Aktuelle Urologie最新文献

Penile carcinoma is a rare malignancy, predominantly derived from squamous epithelium, with a partially aggressive clinical course. The 2022 WHO classification distinguishes HPV-associated (HPV(+)) and HPV-independent (HPV(-)) subtypes, a differentiation that bears significant prognostic and therapeutic implications. HPV(-) carcinomas often develop as result of chronic inflammation, e.g. lichen sclerosus. While HPV(+) tumours, such as the warty subtype, often exhibit an indolent course, basaloid and sarcomatoid variants are associated with poor prognosis and an increased risk of metastasis.The prognostic value of HPV status alone is still inconsistent across studies. In contrast, p16 overexpression as surrogate marker for HPV infection, has been linked to improved survival outcomes. A combined assessment of HPV and p16 status is therefore recommended, particularly for therapeutic decision-making. In HPV(-) tumours, additional analysis of p53 expression is advisable, as TP53 mutations - frequently observed in this group - are associated with more aggressive tumour biology.Beyond conventional platinum-based chemotherapy, targeted therapies are gaining attention. Antibody-drug conjugates (ADCs), such as enfortumab vedotin (targeting Nectin-4) and sacituzumab govitecan (targeting Trop-2) have shown promising efficacy in other tumour types. Both targets are also expressed in penile carcinoma, and early clinical trials are underway. HER2 is expressed in a relevant proportion of cases and may be an additional therapeutic target.Immune checkpoint inhibitors like atezolizumab have so far demonstrated limited efficacy in penile cancer, despite high rates of PD-L1 expression. This discrepancy may be attributed to the immunosuppressive tumour microenvironment. EGFR-targeted monoclonal antibody therapies are also a potential treatment option.Accurate histopathological and molecular characterisation is critical for personalised treatment approaches and should become an integral component of the clinical management of penile carcinoma.

Prostate cancer is the most common malignancy in men, yet predictive biomarkers for assessing individual risk remain insufficient. Recent research has highlighted PIWI-interacting RNA 26719 (piRNA-26719) as a potential tumor-associated gene 1 2. This study aims to identify and characterize the expression and function of piRNA-26719 in prostate cancer.The expression of piRNA-26719 was analyzed in a high-risk prostate cancer cohort (n=121, PSA preoperative >20ng/ml) and prostate cancer cell lines using quantitative RT-PCR. Functional analyses, including RNA interference (RNAi) and subsequent assays for cell proliferation, apoptosis, and cell cycle distribution, were conducted in prostate cancer cell lines.piRNA-26719 was biochemically validated. Expression analysis revealed a trend toward upregulation of piRNA-26719 in primary high-risk prostate tumors compared to benign hyperplasia, with significant overexpression in lymph node metastases. Functional studies demonstrated that inhibition of piRNA-26719 led to decreased proliferation in prostate cancer cells. Apoptosis assays confirmed the induced activation of caspase-dependent apoptosis, and cell cycle analysis indicated S-phase arrest in piRNA-26719-inhibited cells, but not in the less malignant 22RV1 line.These findings suggest an oncogenic role for piRNA-26719 in high-risk prostate cancer, particularly in aggressive forms, as evidenced by its overexpression in metastatic tissues. The oncogenic function of piRNA-26719 in prostate cancer is supported by its critical role in cellular proliferation, apoptosis, and cell cycle progression. These results warrant further investigation into piRNA-26719's potential as a prognostic biomarker and therapeutic target in prostate cancer management.

For many decades, the treatment of metastatic urothelial carcinoma (mUC) has been dominated by platinum-containing chemotherapies. The latest version is the introduction of immune checkpoint inhibitors, especially in combination with modern antibody-drug conjugates (ADC) and FGFR3 inhibitors, but this therapeutic standard has been overtaken in some indications. Nevertheless, biomarker-guided therapy decisions have rarely been used to date. However, the biomarkers available to date have only helped in isolated therapeutic situations. For ADCs, however, this could change substantially when there is high expression variability of various targets such as NECTIN-4, Her2neu, EGFR and TROP2. The presence of activating FGFR3 mutations or fusions also opens up a clearly defined, albeit small, therapeutic niche that could possibly become larger in the future for localised stages of urothelial carcinoma. Biomarker stratification of tumours will presumably become indispensable in the future if we are to control and use these therapeutic innovations in a targeted and precise manner. Current developments therefore possess great potential for genuine precision oncology.