PURPOSE: Determining the frequency and distribution of pathogenic germline variants (PGVs) in Austrian prostate cancer (PCa) patients and to assess the accuracy of different clinical risk scores to correctly predict PGVs. METHODS: This cross-sectional study included 313 men with advanced PCa. A comprehensive personal and family history was obtained based on predefined questionnaires. Germline DNA sequencing was performed between 2019 and 2021 irrespective of family history, metastatic or castration status or age at diagnosis. Clinical risk scores for hereditary cancer syndromes were evaluated and a PCa-specific score was developed to assess the presence of PGVs. RESULTS: PGV presence was associated with metastasis (p = 0.047) and castration resistance (p = 0.011), but not with personal cancer history or with relatives with any type of cancer. Clinical risk scores (Manchester score, PREMM5 score, Amsterdam II criteria or Johns Hopkins criteria) showed low sensitivities (3.3-20%) for assessing the probability of PGV presence. A score specifically designed for PCa patients stratifying patients into low- or high-risk regarding PGV probability, correctly classified all PGV carriers as high-risk, whereas a third of PCa patients without PGVs was classified as low risk of the presence of PGVs. CONCLUSION: Application of common clinical risk scores based on family history are not suitable to identify PCa patients with high PGV probabilities. A PCa-specific score stratified PCa patients into low- or high-risk of PGV presence with sufficient accuracy, and germline DNA sequencing may be omitted in patients with a low score. Further studies are needed to evaluate the score.
- MeSH
- genetická predispozice k nemoci MeSH
- lidé MeSH
- nádory prostaty * genetika patologie MeSH
- průřezové studie MeSH
- rizikové faktory MeSH
- zárodečné buňky patologie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Rakousko MeSH
PURPOSE OF REVIEW: Due to the limited number of cases, there are no guidelines for basal cell carcinoma (BCC) of the prostate. This review combines an unpublished case report of a 55-year-old patient with BCC with an assessment of the latest literature. RECENT FINDINGS: BCC of the prostate has previously been described in only approximately 140 cases. We describe the diagnostic process, including the uropathological and DNA-sequencing results, which allowed us to start an experimental treatment with pemigatinib. BCC of the prostate is associated with an aggressive biological and clinical behavior, such as recurrence and metastasis. Several immunohistochemical stainings are available to differentiate BCC from adenocarcinoma of the prostate. Based on pathology and results from next-generation sequencing (NGS), patients can be offered targeted therapies. SUMMARY: With the aid of histological work-up and immunostaining, prostatic BCC can be accurately diagnosed. Our patient underwent radical prostatectomy and staged extended lymphadenectomy due to lymph node recurrence. The patient subsequently developed progressive disease and was treated with the FGFR-inhibitor pemigatinib. The patient's liver metastasis significantly responded. The present case confirms the possibility of aggressive behavior of prostatic BCC and highlights the importance of a thorough uropathological and molecular biological analysis with a precision medicine strategy.
- MeSH
- bazocelulární karcinom * diagnóza patologie chirurgie MeSH
- lidé středního věku MeSH
- lidé MeSH
- lymfadenektomie MeSH
- morfoliny MeSH
- nádory kůže * chirurgie MeSH
- nádory prostaty * diagnóza farmakoterapie genetika MeSH
- prostata patologie MeSH
- prostatektomie MeSH
- pyrimidiny MeSH
- pyrroly MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- přehledy MeSH
- MeSH
- epigeneze genetická MeSH
- epigenomika metody MeSH
- lidé MeSH
- management nemoci MeSH
- metylace DNA * MeSH
- náchylnost k nemoci MeSH
- nádorové biomarkery * MeSH
- nádory prostaty rezistentní na kastraci krev diagnóza genetika terapie MeSH
- prognóza MeSH
- stanovení celkové genové exprese MeSH
- tekutá biopsie * metody MeSH
- výpočetní biologie metody MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- dopisy MeSH
- práce podpořená grantem MeSH
BACKGROUND: Men with germline BRCA1/2 mutations are not well studied compared to their female counterparts. This study evaluates the cancer characteristics, family history of cancer, and outcomes of male BRCA1/2 mutation carriers. METHODS: All men with germline BRCA1/2 mutations who attended genetic assessment between October 1995 and October 2019 at the Medical University of Vienna were identified. Clinicohistopathological features, family history of cancer, and outcomes were assessed by mutation status. RESULTS: Of the 323 men included, 45 (13.9%) had a primary cancer diagnosis, many of whom were BRCA2 carriers (75.5%). Breast cancer (BC) was the most common cancer (57.8%) followed by prostate cancer (15.6%). Invasive ductal carcinoma and hormone receptor positive tumors were the most common. Among 26 BC-affected patients, 42% did not have any relatives with cancer. Parent of origin was only known in half of the 26 men, with 42% of them inherited through the maternal lineage versus 8% through the paternal. BRCA2 carriers and those with a family history of BC had worse overall survival (20 y vs. 23 y BRCA1 carriers; P = 0.007; 19 y vs. 21 y for those without family history of BC; P = 0.036). CONCLUSION: Male BRCA2 carriers were most likely to develop cancer and had worse prognosis. In our dataset, BC was the most common cancer, likely due to referral bias. Not all mutation carriers present with BC or have a family history of cancer to warrant genetic testing.
- Publikační typ
- časopisecké články MeSH
PURPOSE OF REVIEW: Despite the plethora of publications discussing the severe respiratory coronavirus 2 (SARS-CoV-2), evidence of viral secretion in urine is sparse. RECENT FINDINGS: We could identify 34 publications including a total of 2172 patients. Among those, 549 patients were tested for SARS-CoV-2 secretion in urine, which was detected in only 38 patients (6.9%). Within the seven studies displaying positive results, the majority of positive patients (86.8%) was from not yet peer-reviewed studies including weak data and heterogeneous techniques for sample testing. Furthermore, none of the studies available in the literature addressed the virulence of detected viral RNA in urine. SUMMARY: Overall, only seven studies were able to detect SARS-CoV-2 secretion in urine, all of them with a considerably low rate of positivity. However, these studies were of rather low quality considering their methodology. Despite this, as SARS-CoV-2 has been detected in urine, it is of importance to discuss safety and urinary hygiene protocols. Until further research provides valid data on viral shedding and virulence in urine, potential risk of transmission through urine cannot be ruled out. Therefore, safety and hygiene measures need to be discussed.
- MeSH
- Betacoronavirus izolace a purifikace MeSH
- koronavirové infekce moč MeSH
- lidé MeSH
- pandemie MeSH
- virová pneumonie moč MeSH
- vylučování virů * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
PURPOSE OF REVIEW: This review provides an overview of currently ongoing clinical trials evaluating the combination of immune checkpoint inhibitors (CPI) with other therapies in locally advanced or metastatic urothelial cancer and the rationale for this combination approach. We discuss the preliminary results from early data presented at recent meetings regarding the efficacy and safety of novel combination therapies including a CPI for metastatic urothelial cancer. RECENT FINDINGS: CPI emerged as novel first-line or second-line treatment options in advanced and metastatic urothelial cancer (mUC). Although the response rates and their sustainability are promising, it is far from a home run. Combination therapies have already shown improved efficacy in several other tumor entities. SUMMARY: Numerous clinical trials currently investigate combinations of CPI with other CPI, previously established systemic chemotherapy, targeted therapies, vaccines, or accompanied with radiotherapy. Preliminary data shows promising results. These results suggest that targeting pathways of immune response combined with established or novel oncological therapies may lead to a synergistic antitumor effect.
- MeSH
- inhibitory kontrolních bodů terapeutické užití MeSH
- karcinom z přechodných buněk farmakoterapie sekundární MeSH
- klinické zkoušky jako téma MeSH
- kombinovaná terapie MeSH
- lidé MeSH
- protinádorové látky imunologicky aktivní terapeutické užití MeSH
- urologické nádory farmakoterapie patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
PURPOSE OF REVIEW: To acquaint urologists with aristolochic acid nephropathy, an iatrogenic disease that poses a distinct threat to global public health. In China alone, 100 million people may currently be at risk. We illustrate the power of molecular epidemiology in establishing the cause of this disease. RECENT FINDINGS: Molecular epidemiologic approaches and novel mechanistic information established a causative linkage between exposure to aristolochic acid and urothelial carcinomas of the bladder and upper urinary tract. Noninvasive tests are available that detect urothelial cancers through the genetic analysis of urinary DNA. Combined with cytology, some of these tests can detect 95% of patients at risk of developing bladder and/or upper urothelial tract cancer. Robust biomarkers, including DNA-adduct and mutational signature analysis, unequivocally identify aristolochic acid-induced tumours. The high mutational load associated with aristolochic acid-induced tumours renders them candidates for immune-checkpoint therapy. SUMMARY: Guided by recent developments that facilitate early detection of urothelial cancers, the morbidity and mortality associated with aristolochic acid-induced bladder and upper tract urothelial carcinomas may be substantially reduced. The molecular epidemiology tools that define aristolochic acid-induced tumours may be applicable to other studies assessing potential environmental carcinogens.
- MeSH
- adukty DNA genetika metabolismus MeSH
- balkánská nefropatie chemicky indukované MeSH
- karcinogeny MeSH
- kyseliny aristolochové toxicita MeSH
- léky rostlinné čínské škodlivé účinky MeSH
- lidé MeSH
- nádory močového měchýře chemicky indukované MeSH
- urologické nádory chemicky indukované MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
PURPOSE OF REVIEW: Immune-checkpoint inhibitors (CPIs) have been implemented in the treatment algorithm of metastatic urothelial cancer as they have shown higher and more sustained responses compared with conventional second-line chemotherapy. Recently, several clinical trials have reported on CPIs in earlier disease stages such as muscle-invasive bladder cancer (MIBC). This review summarizes ongoing clinical trials and results from early phase clinical trials in muscle invasive and locally advanced bladder cancer. RECENT FINDINGS: In phase II clinical trials, neoadjuvant use of CPIs as mono and combination therapy, in patients with MIBC planned for radical cystectomy, has shown promising pathological complete response rates. Whether this will translate in survival benefit remains to be assessed. Combination of CPIs and conventional chemotherapy or other targeted agents promises to increase the efficacy of perioperative systemic therapy with potentially additive toxicities. Recently, preclinical models of combined trimodal therapy with CPIs delivered the proof of principle leading to several ongoing trials in this setting. SUMMARY: First results of clinical trials evaluating CPIs in MIBC demonstrate very promising results that warrant further investigation as they could revolutionize management of MIBC in the near future. The trend and hope are toward higher rates of safe and sustained bladder preservation.
- MeSH
- cystektomie MeSH
- inhibitory kontrolních bodů terapeutické užití MeSH
- invazivní růst nádoru MeSH
- karcinom z přechodných buněk farmakoterapie patologie MeSH
- klinické zkoušky, fáze II jako téma * MeSH
- lidé MeSH
- nádory močového měchýře farmakoterapie patologie MeSH
- nádory svalů farmakoterapie patologie MeSH
- neoadjuvantní terapie metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
