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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.

Purpose: The PARP inhibitor rucaparib is approved in the United States for patients with metastatic castration-resistant prostate cancer (mCRPC) and a deleterious germline and/or somatic BRCA1 or BRCA2 (BRCA) alteration. While sequencing of tumor tissue is considered the standard for identifying patients with BRCA alterations (BRCA+), plasma profiling may provide a minimally invasive option to select patients for rucaparib treatment. Here, we report clinical efficacy in patients with BRCA+ mCRPC identified through central plasma, central tissue, or local genomic testing and enrolled in TRITON2. Patients and Methods: Patients had progressed after next-generation androgen receptor–directed and taxane-based therapies for mCRPC and had BRCA alterations identified by central sequencing of plasma and/or tissue samples or local genomic testing. Concordance of plasma/tissue BRCA status and objective response rate and prostate-specific antigen (PSA) response rates were summarized. Results: TRITON2 enrolled 115 patients with BRCA+ identified by central plasma (n = 34), central tissue (n = 37), or local (n = 44) testing. Plasma/tissue concordance was determined in 38 patients with paired samples and was 47% in 19 patients with a somatic BRCA alteration. No statistically significant differences were observed between objective and PSA response rates to rucaparib across the 3 assay groups. Patients unable to provide tissue samples and tested solely by plasma assay responded at rates no different from patients identified as BRCA+ by tissue testing. Conclusions: Plasma, tissue, and local testing of mCRPC patients can be used to identify men with BRCA+ mCRPC who can benefit from treatment with the PARP inhibitor rucaparib.

(1) Background: Prostate cancer (PCa) is the most frequently diagnosed cancer in men. Wide application of prostate specific antigen test has historically led to over-treatment, starting from excessive biopsies. Risk calculators based on molecular and clinical variables can be of value to determine the risk of PCa and as such, reduce unnecessary and invasive biopsies. Urinary molecular studies have been mostly focusing on sampling after initial intervention (digital rectal examination and/or prostate massage). (2) Methods: Building on previous proteomics studies, in this manuscript, we aimed at developing a biomarker model for PCa detection based on urine sampling without prior intervention. Capillary electrophoresis coupled to mass spectrometry was applied to acquire proteomics profiles from 970 patients from two different clinical centers. (3) Results: A case-control comparison was performed in a training set of 413 patients and 181 significant peptides were subsequently combined by a support vector machine algorithm. Independent validation was initially performed in 272 negative for PCa and 138 biopsy-confirmed PCa, resulting in an AUC of 0.81, outperforming current standards, while a second validation phase included 147 PCa patients. (4) Conclusions: This multi-dimensional biomarker model holds promise to improve the current diagnosis of PCa, by guiding invasive biopsies.

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.

Purpose: We performed an exploratory analysis of prostate cancer-related pain and fatigue on health-related quality of life in patients with metastatic castration-sensitive prostate cancer receiving apalutamide (240 mg/day) or placebo, with continuous androgen deprivation therapy (ADT), in the phase 3, randomized, double-blind, placebo controlled TITAN trial (NCT02489318). Materials and Methods: Patient-reported outcomes for pain and fatigue were evaluated using the Brief Pain Inventory-Short Form and Brief Fatigue Inventory. Time to deterioration (TTD) was estimated by Kaplan-Meier method; hazard ratios and 95% confidence intervals were calculated using Cox proportional hazards model. General estimating equations for logistic regression estimated treatment-related differences in the likelihood of worsening pain or fatigue. Results: Compliance for completing the Brief Pain Inventory-Short Form and Brief Fatigue Inventory was high (96% to 97%) in the first year. Median followup times were similar between treatments (19 to 22 months). Median pain TTD was longer with apalutamide than placebo for pain at its least in the last 24 hours (28.7 vs 21.8 months, respectively; p=0.0146), pain interfered with mood (not estimable vs 22.4 months; p=0.0017), pain interfered with walking ability (28.7 vs 20.2 months; p=0.0027), pain interfered with relations (not estimable vs 23.0 months; p=0.0139) and pain interfered with sleep (28.7 vs 20.9 months; p=0.0167). Likelihood for fatigue and worsening fatigue were similar between groups. Conclusions: Patients with metastatic castration-sensitive prostate cancer receiving apalutamide plus ADT vs placebo plus ADT reported consistently favorable TTD of pain. No difference for change in fatigue was observed with apalutamide vs placebo. Janssen Research Development; Janssen Global Services, LLC The authors would like to thank the patients who participated in this study and their families, as well as the investigators, study coordinators, study teams and nurses. The TITAN study was funded by Janssen Research & Development. Editorial assistance was provided by Patricia McChesney, PhD, of Parexel, with funding from Janssen Global Services, LLC.

Bone metastatic (BM) prostate cancer (PCa) belongs to the most lethal form of PCa, and therapeutic options are limited. Molecular profiling of metastases contributes to the understanding of mechanisms defining the bone metastatic niche. Our aim was to explore the transcriptional profile of PCa BM and to identify genes that drive progression. Paraffin-embedded tissues of 28 primary PCa and 30 BM were submitted to RNA extraction and analyzed by RNA sequencing using the Nanostring nCounter gene expression platform. A total of 770 cancer-related genes were measured using the Nanostring™ PanCancer progression panel. Gene Ontology (GO), KEGG, Reactome, STRING, Metascape, PANTHER, and Pubmed were used for data integration and gene annotation. We identified 116 differentially expressed genes (DEG) in BM compared to primaries. The most significant DEGs include CD36, FOXC2, CHAD, SPP1, MMPs, IBSP, and PTX3, which are more highly expressed in BM, and ACTG2, MYH11, CNN1, FGF2, SPOCK3, and CHRDL1, which have a lower expression. DEGs functionally relate to extracellular matrix (ECM) proteoglycans, ECM-receptors, cell-substrate adhesion, cell motility as well as receptor tyrosine kinase signaling and response to growth factors. Data integration and gene annotation of 116 DEGs were used to build a gene platform which we termed “Manually Annotated and Curated Nanostring-data Platform”. In summary, our results highlight the significance of certain genes in PCa BM to which essential pro-metastatic functions could be ascribed. Data from this study provide a comprehensive platform of genes that are related to PCa BM and provide evidence for further investigations.

Androgen deprivation therapy (ADT) plays a crucial role in treatment of advanced prostate cancer (PCa). The additional application of new drugs results in prolonged overall survival, both in the hormone sensitive and castration resistant state. Consequently, the long-term use of ADT moves potential side effects into the focus of interest. In this context special consideration must be given to cardiovascular events.Review of current evidence on potential differences regarding the cardiovascular risk profile of gonadotropin-releasing hormone (GnRH) agonists compared to GnRH antagonists.Narrative review based on an expert consensus supported by a literature search in PubMed (MEDLINE) and the abstract databases of ASCO and ESMO was conducted for publications published between January 2015 and January 2021. Significant meta-analyses, randomized controlled trials (RCTs) and real-world data (RWD) revealing relevant results for clinical practice were taken into account. Selection of studies was performed based on the clinical relevance for everyday practice.The search yielded three relevant meta-analyses, two prospective RCTs as well as three RWD publications that are of importance for clinical practice. Overall, a decreased incidence of cardiovascular events was reported for GnRH antagonists compared to GnRH agonists. Only one RWD publication described comparable rates of complications for both drug classes.GnRH antagonists have a lower risk of treatment related cardiovascular events compared to GnRH agonists. Risks should be minimized by taking known cardiovascular risk factors into account before initiating therapy.HINTERGRUND: Die Androgendeprivationstherapie (ADT) spielt in der Behandlung des fortgeschrittenen Prostatakarzinoms eine zentrale Rolle. Der zusätzliche Einsatz neuer Medikamente führt sowohl in der hormonsensitiven Situation als auch der Kastrationsresistenz zu einem verlängerten Gesamtüberleben. Ein dadurch bedingter, langjähriger Einsatz der ADT rückt mögliche Komplikationen in den Vordergrund. Dies gilt insbesondere für kardiovaskuläre Ereignisse.Das Ziel der Arbeit war die Prüfung der aktuellen Datenlage zu möglichen Unterschieden des kardiovaskulären Risikoprofils von Gonadotropin-Releasing-Hormon- (GnRH-)Agonisten und GnRH-Antagonisten.Narrativer Bericht basierend auf einem Expertenkonsens, unterstützt von einer Literaturrecherche in PubMed (MEDLINE) und den Abstract Datenbanken von ASCO und ESMO zwischen Januar 2015 und 2021. Berücksichtigt wurden für den Behandlungsalltag bedeutsame Metaanalysen, vergleichenden randomisierte klinische Studien (RCT) und „real world data“ (RWD). Die Studienauswahl wurde hinsichtlich der klinischen Relevanz für den Praxisalltag vorgenommen.Es wurden drei für die Thematik relevante Metaanalysen, zwei prospektive RCT sowie drei RWD-Publikationen identifiziert. Dabei zeigt sich übereinstimmend ein Vorteil für GnRH-Antagonisten mit einer geringeren Inzidenz kardiovaskulärer Ereignisse im Vergleich zu GnRH-Agonisten. Lediglich eine RWD-Untersuchung berichtet über eine vergleichbare Komplikationsrate mit beiden Substanzgruppen.Die GnRH-Antagonisten weisen ein geringeres Risiko für das Auftreten kardiovaskulärer Ereignisse als GnRH-Agonisten auf. Eine Risikominimierung sollte durch Berücksichtigung bekannter kardiovaskulärer Risikofaktoren vor Therapieeinleitung vorgenommen werden.

BACKGROUND: Plasma tumor DNA fraction is prognostic in metastatic cancers. This could improve risk stratification before commencing a new treatment. We hypothesized that a second sample collected after one cycle of treatment could refine outcome prediction of patients identified as poor prognosis based on plasma DNA collected pre-treatment. PATIENTS AND METHODS: Plasma DNA [128 pre-treatment, 134 cycle 2 day 1 (C2D1), and 49 progression] from 151 chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC) patients in a phase II study of abiraterone acetate (NCT01867710) were subjected to custom targeted next-generation sequencing covering exons of these genes: TP53, AR, RB1, PTEN, PIK3CA, BRCA1, BRCA2, ATM, CDK12, CHEK2, FANCA HDAC2 and PALB2. We also captured 1500 pan-genome regions enriched for single nucleotide polymorphisms to allow detection of tumor DNA using the rolling B-allele method. We tested associations with overall survival (OS) and progression-free survival (PFS). RESULTS: Plasma tumor DNA detection was associated with shorter OS [hazard ratio (HR): 2.89, 95% confidence intervals (CI): 1.77-4.73, P ≤ 0.0001] and PFS (HR: 2.05; 95% CI: 1.36-3.11, P < 0.001). Using a multivariable model including plasma tumor DNA, patients who had a TP53, RB1 or PTEN gene alteration pre-treatment and at C2D1 had a significantly shorter OS than patients with no alteration at either time point (TP53: HR 7.13, 95% CI 2.37-21.47, P < 0.001; RB1: HR 6.24, 95% CI 1.97-19.73, P = 0.002; PTEN: HR 11.9, 95% CI 3.6-39.34, P < 0.001). Patients who were positive pre-treatment and converted to undetectable had no evidence of a difference in survival compared with those who were undetectable pre-treatment (P = 0.48, P = 0.43, P = 0.5, respectively). Progression samples harbored AR gain in all patients who had gain pre-treatment (9/49) and de novo AR somatic point mutations were detected in 8/49 patients. CONCLUSIONS: Plasma gene testing after one cycle treatment refines prognostication and could provide an early indication of treatment benefit.

CONTEXT: Several recent randomised trials have evaluated the role of combination systemic treatment using androgen deprivation therapy (ADT) plus chemotherapy or an androgen receptor signaling inhibitor (ARSI) in patients with high-risk and/or unfavourable nonmetastatic prostate cancer (nmPC). OBJECTIVE: To assess the outcomes associated with adding combination systemic treatment to primary definitive local therapy in patients with high-risk and/or unfavourable nmPC. EVIDENCE ACQUISITION: We queried the PubMed, Web of Science, and Scopus databases and conference abstracts to identify prospective randomised trials examining the value of adding chemotherapy or an ARSI to ADT and primary local therapy with curative intent for nmPC. The primary endpoints were overall survival (OS), cancer-specific survival (CSS), metastasis-free survival (MFS), and failure-free survival (FFS). Secondary endpoints included adverse events (AEs) and pathologic outcomes. EVIDENCE SYNTHESIS: We identified 15 randomised studies, of which nine evaluated chemohormonal and six investigated ARSI-based treatment strategies. In both radical prostatectomy (RP) and radiation therapy (RT) settings, addition of docetaxel to ADT was associated with significantly better CSS (pooled hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.49-0.95; p = 0.025), MFS (pooled HR 0.82, 95% CI 0.71-0.95; p = 0.008), and FFS (pooled HR 0.70, 95% CI 0.62-0.79; p < 0.001); the difference did not meet the conventional level of statistical significance for OS (pooled HR 0.86, 95% CI 0.73-1.01; p = 0.072). For patients treated with RT alone, docetaxel-based combination treatment did not meet the significance threshold set for OS (p = 0.3), CSS (p = 0.072), or MFS (p = 0.079), but the difference for FFS was statistically significant (pooled HR 0.72, 95% CI 0.63-0.84; p < 0.001). On network meta-analyses including RT studies, ARSI + ADT outperformed docetaxel + ADT for survival endpoints and had a more favourable AE profile. CONCLUSIONS: Intensification of systemic therapy with docetaxel or an ARSI in addition to ADT improves oncologic endpoints in high-risk and/or unfavourable nmPC treated with local definitive therapy. The highest efficacy was achieved with ARSI + ADT, specifically in patients treated with RT. PATIENT SUMMARY: Our findings highlight that selected patients with high-risk nonmetastatic prostate cancer benefit from intensification of systemic therapy beyond hormonal treatment. ispartof: EUROPEAN UROLOGY vol:82 issue:1 pages:82-96 ispartof: location:Switzerland status: published

Das metastasierte kastrationsresistente Prostatakarzinom (mCRPC) galt lange Zeit als Behandlungsresistent. Heute stehen uns in Deutschland mit Abirateron, Enzalutamid, Docetaxel, Cabazitaxel und Radium-223 funf Substanzen zur Verfugung, die alle in Phase-III-Studien zu einer signifikanten Zunahme der Uberlebenszeit fuhrten. Es werden die aktuellen Behandlungsmoglichkeiten beim mCRPC dargestellt. Zulassungsrelevante Studien mit erganzenden Informationen aus Medline und Abstracts internationaler Kongresse (ASCO; ASCO-GU [American Society of Clinical Oncology-Genitourinary Cancers Symposium], ESMO [Europaischen Gesellschaft fur Medizinische Onkologie]) werden zusammengefasst. Die Androgenrezeptor- (AR)-gerichteten Medikamente Abirateron und Enzalutamid fuhren sowohl vor als auch nach Docetaxel zu einer signifikanten Verlangerung des Gesamtuberlebens. Nach Docetaxel kann zudem Cabazitaxel eingesetzt werden, das aufgrund seiner geringen Affinitat zum P‑Glykoprotein auch bei Patienten mit Docetaxel-Resistenz wirksam ist. In der dritten Behandlungslinie steht Mannern mit einer rein ossaren symptomatischen Erkrankung der Alpha-Strahler Radium-223 zur Verfugung. Liegt eine Kastrationsresistenz mit einer kurzen PSA-Verdopplungszeit (prostataspezifisches Antigen) aber ohne bildmorphologischen Nachweis von Metastasen vor, verlangern Apalutamid, Darolutamid und Enzalutamid signifikant die Zeit bis zum Auftreten von Metastasen. Die PSMA-Ligandentherapie (prostataspezifisches Membranantigen) und neue zielgerichtete Medikamente wie PARP-Inhibitoren (Poly[-ADP-Ribose-]Polymerase) stellen weitere wichtige neue Behandlungsoptionen dar. Kombinationsbehandlungen mit Immuntherapien werden in klinischen Studien uberpruft. Umfassende molekulare Analysen von Tumorgewebe, zirkulierender Tumorzellen und -DNA legen nahe, dass auch beim Prostatakarzinom kunftig die personalisierte Medizin eine immer grosere Rolle spielen wird.

INTRODUCTION AND OBJECTIVE:The final analysis of TITAN confirmed improvement in long-term outcomes in metastatic castration-sensitive prostate cancer (mCSPC) with apalutamide (APA) + androgen depri...

Zusammenfassung Hintergrund Die Androgendeprivationstherapie (ADT) ist fester Therapiebestandteil des fortgeschrittenen oder metastasierten Prostatakarzinoms (PCa). Ziel der vorliegenden Versorgungsforschungsstudie war der Vergleich von Verordnungsmustern, Hospitalisierungsraten und Krankenhauskosten beim initialen Einsatz verschiedener GnRH-Agonisten und -Antagonisten (GnRHa). Material und Methoden Anonymisierte GKV-Daten von > 70 Krankenkassen aus 2010 bis 2015 (n = 4 205 227) wurden analysiert (1 Jahr Vorbeobachtung, 1 Indexquartal mit initialer GnRHa-Verordnung, ≥ 2 Jahre Follow-Up (FU)). Ergebnisse Die Studienpopulation umfasste 2382 PCa-Patienten im Alter von durchschnittlich 75 Jahren. Leuprorelin (Leu) wurde mit 56,6 % am häufigsten verordnet. Bei erstmaliger GnRHa-Anwendung hatten 70 % aller Patienten keine Lymph- oder Fernmetastasen. Nach der initialen Verordnung wurden bei 11,2 % die GnRHa abgesetzt, bei 17,6 % nach durchschnittlich 457 Tagen (Median: 399 Tage) umgestellt, in der Hybrid (Hyb)-Gruppe durchschnittlich 100 Tage schneller als bei den Agonisten (p = 0,016). Die Prävalenzrangfolge der häufigsten Komorbiditäten war über die Zeit gleichbleibend: Hypertonie, Hyperlipidämie, kardiovaskuläre Erkrankungen (CVD) und Diabetes. Die Hypertonieprävalenz zeigte einen signifikant höheren Anstieg unter Agonisten (16,4 %; vs. Antagonist 6,9 % p = 0,022; vs. Hybride 11,6 % p = 0,006). Bei der CVD gab es hinsichtlich der relativen Wachstumsraten zwischen den 3 zusammengefassten Therapieklassen keine signifikanten Unterschiede. Insgesamt waren 23,9 % aller Patienten nach 3 Jahren FU verstorben. Die Mortalitätsrate war am niedrigsten für Triptorelin (Trp, 22,1 %) und am höchsten für Goserelin (Gos, 29,4 %, n.s.). Im Indexquartal hatten 26,4 % der Patienten mind. einen Krankenhausaufenthalt [min; max: Trp 22,4 %; Gos 30,3 %] mit einer mittleren Krankenhausverweildauer/Patient von 3 Tagen [Trp 2,4; Gos 4,5]. Die jährliche Hospitalisierungsrate lag bei 36,2 – 40,7 %, die mittlere Krankenhausverweildauer im gesamten FU zwischen 17,6 (Trp) und 20,8 (Hyb) Tagen. Die Krankenhauskosten im Indexquartal betrugen ca. 1200 EUR [Trp 988; Gos 1803] und pro FU-Jahr ca. 3000 EUR. In der Trp-Kohorte lagen die Gesamtkosten (Indexquartal + 3 Jahre) mehr als 1000 EUR unter dem Durchschnitt von 9476 EUR [Trp 8116; Leu 9779; n.s.]. Schlussfolgerung Diese GKV-Versorgungsforschungsstudie beschreibt die Anwendung von GnRHa zur initialen Therapie beim fortgeschrittenen PCa in Deutschland und zeigt substanzabhängige Unterschiede in den Verordnungsmustern, Hospitalisierungsraten und Krankenhauskosten.

Summary High-grade prostatic intraepithelial neoplasia (HGPIN) is a facultative precursor lesion of prostate cancer (PCa). Multifocal HGPIN in needle biopsies in the absence of PCa indicates a higher risk of cancer detection in subsequent biopsies. Therefore, a reliable diagnosis of HGPIN is of high clinical relevance guiding the management of patients with cancer-negative biopsies. Detection of HGPIN is merely based on morphological features while biomarkers aiding in the diagnosis of HGPIN and its differentiation from benign glands and other glandular lesions are lacking yet. Here, we investigated the expression of cyclin-dependent kinase 19 (CDK19) by immunohistochemistry on prostate needle biopsies of 140 patients who were all diagnosed with PCa using whole-tissue sections and compared CDK19 levels between HGPIN, PCa, and adjacent benign glands. In addition, CDK19 was compared with AMACR expression in a subset of intraductal carcinomas (IDCs) on radical prostatectomy (RP) specimens. HGPIN was present in 65.7% of biopsies and in 88% associated to adjacent PCa. CDK19 overexpression defined as moderate to high CDK19 expression visible at low magnification was found in 82.6% of HGPIN. In contrast, 89.3% of benign glands were CDK19-negative or demonstrated only low CDK19 expression highlighting a high sensitivity and specificity to accurately detect HGPIN based on CDK19 expression levels. CDK19 was overexpressed in 59% of PCa but did not correlate significantly with the expression of intermingled HGPIN. On RP, CDK19 and AMACR showed no significant difference in the detection rate of IDC. In summary, assessment of CDK19 facilitates accurate and simplified diagnosis of HGPIN with high sensitivity and specificity and aides the differentiation to non-neoplastic glandular alterations. Considering the high clinical significance of diagnosis HGPIN that still has a limited reproducibility among pathologists, we suggest CDK19 as diagnostic biomarker for HGPIN.