Priapism is an abnormal prolonged penile erection that persists in the absence of any sexual stimulation. Priapism can be subcategorized into three types: ischaemic (low-flow or veno-occlusive), non-ischaemic (high-flow or arterial) and stuttering priapism. Ischaemic priapism is the most common subtype and is associated with multiple aetiologies, most commonly haemoglobinopathies and antipsychotic medications. The mechanisms underlying stuttering priapism are complex, and involve dysregulation of the nitric oxide signalling pathway, Rho-Rho kinase pathway, adenosine, opiorphins, oxidative stress and androgens. The investigation and management of priapism involve a stepwise approach. A clinical history, examination and a blood-gas analysis from the corpus cavernosum helps to distinguish between ischaemic and non-ischaemic subtypes. Colour Doppler ultrasonography and penile MRI can be used in more complex cases, or those with a delayed presentation. Treatment involves cavernosal blood aspiration followed by instillation of an α-adrenergic receptor agonist such as phenylephrine, proceeding to penile shunt surgery (within the first 24-48 h) if the priapism persists. Insertion of a penile prosthesis is indicated when a shunting procedure or penoscrotal decompression fails, or if a patient presents with a priapism persisting longer than 36-48 h depending on the guidelines used. For non-ischaemic priapism following failed conservative treatment, selective arterial embolization of the arteriocorporal fistula can be performed. The aetiology and pathophysiology of the different priapism subtypes help to determine the management of specific patients.

Atypical intraductal proliferation (AIP) is considered a borderline lesion, characterized by architectural complexity and cytological atypia greater than that seen in high-grade prostatic intraepithelial neoplasia, but insufficient to fulfil the diagnostic criteria for intraductal carcinoma (IDC). Consequently, AIP remains diagnostically challenging, and the clinical significance of this lesion is still uncertain. Emerging evidence suggests that AIP in prostate biopsy specimens is a strong predictor of unsampled IDC and other adverse pathological features, warranting reconsideration of the AIP role in prostate cancer risk stratification. Results from prospective and molecular studies indicate that AIP frequently coexists with intermediate-risk prostate cancer and shares molecular alterations with IDC, such as PTEN loss and ERG overexpression, reinforcing AIP potential as a marker of occult aggressive disease. Considering the growing emphasis on precision diagnostics and active surveillance in prostate cancer management, understanding the implications of AIP is particularly relevant.

Persistent Müllerian duct syndrome (PMDS) is a rare difference of sex development, characterized by the presence of Müllerian duct derivatives in 46,XY individuals with male-typical development. PMDS typically presents during childhood with features of cryptorchidism, inguinal hernia or transverse testicular ectopia. Untreated PMDS is associated with risks of infertility and malignancy. Infertility is common, arising from cryptorchidism, anatomical malformations (such as epididymal aplasia) or extrinsic compression of the ejaculatory duct by Müllerian structures. At the time of diagnosis, just one in five men with PMDS are reported to have conceived naturally. Preservation of fertility potential requires prompt diagnosis and management via a holistic patient-centred approach that addresses the underlying cause. With cryptorchidism, which is a common manifestation of PMDS, early orchidopexy is the key initial intervention. The input of fertility specialists and assisted reproductive techniques can further support successful conception. Beyond its effects on fertility, PMDS carries a risk of malignant transformation in the testes and Müllerian structures, warranting complex management with inclusion of a multi-disciplinary team and consideration of orchidopexy, orchidectomy, excision of Müllerian remnants and onward surveillance. Thus, although rare, PMDS is an important cause of male factor infertility that might be encountered by urologists. Preservation of fertility potential requires a high index of clinical suspicion and timely intervention. Raising awareness of PMDS among clinicians is crucial to improve its detection, advance its clinical management and provide a basis for future research.

Prostate-specific membrane antigen (PSMA) is upregulated in prostate cancer cells relative to other cells. The increased expression and enzymatic activity of PSMA in high-stage disease confers a selective advantage on such cells, contributing to their increased proliferation, the tendency to metastasize and the development of a castration-resistant phenotype. The decades of radiobiochemical advances in the development of PSMA targeting radiolabelled ligands has led to the subsequent FDA approval of a number of radiotracers and radiotherapeutics for clinical use. Novel developments in therapeutic advances using PSMA-based combinatorial approaches include PSMA-targeted antibody-drug conjugates and PSMA-targeted radionuclide payloads. Combining and sequencing some of these strategies with standard therapy options such as surgery, radiotherapy and androgen receptor pathway inhibitors could improve patient outcomes. Immunotherapy and chimeric antigen receptor T cell therapy are relevant to PSMA-based therapies as PSMA can serve as a specific target antigen for these treatments, enabling precise tumour recognition and enhanced efficacy of prostate cancer therapies.

2024 marked the twentieth anniversary of FDA approval for taxane therapy, namely docetaxel, in the treatment of advanced prostate cancer. Approval of this treatment modality signified a breakthrough in the field, as it demonstrated for the first time that a non-antiandrogen targeting agent could significantly improve survival of patients with prostate cancer. New evidence has further solidified the role of taxanes, demonstrating that it improves survival when used in combination with androgen-targeting therapy in early-stage metastatic hormone-sensitive prostate cancer. Consequently, taxane therapy is currently considered a gold standard and mainstay in the treatment of prostate cancer. In this Review, we present an up-to-date analysis of the pivotal role of taxanes in the treatment of prostate cancer, discuss reasons why taxanes are effective and discuss how the mechanisms that confer resistance to taxanes in prostate cancer might be exploited to develop more effective therapeutic strategies.

The sperm tail is a modified motile cilium analogous to those found in tissues including the lung and brain. They have been evolutionarily sculpted to optimize motility and, therefore, fertility, through the dynamic and challenging environment of the female reproductive tract. Sperm tails are composed of three structurally distinct regions: the midpiece, the principal piece and the end piece. The most proximal region - the midpiece - is surrounded by a mitochondrial sheath, which has been proposed to provide structural integrity and ATP as fuel for sperm tail movement. Despite the main phases of mitochondrial sheath assembly being described, the specific biological mechanisms that underpin its formation and maturation remain poorly defined and, in many cases, unknown. Moreover, emerging evidence has highlighted that the precise contribution of the mitochondrial sheath to energy production in sperm has been misunderstood. ATP generation via glycolysis and mitochondrial respiration, previously believed to be physically uncoupled, engage in crosstalk to maximize sperm function, competition and overall fertility. Understanding these processes could not only provide vital insights into the aetiology of male infertility and offer targets for contraceptive development but could also provide insights into mechanisms of relevance to other tissues in which mitochondrial dynamics is challenging to monitor.

The diagnostic workflow for prostate cancer detection has evolved substantially with advances in imaging technologies and biopsy techniques. Currently, MRI is the standard modality for prostate imaging in cancer detection. However, the rising incidence of prostate cancer and the limited accessibility and high cost of MRI created a growing need for more cost- and time-effective alternative imaging modalities. Micro-ultrasound (microUS), which enables prostatic ductal anatomy to be imaged with a 70-micron resolution, provides an alternative. Level 1 evidence currently shows the non-inferiority of microUS in detecting Grade Group ≥2 prostate cancer in biopsy-naive men compared with MRI. Clinical trials are ongoing to investigate microUS in various other indications. Inter-reader variability needs to be optimized, possibly through the incorporation of artificial intelligence (AI) assistance.

Bladder cancer is a highly prevalent disease in the Western World, and the treatment paradigm is actively evolving. For decades, the most commonly used standard of care for localized muscle-invasive disease has been neoadjuvant chemotherapy followed by open radical cystectomy with urinary diversion. Considering the high postoperative morbidity of this procedure, efforts have focused on improving patient outcomes. Over the past decade, substantial advances have been introduced in imaging, prehabilitation, perioperative care, robotic surgery and organ-sparing techniques. Bladder preservation after complete clinical response to neoadjuvant treatment or after trimodal treatment is increasingly being implemented. In addition, novel biomarkers are increasingly being used to monitor treatment response and select patients for adequate therapy. Last, innovative approaches, such as intraoperative imaging, sentinel lymph-node biopsy or the use of artificial intelligence, are currently under investigation.

'Digital twins', also called 'digital patient twins' or 'virtual human twins' - digital patient-specific models derived from multimodal health data - are a strong focus in health care and are emerging as a promising tool for improving personalized care in uro-oncology. These models can integrate clinical, genomic, imaging and histopathological information to simulate organ behaviour and disease progress as well as predict responses to treatments. The concept of digital twins has shown potential in various fields, but its application in uro-oncology is still evolving, with few assessments of their feasibility and clinical utility. The advent of artificial intelligence adds a new dimension to their development, potentially enabling the synthesis of diverse, high-quality datasets to improve modelling accuracy and support real-time decision-making. However, substantial challenges exist, including data integration, patient privacy, computational demands and ethical frameworks. In addition, the interpretability of predictions remains essential for gaining clinical trust and guiding patient-centred decisions. The use of digital twins in uro-oncology has the potential to improve patient stratification and treatment planning; however, barriers must be overcome for their successful implementation in clinical routine. By integrating new technologies, fostering interdisciplinary collaboration and prioritizing transparency, digital twins could shape the future of precision uro-oncology.

Interest in using polygenic scores (PGS) to improve the risk stratification for and early detection of prostate cancer is considerable. Despite the absence of clinical guidelines for the use of prostate cancer PGS in patient care, existing and emerging standards for the clinical translation and reporting of genetic testing generally and PGS specifically provide a relevant framework to help guide these efforts. This framework is intended to harmonize advances in the development of PGS clinical assays and standardization of PGS reporting in the context of prostate cancer PGS specifically. The analytical and clinical validity of prostate cancer PGS have been progressively refined, but evidence firmly establishing clinical utility beyond modelling studies is still lacking. Standardized approaches for designing, explaining and reporting prostate cancer PGS are key to accelerating clinical implementation in a manner that would increase access to the benefits of precision prostate cancer screening to patients across ancestry backgrounds.

Immune-checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PD1) and programmed cell death 1 ligand 1 (PDL1) have improved survival for patients with different types of solid tumour. However, clinical response in patients with muscle-invasive bladder cancer (MIBC) is limited, with only 20-30% demonstrating a sustained response. An improved understanding of ICI mechanisms and robust biomarkers will increase efficacy and enable patient stratification in MIBC. Hypoxia (low oxygen tension) and neutrophil infiltration are prevalent in MIBC and are associated with immunotherapy resistance. Hypoxia-associated extracellular matrix (ECM) remodelling can induce pro-tumour or anti-tumour neutrophil polarization through biomechanical and biochemical signalling. Hypoxia-associated ECM mechanisms alter neutrophil recruitment, polarization, activation and affect T cell-centric immunotherapies. However, the specific mechanisms by which hypoxia, ECM and neutrophils confer immunotherapy resistance in MIBC are not yet fully understood. ICI resistance could be overcome by targeting specific ECM remodelling-related and neutrophil-related pathways to elicit durable and efficacious responses in 70-80% of patients with MIBC who are currently non-responsive to ICIs.