Despite its increasing clinical use, evidence regarding the effects of puberty suppression using gonadotropin-releasing hormone analogues on sexual development and well-being in transgender and gender-diverse (TGD) adolescents remains limited. Thus, expert recommendations integrating available evidence and clinical experience are essential to guide multidisciplinary care. Targeted literature review coupled with expert opinion - including endocrine, urological, psychological, sexological and gynaecological perspectives - and input from a round table session at the European Professional Association for Transgender Health Conference in 2025, generated recommendations around providing developmentally appropriate information on puberty, puberty suppression and sexual development. These include attention to psychosocial factors such as stigma; individualized decision making regarding fertility and surgical options; and promotion of positive communication about sexuality. Remaining knowledge gaps emphasize the need for longitudinal and interdisciplinary research, combining qualitative and quantitative approaches to advance our understanding of sexual development during puberty suppression, and how it affects sexual pleasure and genital sensitivity. The first exploratory studies have shown similar sexual well-being in young adults who received puberty suppression and those who received gender-affirming hormone treatment without puberty suppression. Another priority is the development of TGD-specific tools to assess sexual development, functioning and satisfaction, that capture the diversity and intersectionality of sexual experiences of TGD individuals. These recommendations aim to support individuals considering puberty suppression and their families and clinicians to optimize their care and well-being.
Unconventional T cells - including γδ T cells, mucosal-associated invariant T cells, natural killer T cells, double-positive (CD4⁺CD8⁺) and double-negative (CD4- CD8-) T lymphocytes - are an underexplored component of immune surveillance in urological cancers. Unlike conventional αβ T cells, these populations recognize mainly non-peptidic antigens independently of classic major histocompatibility complex restriction, enabling rapid responses to cellular stress, microbial cues and metabolic dysregulation within tissues and the tumour microenvironment. Emerging evidence suggests that each subset exhibits context-dependent behaviour across prostate cancer, bladder cancer and renal cell carcinoma, ranging from cytotoxic to immunoregulatory. Together, these unconventional T cell subsets offer a foundation for novel diagnostic and therapeutic strategies. Combination approaches currently in clinical trials that integrate checkpoint blockade, adoptive cell transfer or Bacillus Calmette-Guérin-based immunotherapy could be guided by emerging insights into how these cells recognize or are shaped by tumour cells. Research in mechanistic and translational studies involving unconventional T cells is gaining momentum and could ultimately redefine immune targeting in urological cancers.
Crucial unmet needs for standardization and clinical integration of actionable biomarkers persist across the bladder cancer disease spectrum. To address these gaps, the International Bladder Cancer Group (IBCG) convened a global multidisciplinary panel to develop evidence-based consensus recommendations on biomarker use in bladder cancer. Recommendations were formulated across the disease spectrum using a modified Delphi process. In patients with asymptomatic microhaematuria, biomarker use should be guided by a risk-stratified approach. For patients with established non-muscle-invasive bladder cancer, no biomarker prospectively validated is available to guide intravesical therapy selection, although approved commercial tests might aid in adjudicating equivocal cytology or cystoscopy findings in patients with high-grade disease. In muscle-invasive bladder cancer, no validated biomarkers exist to guide the choice between bladder preservation and radical cystectomy, or to inform the choice of neoadjuvant therapy. Circulating tumour DNA is prognostic following neoadjuvant therapy and radical cystectomy, and provides predictive value for selecting patients who are most likely to benefit from adjuvant treatment with approved immunotherapy regimens. In addition, circulating tumour DNA has prognostic value in patients with metastatic urothelial carcinoma. The IBCG recommends assessing FGFR3 genomic alterations and HER2 immunohistochemistry in patients with locally advanced and/or metastatic bladder cancer to inform therapeutic selection. The IBCG consensus recommendations provide practical, stage-specific guidance on the use of biomarkers for diagnosis, risk stratification and treatment selection in patients with bladder cancer and define priorities for future validation and trial design.
The US military’s proposal for routine testosterone screening presents a unique opportunity to improve men’s health. However, translating policy into practice will require evidence-based screening, accurate diagnosis, appropriate patient selection and careful consideration of fertility, lifestyle factors and long-term monitoring.
Mohs micrographic surgery offers a tissue-sparing alternative to penectomy for penile squamous cell carcinoma involving the glans and distal urethra, yet technical guidance remains scarce. We detail the surgical approach, specimen handling and reconstruction strategies to help surgeons navigate this challenging procedure and improve patient access to organ-preserving care.
Several studies have demonstrated that a posterior approach to nerve sparing by preserving more anterolateral periprostatic tissue can improve erectile function by more than twofold. Review of the evidence regarding periprostatic nerve distribution suggests a potential underappreciation of the distribution and functional relevance of nerve fibres along the anterior prostate.
Cystic fibrosis (CF) is primarily recognized for its severe systemic effects, especially in the lungs, pancreas and digestive tract. Thus, the effect of CF transmembrane conductance regulator (CFTR) dysfunction on male fertility has been relatively overlooked despite its important roles in spermatogenesis orchestration and spermatozoa function. CFTR has physiological functions as a chloride and bicarbonate channel and a role in regulating water movement. CFTR participates in spermatogenesis, and evidence suggests its involvement in seminiferous intratubular fluid control, maintenance of the blood-testis barrier, and improvement in follicle-stimulating hormone signalling, among other functions. Emerging evidence also suggests that CFTR variant carriers, typically considered to be healthy, have reduced sperm quality. Diminished CFTR expression has been observed in spermatozoa from men with various sperm quality abnormalities (teratozoospermia, asthenozoospermia and oligozoospermia), and correlates positively with sperm motility and morphology. CFTR is thought to be involved in sperm capacitation and osmoregulation via interactions with ion and water channels. Advances in CF therapy, such as CFTR modulators, gene therapy and liposome-mediated CFTR delivery, might affect CFTR's role in sperm function and could potentially be applied to improve the fertility of individuals with CFTR dysfunction.
Urolithiasis is increasingly common, with rising rates driven by obesity, diabetes and metabolic syndrome. Patients with cancer have additional, unique risks of stone formation owing to effects on fluid and electrolyte balance, systemic cancer therapies, tumour lysis syndrome and anatomical alterations after urinary diversion or nephrectomy. Moreover, urolithiasis itself has been linked to increased rates of renal cell carcinoma, urothelial carcinoma and bladder cancer, potentially mediated by chronic inflammation, recurrent infections and shared metabolic or environmental factors. Management in this setting is complex and must be individualized. Percutaneous nephrolithotomy achieves the highest stone-free rates in patients with altered urinary tract anatomy, whereas retrograde intrarenal surgery and shock wave lithotripsy have more selective roles. Preventive strategies focus on thorough metabolic evaluation, hydration optimization and addressing cancer-specific risk factors such as hypercalcaemia, acidosis and chronic urinary stasis. Despite these insights, data on the epidemiology, mechanistic underpinnings and optimal management of urolithiasis in patients with cancer remain limited. Prospective studies are needed to clarify causal relationships, refine preventive strategies and develop evidence-based treatment algorithms for this growing and complex population.
Spinal cord injury (SCI) is a life-changing and costly condition. SCI causes major disturbances in sensory, motor and autonomic function, resulting in permanent loss of function and strongly affecting the physical, psychological and social well-being of patients and caregivers. A particularly debilitating consequence of SCI is loss of voluntary control over bladder function, which substantially affects patients' dignity, health and quality of life. Current understanding of the complex pathophysiological mechanisms of SCI and associated comorbidities has heavily relied on the use of animal models, which have also been crucial in devising new therapeutic approaches and fine-tuning existent ones. However, a debate about the persistent challenges in translating preclinical data into treatment is ongoing. Technological advances are generating innovative modelling approaches with the support of regulatory bodies, aiming to reduce or eventually substitute animal use. In this Review, we address the current use of animal SCI models in neuro-urological research and debate whether we will still be using these models by 2035.
The updated National Institute for Health and Care Excellence fertility problems guideline (NG257) provides clear guidance for stakeholders managing fertility issues. This update includes changes in the assessment and management of male fertility, addressing genetic testing, sperm DNA integrity testing and varicocele management, and also identifies key areas for future research.
A combination of a PDE5 inhibitor with tamoxifen has been shown to prevent fibrosis in in vitro and in vivo models of acute Peyronie’s disease. The latest clinical findings suggest that such a combination is efficacious in halting or reversing the progression of the disease.
Efforts to improve equity for women in oncology drug development have thus far focused on representation in clinical trials. However, it is now time to take the next step: ensuring trials capture outcomes that matter for women. Incorporating sex-specific analyses and biological variables can reveal differences in efficacy and toxicity and advance equitable care.
Becoming a patient advocate can be life changing, especially in the complex world of rare diseases. As patients, those of us who can must use our knowledge and experience to influence how services are designed and delivered to achieve the best health and well-being outcomes.
Mature sperm acquire mRNAs from epididymal extracellular vesicles during post-testicular maturation. These findings challenge the idea that sperm mRNAs are merely residual transcripts and suggest an underappreciated mechanism of paternal epigenetic inheritance.
Prostate cancer disproportionately affects men of African ancestry, yet the molecular mechanisms underlying these disparities remain poorly defined. Genomic studies have begun to reveal ancestry-linked risk alleles and somatic alterations, but the role of epigenetic dysregulation is only emerging. Drawing on multi-ancestral comparative analyses, with emphasis on cohorts from sub-Saharan Africa, we speculate that germline and somatic variation converge in epigenetic machinery genes to drive tumour evolution. African tumours harbour a heightened burden and diversity of both inherited and acquired variants, supporting a model of 'oncogenic cooperation' whereby germline diversity interacts with somatic mutations to broaden the range of pathogenic interactions. Limited yet complementary methylation analyses reveal tumour-specific and ancestry-specific reprogramming of promoters, enhancers and heterochromatin, suggesting that African tumours might be epigenetically primed for aggressive phenotypes. Chromatin remodelling defects emerge as potentially under-recognized disparity drivers, promoting genomic instability, altered gene regulation and therapeutic resistance. Collectively, these findings support a genome-epigenome-environment model in which inherited susceptibility, somatic variation and environmentally reinforced epigenetic reprogramming converge to shape aggressive African-associated prostate cancer. However, current insights are limited by European-centred baselines, under-representation of African cohorts and platform mismatches. Reducing prostate cancer health disparities requires equitable prostate cancer genomics and epigenomic research efforts that embrace the rich African ancestral population identifier.
