Background: Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a frequent disease affecting men of every age and accounting for a great number of consultations at urology departments. Previous studies suggested a negative impact of CP/CPPS on fertility. As increasing attention has been attributed to additional aspects, such as sperm DNA integrity and sperm protein alterations, besides the WHO standard semen analysis when assessing male fertility, in this prospective study, we aimed to further characterize the fertility status in CP/CPPS patients with a focus on these parameters. Methods: Sperm DNA fragmentation measured by sperm chromatin structure assay (SCSA) and protamine 1 to protamine 2 mRNA ratio assessed by RT-qPCR were analyzed along with conventional ejaculate parameters and inflammatory markers in 41 CP/CPPS patients and 22 healthy volunteers. Results: We found significant differences between the groups concerning multiple conventional ejaculate parameters. A significant increase in sperm DNA fragmentation was shown in CP/CPPS patients with association to other sperm parameters. The majority of CP/CPPS patients exhibited protamine mRNA ratios out of the range of regular fertility. Conclusions: This is a pioneering study with a strong practical orientation revealing that CP/CPPS leads to increased sperm DNA damage and changes in sperm protamine levels, emphasizing an unfavorable impact of CP/CPPS on fertility.

Multiparametric magnetic resonance imaging (mpMRI) has emerged as a new cornerstone in the diagnostic pathway of prostate cancer. However, mpMRI is not devoid of factors influencing its detection rate of clinically significant prostate cancer (csPCa). Amongst others, prostate volume has been demonstrated to influence the detection rates of csPCa. Particularly, increasing volume has been linked to a reduced cancer detection rate. However, information about the linkage between PI-RADS, prostate volume and detection rate is relatively sparse. Therefore, the current study aims to assess the association between prostate volume, PI-RADS score and detection rate of csP-Ca, representing daily practice and contemporary mpMRI expertise. Thus, 1039 consecutive patients with 1151 PI-RADS targets, who underwent mpMRI-guided prostate biopsy at our tertiary referral center, were included. Prior mpMRI had been assessed by a plethora of 111 radiology offices, including academic centers and private practices. mpMRI was not secondarily reviewed in house before biopsy. mpMRI-targeted biopsy was performed by a small group of a total of ten urologists, who had performed at least 100 previous biopsies. Using ROC analysis, we defined cut-off values of prostate volume for each PI-RADS score, where the detection rate drops significantly. For PI-RADS 4 lesions, we found a volume > 61.5 ccm significantly reduced the cancer detection rate (OR 0.24; 95% CI 0.16–0.38; p < 0.001). For PI-RADS 5 lesions, we found a volume > 51.5 ccm to significantly reduce the cancer detection rate (OR 0.39; 95% CI 0.25–0.62; p < 0.001). For PI-RADS 3 lesions, none of the evaluated clinical parameters had a significant impact on the detection rate of csPCa. In conclusion, we show that enlarged prostate volume represents a major limitation in the daily practice of mpMRI-targeted biopsy. This study is the first to define exact cut-off values of prostate volume to significantly impair the validity of PI-RADS assessed in a real-world setting. Therefore, the results of mpMRI-targeted biopsy should be interpreted carefully, especially in patients with prostate volumes above our defined thresholds.

Immune checkpoint inhibitor (ICI) therapies have been established as the standard-of-care in various uro-oncological cancers. Immune-related adverse events (irAEs) are frequent, but their degree rarely leads to the discontinuation of immunotherapies. Unplanned permanent treatment discontinuation may negatively impact the outcomes of patients, but there are emerging data about a positive correlation between emergence of severe irAEs and therapeutic cancer responses. In this study, a retrospective analysis of patients treated for urothelial carcinoma (UC) with ICI-based immunotherapy was conducted. irAEs were classified according to the Common Terminology Criteria for Adverse Events (CTCAEs) and radiological responses according to the Response Evaluation Criteria In Solid Tumors (RECISTs). Out of 108 patients with metastatic urothelial cancer that underwent immunotherapy, 11 experienced a severe irAE that required permanent discontinuation of ICI therapy. The most frequent irAEs leading to discontinuation were hepatitis (n = 4), pneumonitis (n = 2), and gastritis or colitis (n = 2). Prior to discontinuation (R1), the radiological best response was complete remission (CR) in three patients, partial response (PR) in six, and stable disease (SD) in wo patients. After the discontinuation of ICI therapy (R2), the best responses were CR in six, PR in three, and SD in two patients. Following discontinuation, the majority of these patients showed a sustained treatment response, despite not receiving any cancer-specific treatment. The median time of response after discontinuation of ICI therapy was 26.0 (5.2–55.8) months. We propose accurate counseling and close follow-ups of patients following their discontinuation of ICI therapy due to irAEs, as responses can be durable and deep, and many patients do not require immediate subsequent therapies, even in urothelial cancer. More data are required to find predictors of the length of response to appropriately counsel patients.

Objective: Over the last decade, active surveillance (AS) of low-risk prostate cancer has been increasing. The mpMRI fusion-guided biopsy of the prostate (FBx) is considered to be the gold standard in preoperative risk stratification. However, the role of FBx remains unclear in terms of risk stratification of low-risk prostate cancer outside high-volume centers. The aim of this study was to evaluate adverse pathology after radical prostatectomy (RP) in a real-world setting, focusing on patients diagnosed with Gleason score (GS) 6 prostate cancer (PCa) and eligible for AS by FBx. Subjects and Methods: Between March 2015 and March 2022, 1297 patients underwent FBx at the Department of Urology, Ludwig-Maximilians-University of Munich, Germany. MpMRI for FBx was performed by 111 different radiology centers. FBx was performed by 14 urologists from our department with different levels of experience. In total, 997/1297 (77%) patients were diagnosed with prostate cancer; 492/997 (49%) of these patients decided to undergo RP in our clinic and were retrospectively included. Univariate and multivariable logistic regression analyses were performed to evaluate clinical and histopathological parameters associated with adverse pathology comparing FBx and RP specimens. To compare FBx and systematic randomized biopsies performed in our clinic before introducing FBx (SBx, n = 2309), we performed a propensity score matching on a 1:1 ratio, adjusting for age, number of positive biopsy cores, and initial PSA (iPSA). Results: A total of 492 patients undergoing FBx or SBx was matched. In total, 55% of patients diagnosed with GS 6 by FBx were upgraded to clinically significant PCa (defined as GS ≥ 7a) after RP, compared to 52% of patients diagnosed by SBx (p = 0.76). A time delay between FBx and RP was identified as the only correlate associated with upgrading. A total of 5.9% of all FBx patients and 6.1% of all SBx patients would have been eligible for AS (p > 0.99) but decided to undergo RP. The positive predictive value of AS eligibility (diagnosis of low-risk PCa after biopsy and after RP) was 17% for FBx and 6.7% for SBx (p = 0.39). Conclusions: In this study, we show, in a real-world setting, that introducing FBx did not lead to significant change in ratio of adverse pathology for low-risk PCa patients after RP compared to SBx.

Introduction: Higher intraoperative opioid doses may be associated with worse long-term oncological outcomes after radical prostatectomy (RP) for prostate cancer. We aimed to evaluate the impact of higher doses of intraoperative opioids and type of anesthesia on biochemical recurrence (BCR) and mortality after RP in a high-volume tertiary center. Methods: All patients underwent RP at our center between 2015 and 2021. The role of major intraoperative opioid agents, such as sufentanil remifentanil, and morphine milligram equivalents (MMEs), as well as the type of anesthesia [total intravenous anesthesia (TIVA), versus a combination of TIVA and epidural anesthesia, versus solely epidural anesthesia], was assessed in predicting BCR and survival after RP. Results: A total of 1137 patients who had a median age of 66 years (interquartile range: 61–72) were included. Overall, 1062 (93%) patients received TIVA, 37 (3%) received TIVA and epidural anesthesia, and 41 (4%) only epidural anesthesia. At a median follow-up of 431 days (interquartile range: 381–639) from RP, 257 (24%) patients developed a BCR. Accordingly, at a median follow-up of 500 days (interquartile range: 450–750), 33 (2.9%) patients died. The type of anesthesia, as well as the dosage or type of the selected intraoperative opioid agents, did not affect either BCR or long-term overall survival. Conclusions: These findings suggest that intraoperative opioid application during RP has no negative oncological impact in the short and long term in patients with localized prostate cancer. Accordingly, combined TIVA and epidural anesthesia, as well as solely epidural anesthesia were associated with similar short- and long-term outcomes compared to TIVA.

Background: PSMA PET/CT (Prostate-specific membrane antigen positron emission tomography / computed tomography) has revolutionized prostate cancer imaging. While PSMA expression is influenced by androgen receptor pathway inhibitors (ARPI), few studies have examined the specific effects of apalutamide, a widely used ARPI for hormone-sensitive metastatic prostate cancer. This study evaluated the impact of apalutamide on PSMA radioligand uptake. Methods: We evaluated 17 patients with metastatic hormone-sensitive prostate cancer (mHSPC) who underwent [ ¹⁸ F]PSMA-1007 PET/CT imaging prior to (PET1) (time from PET1 to initiation of apalutamide: 0.40 months; range 0.03–5.90 months) and during apalutamide treatment (PET2) (time from apalutamide initiation to PET2: 5.30 months; range 1.70–20.30 months). Biodistribution and tumor uptake were calculated using whole body total tumor volume (TTV), TTV-SUV _max and TTV-SUV _mean and changes between imaging time points were analysed. Results: All patients demonstrated significant clinical and biochemical PSA responses after treatment initiation (median PSA (ng/mL) 46.40 vs. 0.03, p = 0.001). On PSMA PET/CT during apalutamide therapy, patients showed an overall decrease in TTV-SUV _max , TTV-SUV _mean and TTV. Median decreases in TTV-SUV _max and TTV-SUV _mean were − 54% and − 28%, respectively ( p = 0.006, p = 0.020). TTV exhibited a significant median decrease by -53% ( p = 0.006). In 4/17 (23.5%) patients imaging and biochemical response revealed discordant results. Conclusions: This pilot study indicates that, in mHSPC patients, PSMA upregulation is unlikely with intermediate to long-term apalutamide therapy. However, an increase of imaging parameters with synchronous decrease of PSA levels should raise suspicion of early imaging progression, resulting in close monitoring. Further research is warranted to explore early treatment response in the hormone-sensitive stadium.