Axel Stuart Merseburger’s research while affiliated with Universitätsklinikum Schleswig - Holstein and other places

Zusammenfassung Die Behandlung älterer Patienten erfordert eine besondere Aufmerksamkeit für Arzneimittelinteraktionen, da mit einer Zunahme der altersbedingten Morbidität eine Polypharmazie immer relevanter wird. Insbesondere bei Medikamenten mit einer geringen therapeutischen Breite können Arzneimittelinteraktionen klinische Konsequenzen haben, die eine Anpassung der Dosis oder das Beenden oder Wechseln der Begleitmedikation erfordern. Oft sind diese Interaktionen auf eine pharmakokinetische Veränderung des Arzneimittelabbaus über das Cytochrom-P450(CYP)-Enzymsystem zurückzuführen, vor allem über CYP3A4. Diese Enzymisoform ist an dem Metabolismus von etwa der Hälfte der therapeutisch verwendeten Arzneimittel beteiligt, sodass sich auch viele CYP3A4-Substrate unter den eingesetzten Medikamenten bei Prostatakrebspatienten befinden. Unter den starken CYP3A4-Induktoren Apalutamid und Enzalutamid sind in diesem Zusammenhang – im Gegensatz zu Darolutamid – in vielen Fällen deutlich erniedrigte Plasmakonzentrationen bei den gleichzeitig verabreichten Arzneimitteln zu erwarten. Bei Abirateron handelt es sich hingegen um einen moderaten CYP2D6-Inhibitor. Da über dieses Isoenzym deutlich weniger Wirkstoffe biotransformiert werden, ist das Interaktionsspektrum anders zu bewerten. Um im Vorfeld einer Pharmakotherapie das Ausmaß einer Wechselwirkung besser abschätzen zu können, ist es hilfreich, die Abbauwege der einzelnen Wirkstoffe besser zu verstehen, um im Zweifel rechtzeitig das Therapiemonitoring intensivieren, Dosisveränderungen und Wechsel einer Pharmakotherapie vornehmen zu können.

Zusammenfassung Die „Penisfraktur“ stellt einen seltenen urologischen Notfall dar. Laut Literatur ist die klinische Diagnose bei anamnestisch typischem Unfallhergang und klinischem Bild ausreichend. An bildgebender Diagnostik eignen sich Sonografie, Kavernosografie oder MRT. Die Sonografie ist schnell anzuwenden, günstig und flächendeckender verfügbar, als eine MRT-Untersuchung, die jedoch eine höhere Auflösung hat. Die Therapieempfehlung der aktuellen Literatur ist die schnellstmögliche operative Versorgung. In dieser retrospektiven monozentrischen Kohortenstudie wurden alle Patienten ausgewertet, die sich mit Verdacht auf eine Penisfraktur zwischen dem 01.01.2018 und dem 30.09.2024 in der Abteilung für Urologie am Campus Lübeck des Universitätsklinikums Schleswig-Holstein vorgestellt haben. Insgesamt wurden 16 Patienten ausgewertet. 8 Patienten stellten sich noch am gleichen Tag des Traumas vor. MRT-morphologisch konnte bei 13 von 16 Patienten eine Ruptur der Corpora cavernosa bestätigt werden. Bei 3 Patienten bestätigte sich der Verdacht nicht. Bei 11 Patienten korrelierten sonografischer und MRT-morphologischer Befund, bei 2 Patienten war die Sonografie falsch-negativ und bei 2 falsch-positiv. Bei einem Patienten waren sowohl Sonografie als auch MRT nicht eindeutig. Klinisch zeigte sich bei ca. 23% der nachgewiesenen Frakturen eine Deviation des Penis, bei 92% zeigte sich ein Hämatom und etwa 23% der Patienten mit einer Ruptur berichteten ein „knallendes Geräusch“ gehört zu haben. Die Diagnosestellung ist sowohl klinisch, sonografisch als auch MRT-morphologisch möglich. Zur ersten Einschätzung, ob eine Kontinuitätsunterbrechung der Tunica albuginea vorliegt, ist die Sonografie geeignet. Beim geübten Anwender kann diese auch ausreichen. Bei seltenem Krankheitsbild mit anwenderabhängiger individueller sonografischer Expertise stellt das MRT eine sensitivere Bildgebung dar, die Differenzialdiagnosen ausschließen und Defekte lokalisieren kann. Zusammenfassend ist ein MRT laut Literatur für die Therapieplanung hilfreich, aber nicht notwendig zur operativen Versorgung. Mit einer Korrelation von Sonografie und MRT in 69% der von uns untersuchten Fälle, stellt die Sonografie ein ausreichendes Diagnostikum zur Indikationsstellung einer Operation dar. Basierend auf unseren Daten bewerten wir eine positive Sonografie als ausreichend zur Einleitung der weiteren Therapie. Bei negativer Sonografie und klinisch bestehendem Verdacht würden wir jedoch, basierend auf unserer Auswertung, die MRT-Durchführung empfehlen.

Objectives A “penile fracture” is a rare urological emergency. According to literature, the clinical diagnosis is sufficient. Imaging diagnostics such as sonography or MRI are suitable. Sonography is quick to use, inexpensive and more widely available than an MRI examination, which, however, has a higher resolution. The treatment recommendation in current literature is surgical treatment as quickly as possible. Methods This study is a retrospective and monocentric kohort study. Included were all patients consulting medical advice with a suspected penile fracture at the University Hospital of Luebeck between 01.01.2018 and 31.12.2023. Results 15 patients were analysed. 7 patients presented on the same day as the trauma, 3 patients on the following day. Clinically, 20% of fractures showed a deviation of the penis, 80% showed a haematoma and 20% of patients with a rupture reported having heard a “cracking sound”. MRI morphology confirmed a rupture of the corpora cavernosa in 13 of 15 patients. The suspicion was not confirmed in 2 patients. Sonographic and MRI morphological findings correlated in 11 patients, sonography was false negative in two patients and false positive in one. In one patient, both sonography and MRI were inconclusive. Conclusions The diagnosis can be made clinically, sonographically and with using MRI. Sonography is suitable for the initial assessment of whether there is an interruption in the continuity of the tuniga albuginea. For experienced users, this may also be sufficient to localize the defect. However, in rare cases with user-dependent individual sonographic expertise, MRI is a more sensitive imaging technique. In summary, according to the literature, an MRI is helpful for treatment planning, but not necessary for surgical treatment, especially if the approach is not only localized. With a correlation of sonography and MRI in 73% of the cases we examined, sonography is a sufficient diagnostic tool for determining the indication for surgery. Based on our data, we consider a positive sonography to be sufficient for the initiation of further therapy. However, based on our evaluation, we would recommend MRI in the case of a negative ultrasound and clinically existing suspicion. Conflicts of Interest None.

TPS274 Background: Prostate cancer remains the most common malignancy among men and the fifth leading cause of cancer-related mortality globally. Over the past 15 years, advances in imaging techniques and therapeutic options have significantly transformed the management of recurrent, advanced, and metastatic prostate cancer. However, treatment efficacy and toxicity are highly influenced by prior therapy sequences, highlighting the need for a deeper understanding of the optimal treatment sequence. The prospective real-world evidence registry, PROCARE, addresses this gap by documenting treatment patterns, imaging exams, oncologic outcomes, and safety profiles in routine clinical practice. Methods: This study focuses on four distinct patient cohorts: biochemical recurrence after local treatment with curative intent (e.g. radical prostatectomy, radiotherapy of the prostate or combination thereof), non-metastatic castration-resistant prostate cancer (nmCRPC), metastatic hormone-sensitive prostate cancer (mHSPC), and metastatic castration-resistant prostate cancer (mCRPC). PROCARE is a comprehensive long-term follow-up registry designed to document treatment patterns and outcomes in patients receiving systemic treatment. The study aims to enroll 5,000 patients across 50 sites in Germany. Recruitment is being conducted independently for each cohort, beginning with the mHSPC and mCRPC cohorts. First patient in was in January 2024. Patients will remain in the registry from the time of enrollment until death, withdrawal of consent, or study cohort closure. Throughout the study, additional blood samples will be collected at baseline and with each treatment change, respectively, and at first routine follow-up visit thereafter for exploratory research purposes, such as assessing circulating tumor DNA and RNA, as well as genome-wide single nucleotide polymorphisms (SNPs). This approach will enable a deeper understanding of treatment distribution, sequencing, efficacy, and safety in the real-world setting, contributing valuable insights into the evolving therapeutic landscape. Furthermore, analyses from liquid biopsies might provide important insights potentially guiding future therapeutic strategies for recurrent and metastatic prostate cancer. Clinical trial information: DRKS00033411 .

474 Background: In the JAVELIN Renal 101 phase 3 trial, 1L avelumab + axitinib resulted in significantly longer progression-free survival (PFS) and a higher objective response rate (ORR) vs sunitinib in patients with aRCC, with an acceptable safety profile. The AVION study is evaluating the effectiveness and safety of avelumab + axitinib in routine clinical practice in various countries. We report data from the primary analysis. Methods: AVION is a prospective noninterventional study of patients with aRCC receiving 1L avelumab + axitinib in Germany, Greece, Belgium, or Russia. Patients are observed for 24 months. The primary objective is to evaluate the overall survival (OS) rate at 12 months. Secondary objectives include evaluation of OS rate at 24 months, median OS, PFS, ORR, duration of response (DOR), and safety. Results: By data cutoff (Jul 5, 2024), 104 patients were analyzed. Median age was 70 years (range, 37-87) and 70.2% were male. ECOG PS was 0-1 in 92.3%, 2 in 6.7%, and not reported (NR) in 1.0%. International Metastatic RCC Database Consortium (IMDC) risk group was favorable, intermediate, poor, and NR in 26.0%, 45.2%, 12.5%, and 16.3%, respectively. Tumor histology was clear cell, sarcomatoid, and other in 89.4%, 3.8%, and 6.7%, respectively. Prior anticancer treatment included adjuvant drug treatment, surgery (nephrectomy), or radiotherapy in 3.8%, 75.0% (66.3%), and 8.7%, respectively. At data cutoff, avelumab or axitinib treatment was ongoing in 21 (20.0%). Median OS was not reached (95% CI, not estimable [NE]) and the 12-month OS rate was 82.7% (95% CI, 73.5-88.9). Median PFS (95% CI) was 11.3 months (8.1-NE) and 6- and 12-month PFS rates (95% CI) were 72.5% (62.1-80.5) and 48.4% (37.5-58.5), respectively. Among 87 patients with available response data (assessed up to 12 months), ORR was 46.0% (95% CI, 35.2-57.0), comprising complete or partial response in 4.6% and 41.4%, respectively; disease control rate was 79.3% (95% CI, 69.3-87.3); and median DOR was not reached. Treatment-related adverse events (TRAEs) occurred in 67.3% and were grade ≥3 or serious in 20.2% and 14.4%, respectively. TRAEs led to permanent discontinuation of avelumab or axitinib in 6.7% or 9.6%, respectively, and led to death in 1.0%. The most common TRAEs of any grade (≥6%) were diarrhea (19.2%), fatigue (13.5%), hypothyroidism (8.7%), and nausea (7.7%). Follow-up is ongoing. Conclusions: Results from the AVION study are generally consistent with JAVELIN Renal 101 and previous observational studies, demonstrating the effectiveness, safety, and favorable tolerability with low discontinuation rates of avelumab + axitinib in a heterogeneous real-world population.

147 Background: LIBERTAS is investigating APA in combination with intermittent ADT as an ADT de-escalation strategy for patients with mCSPC. The objective is to evaluate whether APA + intermittent ADT in pts who achieved PSA <0.2 ng/mL after 6 mo initial treatment with APA + ADT provides noninferior radiographic progression-free survival (rPFS) and reduces hot flash burden compared with APA + continuous ADT. In the TITAN study, 54% (263/490) of pts with mCSPC treated with APA + ADT achieved PSA ≤0.2 ng/mL within 3 mo (1). Pts who also achieved PSA ≤0.02 ng/mL vs PSA >0.2 ng/mL showed better overall survival rates (2). Here, we present initial findings of pts enrolled early in LIBERTAS. Methods: LIBERTAS enrolled pts with mCSPC, inclusive of all gender identities. Eligible pts have ≤3 mo ADT prior to enrollment, except for pts receiving ADT as part of their gender-affirming care (GAC), and ECOG PS 0 or 1. Pts have metastasis documented by conventional imaging (CT, MRI, or bone scan) and/or regional lymph node metastases by next-generation imaging (NGI); pts undergoing GAC are eligible with or without evidence of metastasis by conventional imaging or NGI. In the initial 6-mo treatment phase, all pts receive APA 240 mg/d + ADT. In the main treatment phase, 240 pts with confirmed PSA <0.2 ng/mL after the initial treatment phase will be randomized 1:1 to APA 240 mg/d + intermittent or continuous ADT. Stratification: tumor volume and prior treatment for localized PC. Primary end points: rPFS, measured by 18-mo event-free survival rate, and reduction of hot flash burden, measured by the severity-adjusted hot flash score. Results: As of September 20, 2024, 420 pts at 73 sites in 9 countries have enrolled in the initial treatment phase, completing the enrollment goal ahead of schedule. Demographics include 70.5% White, 9.5%, Asian, and 8.6% Black. At baseline, pts had a median (range) age of 70 yrs (48-88) and median PSA 15.0 ng/mL (0.02-6000 ng/mL). At data cutoff, 87 pts had been randomized to the main treatment phase. Among 350 pts with at least 2 evaluable PSA values collected during the initial treatment phase, 246 (70.3%) achieved PSA <0.2 ng/mL and 307 (87.7%) experienced ≥90% PSA decline from baseline at some point during the initial treatment phase. Hot flash compliance, defined as the percentage of data collected per protocol across all sites and visits, exceeded 80%. No new safety signals were observed. Conclusions: Treatment with 6 mo of APA + ADT in this prospective trial resulted in deep PSA responses in the majority of pts with mCSPC. The LIBERTAS study remains on track for successful completion of expected randomization for the standard APA + ADT vs APA + ADT de-escalation. 1. Chowdhury, Ann Oncol 2023. 2. Merseburger, BJU Int 2024. Clinical trial information: NCT05884398 .

Zusammenfassung Obwohl Subgruppenanalysen in klinischen Studien teilweise geschlechtsspezifische Unterschiede in den Ergebnissen aufweisen, gibt es nur selten eine Zulassungsbeschränkung auf nur ein Geschlecht oder geschlechtsangepasste Dosierungsempfehlungen. Außerdem sind Differenzen in den geschlechtsspezifischen Studieneinschlussraten im Vergleich zu den jeweiligen Inzidenz- oder Prävalenzraten wahrzunehmen. Der folgende Artikel beleuchtet geschlechtsspezifische Unterschiede in uro-onkologischen klinischen Studien.

The testes and epididymis are traversed by a system of tubules in which sperm cells are generated, matured, nourished, and transported. Among these are the efferent ductules, which connect the rete testis to the duct of the epididymis. In the Terminologia Anatomica (TA), the efferent ductules are assigned to the testicles, while numerous anatomy, pathology, and urology textbooks assign them to the epididymis. Developmentally, they are derivatives of the Wolffian duct; as is the epididymal duct, which unquestionably belongs to the epididymis. Allocation of the efferent ductules to the compartment of the epididymis has been established clinically. The precise identification of tissue components of the epididymis is essential for the prognostic assessment of testicular cancers. In primary germ cell tumors of the testis, tumor infiltration into the epididymis can influence the tumor stage and can be associated with a worse clinical prognosis than localized tumor disease. Thus, it is desirable to update the TA, assigning the efferent ductules to the epididymis.