{"title":"Predicting surgical outcome for renal tumours","authors":"Isobel Leake","doi":"10.1038/s41585-024-00987-4","DOIUrl":"https://doi.org/10.1038/s41585-024-00987-4","url":null,"abstract":"<p>A new 3D method of calculating contact surface area (CSA) for renal tumours is reported in <i>Urologic Oncology</i>. This method can reliably predict perioperative outcomes following robot-assisted partial nephrectomy (RAPN).</p><p>Several scores can be used to assess renal tumour complexity and complications, including R.E.N.A.L. and PADUA, but these scores were developed prior to the concept of 3D reconstruction. The idea of the CSA calculation was introduced 10 years ago to quantify the contact area between the renal tumour and surrounding healthy parenchyma. However, the CSA calculation assumes that renal tumours are spherical.</p>","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"9 1","pages":""},"PeriodicalIF":15.3,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142804543","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}
{"title":"Diagnosis of ccRCC","authors":"Isobel Leake","doi":"10.1038/s41585-024-00988-3","DOIUrl":"https://doi.org/10.1038/s41585-024-00988-3","url":null,"abstract":"<p>Diagnosis of clear cell renal cell carcinoma (ccRCC) is challenging, particularly as [<sup>18</sup>F]FDG PET–CT is not routinely recommended. Novel single-domain antibody (sdAb) tracers could be useful in cancer imaging owing to their small size and high target recognition.</p><p>In the first part of a study published in the <i>Journal of Nuclear Medicine</i>, Zhou et al. analysed CD70 expression in RCC and normal kidney tissues, given its known potential as a diagnostic and therapeutic target. Normal kidney tissue did not express CD70, and CD70 expression was significantly higher in ccRCC than in papillary RCC (<i>P</i> < 0.001) and chromophobe RCC (<i>P</i> < 0.001). Notably, CD70 expression was unaffected by tumour differentiation or metastasis status.</p>","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"96 1","pages":""},"PeriodicalIF":15.3,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142804478","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}
{"title":"Neoadjuvant therapy in MIBC","authors":"Isobel Leake","doi":"10.1038/s41585-024-00989-2","DOIUrl":"https://doi.org/10.1038/s41585-024-00989-2","url":null,"abstract":"<p>Efficacious neoadjuvant therapy is an unmet need in cisplatin-ineligible patients with muscle-invasive bladder cancer (MIBC). Several early-phase clinical trials have investigated the use of immune checkpoint inhibitors (ICIs) in this context, with some promising results. A study in <i>Nature Medicine</i> set out to test whether the efficacy of ICIs could be improved in combination with other therapies.</p><p>Cretostimogene grenadenorepvec is an oncolytic immunotherapy, which also selectively expresses granulocyte–macrophage colony-stimulating factor (thought to boost cancer control). The authors conducted a phase Ib trial of intravesical cretostimogene and nivolumab (an ICI) to test the safety and efficacy of this combination.</p>","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"28 1","pages":""},"PeriodicalIF":15.3,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142804533","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}
{"title":"Virtual reality for nephrolithotomy","authors":"Isobel Leake","doi":"10.1038/s41585-024-00990-9","DOIUrl":"https://doi.org/10.1038/s41585-024-00990-9","url":null,"abstract":"<p>Percutaneous nephrolithotomy (PCNL) is the main surgical option for the management of large or complex renal stones. A study in the <i>Journal of Urology</i> investigated whether immersive virtual reality (iVR) could improve surgical planning and clinical outcomes in patients undergoing PCNL.</p><p>Patients undergoing PCNL (<i>n</i> = 175) were randomly allocated to a CT-only or CT plus iVR group. The iVR models incorporated CT images to enable the surgeon to visualize and manipulate anatomy and to simulate the percutaneous approach to the proposed calyx.</p>","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"78 1","pages":""},"PeriodicalIF":15.3,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142804540","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}
{"title":"Personalized 3D models for prostate cancer surgery","authors":"Maria Chiara Masone","doi":"10.1038/s41585-024-00986-5","DOIUrl":"https://doi.org/10.1038/s41585-024-00986-5","url":null,"abstract":"<p>Nerve-sparing surgery is the standard approach used in radical prostatectomy to enhance functional outcomes, but secondary resection might be needed in case of uncertainty regarding the complete removal of the tumour. However, direct visual guidance for resecting positive surgical margins (PSMs) during secondary resection is lacking.</p><p>In a study published in <i>BJU International</i>, a 3D-printed prostate model was used to improve surgical precision of targeted secondary resection during nerve-sparing robot-assisted radical prostatectomy. Overall, 100 patients undergoing nerve-sparing robot-assisted radical prostatectomy were enrolled in this prospective, multicentre study. 3D models were derived from pelvic MRI to guide intraoperative secondary resection of PSMs. This approach led to a successful conversion of PSMs to negative surgical margins in 83% of patients, 95% of whom achieved undetectable PSA levels postoperatively. These results indicate that PSMs marked on a 3D model by the pathologist can improve communication between the pathologist and surgeon, ultimately improving accuracy of the secondary resection site identification. The authors acknowledged some limitations of this study, including the lack of a control group, but concluded that the integration of personalized 3D models in surgical practice could substantially optimize precision in prostate cancer secondary resection.</p>","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"1 1","pages":""},"PeriodicalIF":15.3,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142804542","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}
Jan Krhut, Hanne Kobberø, Reine Kanaan, Mikkel Fode, Mads Poulsen, Peter Zvara
{"title":"The mechanism of action of neuromodulation in the treatment of overactive bladder","authors":"Jan Krhut, Hanne Kobberø, Reine Kanaan, Mikkel Fode, Mads Poulsen, Peter Zvara","doi":"10.1038/s41585-024-00967-8","DOIUrl":"https://doi.org/10.1038/s41585-024-00967-8","url":null,"abstract":"<p>Neuromodulation has been used in the treatment of various pelvic organ dysfunctions for almost 40 years and several placebo-controlled studies have confirmed its clinical effect. Many neuromodulation methods using different devices and stimulation parameters, targeting different neural structures have been introduced, but only a limited number have been adopted into routine clinical use. A substantial volume of basic research and clinical studies addressing specific effects of neuromodulation in the treatment of overactive bladder (OAB) have been published to date; however, their mechanistic implications have not been comprehensively summarized. Thus, our understanding of the mechanism of action of neuromodulation in OAB treatment is mainly based on postulated theories. Results from animal experiments suggest that different neuromodulation methods used to treat OAB share the same basic principles. The most likely explanation for the effect of neuromodulation in OAB therapy is the suppression of bladder afferent signalling, promotion of spinal guarding reflexes and modulation of non-specific supraspinal regulatory circuits.</p>","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"28 1","pages":""},"PeriodicalIF":15.3,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142793381","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}
{"title":"Serial ctDNA to understand PARPi resistance","authors":"Annette Fenner","doi":"10.1038/s41585-024-00984-7","DOIUrl":"https://doi.org/10.1038/s41585-024-00984-7","url":null,"abstract":"<p>Poly(ADP-ribose) polymerase inhibition (PARPi) is an effective therapy for castration-resistant prostate cancer (CRPC) with defects in homologous recombination repair (HRR) genes. However, resistance to PARPi can arise, for example via mutations that restore <i>BRCA</i> function. Reversion mutations in HRR genes can result in PARPi resistance, but these cannot arise in patients with homozygous mutations, possibly explaining why patients with homozygous <i>BRCA2</i> mutations exhibit more durable responses to PARPi. The mechanisms of resistance in patients with homozygous mutations is unknown and how such mutations occur is not well understood.</p><p>A study in <i>Cancer Cell</i> has sought to elucidate these mechanisms, using data from the phase II TOPARP-B trial, which demonstrated antitumour activity of olaparib in patients with metastatic CRPC who had biallelic DNA-damage repair mutations. Notably, the most durable responses were seen in patients with <i>BRCA2</i> homozygous deletion. These data were also supported by the PROFound trial, which showed reduced radiological progression-free survival (rPFS) in patients with <i>BRCA2</i> heterozygous mutations compared with those with a homozygous mutation.</p>","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"18 1","pages":""},"PeriodicalIF":15.3,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142793380","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}
{"title":"PFOA affects androgen metabolism","authors":"Louise Lloyd","doi":"10.1038/s41585-024-00985-6","DOIUrl":"https://doi.org/10.1038/s41585-024-00985-6","url":null,"abstract":"<p>A novel, endocrine-disrupting property of the perfluoroalkyl substance perfluorooctanoic acid (PFOA) affecting androgen metabolism has been discovered. This discovery has implications for our understanding of the effect of PFOA on the actions of androgens.</p><p>In spectrofluorimetric inhibitor screens and inhibition studies, PFOA was identified to potently, competitively and specifically inhibit aldo-keto reductase 1C2 (AKR1C2), which catalyses the reduction of 5α-dihydrotestosterone (5α-DHT) to the inactive steroid 3α-androstanediol, in the nanomolar range. This property was found to be a result of valine being present in the binding pocket. Thus, PFOA inhibited the reduction of 5α-DHT, resulting in its accumulation. Androgen receptor transactivation was increased by PFOA-induced blocking of 5α-DHT metabolism owing to inhibition of AKR1C2.</p>","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"220 1","pages":""},"PeriodicalIF":15.3,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142788537","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}
{"title":"PEACEing together prostate cancer therapy","authors":"Louise Lloyd","doi":"10.1038/s41585-024-00982-9","DOIUrl":"https://doi.org/10.1038/s41585-024-00982-9","url":null,"abstract":"<p>Results of the PEACE-1 open-label, randomized, controlled, phase III trial have been published in <i>The Lancet</i>. In this study, the efficacy and safety of adding prostate radiotherapy to the treatment regimen in de novo metastatic castration-sensitive prostate cancer was investigated. In total, 1,172 men were randomly assigned to receive standard of care or standard of care plus abiraterone, plus radiotherapy or plus abiraterone and radiotherapy. After a median follow-up duration of 6 years, radiographic progression-free and castration-free survival were improved for men who received standard of care plus abiraterone and radiotherapy. However, overall survival was not affected.</p>","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"27 1","pages":""},"PeriodicalIF":15.3,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142788536","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}
{"title":"JAK–STAT signalling and prostate basal cell fate","authors":"Louise Lloyd","doi":"10.1038/s41585-024-00983-8","DOIUrl":"https://doi.org/10.1038/s41585-024-00983-8","url":null,"abstract":"<p>A rare intermediate population of basal cells expressing luminal markers has been identified. Markers of this cell population include <i>Nkx3.1</i>, <i>Pbsn</i>, <i>C1rb</i>, <i>Fgl1</i> and <i>Mmp7</i>. In these cells, termed Basal-B cells, activated JAK–STAT signalling was identified and its inhibition reduced expression of the markers characterizing these cells. Inflammation increased Basal-B cell-to-luminal cell transdifferentiation and JAK–STAT inhibition decreased this process. Deletion of PTEN increased the numbers of NKX3.1-expressing Basal-B-like cells. Thus, Basal-B cells have been identified as a crucial intermediate population within the prostate basal cell population. Moreover, JAK–STAT signalling was identified as a potential target for patients with prostate inflammation.</p>","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"20 1","pages":""},"PeriodicalIF":15.3,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142788538","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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