Errors in transrectal ultrasonic planimetry of the prostate: Computer simulation of volumetric errors applied to a screening population

Three systemic errors in routine ultrasonic planimetric volume measurements of the prostate were assessed. A computer model using ellipsoids was used to simulate the step section technique and different forms of rotational movements of the prostate during planimetry. The planimetric volume was up to 12% smaller than the exact volume, depending on the degree of rotational movement, the shape, and the length of the ellipsoid. In vivo study of a screening popul

Creating a potential diagnostic for prostate cancer risk stratification (InformMDx™) by translating novel scientific discoveries concerning cAMP degrading phosphodiesterase-4D7 (PDE4D7)

Increased PSA-based screening for prostate cancer has resulted in a growing number of diagnosed cases. However, around half of these are ‘indolent’, neither metastasizing nor leading to disease specific death. Treating non-progressing tumours with invasive therapies is currently regarded as unnecessary over-treatment with patients being considered for conservative regimens, such as active surveillance (AS). However, this raises both compliance and protocol issues. Great clinical benefit could accrue from a biomarker able to predict long-term patient outcome accurately at the time of biopsy and initial diagnosis. Here we delineate the translation of a laboratory discovery through to the precision development of a clinically validated, novel prognostic biomarker assay (InformMDx™). This centres on determining transcript levels for phosphodiesterase-4D7 (PDE4D7), an enzyme that breaks down cyclic AMP, a signalling molecule intimately connected with proliferation and androgen receptor function. Quantifiable detection of PDE4D7 mRNA transcripts informs on the longitudinal outcome of post-surgical disease progression. The risk of post-surgical progression increases steeply for patients with very low ‘PDE4D7 scores’, while risk decreases markedly for those patients with very high ‘PDE4D7 scores’. Combining clinical risk variables, such as the Gleason or CAPRA (Cancer of the Prostate Risk Assessment) score, with the ‘PDE4D7 score’ further enhances the prognostic power of this personalized, precision assessment. Thus the ‘PDE4D7 score’ has the potential to define, more effectively, appropriate medical intervention/AS strategies for individual prostate cancer patients

Can active surveillance really reduce the harms of overdiagnosing prostate cancer? A reflection of real life clinical practice in the PRIAS study

Background: Active surveillance (AS) for low-risk prostate cancer (PCa) appears to provide excellent long-term PCa-specific and overall survival. The choice for AS as initial treatment is mainly based on avoiding side effects from invasive treatment; but AS entails regular check-ups and the possibility of still having to switch or deciding to switch to invasive treatment. Here, we assessed the long-term follow-up data from AS in real life clinical practices. Methods: Data from the first 500 men, enrolled in PRIAS before July 2008 by 30 centers across 8 countries, were analyzed to provide long-term follow-up results. Men were advised to be regularly examined with prostate-specific antigen (PSA) tests, digital rectal examinations, and prostate biopsies. Men were advised to switch to invasive treatment if they had disease reclassification [Gleason score (GS) >= 3+ 4 on biopsy, more than two positive biopsy cores, a stage higher than cT2] or a PSA-doubling time of 0-3 years. We assessed time on AS, outcomes and reasons for discontinuing AS, and rates of potential unnecessary biopsies and treatments. Results: The median follow-up time was 6.5 years. During this period, 325 (65%) men discontinued after a median of 2.3 years and 121 (24%) men had no recent (> 1 year) data-update after a median of 7.3 years. The remaining 54 (11%) men were confirmed to be still on AS. Most men discontinued based on protocol advice; 38% had other reasons. During follow-up, 838 biopsy sessions were performed of which 79% to 90% did not lead to reclassification, depending on the criteria. Of the 325 discontinued men, 112 subsequently underwent radical prostatectomy (RP), 126 underwent radiotherapy, 57 switched to watchful waiting (WW) or died, and 30 had another or unknown treatment. RP results were available of 99 men: 34% to 68%, depending on definition, had favorable outcomes; 50% of unfavorable the outcomes occurred in the first 2 years. Of the 30 (6%) men who died, 1 man died due to PCa. Conclusions: These data, reflecting real life clinical practice, show that more than half of men switched to invasive treatment within 2.3 years, indicating limitations to the extent in which AS is able to reduce the adverse effects of overdiagnosis. Therefore, despite guidelines stating that PCa diagnosis must be uncoupled from treatment, it remains important to avoid overdiagnosing PCa as much as possible.Peer reviewe

Perfluorinated alkyl acids and fecundity assessment in striped mullet (\u3ci\u3eMugil cephalus\u3c/i\u3e) at Merritt Island national wildlife refuge

This study investigated wild caught striped mullet (Mugil cephalus) at Merritt Island National Wildlife Refuge (MINWR) for levels of 15 perfluoroalkyl acids (PFAA) in tandem with individual fecundity measurements (Oocyte sub-stage 2 late, n=42) and oocyte reproductive stages (Stages 1–5, n=128). PFAAmeasurementswere quantified in stripedmullet liver (n=128),muscle (n=49), and gonad (n=10). No significant negative impacts of liver PFAA burden on wild-caught,mullet fecundity endpoints were observed in this study; however, changes in PFAAwere observed in the liver asmullet progressed through different sub-stages of oocyte development. Of the PFAA with significant changes by sub-stage of oocyte development, the carboxylic acids (perfluorooctanoic acid, perfluorononanoic acid, and perfluorotridecanoic acid) increased in the liver with increasing sub-stage while the sulfonic acid and its precursor (perfluorooctanesulfonic acid (PFOS) and perfluorooctanesulfonamide, respectively) decreased in the liver with increasing sub-stage of oocyte development. This is a unique find and suggests PFAA change location of compartmentalization as mullet progress towards spawning. Investigations also revealed higher than expected median muscle and gonad levels of PFOS in striped mullet collected at MINWR (9.01 ng/g and 80.2 ng/g, respectively)

Urinary Incontinence and Sexual Function After the Introduction of NeuroSAFE in Radical Prostatectomy for Prostate Cancer

Background: Nerve-sparing (NS) radical prostatectomy (RP) results in better functional outcomes. Intraoperative neurovascular structure–adjacent frozen section examination (NeuroSAFE) significantly increases the frequency of NS surgery. The effect of NeuroSAFE on postoperative erectile function (EF) and continence is not yet clear. Objective: To describe EF and continence outcomes for men undergoing RP with the NeuroSAFE technique. Design, setting, and participants: Between September 2018 and February 2021, 1034 men underwent robot-assisted RP. Data for patient-reported outcomes were collected via validated questionnaires. Intervention: NeuroSAFE technique for RP. Outcome measurements and statistical analysis: Continence was assessed using the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) or Expanded Prostate Cancer Index Composite short form (EPIC-26) and defined as use of 0–1 pads/d. EF was evaluated using EPIC-26 or the International Index of Erectile Function short form (IIEF-5), with data converted according to the Vertosick method and categorized. Descriptive statistics were used to asses and describe tumor characteristics and continence and EF outcomes. Results and limitations: Of the 1034 men who underwent RP after introduction of the NeuroSAFE technique, 63% and 60% completed a preoperative and at least one postoperative questionnaire on continence and EF, respectively. Of the men who underwent unilateral or bilateral NS surgery, use of 0–1 pads/d was reported by 93% after 1 yr and 96% after 2 yr; the corresponding rates for men who underwent non-NS surgery were 86% and 78%. Overall, use of 0–1 pads/d was reported by 92% of the men at 1 yr and by 94% at 2 yr after RP. Men in the NS group had a good or intermediate Vertosick score after RP more often than the non-NS group. Overall, 44% of the men had a good or intermediate Vertosick score at 1 and 2 yr after RP. Conclusions: After introduction of the NeuroSAFE technique, the continence rate was 92% at 1 yr and 94% at 2 yr after RP. The NS group had a greater percentage of men with an intermediate or good Vertosick score and a higher continence rate after RP in comparison to the non-NS group. Patient summary: Our study shows that after introduction of the NeuroSAFE technique during removal of the prostate, the continence rate among patients was 92% at 1 year and 94% at 2 years after surgery. Some 44% of the men had a good or intermediate score for erectile function 1 and 2 years after surgery.</p

Relationship Between Baseline Prostate-specific Antigen on Cancer Detection and Prostate Cancer Death:Long-term Follow-up from the European Randomized Study of Screening for Prostate Cancer

Background: The European Association of Urology guidelines recommend a risk-based strategy for prostate cancer screening based on the first prostate-specific antigen (PSA) level and age. Objective: To analyze the impact of the first PSA level on prostate cancer (PCa) detection and PCa-specific mortality (PCSM) in a population-based screening trial (repeat screening every 2–4 yr). Design, setting, and participants: We evaluated 25 589 men aged 55–59 yr, 16 898 men aged 60–64 yr, and 12 936 men aged 65–69 yr who attended at least one screening visit in the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial (screening arm: repeat PSA testing every 2–4 yr and biopsy in cases with elevated PSA; control arm: no active screening offered) during 16-yr follow-up (FU). Outcome measurements and statistical analysis: We assessed the actuarial probability for any PCa and for clinically significant (cs)PCa (Gleason ≥7). Cox proportional-hazards regression was performed to assess whether the association between baseline PSA and PCSM was comparable for all age groups. A Lorenz curve was computed to assess the association between baseline PSA and PCSM for men aged 60–61 yr. Results and limitations: The overall actuarial probability at 16 yr ranged from 12% to 16% for any PCa and from 3.7% to 5.7% for csPCa across the age groups. The actuarial probability of csPCa at 16 yr ranged from 1.2–1.5% for men with PSA &lt;1.0 ng/ml to 13.3–13.8% for men with PSA ≥3.0 ng/ml. The association between baseline PSA and PCSM differed marginally among the three age groups. A Lorenz curve for men aged 60–61 yr showed that 92% of lethal PCa cases occurred among those with PSA above the median (1.21 ng/ml). In addition, for men initially screened at age 60–61 yr with baseline PSA &lt;2 ng/ml, further continuation of screening is unlikely to be beneficial after the age of 68–70 yr if PSA is still &lt;2 ng/ml. No case of PCSM emerged in the subsequent 8 yr (up to age 76–78 yr). A limitation is that these results may not be generalizable to an opportunistic screening setting or to contemporary clinical practice. Conclusions: In all age groups, baseline PSA can guide decisions on the repeat screening interval. Baseline PSA of &lt;1.0 ng/ml for men aged 55–69 yr is a strong indicator to delay or stop further screening. Patient summary: In prostate cancer screening, the patient's baseline PSA (prostate-specific antigen) level can be used to guide decisions on when to repeat screening. The PSA test when used according to current knowledge is valuable in helping to reduce the burden of prostate cancer.</p

Reasons for Discontinuing Active Surveillance : Assessment of 21 Centres in 12 Countries in the Movember GAP3 Consortium

Background: Careful assessment of the reasons for discontinuation of active surveillance (AS) is required for men with prostate cancer (PCa). Objective: Using Movember's Global Action Plan Prostate Cancer Active Surveillance initiative (GAP3) database, we report on reasons for AS discontinuation. Design, setting, and participants: We compared data from 10 296 men on AS from 21 centres across 12 countries. Outcome measurements and statistical analysis: Cumulative incidence methods were used to estimate the cumulative incidence rates of AS discontinuation. Results and limitations: During 5-yr follow-up, 27.5% (95% confidence interval [CI]: 26.4-28.6%) men showed signs of disease progression, 12.8% (95% CI: 12.0-13.6%) converted to active treatment without evidence of progression, 1.7% (95% CI: 1.5-2.0%) continued to watchful waiting, and 1.7% (95% CI: 1.4-2.1%) died from other causes. Of the 7049 men who remained on AS, 2339 had follow-up for >5 yr, 4561 had follow-up for Conclusions: Our descriptive analyses of current AS practices worldwide showed that 43.6% of men drop out of AS during 5-yr follow-up, mainly due to signs of disease progression. Improvements in selection tools for AS are thus needed to correctly allocate men with PCa to AS, which will also reduce discontinuation due to conversion to active treatment without evidence of disease progression. Patient summary: Our assessment of a worldwide database of men with prostate cancer (PCa) on active surveillance (AS) shows that 43.6% drop out of AS within 5 yr, mainly due to signs of disease progression. Better tools are needed to select and monitor men with PCa as part of AS. (C) 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.Peer reviewe

Semantics in active surveillance for men with localized prostate cancer - results of a modified Delphi consensus procedure

Active surveillance (AS) is broadly described as a management option for men with low-risk prostate cancer, but semantic heterogeneity exists in both the literature and in guidelines. To address this issue, a panel of leading prostate cancer specialists in the field of AS participated in a consensus-forming project using a modified Delphi method to reach international consensus on definitions of terms related to this management option. An iterative three-round sequence of online questionnaires designed to address 61 individual items was completed by each panel member. Consensus was considered to be reached if >= 70% of the experts agreed on a definition. To facilitate a common understanding among all experts involved and resolve potential ambiguities, a face-to-face consensus meeting was held between Delphi survey rounds two and three. Convenience sampling was used to construct the panel of experts. In total, 12 experts from Australia, France, Finland, Italy, the Netherlands, Japan, the UK, Canada and the USA participated. By the end of the Delphi process, formal consensus was achieved for 100% (n = 61) of the terms and a glossary was then developed. Agreement between international experts has been reached on relevant terms and subsequent definitions regarding AS for patients with localized prostate cancer. This standard terminology could support multidisciplinary communication, reduce the extent of variations in clinical practice and optimize clinical decision making.Peer reviewe