Nature Reviews Urology最新文献

Non-muscle-invasive bladder cancer (NMIBC) is the most common type of bladder cancer presentation and is characterized by a varying probability of recurrence and progression. Sporadically, patients with NMIBC might also develop tumour metastases without any pathological evidence of muscle-invasive disease within the bladder, a condition known as metastatic NMIBC. In the published literature, this phenomenon is limited to several case reports and small reviews, with few data regarding the possible aetiologies. Several possible factors can be potentially associated with metastatic NMIBC, including tumour understaging, the number of transurethral resection procedures received by the patient, the presence of circulating tumour cells, the modality used for diagnostic cystoscopy and possible gender-associated differences. In this Perspective, our aim was to integrate and report currently available data on this relatively rare entity and provide some potential aetiological explanations.

Increasing evidence suggested the multifactorial nature of nocturia, but the true pathogenesis of this condition still remains to be elucidated. Contemporary clinical medications are mostly symptom based, aimed at either reducing nocturnal urine volume or targeting autonomic receptors within the bladder to facilitate urine storage. The day-night switch of the micturition pattern is controlled by circadian clocks located both in the central nervous system and in the peripheral organs. Arousal threshold and secretion of melatonin and vasopressin increase at night-time to achieve high-quality sleep and minimize nocturnal urine production. In response to the increased vasopressin, the kidney reduces the glomerular filtration rate and facilitates the reabsorption of water. Synchronously, in the bladder, circadian oscillation of crucial molecules occurs to reduce afferent sensory input and maintain sufficient bladder capacity during the night sleep period. Thus, nocturia might occur as a result of desynchronization in one or more of these circadian regulatory mechanisms. Disrupted rhythmicity of the central nervous system, kidney and bladder (known as the brain-kidney-bladder circadian axis) contributes to the pathogenesis of nocturia. Novel insights into the chronobiological nature of nocturia will be crucial to promote a revolutionary shift towards effective therapeutics targeting the realignment of the circadian rhythm.

Androgen receptor stimulation by testosterone and dihydrotestosterone is crucial for prostate cancer progression. Despite the initial effectiveness of androgen deprivation therapy (ADT), castration-resistant prostate cancer eventually develops in most men. A common germline missense-encoding polymorphism in HSD3B1 increases extra-gonadal androgen biosynthesis from adrenal precursors owing to increased availability of the encoded enzyme 3β-hydroxysteroid dehydrogenase 1 (3βHSD1) — hence, it is called the adrenal-permissive enzyme. This mechanism explains the more rapid progression to castration-resistant prostate cancer in men who inherit this allele than in men without it via sustained androgen receptor activation despite ADT. Multiple clinical studies, including data derived from prospective phase III studies, have linked adrenal-permissive allele inheritance to inferior clinical responses to ADT and increased mortality, but reversal is possible with upfront adrenal androgen blockade. The adrenal-permissive allele exhibits divergent frequencies across various groups worldwide, which could contribute to differences in clinical outcomes among these populations. Large-scale data from the Million Veteran Program have shown homozygous HSD3B1 adrenal-permissive allele inheritance to be an independent biomarker of prostate cancer-specific mortality. Together, these observations support the integration of HSD3B1 into germline testing and clinical trials as it might help to identify groups at increased likelihood of benefiting from early, intensified, AR-targeting interventions. Lastly, 3βHSD1 is a promising target for pharmacological inhibition, which enables new strategies for systemic prostate cancer therapy.

The clinical diagnosis of renal cell carcinoma (RCC) is constantly evolving. Diagnostic imaging of RCC relying on enhanced computed tomography (CT) and magnetic resonance imaging (MRI) is commonly used for renal mass characterization and assessment of tumour thrombosis, whereas pathology is the gold standard for establishing diagnosis. However, molecular imaging is rapidly improving the clinical management of RCC, particularly clear-cell RCC. Molecular imaging aids in the non-invasive visualization and characterization of specific biomarkers such as carbonic anhydrase IX and CD70 within the tumours, which help to assess tumour heterogeneity and status. Target-specific molecular imaging of RCCs will substantially improve the diagnostic landscape of RCC and will further facilitate clinical decision-making regarding initial staging and re-staging, monitoring of recurrence and metastasis, patient stratification and selection, and the prediction and evaluation of treatment responses.

A study published in Nature investigating tumour metabolism in kidney cancers provides insight into the influence of mitochondria and cellular metabolism on metastasis in this disease.

In this study, a ¹³C-labelled nutrient, [U-¹³C]glucose, was administered through a peripheral intravenous line to patients with varying subtypes of renal cell carcinoma (RCC) undergoing partial or radical nephrectomy during their surgery. Overall, 59 patients, 37 of whom had clear cell RCC (ccRCC), were included.

From 23 to 25 October 2024, Madrid hosted the 54th edition of the annual meeting of the International Continence Society (ICS), the leading multi-disciplinary event in the continence field, bringing together healthcare professionals in the fields of urology, gynaecology, physiotherapy and nursing with the common interest of treating incontinence.

The future of continence was the central theme of the meeting, with discussions exploring cutting-edge research and innovations. Talks from multiple sessions highlighted that we are entering a digital revolution in continence care, from the development of mobile apps for self-monitoring and remote patient monitoring to the many abstracts and talks about the use of artificial intelligence (AI) and machine learning in functional urology. Examples of AI application in the continence field presented at the meeting ranged from risk prediction to the analysis of genetic background to the improvement of phenotyping and diagnosis starting from already available data. Some of these topics were also organically covered in a round table discussion in which Andrew Gammie, Wouter Van Dort and Thomas van Steenbergen discussed rationale, methods, potential and challenges of big data analysis in urodynamics.

The decline in male fertility correlates with the global rise in obesity and dyslipidaemia, representing significant public health challenges. High-fat diets induce metabolic alterations, including hypercholesterolaemia, hepatic steatosis and atherosclerosis, with detrimental effects on testicular function. Testicular tissue, critically dependent on lipids for steroidogenesis, is particularly vulnerable to these metabolic disruptions. Excessive lipid accumulation within the testes, including cholesterol, triglycerides and specific fatty acids, disrupts essential sperm production processes such as membrane formation, maturation, energy metabolism and cell signalling. This leads to apoptosis, impaired spermatogenesis, and abnormal sperm morphology and function, ultimately compromising male fertility. During spermiogenesis, round spermatids undergo extensive reorganization, including the formation of the acrosome, manchette and specialized filamentous structures, which are essential for defining the final sperm cell shape. In this Perspective, we examine the impact of high-fat diets on the cytoskeleton of spermatogenic cells and its consequences to identify the mechanisms underlying male infertility associated with dyslipidaemia. Understanding these processes may facilitate the development of therapeutic strategies, such as dietary interventions or natural product supplementation, that aim to address infertility in men with obesity and hypercholesterolaemia. The investigation of cytoskeleton response to lipid stress extends beyond male reproduction, offering insights with broader implications.

The multicentre, randomized, phase III trial TiNivo-2 was conducted to assess the efficacy of the vascular endothelial growth factor receptor inhibitor tivozanib alone versus in combination with the immune checkpoint inhibitor (ICI) nivolumab in patients with advanced renal cell carcinoma (RCC) who had progressed during or after 1–2 previous lines of therapy including one ICI. Progression-free survival (PFS) was higher in patients in the monotherapy group (7.4 months) than in patients receiving combination therapy (5.7 months; HR 1.10, 95% CI 0.84–1.43; P = 0.49). These results show that re-challenging patients with advanced RCC with ICI therapy is not advisable and suggest tivozanib monotherapy as a viable treatment option in the post-ICI setting.

A new phase III, randomized, controlled trial was carried out to assess the efficacy of ¹⁷⁷Lu-PSMA-617 in patients with taxane-naive metastatic castration-resistant prostate cancer (mCRPC). A total of 468 patients with PSMA⁺ mCRPC who experienced disease progression after receiving an androgen receptor pathway inhibitor (ARPI) were randomly allocated to receive ¹⁷⁷Lu-PSMA-617 or a different ARPI. Treatment with ¹⁷⁷Lu-PSMA-617 resulted in improved median radiographic progression-free survival (PFS) compared with a change of ARPI (11.60 months (95% CI 9.30–14.19) versus 5.59 months (95% CI 4.21–5.95)), with a good safety profile. These results showed that ¹⁷⁷Lu-PSMA-617 prolonged radiographic PFS and could be a valid therapeutic alternative for patients considered for a change of ARPI.