We recently published the first dosimetry data, to our knowledge, for the radioligand therapy agent 177Lu-rhPSMA-10.1, providing an intrapatient comparison with 177Lu-PSMA-I&T in patients with metastatic prostate cancer. Here, we report efficacy and safety findings from these patients. Methods: Four consecutive patients with prostatespecific membrane antigen (PSMA)-positive metastatic prostate cancer received up to 6 cycles of 177Lu-rhPSMA-10.1 (7.4-7.7 GBq per cycle). Efficacy (prostate -specific antigen response according to Prostate Cancer Working Group 3 criteria and the Response Evaluation Criteria in PSMA PET/CT), progression -free survival, and overall survival were evaluated. Adverse events were recorded from the first dose until 16-24 mo after treatment. Results: The patients received a total activity of 29.6-59.4 GBq (4-6 cycles). Prostate -specific antigen was reduced by 100%, 99%, 88%, and 35%. Progression -free survival was not reached for 2 patients at 24 and 18 mo of follow-up and was 15 and 12 mo for the other 2 patients. One patient had a sustained complete response with 2 y of follow up. All patients were alive at the last time point of data collection. No serious adverse events were reported. Conclusion: 177Lu-rhPSMA-10.1 demonstrated encouraging preliminary efficacy and was well tolerated. Formal clinical trials are now under way to evaluate its potential prospectively (NCT05413850).

PurposeRadioligand therapy is an increasingly important option for the treatment of metastatic castrate-resistant prostate cancer (mCRPC). Radiohybrid ligands targeting prostate-specific membrane antigen (PSMA) are a novel group of theranostic radioligand therapy agents for which higher tumour absorbed radiation doses have been demonstrated compared to established PSMA ligands. Here, we report data from ten patients who were treated within a compassionate use program with the radiohybrid PSMA-ligand [177Lu]Lu-rhPSMA-10.1 after experiencing disease progression under treatment with [177Lu]Lu-PSMA-I&T.MethodsTen patients with advanced PSMA-positive prostate cancer who showed progression under treatment with [177Lu]Lu-PSMA-I&T received up to three cycles of rescue therapy with [177Lu]Lu-rhPSMA-10.1 (7.4-8.1 GBq per cycle). Efficacy (PSA response according to PCWG3 and RECIP) and overall survival were evaluated. Adverse events were recorded from first application.ResultsDespite progression with [177Lu]Lu-PSMA-I&T, after the first cycle of [177Lu]Lu-rhPSMA-10.1 rescue therapy, five patients (50%) showed a decrease in serum PSA level. In imaging, three of the ten patients (30%) showed a partial radiologic response. Four of the five patients with a decrease of serum PSA under [177Lu]Lu-rhPSMA-10.1 had initially responded to treatment with [177Lu]Lu-PSMA-I&T but had become resistant. However, the remaining patient had shown continuous disease progression during [177Lu]Lu-PSMA-I&T therapy but showed an immediate response to [177Lu]Lu-rhPSMA-10.1. The additional treatment with [177Lu]Lu-rhPSMA-10.1 was generally well tolerated by all patients.ConclusionsPatients showing tumour progression while receiving [177Lu]Lu-PSMA-I&T radioligand therapy may benefit from rescue therapy with the novel radiohybrid PSMA ligand, [177Lu]Lu-rhPSMA-10.1. Higher tumour absorbed radiation doses with [177Lu]Lu-rhPSMA-10.1 may overcome primary and acquired radiation resistance.

As the use of radioligand therapy moves earlier in the prostate cancer timeline, minimizing the absorbed dose to normal organs while maintain-ing high tumor radiation doses becomes more clinically important because of the longer life expectancy of patients. We performed an intrapatient comparison of pretherapeutic dosimetry with the novel radiohybrid prostate-specific membrane antigen-targeting radiophar-maceutical 177Lu-rhPSMA-10.1, along with 177Lu-PSMA-I&T, in patients with metastatic castration-resistant prostate cancer. Methods: Four consecutive patients with advanced histologically proven metastatic castration-resistant prostate cancer who were scheduled for radioligand therapy were evaluated. Before undergoing therapy, each patient received 1.06 +/- 0.05 GBq of 177Lu-rhPSMA-10.1 and 1.09 +/- 0.02 GBq of 177Lu-PSMA-I&T at least 7 d apart. For dosimetric assessment, whole-body planar scintigraphy was performed after 5 min, 4 h, 1 d, 2 d, and 7 d. In addition, SPECT/CT images were acquired over the thorax and the abdomen, 4 h, 1 d, 2 d, and 7 d after injection. Dosimetry of the whole body and salivary glands was based on the evaluation of the counts in whole-body planar imaging. Dosimetry of the kidneys, liver, spleen, bone marrow, and tumor lesions (<= 4 per patient) was based on the activity in volumes drawn on SPECT/CT images. Doses were calcu-lated using OLINDA/EXM version 1.0. The therapeutic index (TI), or ratio between mean dose of the metastases and mean dose of the kidneys, was calculated for each patient. Results: We found the dose to the kid-neys to be higher with 177Lu-rhPSMA-10.1 than with 177Lu-PSMA-I&T (0.68 +/- 0.30 vs. 0.46 +/- 0.10 mGy/MBq); however, 177Lu-rhPSMA-10.1 delivered an average of a 3.3 times (range, 1.2-8.3 times) higher absorbed radiation dose to individual tumor lesions. Consequently, intraindividual comparison revealed a 1.1-3.1 times higher TI for 177Lu-rhPSMA-10.1 than for 177Lu-PSMA-I&T in all evaluated patients. The effective whole-body dose was 0.038 +/- 0.008 mSv/MBq for 177Lu-rhPSMA-10.1 and 0.022 +/- 0.005 mSv/MBq for 177Lu-PSMA-I&T. Conclusion: Using 177Lu-rhPSMA-10.1 can significantly increase the tumor-absorbed dose and improve the TI compared with 177Lu-PSMA-I&T. An improved TI gives the flexibility to maximize tumor-absorbed doses up to a predefined renal dose limit or, in earlier disease, to reduce the radiation exposure to the kidney while still achieving an effective tumor dose. The function of at-risk organs such as the kidneys is being assessed in a prospective clinical trial.

Frauen erkranken seltener an einem Harnblasenkarzinom, sind jedoch häufiger von fortgeschritteneren Tumorstadien und ungünstigeren Krankheitsverläufen betroffen. Es ist bis heute unklar, welche Ursachen für den aggressiveren Verlauf des Harnblasenkarzinoms bei der Frau verantwortlich sind. Mittels einer PubMed-Recherche wurden Original- und Übersichtsartikel in einem Zeitraum von 2004 bis 2022 ausgewertet. Es ist am ehesten von einer multifaktoriellen Genese auszugehen. In der Literatur werden v. a. epidemiologische und klinische Aspekte als mögliche Ursachen genannt. Ferner werden in letzter Zeit zunehmend auch genetische und hormonelle Faktoren sowie die Rolle des Urobioms diskutiert. Durch eine frühere Diagnosestellung und bessere operative Therapie kann der onkologische Verlauf der Harnblasenkarzinomerkrankung der Frau günstig beeinflusst werden. Weitere Analysen der genetischen, hormonellen und mikrobiologischen Faktoren könnten neue Wege in der Prävention, Diagnostik und Therapie des Harnblasenkarzinoms eröffnen.

IgG4-related pseudotumours (IgG4-RPT) represent a distinctive manifestation in the broad spectrum of IgG4-related diseases (IgG4-RD). Due to their wide morphology and rarity, IgG4-RPTs represent a diagnostic challenge in the differential between reactive lesions and a fibrous soft tissue tumours. Thus, our aim was to characterise our cases and review the literature, focusing on the macroscopic and microscopic features of the lesions. In this paper, we summarise the possible presentations and histomorphological features of IgG4-RPT based on data collected from the literature and from cases at our institute and provide an overview of the pathogenesis and histological characteristics based on the knowledge accumulated in recent years. We collected surgical cases with a diagnosis of IgG4-RPT over the period 2013-2020 at two centres and analysed their macroscopic, histological, and immunohistochemical profiles. Furthermore, we performed a literature research in the MEDLINE and EBSCO databases regarding case reports and studies with the explicit diagnosis of IgG4-RPT. Our cases consist of nine men and three women, with an average age of 60±14 years, representing about 0.05% of the lesions evaluated at the two departments. The involved sites include the kidney, lung, gallbladder, pterygopalatine fossa, spleen, tongue, mediastinum, and submandibular gland. Grossly, nine lesions showed sharp margins. On histological examination, all the lesions showed an abundant inflammatory infiltrate with lymphocytes and IgG4-positive plasma cells as well as characteristic fibroblastic storiform proliferation. The literature search revealed 266 cases and similar histomorphological features in 23 locations. In 30 of these cases (11%), IgG4-RPTs were multifocal. IgG4-RPT are exceedingly rare lesions, which makes them challenging to diagnose. They can affect different sites, and the histomorphological presentation may differ.

Introduction Penile cancer (PeCa) is an orphan disease in European countries. The current guidelines are predominantly based on retrospective studies with a low level of evidence. In our study, we aimed to identify predictors for guideline-conform treatment and hypothesize that reference centers for PeCa and physicians' experience promote guideline compliance and therefore correct local tumor therapy. Methods This study is part of the European PROspective Penile Cancer Study (E-PROPS), an international collaboration group evaluating therapeutic management for PeCa in Central Europe. For this module, a 14-item-survey was developed and sent to 681 urologists in 45 European centers. Three questions focused on therapeutic decisions for PeCa in clinical stage Tis, Ta-T1a, and T1b. Four questions addressed potential personal confounders. Survey results were analyzed by bootstrap-adjusted stepwise multivariate linear regression analysis to identify predictors for EAU guideline-conform local treatment of PeCa. Results For local therapy of cTis 80.4% recommended guideline-conform treatment, for cTa-cT1a 87.3% and for cT1b 59.1%. In total, 42.4% chose a correct approach in all tumor stages. The number of PeCa patients treated at the hospital, a higher level of training of the physicians, resource-based answering and the option of penile-sparing surgery offered at the hospital matched with giving guideline-conform recommendations and thus accurate local tumor treatment. Conclusion Patients with PeCa are best treated by experienced physicians, in centers with a high number of cases, which also offer a wide range of local tumor therapy. This could be offered in reference centers.

Veränderte Rahmenbedingungen führen in Deutschland zu einem Nachwuchsmangel. Um Ansatzpunkte für eine Verbesserung zu finden, führte die Bayerische Urologenvereinigung in Zusammenarbeit mit der German Society of Residents in Urology (GeSRU) im Sommer 2017 eine Online-Umfrage unter urologischen Weiterbildungsassistenten durch.

The adjuvant treatment of non-muscle-invasive bladder cancer (NMIBC) is based on the individual risk profile (RP) and its sufficient transfer from the clinic to the doctor's office. The objectives of our study were to verify the importance and degree of transfer of RP and recommendation for risk-adapted adjuvant treatment (RAAT) in patients with NMIBC as well as to develop appropriate tools for this purpose, if necessary. An email-based survey distributed to urologists in Brandenburg, Berlin, Bavaria and Lower Saxony explored the questions mentioned above. In addition, a tool for risk stratification and information transfer for patients with NMIBC was developed and validated. From a total of 134 questionnaires analyzed, 55 were from clinic urologists (CUs) and 79 were from ambulant urologists (AUs). Although 9 out of 10 urologists considered the RP of importance, only 29 % of CUs and 24 % of AUs (p = 0.553) confirmed that the RP was always mentioned in medical reports. The recommendation for RAAT was confirmed from 62 % of CUs and 20 % of AUs (p < 0.001). A recommendation for RAAT in the medical report was requested by 86 % of AUs. The risk calculator presented here - to our knowledge the first with integration of the 2004 WHO grading - is delivered in all mathematically possible constellations a RP, according to guideline recommendations. Urologists in the clinic and doctor's office both attach considerable importance to the determination and transfer of RP and the recommendation for RAAT. There was evidence to suggest an overestimation of the quality of medical reports by the CU. The risk calculator provides an easy and cost-neutral option to improve risk stratification and information transfer from the clinic to the doctor's office.

______________________________________________________________________________________________________group (p = 0.056), and the 5-year actuarial grade 2+ GI toxicity rate was lower in the IMRT group than in the 3D-CRT group (5.0% vs. 12.1%, p <0.01).A lower incidence of acute genitourinary (GU) grade 2+ toxicities occurred in the IMRT group than in the 3D-CRT group (7.1% vs. 16.4%,p = 0.001).The 5-year actuarial grade 2+ GU toxicity rate for the IMRT vs. the 3D-CRT group was 16.3% vs. 21.7%(p = 0.103), respectively. Conclusion:IMRT combined with I-125 brachytherapy in prostate cancer patients found a lower incidence of toxicities than 3D-CRT combination, without compromise of biochemical outcomes.

Die leitlinienkonforme adjuvante Therapie bei nicht muskelinvasivem Harnblasenkarzinom (NMIBC) basiert auf dem individuellen Risikoprofil (RP) und dessen suffizienter Weitergabe aus der Klinik in die Praxis. Ziel der Arbeit war es, Stellenwert und Grad der Übermittlung von RP und Empfehlung einer risikoadaptierten adjuvanten Therapie (raTh) bei Patienten mit NMIBC zu verifizieren und bei Bedarf geeignete Hilfsmittel zu entwickeln.

Purpose: To assess the efficacy of individual sentinel node (SN)-guided pelvic intensity modulated radiation therapy (IMRT) by determining nodal clearance rate [(n expected nodal involvement - n observed regional recurrences)/n expected nodal involvement] in comparison with surgically staged patients.Methods and Materials: Data on 475 high-risk prostate cancer patients were examined. Sixty-one consecutive patients received pelvic SN-based IMRT (5 x 1.8 Gy/wk to 50.4 Gy [pelvic nodes + individual SN] and an integrated boost with 5 x 2.0 Gy/wk to 70.0 Gy to prostate + [base of] seminal vesicles) and neo-/adjuvant long-term androgen deprivation therapy; 414 patients after SN-pelvic lymph node dissection were used to calculate the expected nodal involvement rate for the radiation therapy sample. Biochemical control and overall survival were estimated for the SNI-MRT patients using the Kaplan-Meier method. The expected frequency of nodal involvement in the radiation therapy group was estimated by imputing frequencies of node-positive patients in the surgical sample to the pattern of Gleason, prostatespecific antigen, and T category in the radiation therapy sample.Results: After a median follow-up of 61 months, 5-year OS after SN-guided IMRT reached 84.4%. Biochemical control according to the Phoenix definition was 73.8%. The nodal clearance rate of SN-IMRT reached 94%. Retrospective follow-up evaluation is the main limitation.Conclusions: Radiation treatment of pelvic nodes individualized by inclusion of SNs is an effective regional treatment modality in high-risk prostate cancer patients. The pattern of relapse indicates that the SN-based target volume concept correctly covers individual pelvic nodes. Thus, this SN-based approach justifies further evaluation, including current dose-escalation strategies to the prostate in a larger prospective series. (C) 2016 Elsevier Inc. All rights reserved.

Extended pelvic lymph node dissection allows exact lymph node staging and has the potential to improve prognosis. In addition to these advantages, there are some perioperative and postoperative complications. In case of transection of the obturator nerve, a microsurgical end-to-end anastomosis should be performed. The most frequent postoperative complication is (symptomatic) lymphocele which is predominantly diagnosed after extraperitoneal surgery. Meticulous lymph node dissection with clipping of lymphatic vessels, sparing the lateral wall of the external iliac artery from dissection, sufficient postoperative drainage, and application of low molecular weight heparin in the upper arm may reduce their incidence. Instillation of sclerosing agents and sufficient drainage are normally successful. If not, laparoscopic fenestration of lymphocele should be performed. Regular ultrasound examinations are necessary to diagnose and treat postoperative lymphocele in a timely manner.

Die ausgedehnte pelvine Lymphadenektomie liefert exakte Angaben zum Lymphknotenstatus und verbessert darüber hinaus möglicherweise den Krankheitsverlauf. Diesen Vorteilen stehen mögliche peri- und postoperative Komplikationen gegenüber. Bei intraoperativer Läsion des N. obturatorius sollte eine mikrochirurgische epineurale Nervennaht erfolgen. Postoperativ sollte der Patient aufgeklärt, neurologisch vorgestellt und krankengymnastisch behandelt werden.