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Introduction Prostate cancer (PCa) detection is usually achieved by PSA measurement and, if indicated, further diagnostics. The recent EAU guidelines recommend a first PSA test at the age of 50 years, if no family history of PCa or BRCA2 mutation exists. However, some men might harbor significant PCa at younger age; thus we evaluated the histopathological results of men treated with radical prostatectomy (RP) in their 40 s at our institution. Materials and methods We relied on the data of all patients who underwent RP in our institution between 1992 and 2020 and were younger than 50 years at the time of surgery. The histopathological results are descriptively presented. Moreover, we tested the effect of a positive family history on the descriptive results. Results Overall, 1225 patients younger than 50 years underwent RP at our institution. Median age was 47 years. Most patients showed favorable histopathological characteristics. However, 20% of patients had extraprostatic disease (≥ pT3a), 15% had ISUP Gleason grade group ≥ 3, and 7% had positive lymph nodes (pN1). Patients with a known positive family history did not have a higher rate of adverse disease as their counterparts with a negative family history. Discussion Our data show that the majority of patients who were diagnosed with PCa at a very young age had favorable histopathological RP characteristics. However, a non-negligible proportion of patients already showed locally advanced disease and would have probably benefited from earlier PCa detection. This should be kept in mind when PCa screening recommendations are proposed.

Zusammenfassung Hintergrund Die Osteoprotektion bei Prostatakarzinompatienten spielt nicht nur in der ossär metastasierten kastrationsresistenten (mCRPC) Situation eine Rolle. Auch im ossär metastasiertem hormonsensitiven Stadium (mHSPC) und im Allgemeinen begleitend zur Androgendeprivationstherapie (ADT) wird eine Osteoprotektion empfohlen. Diese Studie soll die Anwendungsrealität der verschiedenen Arten der Osteoprotektion beim metastasierten Prostatakarzinom in Deutschland aufzeigen. Material und Methoden Es wurde ein Online-Fragebogen bestehend aus 16 Fragen zur Erfassung der Behandlungsrealität in Deutschland entwickelt und an Mitglieder der Arbeitskreise Onkologie und urologische Onkologie (AKO/AUO) sowie an Kollegen der Klinik für Urologie des Universitätsklinikums Schleswig-Holstein (Campus Lübeck), des Klinikums Braunschweig und der Technischen Universität München verschickt. Mithilfe der aktuellen Studienlage, Fachinformationen und Leitlinien wurden ferner Entscheidungspfade für das ossär metastasierte Prostatakarzinom und für den ADT-induzierten Knochenschwund entwickelt. Ergebnisse Zusammenfassend ergab die Auswertung, dass die Osteoprotektion beim ossär mCRPC zur Routine gehört. Beim ossär mHSPC hingegen wird eine Osteoprotektion seltener indiziert und ist zur Reduktion eines ADT-induzierten Knochenschwundes noch weniger im Einsatz. Denosumab wird häufiger genutzt als Zoledronsäure. Die vorgestellten Entscheidungspfade illustrieren die verschiedenen Dosierungs- und Applikationsschemata in den verschiedenen Stadien des metastasierten Prostatakarzinoms. Schlussfolgerung Die Osteoprotektion beim Prostatakarzinom ist facettenreich und nicht nur auf das ossär mCRPC beschränkt. Osteoprotektive Maßnahmen sind ein wichtiger Baustein im ganzheitlichen Therapiekonzept des metastasierten Prostatakarzinoms.

Aim and Objectives: We aimed to test the impact of age on long-term urinary continence (≥12 months) in patients undergoing robotic-assisted radical prostatectomy. Methods and Materials: We relied on an institutional tertiary-care database to identify the patients who underwent robotic-assisted radical prostatectomy between January 2014 and January 2021. Patients were divided into three age groups: age group one (≤60 years), age group two (61–69 years) and age group three (≥70 years). Multivariable logistic regression models tested the differences between the age groups in the analyses addressing long-term urinary continence after robotic-assisted radical prostatectomy. Results: Of the 201 prostate cancer patients treated with robotic-assisted radical prostatectomy, 49 (24%) were assigned to age group one (≤60 years), 93 (46%) to age group two (61–69 years) and 59 (29%) to age group three (≥70 years). The three age groups differed according to long-term urinary continence: 90% vs. 84% vs. 69% for, respectively, age group one vs. two vs. three (p = 0.018). In the multivariable logistic regression, age group one (Odds Ratio (OR) 4.73, 95% CI 1.44–18.65, p = 0.015) and 2 (OR 2.94; 95% CI 1.23–7.29; p = 0.017) were independent predictors for urinary continence, compared to age group three. Conclusion: Younger age, especially ≤60 years, was associated with better urinary continence after robotic-assisted radical prostatectomy. This observation is important at the point of patient education and should be discussed in informed consent.

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Benefit of the 3-level DNA score beyond the CAPRA-S nomogram for prediction of early biochemical recurrence. A) Prognostic impact of different levels of the CAPRA-S score. B)-F) Additional prognostic impact of the 3-level DNA score in subsets of cancers with B) CAPRA-S score 0-1, C) CAPRA-S score 2-3, D) CAPRA-S score 4-5, E) CAPRA-S score 6-8, F) CAPRA-S score 9-12. The 3-level DNA score combines cancers according to the following criteria: negative, DNA diploid and no deletion; intermediate, DNA diploid with deletion (of at least one of PTEN and 6q) or DNA tetraploid without deletion; high, DNA tetraploid with deletion or DNA aneuploidy.

Purpose: Aberrant DNA content has been discussed as a potential prognostic feature in prostate cancer.Experimental Design: We analyzed the clinical significance of DNA ploidy in combination with prognostic relevant deletions of PTEN and 6q15 in 3,845 prostate cancers.Result: The DNA status was diploid in 67.8%, tetraploid in 25.6%, and aneuploid in 6.8% of tumors, and deletions of PTEN and 6q15 occurred in 17.8% and 20.3% of tumors. Abnormal DNA content and deletions were linked to high Gleason score, advanced tumor stage, and positive nodal stage (P < 0.0001 each). The risk of PSA recurrence increased from diploid to tetraploid and from tetraploid to aneuploid DNA status (P < 0.0001 each). However, 40% of patients with Gleason score ≥4+4 and 55% of patients with PSA recurrence had diploid cancers. This fraction decreased to 21% (Gleason ≥4+4) and 29% (PSA recurrence) if PTEN and/or 6q deletion data were added to ploidy data to identify cancers with an aberrant DNA status. The significance of combining both deletions and ploidy was further demonstrated in a combined recurrence analysis. Presence of deletions increased the risk of PSA recurrence in diploid (P < 0.0001), tetraploid (P < 0.0001), and aneuploid cancers (P = 0.0049), and the combination of ploidy data and deletions provided clinically relevant information beyond the CAPRA-S nomogram. Multivariate modeling including preoperatively and postoperatively available parameters identified the “combined DNA status” as a strong independent predictor of poor patient outcome.Conclusions: The combinatorial DNA content analysis involving general (ploidy) and specific events (deletions) has the potential for clinical utility in prostate cancer. Clin Cancer Res; 22(11); 2802–11. ©2016 AACR.

PDF file - 163K, Homozygous CHD1 deletion in areas of prostatic intraepithelial neoplasia (PIN) and invasive cancer cells. Overwiew of a hematoxylin- and eosin stained tissue section containing areas of PIN (a, b) and invasive cancer (c). Corresponding FISH images show complete loss of CHD1 FISH signals (red) in PIN and cancer cells but not in stroma cells indicated by an asterix. The control FISH signals (green) correspond to centromere 6.

PDF file - 101K, GISTIC analysis of genomic rearrangements (cytoband) significantly associated with 5q21 deletion. The cytobands, significance (q value) and peak boundaries are indicated.

PDF file - 155K, Baseline CHD1 mRNA (a) and protein (b) expression levels in prostate cancer cell lines cells. Efficacy of ectopic overexpression of CHD1 in PC-3 cells on mRNA (c) and protein level (d) by Taqman PCR and immunoblot analysis, respectively.

PDF file - 44K, Overexpression of RB1 and PTEN in PC-3 cells transfected with PSG5L-RB1 and PSG5L-PTEN as compared to the control vector PLNGY. Lysates were analysed for RB1 (a) and PTEN (b) by immunoblot analysis. Tubulin immunoblot served as loading control.

PDF file - 92K, Impact of sh-RNA mediated knockdown of CHD1 (a), RB1 (b), PTEN (c) and mTOR (d) knockdown on mRNA and protein levels in BPH-1 cells by Taqman.

PDF file - 57K, COX regression multivariate analysis for the predictive factor biochemical recurrence (BCR).

PDF file - 68K, Localization of the CHD1 FISH probe made from two BAC clones relative to the CHD1 gene.

PDF file - 636K, Impact of CHD1 on colony formation, soft agar growth and cell invasiveness. a) Effect of CHD1 overexpression on cell growth. DU-145 cells were transfected with expression vectors encoding CHD1, PLNGY (control) and the known tumor suppressor genes RB1 and PTEN. Effect of CHD1 depletion on cell growth. DU-145 cells were transfected with shCHD1 vector. The control group consisted of shGFP, shRB1 and shPTEN vectors. Cells were selected with puromycin and cultured for two weeks, and colonies were fixed with methanol and stained with Giemsa. b) Soft agar assay showing the impaired anchorage-independent growth of shCHD1 PC-3 cells and control shNeg cells. Representative images of the stained colonies are shown. The bars represent the average number of colonies. c) CHD1 knockdown impairs invasion of PC-3 (shCHD1) cells through matrigel as compared to shNeg control cells. Photographs show representative fields of crystal-violet stained invading cells.

Purpose To investigate the concordance of biopsy and pathologic International Society of Urological Pathology (ISUP) grading in salvage radical prostatectomy (SRP) patients for recurrent prostate cancer. Methods Within a high-volume center database, we identified patients who underwent SRP for recurrent prostate cancer (PCa) between 2004 and 2020. Upgrading, downgrading, concordance, and any discordance between posttreatment biopsy ISUP and ISUP at SRP were tested. Logistic regression models were used to predict ISUP upgrading and ISUP discordance. Models were adjusted for prostatic specific antigen before SRP, age at surgery, initial prostatic specific antigen (PSA), type of primary treatment, time from primary PCa diagnosis to SRP, number of positive cores at biopsy, and original Gleason score. Results Overall, 184 patients with available biopsy and pathologic ISUP grading were identified. Of those, 17.4% (n = 32), 40.8% (n = 75), 19.6% (n = 36), and 22.2% (n = 41) harbored biopsy ISUP 1, ISUP 2, ISUP 3, and ISUP 4-5 grading, respectively. Pathologic ISUP 1, ISUP 2, ISUP 3, and ISUP 4-5 grading was recorded in 6.0% (n = 11), 40.8% (n = 75), 32.1% (n = 59), and 21.2% (n = 39), respectively. Median PSA before SRP was 5.5 ng/ml (interquartile range [IQR]: 3.1-8.1 ng/ml), median age at SRP was 65.1 years (IQR:60.7-69.4 years) and median time from original PCa diagnosis to SRP was 47 months (IQR: 27.3-85.2 months). Concordance of biopsy and pathologic ISUP was identified in 45.1% (n = 83). Conversely, any ISUP discordance, upgrading and downgrading of at least one ISUP group was identified in 54.9% (n = 101), 35.3% (n = 65), and 19.6% (n = 36). In logistic models, none of the preoperative characteristics was associated with upgrading or ISUP discordance (all p > 0.1). Conclusion Discordance between biopsy and pathologic ISUP grading is common at SRP. However, in 45% of SRP cases biopsy ISUP is capable to predict pathologic ISUP. Further studies are necessary to identify characteristics for ISUP upgrading at SRP.

Summary Background The majority of patients with metastatic castration-resistant prostate cancer (mCRPC) will have disease progression of a uniformly fatal disease. mCRPC is driven by both activated androgen receptors and elevated intratumoural androgens; however, the current standard of care is therapy that targets a single androgen signalling mechanism. We aimed to investigate the combination treatment using apalutamide plus abiraterone acetate, each of which suppresses the androgen signalling axis in a different way, versus standard care in mCRPC. Methods ACIS was a randomised, placebo-controlled, double-blind, phase 3 study done at 167 hospitals in 17 countries in the USA, Canada, Mexico, Europe, the Asia-Pacific region, Africa, and South America. We included chemotherapy-naive men (aged ≥18 years) with mCRPC who had not been previously treated with androgen biosynthesis signalling inhibitors and were receiving ongoing androgen deprivation therapy, with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and a Brief Pain Inventory-Short Form question 3 (ie, worst pain in the past 24 h) score of 3 or lower. Patients were randomly assigned (1:1) via a centralised interactive web response system with a permuted block randomisation scheme (block size 4) to oral apalutamide 240 mg once daily plus oral abiraterone acetate 1000 mg once daily and oral prednisone 5 mg twice daily (apalutamide plus abiraterone–prednisone group) or placebo plus abiraterone acetate and prednisone (abiraterone–prednisone group), in 28-day treatment cycles. Randomisation was stratified by presence or absence of visceral metastases, ECOG performance status, and geographical region. Patients, the investigators, study team, and the sponsor were masked to group assignments. An independent data-monitoring committee continually monitored data to ensure ongoing patient safety, and reviewed efficacy data. The primary endpoint was radiographic progression-free survival assessed in the intention-to-treat population. Safety was reported for all patients who received at least one dose of study drug. This study is completed and no longer recruiting and is registered with ClinicalTrials.gov , number NCT02257736 . Findings 982 men were enrolled and randomly assigned from Dec 10, 2014 to Aug 30, 2016 (492 to apalutamide plus abiraterone–prednisone; 490 to abiraterone–prednisone). At the primary analysis (median follow-up 25·7 months [IQR 23·0–28·9]), median radiographic progression-free survival was 22·6 months (95% CI 19·4–27·4) in the apalutamide plus abiraterone–prednisone group versus 16·6 months (13·9–19·3) in the abiraterone–prednisone group (hazard ratio [HR] 0·69, 95% CI 0·58–0·83; p Interpretation Despite the use of an active and established therapy as the comparator, apalutamide plus abiraterone–prednisone improved radiographic progression-free survival. Additional studies to identify subgroups of patients who might benefit the most from combination therapy are needed to further refine the treatment of mCRPC. Funding Janssen Research & Development.

We have compiled stratigraphic ranges of genera of calcareous nannofossils, calcispheres, planktonic foraminifers, larger benthic foraminifers, corals and rudists bivalves, and species of dasycladalean green algae. These taxa comprise the main planktonic and benthic carbonate producers of the Cretaceous, a period of exceptionally high sea level and palaeotemperatures that was characterized by unique assemblages of benthic carbonate producers and the significant rise in pelagic carbonate sedimentation. The autecology, physiological control on calcification, and carbonate-production potential of these groups is summarized. The observed diversity patterns are compared with proxy data of Cretaceous climate and seawater chemistry to elucidate the effect of environmental change on carbonate production and sedimentation. Two characteristic patterns are recognized. Diversity of calcareous nannofossils, calcispheres, planktonic foraminifers and corals trace the evolution of Cretaceous sea-level, while the diversity of dasycladalean algae, larger benthic foraminifers, corals and rudist bivalves show significant reductions at the level of oceanic anoxic events (OAEs). Benthic carbonate producers except for corals thus appear to have been more vulnerable to environmental change, and these general patterns appear to be unrelated to the autecology of the taxa investigated. The expansion of suitable habitats during episodes of high sea level and high temperatures appears to have been a more important control of diversity in calcareous nannofossils, planktonic foraminifers, and corals than changes in seawater chemistry. Aragonitic or aragonite-dominated benthic carbonate producers are most affected during extinction events related to OAEs, and there is a general trend of decreasing aragonite dominance throughout the Cretaceous. This is compensated by the extensive formation of calcitic hemipelagic chalk since the Cenomanian. The trend of decreasing aragonite dominance is independent of the level of biological control on calcification in the different taxa affected. The demise of aragonitic or aragonite-dominated carbonate producers at OAE1a (early Aptian) and OAE2 (Cenomanian–Turonian boundary interval) may be related to short episodes of reduced seawater carbonate-saturation caused by short-lived injections of CO2 from large igneous provinces that initiated OAEs. For OAE1a, this scenario also explains the retreat of carbonate platforms to low latitudes in the early Aptian, as sea-surface water typically has a higher carbonate saturation in warm, lower than in cooler, higher latitude waters. The gradual decrease of aragonite throughout the Cretaceous matches model simulations of seawater carbonate-saturation. An increase in the relative number of azooxanthellate coral genera following OAE1a and OAE2 suggests a disruption of photosymbiosis in the course of these global events due to high temperatures. However, the relative numbers of azooxanthellate genera continued to increase during the Late Cretaceous, when global temperatures declined. Due to the short residence time of major nutrients in seawater, these may have affected carbonate-producing ecosystems regionally. The recent patterns of benthic carbonate production being highest in oligotrophic environments cannot confidently be extrapolated to the Cretaceous. Our database records ranges of genera at the substage level. Higher-resolution stratigraphical studies of neritic carbonate sequences are required to understand what aspect of environmental change in the sequences are required to understand what aspect of environmental change in the sequence of events that unfolded in the context of OAEs caused the demise of benthic carbonate producers.

Contains fulltext : 291600.pdf (Publisher’s version ) (Open Access) BACKGROUND: Innovations in imaging and molecular characterisation and the evolution of new therapies have improved outcomes in advanced prostate cancer. Nonetheless, we continue to lack high-level evidence on a variety of clinical topics that greatly impact daily practice. To supplement evidence-based guidelines, the 2022 Advanced Prostate Cancer Consensus Conference (APCCC 2022) surveyed experts about key dilemmas in clinical management. OBJECTIVE: To present consensus voting results for select questions from APCCC 2022. DESIGN, SETTING, AND PARTICIPANTS: Before the conference, a panel of 117 international prostate cancer experts used a modified Delphi process to develop 198 multiple-choice consensus questions on (1) intermediate- and high-risk and locally advanced prostate cancer, (2) biochemical recurrence after local treatment, (3) side effects from hormonal therapies, (4) metastatic hormone-sensitive prostate cancer, (5) nonmetastatic castration-resistant prostate cancer, (6) metastatic castration-resistant prostate cancer, and (7) oligometastatic and oligoprogressive prostate cancer. Before the conference, these questions were administered via a web-based survey to the 105 physician panel members ("panellists") who directly engage in prostate cancer treatment decision-making. Herein, we present results for the 82 questions on topics 1-3. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Consensus was defined as ≥75% agreement, with strong consensus defined as ≥90% agreement. RESULTS AND LIMITATIONS: The voting results reveal varying degrees of consensus, as is discussed in this article and shown in the detailed results in the Supplementary material. The findings reflect the opinions of an international panel of experts and did not incorporate a formal literature review and meta-analysis. CONCLUSIONS: These voting results by a panel of international experts in advanced prostate cancer can help physicians and patients navigate controversial areas of clinical management for which high-level evidence is scant or conflicting. The findings can also help funders and policymakers prioritise areas for future research. Diagnostic and treatment decisions should always be individualised based on patient and cancer characteristics (disease extent and location, treatment history, comorbidities, and patient preferences) and should incorporate current and emerging clinical evidence, therapeutic guidelines, and logistic and economic factors. Enrolment in clinical trials is always strongly encouraged. Importantly, APCCC 2022 once again identified important gaps (areas of nonconsensus) that merit evaluation in specifically designed trials. PATIENT SUMMARY: The Advanced Prostate Cancer Consensus Conference (APCCC) provides a forum to discuss and debate current diagnostic and treatment options for patients with advanced prostate cancer. The conference aims to share the knowledge of international experts in prostate cancer with health care providers and patients worldwide. At each APCCC, a panel of physician experts vote in response to multiple-choice questions about their clinical opinions and approaches to managing advanced prostate cancer. This report presents voting results for the subset of questions pertaining to intermediate- and high-risk and locally advanced prostate cancer, biochemical relapse after definitive treatment, advanced (next-generation) imaging, and management of side effects caused by hormonal therapies. The results provide a practical guide to help clinicians and patients discuss treatment options as part of shared multidisciplinary decision-making. The findings may be especially useful when there is little or no high-level evidence to guide treatment decisions.

OBJECTIVES To reduce the risk of symptomatic lymphocele (SLC), we present a technique using peritoneal fenestration that allows lymphatic fluid to drain into the abdomen, as SLC formation after open retropubic radical prostatectomy (ORP) with pelvic lymph node dissection (PLND) is a common adverse event. PATIENTS AND METHODS We identified 1513 patients who underwent ORP with PLND between July 2018 and November 2019. Of those, 307 patients (20.3%) received peritoneal fenestration and 1206 (79.7%) no fenestration. The rate of LCs and the necessity for intervention were analysed by uni- and multivariable logistic regression (MLR) models. A propensity score matching was performed, as well. RESULTS The median (interquartile range [IQR]) age was 65 (60-70) years. A median (IQR) of 16 (10-22) lymph nodes were dissected, 22 vs 14 lymph nodes in the fenestration vs non-fenestration group (P

Prostate health index (PHI) and, more recently, Proclarix have been proposed as serum biomarkers for prostate cancer (PCa). In this study, we aimed to evaluate Proclarix and PHI for predicting clinically significant prostate cancer (csPCa).Proclarix and PHI were measured using samples of 344 men from two different centers. All patients underwent prostate biopsy, and among those, 188 men with PCa on biopsy had an additional radical prostatectomy (RP). All men had a prostate-specific antigen (PSA) between 2 and 10 ng/ml. Evaluation of area under the curve (AUC) and performance at predefined cut-offs of Proclarix and PHI risk scores as well as the linear combination thereof was performed to predict csPCa. PSA density was used as an independent comparator.The cohort median age and PSA were 65 (interquartile range [IQR]: 60-71) and 5.6 (IQR: 4.3-7.2) ng/ml, respectively. CsPCa was diagnosed in 161 (47%) men based on the RP specimen. ROC analysis showed that Proclarix and PHI accurately predicted csPCa with no significant difference (AUC of 0.79 and 0.76, p = 0.378) but significantly better when compared to PSA density (AUC of 0.66, p 0.001). When using specific cut-offs, Proclarix (cut-off 10) revealed higher specificity and positive predictive value than PHI (cut-off 27) at similar sensitivities. The combination of Proclarix and PHI provided a significant increase in the AUC (p ≤ 0.007) compared to the individual tests alone and the highest clinical benefit was achieved.Results of this study show that both Proclarix and PHI accurately detect the presence of csPCa. The model combining Proclarix and PHI revealed the synergistic effect and improved the diagnostic performance of the individual tests.

Two recent randomized controlled trials (RCTs) reported overall survival benefit of triplet therapy (androgen receptor axis-targeted therapy agent [ARAT], docetaxel, and androgen deprivation therapy [ADT]) over that of doublet therapy (docetaxel and ADT) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Ranking of therapy options and comparisons between triplet therapy and doublet ARAT and ADT therapy are scarce.To rank therapy options (triplet vs doublet [docetaxel and ADT] vs doublet [ARAT and ADT]) and address them within formal network meta-analyses (NMAs); subsequently, NMAs were refitted following stratification according to (1) low- and high-volume tumor burden and (2) doublet versus triplet therapy.A systematic literature review (PubMed, MEDLINE, Embase, Web of Science, Scopus, and Cochrane database) of RCT trials that investigated the overall survival efficacy of systemic treatment in the setting of mHSPC was conducted. The study search and inclusion criteria were in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.Ten RCTs (n = 9702) were identified. The NMA focusing on the overall cohort of mHSPC demonstrated that triplet therapies (darolutamide, docetaxel, and ADT, and abiraterone, docetaxel, and ADT) were ranked first and second (hazard ratio [HR]: 0.54, 95% confidence interval [CI]: 0.44-0.66; HR: 0.60; 95% CI: 0.46-0.78), followed by doublet therapy (ARAT and ADT) and lastly docetaxel and ADT. Owing to missing data within one RCT, the NMA for low- and high-volume mHSPC focused on nine trials. In high-volume disease, triplet therapy (abiraterone, docetaxel, and ADT) was ranked first (HR: 0.52, 95% CI: 0.38-0.71).Triplet therapy, consisting of an ARAT, docetaxel, and ADT, ranked first in systematic treatment in mHSPC. Moreover, triplet therapy might result in more pronounced overall survival benefit than doublet ARAT and ADT therapy in high-volume mHSPC.We compared different systemic therapy options for metastatic hormone-sensitive prostate cancer and concluded that triplet therapy, consisting of androgen receptor axis-targeted therapy agent, docetaxel, and androgen deprivation therapy, seems to be most beneficial for overall survival. Back to top.

Background Shortening the resuscitation-free interval in cardiac arrest increases the survival rate. Smartphone-based systems can locate and alert nearby rescuers. Objectives Implementation of a first responder system, technical development and adaption to regional structures. Materials and methods The system "Region der Lebensretter" was successfully established in July 2018 in Freiburg. The need of optimization was evaluated every half year and realized according to the PDCA (plan-do-check-act) cycle. The necessary functions were specified (plan), programmed, tested and released (do). Afterwards the changes were evaluated (check) and, if necessary, further optimizations were implemented (act). Results The number of registered rescuers increased from 276 (2nd half year 2018) to 794 (1st half year 2020). The rate of alarm acceptance increased from 30% (2nd half year 2018) to 49% (1st half year 2020). The following features were designed and released: dynamic adjustment of the alarm radius (DAA), critical alert function, connection to automated external defibrillator (AED) database, digital rescuer identification (ID), feedback button "arrived on scene", choice of means of transport for algorithm optimization. The number of existing AEDs increased from 190 to 270. Conclusion The resuscitation-free interval can be shortened by smartphone-based alerting systems. For successful operation, the total number of rescuers and the technical realization is crucial. Further studies are necessary to investigate whether the survival rate of out-of-hospital cardiac arrest can be increased. It appears extremely appropriate to adapt these systems to databases of quality management or research registers.

Background The prognostic value of circulating tumor cells (CTCs) in patients with hormone-naive oligometastatic prostate cancer (HNoMPC) undergoing cytoreductive radical prostatectomy (CRP) is unknown. Objective To determine the pre- and postoperative prognostic value of CTC enumeration in patients undergoing CRP. Design, setting, and participants Thirty-three patients with HNoMPC from the prospective, single-arm ProMPT trial who underwent CRP between 2014 and 2015 at the Martini-Klinik were evaluated. Follow-up visits for all patients were conducted every 6 mo up to 36 mo after CRP and included serial detection of CTCs in 7.5 ml blood samples using the CellSearch system. Intervention CRP. Outcome measurements and statistical analysis CTC enumerations before and after CRP, and their prognostic value on metastatic castration-resistant prostate cancer–free survival and overall survival (OS) were analyzed using Kaplan-Meier plots and univariable Cox-regression analysis. Results and limitations Sixteen patients (48.5%) had positive CTCs prior to CRP. A CTC count of ≥2 before or 6 mo after CRP was a prognostic factor for worse oncologic outcome. Compared with other biomarkers (prostate-specific antigen, lactate dehydrogenase, and bone-specific alkaline phosphatase), the prognostic value of CTCs was highest using Harrell’s C for OS (0.69), while the highest C-index could be achieved for a combination of conventional markers and CTC count (0.74). After progression to metastatic castration-resistant prostate cancer, CTC enumeration of ≥5 was prognostic for OS. The main limitation is the small sample size. Conclusions CTC enumeration contributes to prognostic information, which might help select HNoMPC patients who might benefit most from CRP. Patient summary In this report, we looked at the value of circulating tumor cell (CTC) determination in patients undergoing radical prostatectomy for oligometastatic prostate cancer. We could show that the number of CTCs was a prognostic factor at all analyzed time points and was more closely associated with prognosis than other biomarkers commonly used in daily clinical practice.