Retrospective analysis of the learning curve in perineal robot-assisted prostate biopsy.

INTRODUCTION: Magnetic resonance imaging-transrectal ultrasound (MRI-TRUS)-fusion biopsy (FBx) of the prostate allows targeted sampling of suspicious lesions within the prostate, identified by multiparametric MRI. Due to its reliable results and feasibility, perineal MRI/TRUS FBx is now the gold standard for prostate cancer (PC) diagnosis. There are various systems for performing FBx on the market, for example, software-based, semirobotic, or robot-assisted platform solutions. Their semiautomated workflow promises high process quality independent of the surgeon's experience. The aim of this study was to analyze how the surgeon's experience influences the cancer detection rate (CDR) via targeted biopsy (TB) and the procedure's duration in robot-assisted FBx. PATIENTS AND METHODS: A total of 1716 men who underwent robot-assisted FBx involving a combination of targeted and systematic sampling between October 2015 and April 2022 were analyzed. We extracted data from the patients' electronic medical records retrospectively. Primary endpoints were the CDR by TB and the procedure's duration. For our analysis, surgeons were divided into three levels of experience: ≤20 procedures (little), 21-100 procedures (intermediate), and >100 procedures (high). Statistical analysis was performed via regression analyses and group comparisons. RESULTS: Median age, prostate-specific antigen level, and prostate volume of the cohort were 67 (±7.7) years, 8.13 (±9.4) ng/mL, and 53 (±34.2) mL, respectively. Median duration of the procedure was 26 (±10.9) min. The duration decreased significantly with the surgeon's increasing experience from 35.1 (little experience) to 28.4 (intermediate experience) to 24.0 min (high experience) (p < 0.001). Using TB only, significant PC (sPC) was diagnosed in 872/1758 (49.6%) of the men. The CDR revealed no significant correlation with the surgeon's experience in either group comparison (p = 0.907) or in regression analysis (p = 0.65). CONCLUSION: While the duration of this procedure decreases with increasing experience, the detection rate of sPC in TB is not significantly associated with the experience of the surgeon performing robot-assisted FBx. This robot-assisted biopsy system's diagnostic accuracy therefore appears to be independent of experience.

Primary Results of Patients with Genitourinary Malignancies Presented at a Molecular Tumor Board.

INTRODUCTION: Personalized medicine poses great opportunities and challenges. While the therapeutic landscape markedly expands, descriptions about status, clinical implementation and real-world benefits of precision oncology and molecular tumor boards (MTB) remain sparse, particularly in the field of genitourinary (GU) cancer. Hence, this study characterized urological MTB cases to better understand the potential role of MTB in uro-oncology. METHODS: We analyzed patients with complete data sets being reviewed at an MTB from January 2019 to October 2022, focusing on results of molecular analysis and treatment recommendations. RESULTS: We evaluated 102 patients with GU cancer with a mean patient age of 61.7 years. Prostate cancer (PCa) was the most frequent entity with 52.9% (54/102), followed by bladder cancer (18.6%, 19/102) and renal cell carcinoma (14.7%, 15/102). On average, case presentation at MTB took place 54.9 months after initial diagnosis and after 2.7 previous lines of therapy. During the study period, 49.0% (50/102) of patients deceased. Additional MTB-based treatment recommendations were achieved in a majority of 68.6% (70/102) of patients, with a recommendation for targeted therapy in 64.3% (45/70) of these patients. Only 6.7% (3/45) of patients - due to different reasons - received the recommended MTB-based therapy though, with 33% (1/3) of patients reaching disease control. Throughout the MTB study period, GU cancer case presentations and treatment recommendations increased, while the time interval between initial presentation and final therapy recommendation were decreasing over time. CONCLUSION: Presentation of uro-oncological patients at the MTB is a highly valuable measure for clinical decision-making. Prospectively, earlier presentation of patients at the MTB and changing legislative issues regarding comprehensive molecular testing and targeted treatment approval might further improve patients' benefits from comprehensive molecular diagnostics.

Better Knowledge about Testicular Cancer Might Improve the Rate of Testicular (Self-)Examination: A Survey among 1,025 Medical Students in Germany.

INTRODUCTION: Testicular cancer (TC) is the most common malignancy among young men. Public awareness of the disease and testicular (self-)examination (TSE) is low. This study aims to evaluate the awareness of German medical students on TC. METHODS: A 25-item questionnaire on TC was handed out during a medical student's football tournament in Germany. Data collection was anonymous. RESULTS: Questionnaires were answered by 573 (56%) female and 452 (44%) male medical students. Most students had gaps in their knowledge about TC: 483 (48%) students knew, the most common age at which TC occurs, and 413 (41%) knew its cure rate. Having dealt with TC during their studies was significantly associated with a better knowledge about TC (p = 0.001). These students also had a higher rate of TSE among male students (66% vs. 52%, p = 0.002). This also applies to examining the partner's testicles by female students (25% vs. 13%, p < 0.001). CONCLUSION: Even in a positively selected collective like medical students, the knowledge about TC is low. Better knowledge might improve the chance of detecting the disease early. Therefore, our joint project of urologists, patients, and supporters called Prevention and Advocacy of Testicular Education e.V. (PATE) works on rising public TC awareness in Germany.

Immunological effects of hybrid minimally invasive versus conventional open pancreatoduodenectomy - A single center cohort study.

BACKGROUND: Minimally invasive surgery is a field of rapid development. Evidence from randomized controlled trials in visceral surgery however still falls short of attesting unequivocal superiority to laparoscopic procedures over conventional open approaches with regard to postoperative outcome. The aim of this study was to explore the perioperative immune status of patients undergoing hybrid minimally invasive or conventional open pancreatoduodenectomy in a prospective cohort study. MATERIAL AND METHODS: Subtyping, quantification and functional analysis of circulating immune cells and determination of cytokine-levels in blood samples from patients receiving either hybrid minimally invasive (laPD) or conventional open pancreatoduodenectomy (oPD) was performed. Samples were taken from 29 patients (laPD: n = 14, oPD: n = 15) prior, during and up to six weeks after surgery. Cells were analyzed by flow cytometry, cytokines/chemokines were measured by proximity extension and enzyme-linked immunoassays. RESULTS: Open surgery induced higher levels of circulating inflammatory CD14++CD16+ intermediate monocytes. In contrast, hybrid minimally invasive resection was accompanied by increased numbers of circulating regulatory CD4+CD25+CD127low T-cells and by a reduced response of peripheral blood CD3+CD4+ T-cell populations to superantigen stimulation. Yet, rates of postoperative morbidity and infectious complications were similar. CONCLUSIONS: In summary, the results of this exploratory study may suggest a more balanced postoperative inflammatory response and a better-preserved immune regulation after hybrid minimally invasive pancreatoduodenectomy when compared to open surgery. Whether these results may translate to or be harnessed for improved patient outcome needs to be determined by future studies including larger cohorts and fully laparoscopic or robotic procedures.

PD-L1 as a Urine Biomarker in Renal Cell Carcinoma-A Case Series and Proof-of-Concept Study.

BACKGROUND: Renal cell carcinoma (RCC) is among the most lethal urologic malignancies once metastatic. Current treatment approaches for metastatic RCC (mRCC) involve immune checkpoint inhibitors (ICIs) that target the PD-L1/PD-1 axis. High PD-L1 expression in tumor tissue has been identified as a negative prognostic factor in RCC. However, the role of PD-L1 as a liquid biomarker has not yet been fully explored. Herein, we analyze urine levels of PD-L1 in mRCC patients before and after either ICI therapy or surgical intervention, as well as in a series of patients with treatment-naïve RCC. PATIENTS AND METHODS: The mid-stream urine of patients with mRCC (n = 4) or treatment-naïve RCC, i.e., prior to surgery from two centers (cohort I, n = 49: cohort II, n = 29) was analyzed for PD-L1 by ELISA. The results from cohort I were compared to a control group consisting of patients treated for non-malignant urologic diseases (n = 31). In the mRCC group, urine PD-L1 levels were measured before and after tumor nephrectomy (n = 1) or before and after ICI therapy (n = 3). Exosomal PD-L1 in the urine was analyzed in selected patients by immunoblotting. RESULTS: A strong decrease in urine PD-L1 levels was found after tumor nephrectomy or following systemic treatment with ICIs. In patients with treatment-naïve RCC (cohort I), urine PD-L1 levels were significantly elevated in the RCC group in comparison to the control group (median 59 pg/mL vs. 25.7 pg/mL, p = 0.011). PD-L1 urine levels were found to be elevated, in particular, in low-grade RCCs in cohorts I and II. Exosomal PD-L1 was detected in the urine of a subset of patients. CONCLUSION: In this proof-of-concept study, we show that PD-L1 can be detected in the urine of RCC patients. Urine PD-L1 levels were found to correlate with the treatment response in mRCC patients and were significantly elevated in treatment-naïve RCC patients.

Immune changes induced by periampullary adenocarcinoma are reversed after tumor resection and modulate the postoperative survival.

BACKGROUND: Tumor growth encompasses multiple immunologic processes leading to impaired immunity. Regarding cancer surgery, the perioperative period is characterized by additional immunosuppression, which may contribute to poorer outcomes. In this exploratory study, we assessed plasma parameters characterizing the perioperative immunity with a particular focus on their prognostic value. PATIENTS AND METHODS: 31 patients undergoing pancreatoduodenectomy were enrolled (adenocarcinoma of the pancreatic head and its periampullary region: n = 24, benign pancreatic diseases n = 7). Abundance and function of circulating immune cells and the plasma protein expression were analyzed in blood samples taken pre- and postoperatively using flow cytometry, ELISA and Proximity Extension Assay. RESULTS: Prior to surgery, an increased population of Tregs, a lower level of intermediate monocytes, a decreased proportion of activated T-cells, and a reduced response of T-cells to stimulation in vitro were associated with cancer. On the first postoperative day, both groups showed similar dynamics. The preoperative alterations did not persist six weeks postoperatively. Moreover, several preoperative parameters correlated with postoperative survival. CONCLUSION: Our data suggests systemic immunologic changes in adenocarcinoma patients, which are reversible six weeks after tumor resection. Additionally, the preoperative immune status affects postoperative survival. In summary, our results implicate prognostic and therapeutic potential, justifying further trials on the perioperative tumor immunity to maximize the benefit of surgical tumor therapy.

Mutations in TP53 or DNA damage repair genes define poor prognostic subgroups in primary prostate cancer.

BACKGROUND: Mutations in DNA damage repair genes, in particular genes involved in homology-directed repair, define a subgroup of men with prostate cancer with a more unfavorable prognosis but a therapeutic vulnerability to PARP inhibition. In current practice, mutational testing of prostate cancer patients is commonly done late i.e., when the tumor is castration resistant. In addition, most sequencing panels do not include TP53, one of the most crucial tumor suppressor genes in human cancer. In this proof-of-concept study, we sought to extend the clinical use of these molecular markers by exploring the early prognostic impact of mutations in TP53 and DNA damage repair genes in men with primary, nonmetastatic prostate cancer undergoing radical prostatectomy (RPX). METHODS: Tumor specimens from a cohort of 68 RPX patients with intermediate (n = 11, 16.2%) or high-risk (n = 57, 83.8%) disease were analyzed by targeted next generation sequencing using a 37 DNA damage repair and checkpoint gene panel including TP53. Sequencing results were correlated to clinicopathologic variables as well as PSA persistence or time to PSA failure. In addition, the distribution of TP53 and DNA damage repair gene mutations was analyzed in three large publicly available datasets (TCGA, MSKCC and SU2C). RESULTS: Of 68 primary prostate cancers analyzed, 23 (33.8%) were found to harbor a mutation in either TP53 (n = 12, 17.6%) or a DNA damage repair gene (n = 11, 16.2%). The vast majority of these mutations (22 of 23, 95.7%) were detected in primary tumors from patients with high-risk features. These mutations were mutually exclusive in our cohort and additional data mining suggests an enrichment of DNA damage repair gene mutations in TP53 wild-type tumors. Mutations in either TP53 or a DNA damage repair gene were associated with a significantly worse prognosis after RPX. Importantly, the presence of TP53/DNA damage repair gene mutations was an independent risk factor for PSA failure or PSA persistence in multivariate Cox regression models. CONCLUSION: TP53 or DNA damage repair gene mutations are frequently detected in primary prostate cancer with high-risk features and define a subgroup of patients with an increased risk for PSA failure or persistence after RPX. The significant adverse impact of these alterations on patient prognosis may be exploited to identify men with prostate cancer who may benefit from a more intensified treatment.