Locally advanced renal cell carcinoma (RCC) without distant metastases remains challenging to treat surgically, especially when venous tumor thrombus is present. Neoadjuvant checkpoint inhibitor (CPI) and tyrosine kinase inhibitor (TKI) therapy may downstage tumors and improve resectability, but evidence is limited. This study evaluated radiographic and pathological responses, surgical feasibility, and safety following preoperative systemic therapy. This single-center retrospective analysis of 17 patients with non-metastatic RCC who received ≥ 1 month of CPI, TKI, or CPI + TKI before nephrectomy. Tumor stage, radiographic tumor/thrombus reduction, pathological viable tumor percentage, surgical outcomes, complications by Clavien-Dindo, and disease-free survival (DFS) were collected. Median pretreatment tumor diameter was 9.1 cm; 71

Circulating tumor cells and liquid biopsy-based biomarkers might one day play a crucial role in the treatment decision process for patients of several cancer entities. However, clinical studies on liquid biopsy approaches revealed distinct detection rates and thus, different risk scoring for patients. This study delves into the comparison of 2 utilized reverse transcription enzymes, namely, SuperScript IV VILO (VILO) and Sensiscript (SS), aiming to understand their impact on biomarker detection rates. Prostate cancer cell lines were used to assess detection limits, followed by an investigation of biomarker status in clinical liquid biopsy samples of distinct tumor entities. Our findings highlight the superior reverse transcription efficacy of VILO over SS, commonly used in studies employing the AdnaTest platform. The enhanced efficacy of VILO results in a significantly higher number of patients positive for biomarkers. Clinically, the use of a less-sensitive enzyme system may lead to the misclassification of genuinely biomarker-positive patients, potentially altering their prognosis due to inadequate clinical monitoring or inappropriate treatment strategies.

Background Different combination therapies using anti - PD-1 / PD-L1 or CTLA-4 immune checkpoint inhibition (ICI) are widely used in patients with metastatic renal cell carcinoma (mRCC). In the absents of established biomarkers, immune-related adverse events (irAEs) have been discussed as potential predictors of response. Methods In this retrospective cohort study, data of 134 patients with mRCC undergoing ICI treatment (Nivolumab, Ipilimumab and Nivolumab, Pembrolizumab and Axitinib or Avelumab and Axitinib) between 2015 and 2021 were analyzed. To examine the utility of irAEs as predictors of overall survival (OS) and progression-free survival (PFS), separate Kaplan-Meier analyses and Cox proportional regression analyses were applied. Landmark analysis was conducted after 12 weeks to reduce immortal time bias. Result irAEs were observed in 85 patients (63.4%). Cutaneous (n = 52, 38.8%), endocrine (n = 33, 24.6%) and hepatic (n = 19, 14.2%) irAEs were most commonly observed. In Kaplan-Meier analysis, patients experiencing irAEs showed favorable median PFS (15 months, 95% CI, 9.91-20.09) compared to the non-irAE group (5 months, 95% CI, 3.56-6.44, P < .001). The median OS was 25 months (95% CI, 16.79-33.21) in the non-irAE group, while it was not reached in the irAE group (P = .002). In multivariable analysis, the presence of any irAE was associated with favorable PFS (HR 0.46 [95% CI, 0.26-0.82] P = .008) and OS (HR: 0.28 [95% CI, 0.12-0.63] P = .002), respectively. Landmark analysis after 12 weeks showed mixed results depending on the classification of the irAE group at the landmark time. Conclusion The presence of irAEs under ICI therapy in patients with mRCC is associated with better PFS and OS. Thus, manageable irAEs should not be cause for premature discontinuation of ICI therapy, as they seem to indicate favorable outcomes. Considering the time-dependent nature of irAEs is crucial estimating their value as predictive markers.

In our study, the post-radiotherapy quality of life of prostate cancer patients who previously underwent transurethral resection of the prostate (TURP) is compared to those who had thulium laser enucleation of the prostate (ThuLEP) and those who had no prior surgery. It also aims to identify and assess risk factors affecting therapy tolerance in this patient group. We analyzed 132 patients with localized prostate cancer treated with definitive radiotherapy (RT), including 23 who had prior TURP and 19 who previously underwent ThuLEP. A total of 62% of patients underwent irradiation within 12 months after surgery. We included only patients treated with radiotherapy using the IMRT technique. Changes in patient-reported urinary toxicity were evaluated using the International Prostate Syndrome Score (IPSS) and the quality of life index of the World Health Organization (QoL/WHO-PSS) over a three-year post-radiotherapy period. Patients with prior TURP experienced significant deterioration in QoL and IPSS immediately after irradiation (p < 0.001), whereas those without previous surgery showed both less significant differences in IPSS and QoL scores. In conclusion, patients with previous TURP/ThuLEP differ from those without previous surgery in urinary quality of life and acute and chronic urinary symptom profiles after RT. The surgical technique (ThuLEP vs. TURP) and the time interval to irradiation are crucial factors affecting RT tolerance in acute and late settings. The previously operated patient group reported a significantly longer period of increased symptom burden.

417 Background: Today, targeted systemic therapy is standard 1st line treatment of advanced/metastatic renal cell carcinoma (aRCC). Upfront cytoreductive nephrectomy (CN) has been an important treatment option. Recently its role is under debate, especially in combination with the new 1st line treatments. Our study evaluated the current relevance of initial surgical intervention and the role of inductive systemic therapy in aRCC. Methods: We included 33 patients with aRCC from the University Hospitals in Essen and Münster initiating 1st line treatment from 03/18 to 01/23 pre or post surgery. We retrospectively formed two cohorts, either CN followed by systemic therapy (cohort 1; 13 patients) or vice versa (cohort 2; 20 patients). Patients received either Ipilimumab/Nivolumab (Ipi/Nivo) (42.4%) or a checkpoint inhibitor and tyrosine kinase inhibitor (CPI/TKI) combination (57.6%). Progression-free survival (PFS) was estimated with Kaplan-Meier-method from initiation of systemic therapy or CN to progression or death. In Cohort 2, we additionally analyzed the radiologic response of the primary measured by change of the longest diameter. The radiographic response was analysed according to RECIST1.1. Results: Patients’ age ranged from 44 to 80 years with a median of 63 years. Intermediate and poor prognosis occurred in 61.3% and 38.7% of cases. The two cohorts did not differ significantly regarding baseline characteristics. Median PFS was 8 vs. 23 months (p=0.03) in cohort 1 (95% CI 0.9-15.1) compared to cohort 2 (95% CI 18.8-27.2). In cohort 2 the time between start of systemic therapy and surgery was in median 8.5 months (95% CI 3.3-21.1), the primary had a median diameter of 10.7 cm (95% CI 4.5-13.3). Median reduction of the primary was in total 32.2%, 28.9% in the Ipi/Nivo and 34.7% in the CPI/TKI group (p=0.74). In seven patients (35%) response led to modification of the surgical approach, enabling partial instead of radical nephrectomy. Conclusions: The sequence of systemic therapy followed by surgery was associated with a significant PFS benefit. In addition, prior systemic therapy led to a primary reduction and better operability, in some cases even to kidney sparing surgery. Major limitation is the retrospective nature of our analysis and a potential selection bias. However, the sequence of prior systemic therapy followed by surgery in aRCC was associated with notably better outcomes.

Abstract Background With over 65,000 new cases per year in Germany, prostate cancer (PC) is the most common cancer in men in Germany. Localized PC is often treated by radical prostatectomy and has a very good prognosis. Postoperative quality of life (QoL) is significantly influenced by the side effects of surgery. One possible approach to improve QoL is postoperative symptom monitoring using ePROMs (electronic patient-reported outcome measures) to accurately identify any need for support. Methods The PRO-P (“Influence of ePROMS in surgical therapy of PC on the postoperative course”) study is a randomized controlled trial employing 1:1 randomization at 6 weeks postoperatively, involving 260 patients with incontinence (≥ 1 pad/day) at six participating centers. Recruitment is planned for 1 year with subsequent 1-year follow-up. PRO-monitoring using domains of EPIC-26, psychological burden, and QoL are assessed 6, 12, 18, 24, 36, and 52 weeks postoperatively. Exceeding predefined PRO-score cutoffs triggers an alert at the center, prompting patient contact, medical consultation, and potential interventions. The primary endpoint is urinary continence. Secondary endpoints refer to EPIC-26 domains, psychological distress, and QoL. Aspects of feasibility, effect, and implementation of the intervention will be investigated within the framework of a qualitative process evaluation. Discussion PRO-P investigates the effect on postoperative symptom monitoring of a structured follow-up using ePROMs in the first year after prostatectomy. It is one of the first studies in cancer surgery investigating PRO-monitoring and its putative applicability to routine care. Patient experiences with intensified monitoring of postoperative symptoms and reflective counseling will be examined in order to improve primarily urinary continence, and secondly other burdens of physical and psychological symptoms, quality-of-life, and patient competence. The potential applicability of the intervention in clinical practice is facilitated by IT adaption to the certification standards of the German Cancer Society and the integration of the ePROMs survey via a joint patient portal. Positive outcomes could readily translate this complex intervention into routine clinical care. PRO-P might improve urinary incontinence and QoL in patients with radical prostatectomy through the structured use of ePROMs. Trial registration ClinicalTrials.gov NCT05644821. Registered on 09 December 2022.

Zusammenfassung Bei der Low Compliance handelt es sich um keine eigene Krankheitsentität, sondern ein schweres Erscheinungsbild als Folge unterschiedlicher Störungen der Speicher- und Ausscheidungsfunktion der Harnblase. Die verminderte Dehnbarkeit des Detrusors kann zu einer Druckbelastung des oberen Harntrakts führen, aber auch drangdominante LUTS und Harnwegsinfektionen können resultieren. Neurogene Ursachen, v.a. die Querschnittslähmung/Spina bifida aber auch iatrogene Schäden oder eine subvesikale Obstruktion können u.a. zur Entstehung beitragen. Der Beitrag soll über die Verbreitung und komplexen pathogenetischen Mechanismen, aber auch notwendige diagnostische Schritte informieren. Unterschiedliche medikamentöse, interventionelle und operative Behandlungsstrategien werden anhand aktueller wissenschaftlicher Erkenntnisse bewertet und der Leser so in der Betreuung dieses komplexen Patientenklientels unterstützt.

Abstract Background Research on prostate cancer is mostly performed using cell lines derived from metastatic disease, not reflecting stages of tumor initiation or early progression. Establishment of cancer cell lines derived from the primary tumor site has not been described so far. By definition, cancer cells are able to be cultured indefinitely, whereas normal epithelial cells undergo senescence in vitro. Epithelial cells can be immortalized, accomplished by using viral integration of immortalization factors. Viral approaches, however, might be impaired by regulatory and safety issues as well as random integration into regulatory genetic elements, modifying precise gene expression. We intend to use surgical specimen of prostate cancer patients to (i) prove for establishment of cancer cell lines, and (ii) perform non-viral, Sleeping Beauty (SB) transposase-based immortalization of prostate epithelial cells. Methods Radical prostatectomy samples of prostate cancer patients (n = 4) were dissociated and cultured in vitro. Cells were cultivated either without or after non-viral, Sleeping-Beauty transposase-based stable transfection with immortalization factors SV40LT and hTERT. Established cell lines were analyzed in vitro and in vivo for characteristics of prostate (cancer) cells. Results Initial cell cultures without genetic manipulation underwent senescence within ≤ 15 passages, demonstrating inability to successfully derive primary prostate cancer cell lines. By using SB transposase-based integration of immortalization factors, we were able to establish primary prostate cell lines. Three out of four cell lines displayed epithelial characteristics, however without expression of prostate (cancer) characteristics, e.g., androgen receptor. In vivo, one cell line exhibited tumorigenic potential, yet characteristics of prostate adenocarcinoma were absent. Conclusion Whereas no primary prostate cancer cell line could be established, we provide for the first-time immortalization of primary prostate cells using the SB transposase system, thereby preventing regulatory and molecular issues based on viral immortalization approaches. Although, none of the newly derived cell lines demonstrated prostate cancer characteristics, tumor formation was observed in one cell line. Given the non-prostate adenocarcinoma properties of the tumor, cells have presumably undergone oncogenic transformation rather than prostate cancer differentiation. Still, these cell lines might be used as a tool for research on prostate cancer initiation and early cancer progression.

BACKGROUND:Adjustable sling ATOMS-SSP results in ventral compression of the urethra with favorable results in the treatment of men with mild to moderate stress incontinence. However, with transobturator tunneling and mesh fixation, the surgeon has a range of options, which leads to different results and sometimes unfavorable positioning of the silicone cushion. Using retrograde urethrography (RUG), we identified ATOMS patients with considerable misplacement. We then modified the implantation technique when we performed the revision, and now present here our first experiences with this new surgical technique.METHODS:Patients after ATOMS-SSP implantation at our clinic were systematically subjected to a RUG if incontinence persisted after adjustments. In case of unfavorable positioning, a revision was performed with the aim of achieving an idealized urethroproximal position of the silicone pad. During follow-up, a repeat RUG was performed, and both subjective and objective outcome parameters were recorded.RESULTS:Four men met the above criteria and underwent revision with reimplantation using our new technique. All patients postoperatively experienced significantly improved continence. RUGs demonstrated an ideal ATOMS position immediately below the proximal bulbar urethra.CONCLUSIONS:Our proximal implantation technique, presented here for the first time, allows optimal positioning of the ATOMS SSP, which is reflected in the objective parameters and RUG. Its use in primary implantation should also be considered and an expansion to the indication of severe stress incontinence seems possible, but this should only be done in studies.

386 Background: A critical clinical concern after radical prostatectomy for prostate cancer (PCa) is the timely identification of residual disease. Recurrent disease (biochemical recurrence: BCR) develops in approximately 30% of radical prostatectomies within 5 years of surgery. Currently, clinicopathological variables, including pathological tumor stage (pT-stage), Gleason score and PSA, or algorithmic combinatorial calculations (e.g., CAPRA-S) are used to predict BCR. Early and objective prediction of individuals at high risk of BCR would enable stratification of follow-up strategies and facilitate therapeutic therapy. To achieve these goals, we developed a liquid biopsy, the PROSTest, to identify PCa. This is a 27 multigene algorithmic signature with a high sensitivity and specificity (>90%) for PCa detection. We investigated if the PROSTest had utility as a predictive biomarker for BCR. Methods: Prospective recruitment of 60 PCa for radical prostatectomy with assessment of standard pathological, clinical and biomarker (PSA) data. D’Amico Risk scores and CAPRA-S were calculated. Blood was collected for PROSTest measurement pre-surgery. Target genes were amplified using qPCR and scored (0-100) using algorithmic analysis. Pre-surgical PROSTest scores were evaluated as predictors of BCR and compared with standard criteria as well as DR and CAPRA-S scores. Data was evaluated using Mann-Whitney U-test, multiple regression analyses, Kaplan-Meier survival analysis and Cox-proportional modeling. All data: median (range). Results: Consent was obtained in 48 (80%) patients. Median age (range) was 64 (50-82). Gleason was predominantly 7 (85%; 26: 7A, 15: 7B); TNM was primarily T2c (48%) and T3a (32%) with nodal disease evident in 8% and 0% cM1 disease. Resections were R0 (85%) and 7 R1. The median follow-up was 42 days (range: 14-782). Early BCR occurred in 8 (17%) patients. This included 3/7 (43%) of R1 and 5/41 (12%) R0 resections. PSMA imaging confirmed 3 LN recurrences and new visceral ( n=1) and bone ( n=1) disease. D’Amico Risk scores were mostly “high” (88% with risk score ≥50%) and were not associated with early BCR. CAPRA-S scores were higher in those who developed early BCR (5: 1-9) than in those who did not (2: 0-5). Pre-surgical PROSTest scores were elevated in all (median 59: 15-81). Multiple regression analysis identified only PROSTest score ≥60 and nodal status were associated with BCR. The median Recurrence Free Survival (mRFS) was 89 days compared to undefined in those with baseline PROSTest scores ≥60 (HR: 9.7; 95%CI: 2.16-43.7; p=0.003). No recurrences were identified in those with scores <60. Conclusions: Early biochemical recurrence (within 3 months of surgery) can be accurately predicted by elevated (≥60) pre-surgical PROSTest blood gene expression scores. This suggests the marker could be used as a stratification tool for neoadjuvant therapy, or to guide the frequency of monitoring during follow-up.

Delta Ct values of AR-FL, AR-V3, AR-V7 and AR-V9 in LuCaP xenografts (Ct ARs - Ct RPL37A)

A) Genomic structure of the AR gene. B) Sequences of exon 4/8 spanning primers used in 6 different PCR assays (except PCR assay #4). C) PCR assay #4 (22) would lead to two distinct PCR products with the respective size, i.e. AR-V567es and AR-FL. Abbreviations: AR-FL, full length AR; bp, base pairs

A) Detection of a deletion event in LuCaP 86.2. This samples also displays signals of wildtype genomic DNA, displaying an AR-V567es positive sub-clone. B) Detection of an inversion event in LuCaP 136s2. Abbreviations: BPH, benign prostate hyperplasia

In metastatic or locally advanced urothelial carcinoma (UC), therapeutic options have been limited to chemotherapy and immune checkpoint inhibitors. Novel targets and drugs such as antibody drug conjugates have been developed, and enfortumab vedotin targeting nectin-4 and sacituzumab govitecan (SG) targeting trophoblast cell surface antigen 2 (TROP-2), the protein product of the TACSTD2 gene, have been approved. The expression of TROP-2 was investigated within UC and other types of carcinomas, and within the tissue of different healthy organs to understand treatment responses and toxicities. The expression of TROP-2 in the tissues of 42 patients with UC, 13 patients with other types of cancer and in the normal tissues of 11 patients was retrospectively analyzed. Immunohistochemical staining of the TROP-2 protein was performed on a BenchMark ULTRA IHC/ISH System (Roche Tissue Diagnostics; Roche Diagnostics, Ltd.) according to accredited staining protocols in a routine immunohistochemistry accredited and certified facility of the laboratory of immunohistochemistry at the Institute of Pathology (Gerhard-Domagk Institute)- University Hospital Muenster (UKM)-Muenster-Germany]. Different expression levels of TROP-2 were observed, and the highest expression rate of TROP-2 was observed in UC, independent of the tumor stage. However, normal urothelial cells had similar expression levels. Except for ductal carcinoma in situ, the expression of TROP-2 was reduced in other types of cancer and in the healthy tissues from other organs, including pancreas, gall bladder, colon and prostate. Given the treatment response based on the expression level of TROP-2, SG would be effective in almost all cases of UC. However, it would also have an effect on the normal urothelium.

Introduction: Growth arrest-specific protein 6 (Gas 6) is a ligand that plays a role in proliferation and migration of cells. For several tumor entities, high levels of Gas 6 are associated with poorer survival. We examined the prognostic role of Gas 6 in renal cell carcinoma (RCC), especially in papillary RCC (pRCC), which is still unclear. Methods: The patients’ sample collection is a joint collaboration of the PANZAR consortium. Patients’ medical history and tumor specimens were collected from n = 240 and n = 128 patients with type 1 and 2 pRCC, respectively. Expression of Gas 6 was determined by immunohistochemistry. Results: In total, Gas 6 staining was evaluable in 180 of 240 type 1 and 110 of 128 type 2 pRCC cases. Kaplan-Meier analysis disclosed no significant difference in 5-year overall survival for all pRCC nor either subtype. Also, Gas+ and Gas– groups did not significantly differ in any tumor or patient characteristics. Conclusion: Gas 6 was not found to be an independent prognostic marker in pRCC. Future studies are warranted to determine if Gas 6 plays a role as prognostic marker or therapeutic target in pRCC.

A) Expression of AR-FL in LuCaP xenografts displaying significantly lower expression of AR-FL in LuCaP xenograft 136s2. B/C/D) Expression of AR splice variants AR-V3 (C), AR-V7 (D) and AR-V9. Abbreviations: NTC, non-template control

Bioanalyzer images of PCR products of 7 different AR-V567es detection approaches in 6 samples (positive controls: 86.2 and 136s2; negative control: 136p8; patient samples: VL4KJ2 (AR-V567es positive) and 9V9DIB (AR-V567es negative); pSG5-plasmid DNA; NTC). bp numbers indicate PCR product size of either AR-V567es (lower number) or AR-FL (higher number). Red arrows in E and G indicate faint band of a PCR product related to AR-V567es expression in patient sample VL4KJ2; PCR assays #5 and #7. Abbreviations: NTC, non-template control; bp, base pairs