News & Views

The phase III IMvigor011 trial shows that postoperative circulating tumour DNA (ctDNA) can guide adjuvant immunotherapy after cystectomy, improving outcomes in patients with ctDNA-positive tumours while identifying patients with excellent prognosis without treatment. In an era of intensified perioperative therapy, these findings might shift the focus from whom to treat towards when treatment can be safely withheld or stopped.

Large language models have been rapidly adopted in general and clinically; they could also be incorporated into medical education. Results of a recent study suggest that a combination of traditional learning methods and large language model use could improve learning outcomes for medical students.

Previous investigations of the genome of Wilms tumour have demonstrated surprisingly few driver mutations and low tumour mutational burden. Integrating duplex sequencing and use of laser-captured specimens and tumour organoids unveiled a fourfold increased tumour mutational burden and a new vision of clonal architecture in infant Wilms tumour.

New research has provided a comprehensive molecular understanding of fumarate hydratase-deficient renal cell carcinoma, showing distinct molecular divergence from other renal tumour subtypes. These molecular findings have implications for precision oncology for patients with this rare disease.

Use of spatial transcriptomics has helped to create a functional map of cellular organization in the healthy and tumoural human prostate, creating new opportunities for understanding age-related prostatic diseases.

Mapping the N⁶-methyladenosine (m⁶A) transcriptome in prostate cancer has established its clinical potential value as a prognostic biomarker for this disease. A multidisciplinary approach that integrates genomics, transcriptomics, epitranscriptomics, proteomics and clinical oncology is essential to translate the intricacies of m⁶A modification into tangible benefits for patients

Results from the SWOG S1011 and LEA trials show that extended pelvic lymph node dissection during radical cystectomy for muscle-invasive bladder cancer offers no survival benefit. Novel perioperative systemic therapies could lead to true survival improvement for patients with muscle-invasive bladder cancer undergoing radical surgery and have the potential to implement bladder-preserving strategies.

The first study of personalized cancer vaccines for renal cell carcinoma with breakthrough results in the adjuvant setting has been published, showing a 100% efficacy rate and negligible toxic effects. However, important questions remain concerning long-term effectiveness.

The results of the NIAGARA trial have considerably advanced treatment for patients with muscle-invasive bladder cancer, establishing a new therapeutic standard for cisplatin-eligible patients. Future trials will help to answer remaining questions about perioperative treatment optimization.

Bladder instillation of gentamicin is safe and effective in treating recurrent urinary tract infection that has failed to resolve with current guideline-based treatments. It also reduces the rate of antimicrobial resistance.

Artificial intelligence can be leveraged to improve the detection of prostate cancer on magnetic resonance imaging; however, before this technology is implemented in clinical practice, further research is required.

Paternal origins of health and disease is an emerging paradigm highlighting the influence of paternal environmental exposures, including diet and lifestyle, on offspring health. The influence of the paternal gut microbiota on the germ line and offspring outcomes has been investigated in a new study.

Reprogrammed metabolism has been long recognized as a driver of kidney cancer progression, prompting efforts to develop metabolic targeted therapies against this disease. Evidence offers further clarity on the metabolic phenotypes associated with aggressive disease, expanding the potential target space for attacking these tumours at their metabolic roots.

In the KEYNOTE-564 trial, patients with resected clear cell renal cell carcinoma at a high risk of relapse experienced disease-free survival and especially overall survival benefits following treatment with pembrolizumab, which in turn was established as the novel standard adjuvant therapy for these patients. Accurate patient selection is crucial. Managing post-pembrolizumab recurrence is challenging owing to limited evidence for guiding therapeutic decisions based on clinical features.

Bladder cancer progression to microscopically distinct variants such as sarcomatoid, small cell, micropapillary and plasmacytoid is associated with more aggressive clinical behaviour than conventional carcinoma. Advances in molecular profiling led to the identification of molecular subtypes of bladder cancer and provided insights into disease progression to aggressive variants.

In the SELENIB trial, selenium and vitamin E were compared with placebo as chemoprevention for non-muscle-invasive bladder cancer (NMIBC). No difference versus placebo was observed in recurrence-free interval (RFI) with selenium, but vitamin E was associated with worse RFI. Selenium and vitamin E cannot be recommended in chemoprevention for NMIBC. Furthermore, patients with NMIBC taking supplemental vitamin E should be made aware of its potential association with worse RFI.

Sexual interactions between members of the same sex are common but the reasons for these behaviours are not always clear. Results from a study across mammals suggest that increased same-sex behaviour evolved with sociality and might reduce conflict, although increased male–male sexual interactions are associated with increased adult killing.

Much of the Y chromosome has remained obscure owing to the challenge of sequencing repetitive genomic regions. Recently, the Y chromosome has been fully sequenced, revealing extensive heterochromatic areas and 41 new protein-coding genes. Furthermore, 43 Y chromosomes have been sequenced, showing extensive multi-sample variation and providing promising insights into male infertility.

Positive surgical margins are an independent risk factor for biochemical recurrence after radical prostatectomy. However, the identification of residual cancer by eye is highly limited, and frozen sections are not always available or possible for all margins. Prostate-specific membrane antigen-targeted fluorescence guidance might close this gap and enhance the surgeon’s eye.

The relationship between smoking, ethnicity and bladder cancer is complex and multifaceted, with substantial public and personal health as well as clinical implications. New evidence supports that targeted smoking cessation efforts among high-risk populations could reduce the burden of bladder cancer.