in improving the clinical outcomes of lupus nephritis (LN) patients. However, variations of CTX therapeutic outcomes in LN patients are incompletely understood. We investigated the contributions of known allelic variants to CTX therapy outcomes in 77 LN patients. Then, 22 out of the 77 patients were randomly enrolled to evaluate the pharmacokinetic profiles. LN patients with a GSTA1*A mutation (CT heterozygous) had more risk of non-remission (44% vs. 20%, P=0.005). Pharmacokinetic data indicated that patients with a GSTA1*A heterozygous variant had a lower exposure to 4-hydroxycyclophosphamide (4OHCTX) compared to wild-type patients (AUC4OHCTX: 12.8 (9.8, 19.5) vs. 27.5 (18.1, 32.8) h mg/l, P=0.023). Clinical remission was significantly related to higher exposure of 4OHCTX (P=0.038). In conclusion, LN patients with GSTA1*A heterozygous genotypes had poor CTX treatment remission due to less exposure to activated metabolites of CTX.

Objective To assess the effects of α-blockers compared to standard therapy or placebo for ureteric stones of ≤10 mm confirmed by imaging in adult patients presenting with symptoms of ureteric stone disease. Patients and methods We performed a systematic search in multiple databases and grey literature with no restrictions on the language of publication or publication status, up until November 2017. We included randomised controlled trials evaluating ureteric stone passage in adult patients that compared α-blockers with standard therapy or placebo. Two review authors were independently responsible for study selection, data extraction, and risk-of-bias assessment. We performed a meta-analysis using a random-effect model. The quality of evidence was assessed on outcome basis according to Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. Results We included 67 studies, with 10 509 participants overall. Of these, 15 studies with 5 787 participants used a placebo. Stone clearance: treatment with an α-blocker may result in a large increase in stone clearance (risk ratio [RR] 1.45, 95% confidence interval [CI] 1.36-1.55; low-quality evidence), corresponding to 278 more (95% CI: 223-340 more) stone clearances per 1 000 participants. For major adverse events, treatment with an α-blocker may have little effect (RR 1.25, 95% CI: 0.80-1.96; low-quality evidence), which corresponds to five more (95% CI four fewer to 19 more) major adverse events per 1 000 participants. Patients treated with α-blockers may also experience shorter stone expulsion times (mean difference [MD] -3.40 days, 95% CI: -4.17 to -2.63; low-quality evidence), use less diclofenac (MD -82.41 mg, 95% CI: -122.51 to -42.31; low-quality evidence) and likely require fewer hospitalisations (RR 0.51, 95% CI: 0.34-0.77; moderate-quality evidence). Meanwhile, the need for surgical intervention appears similar (RR 0.74, 95% CI: 0.53-1.02; low-quality evidence). Based on a pre-defined subgroup analysis (test for subgroup difference, P = 0.002), there may be a different effect of α-blockers based on stone size with RRs of 1.06 (95% CI: 0.98-1.15; P = 0.16; I² = 62%) for stones of ≤5 mm vs 1.45 (95% CI: 1.22-1.72; P 5 mm. We did not find evidence for possible subgroup effects based on stone location or α-blocker type. Conclusions In patients with ureteric stones, α-blockers likely increase stone clearance but probably also slightly increase the risk of major adverse events. Subgroup analyses suggest that α-blockers may be less effective in smaller (≤5 mm) than larger stones (>5 mm).

Objective: This study examined the expression of renal phospholipase A2 receptor (PLA2R) in idiopathic and secondary membranous nephropathy (MN). Methods: Patients with biopsy-proven MN and non-MN were enrolled. Renal PLA2R was examined using an anti-PLA2R antibody (anti-PLA2R-Ab), and circulating PLA2R-Ab was detected by indirect immunofluorescence. Results: Renal PLA2R was detected along the capillary loop in 84% patients with idiopathic MN but not in those with any other primary glomerulonephritis. Only 1 of 38 patients with class V lupus nephritis showed renal PLA2R positive. In hepatitis B virus-associated MN (HBV-MN), 64% showed renal PLA2R positive, and PLA2R overlapped with HBsAg along the capillary loop. In addition, renal PLA2R positivity was closely associated with serum PLA2R-Ab. Renal PLA2R positive was present in all the patients with serum PLA2R-Ab positive and in 53% of patients with serum PLA2R-Ab negative. However, in patients with renal PLA2R negative, serum PLA2R-Ab was all negative. Conclusion: Renal biopsy PLA2R positivity was common in idiopathic MN and HBV-MN but rare in lupus-associated MN, and it was closely associated with serum PLA2R-Ab production. Further studies examining the association between PLA2R and HBV-MN may shed light on the mechanism of idiopathic MN or HBV-MN.

Background: We previously reported the preliminary findings from a feasibility study of bladder cancer (BCa) screening with urinary molecular markers (Bladder Cancer Urine Marker Project [BLU-P]) that has now been terminated. Objective: To report the final results from BLU-P to determine whether mass screening for BCa is feasible and useful. Design, setting, and participants: BLU-P was a Dutch population-based study initiated in 2008 to evaluate BCa screening. A total of 6500 men were invited to participate in the study, 1984 (30.5%) agreed, and 1747 (88.1%) men completed the protocol and were followed for 2 yr. Intervention: The screening protocol included home hematuria testing followed by molecular markers—nuclear matrix protein 22 (NMP22), microsatellite analysis (MA), fibroblast growth factor receptor 3 (FGFR3) mutation snapshot assay, and a custom methylation-specific (MLPA) test—to determine the need for cystoscopy. Outcome measurements and statistical analysis: Outcomes included the number of cystoscopies and the cancer detection rate within and outside the protocol, as determined by linkage to national registries. Results and limitations: Overall, 409 men (23.4%) tested positive for hematuria and underwent molecular testing. Current smokers (n = 295 [17%]) and past smokers (n = 998 [58%]) were significantly more likely to test positive for hematuria than nonsmokers. Seventy-one of 75 men (94.6%) with positive molecular markers underwent the recommended cystoscopy. Four BCas and one kidney tumor were detected through this sequential protocol, whereas one BCa and one kidney tumor were missed through the screening program. Limitations include the possibility of healthy subject bias. Conclusions: For BCa screening, use of a sequential protocol with home hematuria testing followed by molecular markers substantially reduced the number of cystoscopy recommendations compared with dipstick testing alone. A sequential screening approach may help minimize unnecessary invasive follow-up testing, with very few missed cancers. Nevertheless, this mass screening program had a very low diagnostic yield in an unselected asymptomatic European male population.

Background Inconclusive test results often occur after prostate-specific antigen (PSA)–based screening for prostate cancer (PCa), leading to uncertainty on whether, how, and when to repeat testing. Objective To develop and validate a prediction tool for the risk of PCa 4 yr after an initially negative screen. Design, setting, and participants We analyzed data from 15 791 screen-negative men aged 55–70 yr at the initial screening round of the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer. Outcome measurements and statistical analysis Follow-up and repeat screening at 4 yr showed either no PCa, low-risk PCa, or potentially high-risk PCa (defined as clinical stage >T2b and/or biopsy Gleason score ≥7 and/or PSA ≥10.0 ng/ml). A multinomial logistic regression analysis included initial screening data on age, PSA, digital rectal examination (DRE), family history, prostate volume, and having had a previous negative biopsy. The 4-yr risk predictions were validated with additional follow-up data up to 8 yr after initial screening. Results and limitations Positive family history and, especially, PSA level predicted PCa, whereas a previous negative biopsy or a large prostate volume reduced the likelihood of future PCa. The risk of having PCa 4 yr after an initially negative screen was 3.6% (interquartile range: 1.0–4.7%). Additional 8-yr follow-up data confirmed these predictions. Although data were based on sextant biopsies and a strict protocol-based biopsy indication, we suggest that men with a low predicted 4-yr risk (eg, ≤1.0%) could be rescreened at longer intervals or not at all, depending on competing risks, while men with an elevated 4-yr risk (eg, ≥5%) might benefit from immediate retesting. These findings need to be validated externally. Conclusions This 4-yr future risk calculator, based on age, PSA, DRE, family history, prostate volume, and previous biopsy status, may be a promising tool for reducing uncertainty, unnecessary testing, and overdiagnosis of PCa.

Variations of clinical response of cyclophosphamide (CTX) treatment in lupus nephritis (LN) could still be recognized. LN patients with a GSTA1mutation (CT heterozygous) had a risk of none-response (P=0.005). Pharmacokinetics data indicated that patients with a GSTA1 heterozygous variant had a lower exposure to 4-OHCTX compared to wild-type patients (P=0.023). And clinical efficacy was significantly related to higher exposure to 4- OH-CTX (P=0.038). In conclusion, LN patients with GSTA1 heterozygousgenotypes had poor CTX treatment response due to less exposure to activated 4-OH-CTX.

Study Type – Therapy (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? Radical prostatectomy was previously shown to improve long-term outcomes among men with clinically-detected prostate cancer. Our data suggests that radical prostatectomy is also associated with improved outcomes in men with screen-detected prostate cancer. OBJECTIVE • To examine the long-term outcomes of radical prostatectomy (RP) among men diagnosed with prostate cancer from the screening and control arms of the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer (ERSPC). PATIENTS AND METHODS • Among 42 376 men randomised during the period of the first round of the trial (1993–1999), 1151 and 210 in the screening and control arms were diagnosed with prostate cancer, respectively. • Of these men, 420 (36.5%) screen-detected and 54 (25.7%) controls underwent RP with long-term follow-up data (median follow-up 9.9 years). • Progression-free (PFS), metastasis-free (MFS) and cancer-specific survival (CSS) rates were examined, and multivariable Cox proportional hazards models were used to determine whether screen-detected (vs control) was associated with RP outcomes after adjusting for standard predictors. RESULTS • RP cases from the screening and control arms had statistically similar clinical stage and biopsy Gleason score, although screen-detected cases had significantly lower prostate-specific antigen (PSA) levels at diagnosis. • Men from the screening arm had a significantly higher PFS (P= 0.003), MFS (P < 0.001) and CSS (P= 0.048). • In multivariable models adjusting for age, PSA level, clinical stage, and biopsy Gleason score, the screening group had a significantly lower risk of biochemical recurrence (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.23–0.83, P= 0.011) and metastasis (HR 0.18, 95% CI 0.06–0.59, P= 0.005). • Additionally adjusting for tumour volume and other RP pathology features, there was no longer a significant difference in biochemical recurrence between the screening and control arms. • Limitations of the present study include lead-time bias and non-randomised treatment selection. CONCLUSIONS • After RP, screen-detected cases had significantly improved PFS, MFS and CSS compared with controls within the available follow-up time. • The screening arm remained significantly associated with lower rates of biochemical recurrence and metastasis after adjusting for other preoperative variables. • However, considering also RP pathology, the improved outcomes in the screening group appeared to be mediated by a significantly lower tumour volume.

Study Type – Therapy (outcomes) Level of Evidence 2b What's known on the subject? and What does the study add? Active surveillance aims to reduce overtreatment by selecting patients with low risk prostate cancer (PCa) based on favourable disease characteristics. However, most studies on active surveillance do not have long-term results available; in particular, data on patients with intermediate risk disease are lacking. Our findings demonstrate that withholding radical treatment in men with low or intermediate risk screen-detected localized PCa leads to a substantial delay or even avoidance of radical treatment in a majority of men. Favourable disease-specific outcomes confirm the feasibility of active surveillance for low risk PCa and also support a role for active surveillance in selected patients with intermediate risk PCa. OBJECTIVE • To assess the longer-term feasibility of active surveillance, we aimed to evaluate outcomes of patients with screen-detected localized prostate cancer (PCa) who initially elected to withhold radical treatment for either low or intermediate risk disease. PATIENTS AND METHODS • All men underwent screening for PCa in the Rotterdam and Helsinki arms of the European Randomized Study of Screening for Prostate Cancer (ERSPC); eligible men were diagnosed with PCa prior to the establishment of the ERSPC-affiliated Prostate Cancer Research International: Active Surveillance (PRIAS) study (1994–2007) and were initially expectantly managed in the absence of a fixed follow-up protocol. • Low risk PCa was defined as clinical stage T1/T2, PSA ≤ 10 ng/mL, PSA density < 0.2 ng/mL/mL, Gleason ≤ 6 and maximum two positive biopsy cores, whereas PSA 10–20 ng/mL, Gleason score 7 and three positive biopsy cores were considered intermediate risk features. • Disease-specific, overall and treatment-free survival were analysed using the Kaplan–Meier and competing risks methods. RESULTS • In all, 509 patients with PCa were eligible, of whom 381 were considered low risk and 128 intermediate risk. • During a median follow-up of 7.4 years, a total of 221 patients (43.4%) switched to deferred treatment after a median of 2.6 years. • The calculated 10-year disease-specific survival rates were 99.1% and 96.1% for low and intermediate risk patients, respectively (P= 0.44), and for overall survival 79.0% and 64.5%, respectively (P= 0.003). • Competing risks analysis showed similar results. CONCLUSIONS • Withholding radical treatment in men with low to intermediate risk screen-detected PCa leads to a substantial delay or even avoidance of radical treatment and its potential side-effects in a majority of patients. • Disease-specific outcomes at 7.4 years of follow-up are favourable in low as well as intermediate risk patients. • This confirms the feasibility of active surveillance according to contemporary criteria, and also suggests a potential role for active surveillance in selected men with intermediate risk features.

Background: The European Randomized Study of Screening for Prostate Cancer (ERSPC) risk calculators (RCs) are validated tools for prostate cancer (PCa) risk assessment and include prostate volume (PV) data from transrectal ultrasound (TRUS). Objective: Develop and validate an RC based on digital rectal examination (DRE) that circumvents the need for TRUS but still includes information on PV. Design, setting, and participants: For development of the DRE-based RC, we studied the original ERSPC Rotterdam RC population including 3624 men (885 PCa cases) and 2896 men (547 PCa cases) detected at first and repeat screening 4 yr later, respectively. A validation cohort consisted of 322 men, screened in 2010-2011 as participants in ERSPC Rotterdam. Measurements: Data on TRUS-assessed PV in the development cohorts were re-coded into three categories (25, 40, and 60 cm(3)) to assess the loss of information by categorization of volume information. New RCs including PSA, DRE, and PV categories (DRE-based RC) were developed for men with and without a previous negative biopsy to predict overall and clinically significant PCa (high-grade [HG] PCa) defined as T stage >T2b and/or Gleason score >= 7. Predictive accuracy was quantified by the area under the receiver operating curve. We compared performance with the Prostate Cancer Prevention Trial (PCPT) RC in the validation study. Results and limitations: Areas under the curve (AUC) of prostate-specific antigen (PSA) alone, PSA and DRE, the DRE-based RC, and the original ERSPC RC to predict PCa at initial biopsy were 0.69, 0.73, 0.77, and 0.79, respectively. The corresponding AUCs for predicting HG PCa were higher (0.74, 0.82, 0.85, and 0.86). Similar results were seen in men previously biopsied and in the validation cohort. The DRE-based RC outperformed the PCPT RC (AUC 0.69 vs 0.59; p = 0.0001) and a model based on PSA and DRE only (AUC 0.69 vs 0.63; p = 0.0075) in the relatively small validation cohort. Further validation is required. Conclusions: An RC should contain volume estimates based either on TRUS or DRE. Replacing TRUS measurements by DRE estimates may enhance implementation in the daily practice of urologists and general practitioners. (C) 2011 European Association of Urology. Published by Elsevier B. V. All rights reserved.

Study Type – Prognosis (case control) Level of Evidence 3a What's known on the subject? and What does the study add? Treatment of advanced PC might put patients at an increased risk of cardiovascular events. Recent studies have suggested that the excess mortality is lower among men who were diagnosed with screen detected PC in comparison to men with clinically diagnosed PC, possibly due to the use of medications for cardiovascular disease and the change to a healthier lifestyle of men with a screen detected PC. Men with clinically diagnosed PC have an increased risk of death unrelated to PC itself, i.e., the excess mortality is based on an increased risk of dying from other neoplasm and diseases of the circulatory or respiratory system. OBJECTIVE • To assess the cause-specific mortality unrelated to prostate cancer (PC) itself in patients with screen- and clinically diagnosed PC. PATIENTS AND METHODS • The present study was conducted among participants of the European Randomized Study of Screening for Prostate Cancer. • Based on consensus of the causes of death committee (CODC), all patients who died from PC were excluded. • In the intervention arm, cases were patients with a screen-detected PC, aged 55–74 years, between 1993 and 2001. • These cases were matched to two controls in whom no cancer was found after biopsy, and two controls in whom no cancer was suspected after screening. In the control arm, cases were patients with clinically diagnosed PC, aged 55–74 years, between 1993 and 2001. These cases were matched to four controls without PC. Matching was done with respect to date of birth, screening and/or diagnosis. Men were followed up to 31 December 2007. RESULTS • No statistically significant difference in overall mortality between cases and controls in the intervention arm was observed: relative risk (RR) 1.26 (95% confidence interval [CI] 0.96–1.65; P = 0.102) and RR 1.13 (95% CI 0.86–1.47; P = 0.381). • In the control arm, the overall mortality was statistically significantly higher in cases relative to controls: RR 1.43 (95% CI 1.03–2.00; P = 0.033). • This difference was because of an increased risk of dying from neoplasms and disease of the circulatory or respiratory system among cases: RR 1.61 (95% CI 1.12–2.29; P = 0.009). • The present study was limited by the relatively small sample size. CONCLUSIONS • Increased mortality unrelated to PC itself was observed in men with clinically diagnosed PC, but not in screen-detected PC. • The excess mortality in men with clinically diagnosed PC seems to be as a result of a significantly increased risk of dying from neoplasm and disease of the circulatory or respiratory system. • Results have to be studied more thoroughly in further clinical trials.

Objective To assess the impact of different study designs on outcome data within the European Randomized Study of Screening for Prostate Cancer (ERSPC). Methods Observed data from the Gothenburg centre (effectiveness trial with upfront randomization before informed consent) and the Rotterdam centre (efficacy trial with randomization after informed consent) were compared with expected data, which were retrieved from national cancer registries and life tables. Endpoints were 11-year cumulative prostate cancer (PC) incidence, overall mortality and PC-specific mortality. Results In Gothenburg, the 11-year PC incidence was higher than predicted (5.8%) in both the intervention (12.4%) and control arms (7.3%). The observed overall mortality was higher than predicted (15.9%) in both the intervention (17.8%) and control arms (18.5%). The observed PC-specific mortality in the intervention arm was 0.56% versus 0.83% in the control arm, while the expected mortality was 0.83%. In Rotterdam, the observed PC incidence in the intervention arm (10.4%) was higher than expected (4.4%). The incidence in the control arm was 4.6%. The observed overall mortality was lower than expected: 13.6% in the intervention arm and 14.0% in the control arm versus an expected mortality of 16.1%. The observed PC-specific mortality was lower than expected (0.65%) in both the intervention (0.27%) and control arms (0.41%). Conclusions Our results suggest that an efficacy trial with informed consent prior to randomization may have introduced a ‘healthy screenee bias’. Therefore, an effectiveness trial with consent after randomization may more accurately estimate the PC-specific mortality reduction if population-based screening is introduced.

The complications of prostate needle biopsy (PNB) are important when considering the benefits and harms of prostate cancer screening. Studies from the United States and Canada have recently reported increasing numbers of hospitalizations for infectious complications after PNB.Examine the risk of infectious complications and hospital admissions after PNB in a European screening trial.From 1993 to 2011, 10 474 PNBs were performed in the European Randomized Study of Screening for Prostate Cancer (Rotterdam section). Prophylaxis originally consisted of trimethoprim-sulfamethoxazole. Beginning in 2008, it was changed to ciprofloxacin.Febrile complications and hospital admissions were assessed by questionnaires 2 wk after PNB. Logistic regression was used to identify risk factors for biopsy-related fever and hospital admission.Fever and hospital admission were reported on 392 of 9241 questionnaires (4.2%) and 78 of 9198 questionnaires (0.8%), respectively. Although most fevers were managed on an outpatient basis, 81% of hospital admissions were for infection. Of the 56 available blood cultures, 34 were positive with Escherichia coli as the predominant organism. On multivariable analysis, prostate enlargement and diabetes were significantly associated with an increased risk of fever after PNB, whereas later year of biopsy was the only factor significantly associated with an increased risk of hospital admission.In a European screening trial,5% PNBs resulted in febrile complications. Significant risk factors included diabetes and prostatic enlargement. Although most fevers were managed on an outpatient basis, infection remained the leading cause of hospital admission after PNB. Consistent with prior international reports, the frequency of hospital admissions after PNB significantly increased over time. Nevertheless, the absolute frequency of hospital admissions related to PNB was low and should not dissuade healthy men who would benefit from early prostate cancer diagnosis from undergoing biopsy when clinically indicated.

Background: In a screening program, interval cancers are cancers diagnosed between two screening visits. Objective: To assess the disease-specific survival (DSS) of men with prostate cancer (PCa) detected during the screening interval. Design, setting, and participants: Within the European Randomized Study of Screening for Prostate Cancer section Rotterdam, 42 376 men identified from population registries (55-74 yr of age) were randomized to a screening or control arm. The median follow-up was 11 yr. Intervention: Men with prostate-specific antigen >= 3.0ng/ml were recommended to undergo lateralized sextant biopsy. The screening interval was 4 yr. Measurements: The disease-specific mortality of men with interval cancers was compared with that of men with PCa in the control arm; the secondary end point was overall mortality. An independent committee determined the causes of death. Results and limitations: In the screening arm, 139 men were diagnosed with interval cancer of whom 8 died of the disease. In the control arm, the corresponding numbers were 1149 and 128, respectively. When comparing men with interval cancer to men with PCa in the control arm, no statistically significant difference in disease-specific mortality (hazard ratio [HR]: 1.12; 95% confidence interval [CI], 0.53-2.36; p = 0.77) and overall mortality (HR: 0.98; 95% CI, 0.68-1.38; p = 0.90) was found, adjusted for age, prognostic factors, and treatmentmodality. The follow-up is too limited to address the difference in DSS stratified for screening interval. Conclusions: In the setting of population-based PCa screening at 4-yr intervals, the DSS of men with interval cancer seems to be similar to that of men with PCa in the control arm. Given that interval cancers contribute significantly to PCa mortality, further benefit in DSS in the screening arm may be achieved by decreasing the occurrence of interval cancer. However, the balance between mortality reduction and overdiagnosis should be preserved. Trial registration: ISRCTN49127736. (C) 2011 European Association of Urology. Published by Elsevier B. V. All rights reserved.

We aim to identify and characterize "escapes,'' men who developed metastasis and/or died from prostate cancer (PCa) despite screening, in the framework of the novel international ESCAPE-project. With this knowledge, the ultimate goal is to improve screening strategy. In this article, we focus on the study cohort of the European Randomized Study of Screening for Prostate Cancer (ERSPC), section Rotterdam. In all, 21,210 men were randomized to the screening arm of whom 19,950 were actually screened. The screening interval was 4 years. Men with prostate-specific antigen >= 3.0 ng/ml were recommended to undergo lateralized sextant prostate biopsy. The follow-up was complete until January 1, 2009. Of 19,950 screened men, 2,317 were diagnosed with PCa. Of these cancers 1,946 were detected in a screening round and 371 during an interval. The median follow-up was 11.1 years for the whole cohort and 7.3 years for men diagnosed with PCa. In total, we identified 168 escapes among 2,317 cancers (7.3%) within our screening cohort of 19,950 men (0.8%). More than half of these escapes were found in the initial screening round (94 of 168). Possible mechanisms behind escaping are nonattending, inadequate screening tests, the relative long screening interval, the age cut-off at 75 years, and undertreatment. International cooperation is crucial to compare the escapes of our cohort with other study groups participating in the ESCAPE-project which have different, more aggressive screening strategies. Subsequently, we can achieve improvements of the current screening algorithm, which hopefully will further decrease PCa-specific mortality without increasing overdiagnosis and overtreatment.

Purpose of review Prostate cancer (PCa) screening has long been a source of controversy. In this review, we discuss the interim results of the European Randomized Study of Screening for Prostate Cancer (ERSPC) and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Implications of these studies will also be underlined. Recent findings With systematic prostate-specific antigen-based screening, the ERSPC reported a statistically significant PCa-specific mortality reduction of 20% favouring screening in the intention-to-treat analysis and 31% in the secondary analysis. In contrast, the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial showed no mortality reduction. On the basis of critical appraisal of the study design and methods, it is justified to rely on the results of the ERSPC, as the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial is rather a comparison between a screening group and a less screened group. Summary Despite the effects demonstrated by the ERSPC, there is currently insufficient evidence to introduce a population-based screening programme. The studies evaluating quality of life and cost-efficiency need to be completed with the highest urgency and their results should be considered together with more mature data from the ERSPC to reach an effective implementation of screening on PCa. Meanwhile, we have to improve the screening test, screening protocol and further develop an accurate individualized risk assessment to decrease the rates of overdiagnosis and overtreatment, while the mortality reduction and the detection of clinically relevant PCa should be maintained. Copyright

This study examined the expression of renal phospholipase A2 receptor (PLA2R) in idiopathic and secondary membranous nephropathy (MN).Patients with biopsy-proven MN and non-MN were enrolled. Renal PLA2R was examined using an anti-PLA2R antibody (anti-PLA2R-Ab), and circulating PLA2R-Ab was detected by indirect immunofluorescence.Renal PLA2R was detected along the capillary loop in 84% patients with idiopathic MN but not in those with any other primary glomerulonephritis. Only 1 of 38 patients with class V lupus nephritis showed renal PLA2R positive. In hepatitis B virus-associated MN (HBV-MN), 64% showed renal PLA2R positive, and PLA2R overlapped with HBsAg along the capillary loop. In addition, renal PLA2R positivity was closely associated with serum PLA2R-Ab. Renal PLA2R positive was present in all the patients with serum PLA2R-Ab positive and in 53% of patients with serum PLA2R-Ab negative. However, in patients with renal PLA2R negative, serum PLA2R-Ab was all negative.Renal biopsy PLA2R positivity was common in idiopathic MN and HBV-MN but rare in lupus-associated MN, and it was closely associated with serum PLA2R-Ab production. Further studies examining the association between PLA2R and HBV-MN may shed light on the mechanism of idiopathic MN or HBV-MN. © 2015 S. Karger AG, Basel.

To assess the extent of overestimation of the cumulative probability of death by the Kaplan-Meier method with the competing-risks regression analysis as reference approach.Data were derived from the screening arm of the Rotterdam branch of the European Randomized Study of Screening for Prostate Cancer (ERSPC). The screening arm consisted of 21210 men between the ages of 55 and 74 at study entry. Follow up concerning mortality was complete through 2008. Endpoints were 5 and 10 year cumulative probabilities of prostate cancer death and death from other causes. Relative bias was defined as the ratio of the cumulative probability of death as determined by the Kaplan-Meier method, relative to the cumulative probability obtained by the competing-risks analysis.According to the Kaplan-Meier method, the 5 year cumulative probability of death from prostate cancer was 0.0101, compared with 0.0099 according to the competing-risk analysis [1.8% overestimation]. At 10 year, these numbers were 0.0347 and 0.0321, respectively [8.0% overestimation]. For death from other causes, the cumulative probabilities at 5 year were 0.0399 and 0.0397 according to the Kaplan-Meier and the competing-risks method [0.6% overestimation], respectively. At 10 year, the probabilities were 0.141 and 0.139 [1.7% overestimation], respectively.When competing events are present, the competing-risks regression analysis is to be preferred over the Kaplan-Meier method in the estimation of the cumulative probability of the event of interest.

Study Type--Diagnosis (validating cohort) Level of Evidence 1b. What's known on the subject? and What does the study add? The European Randomized study of Screening for Prostate Cancer (ERSPC) showed a reduction in prostate cancer mortality of 21% for PSA-based screening at a median follow-up of 11 years. In the ERSPC, men are screened at 4-year intervals. A prostate biopsy is recommended for men with a PSA level ≥ 3.0 ng/mL. The study shows that the positive predictive value (PPV) of a prostate biopsy indicated by PSA-based screening remains equal throughout consecutive screening rounds in men without a previous biopsy. In men who have previously had a benign biopsy, the PPV drops considerably, but 20% of the cancers detected still show aggressive characteristics.• To assess the positive predictive value (PPV) of prostate biopsy, indicated by a prostate-specific antigen (PSA) threshold of ≥ 3.0 ng/mL, over time, in the Rotterdam section of the European Randomized study of Screening for Prostate Cancer (ERSPC).• In the Rotterdam section of the ERSPC, a total of 42,376 participants, aged 55-74 years, identified from population registries were randomly assigned to a screening or control arm. • For the ERSPC men undergo PSA screening at 4-year intervals. A total of three screening rounds were evaluated; therefore, only men aged 55-69 years at the first screening were eligible for the present study.• PPVs for men without previous biopsy remained equal throughout the three subsequent screenings (25.5, 22.3 and 24.8% respectively). • Conversely, PPVs for men with a previous negative biopsy dropped significantly (12.0 and 15.2% at the second and third screening, respectively). • Additionally, in men with and without previous biopsy, the percentage of aggressive prostate cancers (clinical stageT2b, Gleason score ≥ 7) decreased after the first round of screening from 44.4 to 23.8% in the second (P0.001) and 18.6% in the third round (P0.001). • Repeat biopsies accounted for 24.6% of all biopsies, but yielded only 8.6% of all aggressive cancers.• In consecutive screening rounds the PPV of PSA-based screening remains equal in previously unbiopsied men. • In men with a previous negative biopsy the PPV drops considerably, but 20% of cancers detected still show aggressive characteristics. • Individualized screening algorithms should incorporate previous biopsy status in the decision to perform a repeat biopsy with the aim of further reducing unnecessary biopsies.

Study Type--Therapy (cohort) Level of Evidence 2b. What's known on the subject? and What does the study add? Radical prostatectomy was previously shown to improve long-term outcomes among men with clinically-detected prostate cancer. Our data suggests that radical prostatectomy is also associated with improved outcomes in men with screen-detected prostate cancer.• To examine the long-term outcomes of radical prostatectomy (RP) among men diagnosed with prostate cancer from the screening and control arms of the Rotterdam section of the European Randomized Study of Screening for Prostate Cancer (ERSPC).• Among 42,376 men randomised during the period of the first round of the trial (1993-1999), 1151 and 210 in the screening and control arms were diagnosed with prostate cancer, respectively. • Of these men, 420 (36.5%) screen-detected and 54 (25.7%) controls underwent RP with long-term follow-up data (median follow-up 9.9 years). • Progression-free (PFS), metastasis-free (MFS) and cancer-specific survival (CSS) rates were examined, and multivariable Cox proportional hazards models were used to determine whether screen-detected (vs control) was associated with RP outcomes after adjusting for standard predictors.• RP cases from the screening and control arms had statistically similar clinical stage and biopsy Gleason score, although screen-detected cases had significantly lower prostate-specific antigen (PSA) levels at diagnosis. • Men from the screening arm had a significantly higher PFS (P = 0.003), MFS (P0.001) and CSS (P = 0.048). • In multivariable models adjusting for age, PSA level, clinical stage, and biopsy Gleason score, the screening group had a significantly lower risk of biochemical recurrence (hazard ratio [HR] 0.43, 95% confidence interval [CI] 0.23-0.83, P = 0.011) and metastasis (HR 0.18, 95% CI 0.06-0.59, P = 0.005). • Additionally adjusting for tumour volume and other RP pathology features, there was no longer a significant difference in biochemical recurrence between the screening and control arms. • Limitations of the present study include lead-time bias and non-randomised treatment selection.• After RP, screen-detected cases had significantly improved PFS, MFS and CSS compared with controls within the available follow-up time. • The screening arm remained significantly associated with lower rates of biochemical recurrence and metastasis after adjusting for other preoperative variables. • However, considering also RP pathology, the improved outcomes in the screening group appeared to be mediated by a significantly lower tumour volume.

Context: Widespread mass screening of prostate cancer (PCa) is not recommended because the balance between benefits and harms is still not well established. The achieved mortality reduction comes with considerable harm such as unnecessary biopsies, overdiagnoses, and overtreatment. Therefore, patient stratification with regard to PCa risk and aggressiveness is necessary to identify those men who are at risk and may actually benefit from early detection. Objective: This review critically examines the current evidence regarding risk-based PCa screening. Evidence acquisition: A search of the literature was performed using the Medline database. Further studies were selected based on manual searches of reference lists and review articles. Evidence synthesis: Prostate-specific antigen (PSA) has been shown to be the single most significant predictive factor for identifying men at increased risk of developing PCa. Especially in men with no additional risk factors, PSA alone provides an appropriate marker up to 30 yr into the future. After assessment of an early PSA test, the screening frequency may be determined based on individualized risk. A limited list of additional factors such as age, comorbidity, prostate volume, family history, ethnicity, and previous biopsy status have been identified to modify risk and are important for consideration in routine practice. In men with a known PSA, risk calculators may hold the promise of identifying those who are at increased risk of having PCa and are therefore candidates for biopsy. Conclusions: PSA testing may serve as the foundation for a more risk-based assessment. However, the decision to undergo early PSA testing should be a shared one between the patient and his physician based on information balancing its advantages and disadvantages. (C) 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Value of characteristics assessed prior to diagnosis predicting aggressive prostate cancer, metastases and mortality in men participating in a screening study were identified.This study included 19950 men, aged 55 to 74 years at first screening, in the European Randomized Study of Screening for Prostate Cancer. Age, Charlson comorbidity, prostate cancer family history, vasectomy status, International Prostate Symptom Score (IPSS) score, digital rectal examination (DRE) status, transrectal ultrasound (TRUS) findings, prostate volume and prostate-specific antigen (PSA) level were assessed. Men were followed for median 11.1 years after first screening visit. Multivariate estimates of the probability of aggressive prostate cancer [stage ≥ T2c, or N1, M1, PSA20 ng/mL, or Gleason score ≥ 8], developing distant metastases and dying from prostate cancer stratified for predictors measured before prostate biopsies. Harrell's concordance index (c-index) was used for predictive accuracy.Among 19950 men, 2420 men (12.1%) were diagnosed with prostate cancer, of which 623 men (3.1%) had aggressive prostate cancer, 157 men (0.8%) developed metastases and 104 men (0.5%) died due to a prostate cancer related cause of death. In multivariate analysis, PSA, DRE, TRUS findings and prostate volume had a significant association with detection of aggressive prostate cancer, metastases and prostate cancer mortality. Family history was significantly associated with aggressive prostate cancer. Accuracy for predicting aggressive prostate cancer c-index = 0.90, distant metastases c-index = 0.87, and prostate cancer specific mortality c-index = 0.87.In a large population of men who were screened for prostate cancer, detection of aggressive prostate cancer, metastases and prostate cancer mortality was predicted based on predictors available before biopsy. These results support the value of a multivariate risk assessment and stratification tools.

Little is known about the outcome of radical prostatectomy (RP) in men initially followed on active surveillance (AS) for low-risk prostate cancer (PCa).Evaluate pathology findings after RP in our prospective AS cohort.All men participated in the Prostate Cancer Research International: Active Surveillance (PRIAS) study. Eligible men were initially diagnosed with low-risk PCa (clinical stage ≤ T2, prostate-specific antigen [PSA] ≤ 10 ng/ml, PSA density0.2 ng/ml per ml, one or two positive biopsy cores, and Gleason score ≤ 6) and underwent RP between December 2006 and July 2011. The study protocol recommends RP in case of risk reclassification on repeat biopsy (Gleason score6 and/or more than two positive cores) or a PSA doubling time ≤ 3 yr.Descriptive statistics were used to report on pathology findings for staging and grading.Pathology results were available in 167 out of 189 RP cases (88.4%). Median time to RP was 1.3 yr (range: 1.1-1.9). Protocol-based recommendations led to deferred RP in 143 men (75.7%); 24 men (12.7%) switched because of anxiety, and 22 (11.6%) had other reasons. Pathology results showed 134 (80.8%) organ-confined cases and 32 (19.2%) cases with extracapsular extension. Gleason scores ≤ 6, 3+4, 4+3, and 8 were found in 79 (47.3%), 64 (38.3%), 21 (12.6%), and 3 (1.8%) cases, respectively. Unfavourable RP results (pT3-4 and/or Gleason score ≥ 4+3) were found in 49 patients (29%), of whom 33 (67%) had a biopsy-related reason for deferred RP.RP results in men initially followed on AS show organ-confined disease and favourable Gleason grading in a majority of cases. Most men in our cohort had a protocol-based reason to switch to deferred RP. A main focus for AS protocols should be to improve the selection of patients at the time of inclusion to minimise reclassification of risk and preserve the chance for curative treatment, if indicated.