Pub Date : 2026-02-07Epub Date: 2025-12-16DOI: 10.1016/S0140-6736(25)02221-4
Valérie Fonteyne, Alison Tree, Elena Castro, Karim Touijer, Jochen Walz
Prostate cancer poses a substantial clinical challenge and accounts for a large proportion of cancer-related deaths worldwide. The therapeutic landscape has undergone a large transformation in the past 5 years, resulting in improved patient outcomes. In this Seminar, we review the pathology, diagnostic strategies, and treatments for prostate cancer. Active surveillance is the preferred treatment option for patients with indolent prostate cancer. For those requiring treatment, local therapies provide effective cancer control. Systemic treatment is essential for advanced and metastatic cases, and a wide range of therapies are now available, including androgen deprivation therapy, chemotherapy, and emerging targeted agents such as lutetium-177-labelled prostate-specific membrane antigen radioligand therapy and PARP inhibitors. Considering toxicity profiles alongside patient preferences is important to facilitating shared decision making. Further research is needed to establish the most effective sequence and combination of treatments for metastatic prostate cancer.
{"title":"Prostate cancer.","authors":"Valérie Fonteyne, Alison Tree, Elena Castro, Karim Touijer, Jochen Walz","doi":"10.1016/S0140-6736(25)02221-4","DOIUrl":"10.1016/S0140-6736(25)02221-4","url":null,"abstract":"<p><p>Prostate cancer poses a substantial clinical challenge and accounts for a large proportion of cancer-related deaths worldwide. The therapeutic landscape has undergone a large transformation in the past 5 years, resulting in improved patient outcomes. In this Seminar, we review the pathology, diagnostic strategies, and treatments for prostate cancer. Active surveillance is the preferred treatment option for patients with indolent prostate cancer. For those requiring treatment, local therapies provide effective cancer control. Systemic treatment is essential for advanced and metastatic cases, and a wide range of therapies are now available, including androgen deprivation therapy, chemotherapy, and emerging targeted agents such as lutetium-177-labelled prostate-specific membrane antigen radioligand therapy and PARP inhibitors. Considering toxicity profiles alongside patient preferences is important to facilitating shared decision making. Further research is needed to establish the most effective sequence and combination of treatments for metastatic prostate cancer.</p>","PeriodicalId":18014,"journal":{"name":"The Lancet","volume":" ","pages":"622-636"},"PeriodicalIF":88.5,"publicationDate":"2026-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145794376","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 : 2026-02-07Epub Date: 2026-01-27DOI: 10.1016/S0140-6736(25)02255-X
Howard Trachtman, Matthias Kretzler, Loreto Gesualdo, Nicholas Cross, Biruh Workeneh, Jessica Kaufeld, Björn Meijers, Zhiming Ye, Qinkai Chen, Vimal K Derebail, Monica Suet Ying Ng, Bo Ji, Maximilian T Lobmeyer, Silke Retlich, Fabia T Licarião Rocha, Srinivasa Prasad, Nima Soleymanlou
<p><strong>Background: </strong>In focal segmental glomerulosclerosis (FSGS), transient receptor potential cation channel, subfamily C, member 6 (TRPC6) overactivity might cause podocyte loss and progressive kidney function decline. This exploratory study assessed the safety and efficacy of a novel once-daily oral selective TRPC6 inhibitor, BI 764198.</p><p><strong>Methods: </strong>This multicentre phase 2, double-blind, placebo-controlled, randomised controlled trial assessed BI 764198 (20 mg, 40 mg, or 80 mg once daily) versus placebo over 12 weeks in participants aged 18-75 years with biopsy-confirmed primary FSGS (based on the absence of clinical evidence of secondary cause) or with a disease-causing TRPC6 variant. The study took place in 31 sites in ten countries, and random allocation was performed centrally in blocks in a 1:1:1:1 ratio and was stratified according to use of corticosteroids. Participants were receiving stable conservative and immunosuppressive therapy, with screening urine protein-creatinine ratio (UPCR) at 1·0 g/g or greater and estimated glomerular filtration rate at 30 mL/min per 1·73 m<sup>2</sup> or greater. The primary endpoint was the proportion of participants with proteinuria response (≥25% UPCR reduction from baseline) at week 12. Other key outcomes were safety and tolerability. The study was registered with ClinicalTrials.gov on Jan 27, 2022 (NCT05213624) and is complete as of Jan 3, 2025.</p><p><strong>Findings: </strong>From March 10, 2022, to Sept 3, 2024, 139 participants were screened and 67 were randomly assigned to receive placebo or BI 764198 at doses of 20 mg, 40 mg, or 80 mg (five participants were randomly assigned in error and were not treated). 62 participants received treatment, two of whom had missing baseline or post-baseline UPCR measurements and were not included in the full analysis set. Overall, 37 participants (60%) were male and 25 participants (40%) were female; the mean age was 40·7 years (SD 12·6); and the majority of the trial cohort were White (39 [63%] of 62). Proteinuria responses were observed in eight (44%) of 18, two (14%) of 14, and six (43%) of 14 participants receiving BI 764198 20 mg, 40 mg, and 80 mg, respectively (16 [35%] of 46 for all BI 764198 doses) versus one (7%) of 14 receiving placebo; corresponding odds ratios (ORs) versus placebo were OR 10·0 (95% CI 1·6-118·1), 1·5 (0·2-19·5), and 6·0 (0·9-73·6) for the three doses of BI 764198, and 4·9 (1·0-48·8) for all doses combined. BI 764198 was well tolerated with no meaningful differences in adverse event frequencies across treatment arms; treatment-emergent adverse events were reported by 44 (71%) of 62 participants, with similar frequencies of adverse events observed in the placebo group (ten [71%] of 14) and BI 764198 groups (34 [71%] of 48).</p><p><strong>Interpretation: </strong>BI 764198 lowered proteinuria and was well tolerated by participants in this trial. This is the first evidence of efficacy with a podocyte-ta
{"title":"TRPC6 inhibition for the treatment of focal segmental glomerulosclerosis: a randomised, placebo-controlled, phase 2 trial of BI 764198.","authors":"Howard Trachtman, Matthias Kretzler, Loreto Gesualdo, Nicholas Cross, Biruh Workeneh, Jessica Kaufeld, Björn Meijers, Zhiming Ye, Qinkai Chen, Vimal K Derebail, Monica Suet Ying Ng, Bo Ji, Maximilian T Lobmeyer, Silke Retlich, Fabia T Licarião Rocha, Srinivasa Prasad, Nima Soleymanlou","doi":"10.1016/S0140-6736(25)02255-X","DOIUrl":"10.1016/S0140-6736(25)02255-X","url":null,"abstract":"<p><strong>Background: </strong>In focal segmental glomerulosclerosis (FSGS), transient receptor potential cation channel, subfamily C, member 6 (TRPC6) overactivity might cause podocyte loss and progressive kidney function decline. This exploratory study assessed the safety and efficacy of a novel once-daily oral selective TRPC6 inhibitor, BI 764198.</p><p><strong>Methods: </strong>This multicentre phase 2, double-blind, placebo-controlled, randomised controlled trial assessed BI 764198 (20 mg, 40 mg, or 80 mg once daily) versus placebo over 12 weeks in participants aged 18-75 years with biopsy-confirmed primary FSGS (based on the absence of clinical evidence of secondary cause) or with a disease-causing TRPC6 variant. The study took place in 31 sites in ten countries, and random allocation was performed centrally in blocks in a 1:1:1:1 ratio and was stratified according to use of corticosteroids. Participants were receiving stable conservative and immunosuppressive therapy, with screening urine protein-creatinine ratio (UPCR) at 1·0 g/g or greater and estimated glomerular filtration rate at 30 mL/min per 1·73 m<sup>2</sup> or greater. The primary endpoint was the proportion of participants with proteinuria response (≥25% UPCR reduction from baseline) at week 12. Other key outcomes were safety and tolerability. The study was registered with ClinicalTrials.gov on Jan 27, 2022 (NCT05213624) and is complete as of Jan 3, 2025.</p><p><strong>Findings: </strong>From March 10, 2022, to Sept 3, 2024, 139 participants were screened and 67 were randomly assigned to receive placebo or BI 764198 at doses of 20 mg, 40 mg, or 80 mg (five participants were randomly assigned in error and were not treated). 62 participants received treatment, two of whom had missing baseline or post-baseline UPCR measurements and were not included in the full analysis set. Overall, 37 participants (60%) were male and 25 participants (40%) were female; the mean age was 40·7 years (SD 12·6); and the majority of the trial cohort were White (39 [63%] of 62). Proteinuria responses were observed in eight (44%) of 18, two (14%) of 14, and six (43%) of 14 participants receiving BI 764198 20 mg, 40 mg, and 80 mg, respectively (16 [35%] of 46 for all BI 764198 doses) versus one (7%) of 14 receiving placebo; corresponding odds ratios (ORs) versus placebo were OR 10·0 (95% CI 1·6-118·1), 1·5 (0·2-19·5), and 6·0 (0·9-73·6) for the three doses of BI 764198, and 4·9 (1·0-48·8) for all doses combined. BI 764198 was well tolerated with no meaningful differences in adverse event frequencies across treatment arms; treatment-emergent adverse events were reported by 44 (71%) of 62 participants, with similar frequencies of adverse events observed in the placebo group (ten [71%] of 14) and BI 764198 groups (34 [71%] of 48).</p><p><strong>Interpretation: </strong>BI 764198 lowered proteinuria and was well tolerated by participants in this trial. This is the first evidence of efficacy with a podocyte-ta","PeriodicalId":18014,"journal":{"name":"The Lancet","volume":" ","pages":"587-598"},"PeriodicalIF":88.5,"publicationDate":"2026-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146093370","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 : 2026-01-03DOI: 10.1016/S0140-6736(25)02596-6
The Lancet
{"title":"No health without peace.","authors":"The Lancet","doi":"10.1016/S0140-6736(25)02596-6","DOIUrl":"https://doi.org/10.1016/S0140-6736(25)02596-6","url":null,"abstract":"","PeriodicalId":18014,"journal":{"name":"The Lancet","volume":"407 10523","pages":"1"},"PeriodicalIF":88.5,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145896660","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 : 2025-12-21Epub Date: 2024-08-28DOI: 10.1016/S0140-6736(24)01564-2
Wyatte C Hall, Julia L Hecht
{"title":"Primary health-care practices for deaf children should include early incorporation of a signed language.","authors":"Wyatte C Hall, Julia L Hecht","doi":"10.1016/S0140-6736(24)01564-2","DOIUrl":"10.1016/S0140-6736(24)01564-2","url":null,"abstract":"","PeriodicalId":18014,"journal":{"name":"The Lancet","volume":" ","pages":"2498-2500"},"PeriodicalIF":98.4,"publicationDate":"2025-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142108869","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 : 2025-12-13Epub Date: 2025-10-23DOI: 10.1016/S0140-6736(25)01497-7
Lana Moayad, Ariana Mihan, Sanne A E Peters, Harriette G C Van Spall
Randomised controlled trials have commonly excluded women who are pregnant, lactating, or of reproductive potential. When there is clinical equipoise, the exclusion of these women raises concerns regarding the principles of autonomy, beneficence, and justice. This exclusion also shifts evidence generation from the monitored setting of randomised controlled trials to clinical settings, where data can take several years to accrue. Here, we highlight key health, ethical, scientific, and regulatory considerations surrounding the inclusion of women who are pregnant, lactating, or of reproductive potential in clinical trials to guide further discussions. We offer recommendations for a judicious approach to inclusivity, highlighting regulatory, sponsor, and clinical trial design considerations. We highlight the need for patient engagement and interdisciplinary discourse throughout the research lifecycle.
{"title":"Inclusion of women who are pregnant, lactating, or of reproductive potential in clinical trials: health, ethical, and regulatory considerations.","authors":"Lana Moayad, Ariana Mihan, Sanne A E Peters, Harriette G C Van Spall","doi":"10.1016/S0140-6736(25)01497-7","DOIUrl":"https://doi.org/10.1016/S0140-6736(25)01497-7","url":null,"abstract":"<p><p>Randomised controlled trials have commonly excluded women who are pregnant, lactating, or of reproductive potential. When there is clinical equipoise, the exclusion of these women raises concerns regarding the principles of autonomy, beneficence, and justice. This exclusion also shifts evidence generation from the monitored setting of randomised controlled trials to clinical settings, where data can take several years to accrue. Here, we highlight key health, ethical, scientific, and regulatory considerations surrounding the inclusion of women who are pregnant, lactating, or of reproductive potential in clinical trials to guide further discussions. We offer recommendations for a judicious approach to inclusivity, highlighting regulatory, sponsor, and clinical trial design considerations. We highlight the need for patient engagement and interdisciplinary discourse throughout the research lifecycle.</p>","PeriodicalId":18014,"journal":{"name":"The Lancet","volume":"406 10521","pages":"2858-2864"},"PeriodicalIF":88.5,"publicationDate":"2025-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145810458","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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