Pub Date : 2024-08-09DOI: 10.1038/s41585-024-00930-7
Maria Chiara Masone
{"title":"Utility of PSA screening in transgender women receiving oestrogens","authors":"Maria Chiara Masone","doi":"10.1038/s41585-024-00930-7","DOIUrl":"10.1038/s41585-024-00930-7","url":null,"abstract":"","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"21 9","pages":"518-518"},"PeriodicalIF":12.1,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141909067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-07DOI: 10.1038/s41585-024-00913-8
Renu S. Eapen, Scott G. Williams, Sean Macdonald, Simon P. Keam, Nathan Lawrentschuk, Lewis Au, Michael S. Hofman, Declan G. Murphy, Paul J. Neeson
High-risk localized prostate cancer remains a lethal disease with high rates of recurrence, metastases and death, despite attempts at curative local treatment including surgery. Disease recurrence is thought to be a result of failure of local control and occult micrometastases. Neoadjuvant strategies before surgery have been effective in many cancers, but, to date, none has worked in this setting for prostate cancer. Prostate-specific membrane antigen (PSMA)-based theranostics is an exciting and rapidly evolving field in prostate cancer. The novel intravenous radionuclide therapy, [177Lu]Lu-PSMA-617 (lutetium PSMA) has been shown to be effective in treating men with metastatic castration-resistant prostate cancer, targeting cells expressing PSMA throughout the body. When given in a neoadjuvant setting, lutetium PSMA might also improve long-term oncological outcomes in men with high-risk localized disease. A component of radiotherapy is potentially an immunogenic form of cancer cell death. Lutetium PSMA could cause cancer cell death, resulting in release of tumour antigens and induction of a tumour-specific systemic immune response. This targeted radioligand treatment has the potential to treat local and systemic tumour sites by directly targeting cells that express PSMA, but might also act indirectly via this systemic immune response. In selected patients, lutetium PSMA could potentially be combined with systemic immunotherapies to augment the antitumour T cell response, and this might produce long-lasting immunity in prostate cancer. Lutetium PSMA is approved for the treatment of advanced prostate cancer and is being studied in a neoadjuvant setting. The influence of lutetium PSMA on the tumour immune microenvironment is unknown. In selected patients, lutetium PSMA could be used as a stand-alone treatment or in combination with immunotherapy to produce long-lasting antitumour immunity.
{"title":"Neoadjuvant lutetium PSMA, the TIME and immune response in high-risk localized prostate cancer","authors":"Renu S. Eapen, Scott G. Williams, Sean Macdonald, Simon P. Keam, Nathan Lawrentschuk, Lewis Au, Michael S. Hofman, Declan G. Murphy, Paul J. Neeson","doi":"10.1038/s41585-024-00913-8","DOIUrl":"10.1038/s41585-024-00913-8","url":null,"abstract":"High-risk localized prostate cancer remains a lethal disease with high rates of recurrence, metastases and death, despite attempts at curative local treatment including surgery. Disease recurrence is thought to be a result of failure of local control and occult micrometastases. Neoadjuvant strategies before surgery have been effective in many cancers, but, to date, none has worked in this setting for prostate cancer. Prostate-specific membrane antigen (PSMA)-based theranostics is an exciting and rapidly evolving field in prostate cancer. The novel intravenous radionuclide therapy, [177Lu]Lu-PSMA-617 (lutetium PSMA) has been shown to be effective in treating men with metastatic castration-resistant prostate cancer, targeting cells expressing PSMA throughout the body. When given in a neoadjuvant setting, lutetium PSMA might also improve long-term oncological outcomes in men with high-risk localized disease. A component of radiotherapy is potentially an immunogenic form of cancer cell death. Lutetium PSMA could cause cancer cell death, resulting in release of tumour antigens and induction of a tumour-specific systemic immune response. This targeted radioligand treatment has the potential to treat local and systemic tumour sites by directly targeting cells that express PSMA, but might also act indirectly via this systemic immune response. In selected patients, lutetium PSMA could potentially be combined with systemic immunotherapies to augment the antitumour T cell response, and this might produce long-lasting immunity in prostate cancer. Lutetium PSMA is approved for the treatment of advanced prostate cancer and is being studied in a neoadjuvant setting. The influence of lutetium PSMA on the tumour immune microenvironment is unknown. In selected patients, lutetium PSMA could be used as a stand-alone treatment or in combination with immunotherapy to produce long-lasting antitumour immunity.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"21 11","pages":"676-686"},"PeriodicalIF":12.1,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141902472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-02DOI: 10.1038/s41585-024-00914-7
Mitchell Olislagers, Florus C. de Jong, Vera C. Rutten, Joost L. Boormans, Tokameh Mahmoudi, Tahlita C. M. Zuiverloon
The global incidence of bladder cancer is more than half a million diagnoses each year. Bladder cancer can be categorized into non-muscle-invasive bladder cancer (NMIBC), which accounts for ~75% of diagnoses, and muscle-invasive bladder cancer (MIBC). Up to 45% of patients with NMIBC develop disease progression to MIBC, which is associated with a poor outcome, highlighting a clinical need to identify these patients. Current risk stratification has a prognostic value, but relies solely on clinicopathological parameters that might not fully capture the complexity of disease progression. Molecular research has led to identification of multiple crucial players involved in NMIBC progression. Identified biomarkers of progression are related to cell cycle, MAPK pathways, apoptosis, tumour microenvironment, chromatin stability and DNA-damage response. However, none of these biomarkers has been prospectively validated. Reported gene signatures of progression do not improve NMIBC risk stratification. Molecular subtypes of NMIBC have improved our understanding of NMIBC progression, but these subtypes are currently unsuitable for clinical implementation owing to a lack of prospective validation, limited predictive value as a result of intratumour subtype heterogeneity, technical challenges, costs and turnaround time. Future steps include the development of consensus molecular NMIBC subtypes that might improve conventional clinicopathological risk stratification. Prospective implementation studies of biomarkers and the design of biomarker-guided clinical trials are required for the integration of molecular biomarkers into clinical practice.
{"title":"Molecular biomarkers of progression in non-muscle-invasive bladder cancer — beyond conventional risk stratification","authors":"Mitchell Olislagers, Florus C. de Jong, Vera C. Rutten, Joost L. Boormans, Tokameh Mahmoudi, Tahlita C. M. Zuiverloon","doi":"10.1038/s41585-024-00914-7","DOIUrl":"https://doi.org/10.1038/s41585-024-00914-7","url":null,"abstract":"<p>The global incidence of bladder cancer is more than half a million diagnoses each year. Bladder cancer can be categorized into non-muscle-invasive bladder cancer (NMIBC), which accounts for ~75% of diagnoses, and muscle-invasive bladder cancer (MIBC). Up to 45% of patients with NMIBC develop disease progression to MIBC, which is associated with a poor outcome, highlighting a clinical need to identify these patients. Current risk stratification has a prognostic value, but relies solely on clinicopathological parameters that might not fully capture the complexity of disease progression. Molecular research has led to identification of multiple crucial players involved in NMIBC progression. Identified biomarkers of progression are related to cell cycle, MAPK pathways, apoptosis, tumour microenvironment, chromatin stability and DNA-damage response. However, none of these biomarkers has been prospectively validated. Reported gene signatures of progression do not improve NMIBC risk stratification. Molecular subtypes of NMIBC have improved our understanding of NMIBC progression, but these subtypes are currently unsuitable for clinical implementation owing to a lack of prospective validation, limited predictive value as a result of intratumour subtype heterogeneity, technical challenges, costs and turnaround time. Future steps include the development of consensus molecular NMIBC subtypes that might improve conventional clinicopathological risk stratification. Prospective implementation studies of biomarkers and the design of biomarker-guided clinical trials are required for the integration of molecular biomarkers into clinical practice.</p>","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"50 1","pages":""},"PeriodicalIF":15.3,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141877447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-08-02DOI: 10.1038/s41585-024-00912-9
Raghav Gupta, Chandan K. Das, Sujit S. Nair, Adriana Marcela Pedraza-Bermeo, Ali H. Zahalka, Natasha Kyprianou, Nina Bhardwaj, Ashutosh K. Tewari
Clinically localized prostate cancer is often treated with radical prostatectomy combined with pelvic lymph node dissection. Data suggest that lymph node dissection does improve disease staging, but its therapeutic value has often been debated, with few studies showing that lymph node removal directly improves oncological outcomes; however, lymph nodes are an important first site of antigen recognition and immune system activation and the success of many currently used immunological therapies hinges on this dogma. Evidence, particularly in the preclinical setting, has demonstrated that the success of immune checkpoint inhibitors is dampened by the removal of tumour-draining lymph nodes. Thus, whether lymph nodes are truly ‘foes’ or whether they are actually ‘friends’ in oncological care is an important idea to discuss. Pelvic lymph node dissection is performed for staging and to prevent recurrence of prostate cancer; however, immune checkpoint inhibition could be affected by lymph node removal. Here, the authors discuss the possibility that lymph nodes could be ‘friends’ rather than ‘foes’ in prostate cancer treatment.
{"title":"From foes to friends: rethinking the role of lymph nodes in prostate cancer","authors":"Raghav Gupta, Chandan K. Das, Sujit S. Nair, Adriana Marcela Pedraza-Bermeo, Ali H. Zahalka, Natasha Kyprianou, Nina Bhardwaj, Ashutosh K. Tewari","doi":"10.1038/s41585-024-00912-9","DOIUrl":"10.1038/s41585-024-00912-9","url":null,"abstract":"Clinically localized prostate cancer is often treated with radical prostatectomy combined with pelvic lymph node dissection. Data suggest that lymph node dissection does improve disease staging, but its therapeutic value has often been debated, with few studies showing that lymph node removal directly improves oncological outcomes; however, lymph nodes are an important first site of antigen recognition and immune system activation and the success of many currently used immunological therapies hinges on this dogma. Evidence, particularly in the preclinical setting, has demonstrated that the success of immune checkpoint inhibitors is dampened by the removal of tumour-draining lymph nodes. Thus, whether lymph nodes are truly ‘foes’ or whether they are actually ‘friends’ in oncological care is an important idea to discuss. Pelvic lymph node dissection is performed for staging and to prevent recurrence of prostate cancer; however, immune checkpoint inhibition could be affected by lymph node removal. Here, the authors discuss the possibility that lymph nodes could be ‘friends’ rather than ‘foes’ in prostate cancer treatment.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"21 11","pages":"687-700"},"PeriodicalIF":12.1,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141877399","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-26DOI: 10.1038/s41585-024-00921-8
Jamie O. Lo, Charles A. Easley
Paternal origins of health and disease is an emerging paradigm highlighting the influence of paternal environmental exposures, including diet and lifestyle, on offspring health. The influence of the paternal gut microbiota on the germ line and offspring outcomes has been investigated in a new study.
{"title":"Paternal microbiome perturbations affect offspring outcomes","authors":"Jamie O. Lo, Charles A. Easley","doi":"10.1038/s41585-024-00921-8","DOIUrl":"10.1038/s41585-024-00921-8","url":null,"abstract":"Paternal origins of health and disease is an emerging paradigm highlighting the influence of paternal environmental exposures, including diet and lifestyle, on offspring health. The influence of the paternal gut microbiota on the germ line and offspring outcomes has been investigated in a new study.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"22 1","pages":"6-7"},"PeriodicalIF":12.1,"publicationDate":"2024-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141766837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-16DOI: 10.1038/s41585-024-00916-5
Maria Chiara Masone
{"title":"Syphilis on the rise — a need for alternative therapies and vaccines","authors":"Maria Chiara Masone","doi":"10.1038/s41585-024-00916-5","DOIUrl":"10.1038/s41585-024-00916-5","url":null,"abstract":"","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"21 8","pages":"457-457"},"PeriodicalIF":12.1,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141625029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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