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Antibody‐drug conjugates (ADCs) represent a novel type of targeted cancer therapy combining the specificity of monoclonal antibodies with the cytotoxicity of conventional chemotherapy. Recently, ADCs have demonstrated practice‐changing efficacy across diverse solid cancers. The anti‐NECTIN‐4 ADC enfortumab vedotin (EV) has just been approved for patients with urothelial cancer and is currently under investigation for patients with castration‐resistant prostate cancer (CRPC e.g. Phase II ENCORE trial). Our objective was to evaluate the efficacy of EV in established prostate cancer (PCa) cell lines and to examine the membranous NECTIN‐4 expression in primary tumours (PRIM) and distant metastases (MET). NECTIN‐4 was heterogeneously expressed in the panel of PCa cell lines. EV led to growth inhibition in NECTIN‐4 expressing PCa cells (22Rv1 and LNCaP), whereas the NECTIN‐4‐negative PC‐3 cells were significantly less responsive to EV, emphasizing the dependence of EV response on its target expression. Immunohistochemical staining revealed moderate membranous NECTIN‐4 expression only in a small subgroup of CRPC patients with lung and peritoneal MET [n = 3/22 with H‐score ≥100, median H‐score 140 (IQR 130–150)], while 100% of PRIM (n = 48/48) and 86.4% of common MET sites (n = 19/22), including lymph node, bone and liver MET, were NECTIN‐4 negative. In summary, EV may be effective in NECTIN‐4‐positive PCa. However, our findings demonstrate that the tumoural NECTIN‐4 expression is predominantly low in metastatic PCa, which suggests that EV may only be effective in a biomarker‐stratified subgroup. [ABSTRACT FROM AUTHOR]

Purpose: Improved survival rates have been observed in castration‐resistant prostate cancer (CRPC) due to advancements in treatment options. However, individuals with brain metastases still have limited therapeutic options and an unfavorable prognosis. Therefore, there is an urgent need to explore new therapeutic avenues, such as antibody‐drug conjugates (ADCs), which have demonstrated significant clinical activity against active brain metastases in solid tumors. Our objective was to determine the expression levels of the ADC targets Trop‐2 and NECTIN‐4 in cerebral metastasized CRPC (mCRPC). Methods: Immunohistochemical staining of Trop‐2 and NECTIN‐4 with evaluation of H‐score was performed in CRPC brain metastases (n = 31). Additionally, we examined Trop‐2 protein expression in prostate cancer cell lines and studied their responsiveness to the anti‐Trop‐2 ADC Sacituzumab govitecan (SG) in vitro. Results: Our analysis revealed that most patients exhibited moderate to strong Trop‐2 expression [n = 27/31 with H‐score ≥100, median H‐score 220 (IQR 180–280)], while NECTIN‐4 was absent in all cerebral metastases. Mechanistically, we demonstrated that the efficacy of SG depends on Trop‐2 expression levels in vitro. Overexpression of Trop‐2 in Trop‐2‐negative PC‐3 cells led to sensitization to SG, whereas CRISPR‐Cas9‐mediated knockdown of Trop‐2 in Trop‐2‐expressing DU‐145 cells conferred resistance to SG. Conclusion: The substantial expression of Trop‐2 in cerebral metastases, along with our preclinical in vitro results, supports the efficacy of SG in treating cerebral mCRPC. Thus, our results extend the understanding of the potential of ADCs in prostate cancer treatment and provide an additional treatment strategy for the challenging subset of patients with cerebral metastases. [ABSTRACT FROM AUTHOR]

This article discusses the relevance of circular RNAs (circRNAs) in the serum of patients undergoing prostate biopsy. circRNAs are a type of stable non-coding RNA that are associated with various diseases, including cancer. The study enrolled 96 patients scheduled for prostate biopsy and found that the levels of circulating circRNAs were not significantly different in patients with prostate cancer compared to those without cancer. However, the levels of serum circZMIZ1 were significantly increased in patients with metastatic prostate cancer. The study suggests that circZMIZ1 could serve as a prognostic biomarker and a potential treatment target for metastatic prostate cancer. [Extracted from the article]

Objectives: Robot‐assisted radical prostatectomy (RARP) has become the therapy of choice for local treatment of prostate cancer. Postoperatively, urologists perform cystography before removing urinary catheters due to concerns about the integrity of the vesicourethral anastomosis. This study aims to evaluate the safety of waiving cystography before early catheter removal after RARP. Methods: A total of 514 patients from two tertiary referral centers who underwent RARP were retrospectively included. Patients received postoperative urinary drainage by transurethral (TUC) or suprapubic catheter (SPC). During the first year, both centers performed routine cystography before removing TUC or SPC on postoperative day 5. In the following year, management changed and catheters were removed without cystography unless indicated by the surgeon. Demographic and perioperative data were analyzed. Postoperative complications and readmission rates were compared between standard cystography (StCG), no cystography (NCG), and selective cystography (SCG). Results: Groups were comparable regarding demographic and oncological parameters. Analysis showed no significant difference regarding major complications and readmission rates between standard and no cystography (p = 0.155 and 0.998 respectively). Omitting routine cystography did not lead to inferior postoperative courses regardless of both urinary drainage used and tumor stage. Subgroup analysis showed an increase of major complications in SCG patients when compared with NCG (p = 0.003) while readmissions remained comparable (p = 0.554). Conclusion: Waiving routine cystography before early catheter removal after RARP appears to be safe and feasible regardless of urinary drainage. However, the selective cystogram at the surgeon's request still plays a role in monitoring patients with an elevated risk profile. [ABSTRACT FROM AUTHOR]

Objective Methods Results Conclusion To evaluate the potential utility of antibody‐drug conjugates targeting trophoblast cell surface antigen‐2 (TROP‐2) in patients with primary penile squamous cell carcinoma (PSCC), patients with recurrence (REC cohort), and patient‐matched distant metastases (MET cohort), and to assess the potential use of TROP‐2 as a predictive non‐invasive biomarker in PSCC.A cohort comprising a PRIM (n = 37), REC (n = 5) and MET subcohort (n = 7), with MET including lymph node and lung metastases, was analysed using quantitative real‐time PCR, ELISA and immunohistochemical staining with evaluation of H‐score.TROP‐2 mRNA and serum protein levels were significantly increased in primary and recurrent PSCC compared to cancer‐free controls (both P < 0.001). Immunohistochemical analysis revealed that most of the PRIM cohort (n = 34/37, median H‐score 260, interquartile range [IQR] 210–300), as well as all patients in the REC (median [IQR] H‐score 200 [165–290]) and MET cohorts (median [IQR] H‐score 280 [260–300]) exhibited moderate to strong membranous TROP‐2 expression. Additionally, The H‐score (membranous TROP‐2 expression) was positively correlated with TROP‐2 mRNA (ρ = 0.69, P < 0.0001, R2 = 0.70) and protein levels (ρ = 0.86, P < 0.0001, R2 = 0.59), indicating its potential as a non‐invasive biomarker in PSCC.In summary, our results support further studies on TROP‐2 as a diagnostic and therapeutic target in primary, recurrent and metastatic PSCC. [ABSTRACT FROM AUTHOR]