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The Key Advances in Urology collection offers a unique series of specially commissioned ‘Year in Review’ articles that highlight the key discoveries made each year. In these articles, leading experts in the field describe their pick of the top 3–5 key advances of the year, outlining their clinical impact and implications for current and future research.
The treatment paradigm for treatment-naive metastatic clear cell renal cell carcinoma continued to evolve in 2019 as three phase III randomized controlled trials were reported comparing sunitinib with combination immune checkpoint inhibitors and VEGF-targeted therapy. Pembrolizumab plus axitinib and avelumab plus axitinib became new treatment options for untreated patients, irrespective of risk group or PD-L1 expression.
In 2019, quality improvement has been a central theme throughout leading articles on nephrolithiasis. Real-world outcomes were published on the natural history of stones and residual fragments, patient compliance with medical therapy and treatment-related opioid use. In-depth review of these topics will enhance provider–patient counselling and shape future paradigms in stone disease.
In men with hormone-sensitive prostate cancer, enzalutamide and apalutamide improve overall survival compared with androgen deprivation therapy alone. Also, radiotherapy of the primary tumour is beneficial in patients with low tumour burden. In the non-metastatic castration-resistant setting, a positive trial for darolutamide was reported. In the metastatic castration-resistant setting, the role of cabazitaxel in treatment sequencing was clarified.
The role of testosterone in female sexuality is still controversial. In 2019, a meta-analysis and a Position Statement on testosterone therapy for hypoactive sexual desire disorder in menopausal women and a Position Statement on the potential sexual adverse effects of hormonal contraception have begun to close this gender gap.
In 2019, the Bladder Cancer Molecular Taxonomy Group (BCMTG) presented a consensus molecular classification comprising six subtypes of muscle-invasive bladder cancer (MIBC). The non-luminal subtypes were the most consistent with previous models. Subsequent studies in 2019 have revealed molecular heterogeneity among the luminal subtypes and their possible clinical ramifications.
Many interesting studies on urological infection have been published in the past year including nonantibiotic therapy for acute cystitis, the utility of the Acute Cystitis Symptom Score, specific identification of health-care-associated urinary tract infection and a multidisciplinary approach to prostatitis.
Immunotherapy and tumour microenvironment modulation are potential new treatment approaches for metastatic prostate cancer, but patient selection might be key to delivering therapeutic benefit. In the past year, four studies have suggested that DNA mismatch repair alterations and CDK12 aberrations are biomarkers of response to immune checkpoint inhibitors.
For the management of bladder cancer, 2018 has been characterized by deepened knowledge on the molecular basis of invasive bladder cancer and its potential interaction with existing therapies, optimization of the use of immune checkpoint inhibitors, and emerging early signals on new therapeutic classes for advanced disease.
The treatment of metastatic kidney cancer is rapidly evolving with the shift from immune checkpoint inhibitor monotherapy to combination therapy. In 2018, the combination of nivolumab–ipilimumab received regulatory approval and multiple positive clinical trials were reported with combinations of PD-1 or PD-L1 inhibitors in conjunction with antiangiogenic drugs.
Since the discovery and confirmation of the human urobiome, highly influential studies to characterize this microbial community and understand how it relates to human health and disease have been undertaken. Technological advances will improve information about the status of the urobiome for clinicians.
2018 has been an exciting year for imaging in urology, especially in the field of prostate cancer. In this context, multiparametric MRI and molecular imaging targeting prostate-specific membrane antigen provide practice-changing developments for detection and diagnostic work-up.
Landmark papers published in 2017 have advanced our understanding of the molecular heterogeneity of urothelial cancer, provided insights into the genomic evolution of the disease in the context of metastasis and therapy, and established new treatment standards for patients with previously limited treatment options.
Treatment paradigms for advanced renal cell carcinoma (RCC) continue to be challenged and refined. Recent studies in metastatic RCC have demonstrated the efficacy of first-line cabozantinib and the safety and efficacy of dual checkpoint blockade; in the adjuvant setting, pazopanib failed to improve progression-free survival in high-risk localized RCC compared with placebo.
Major advances in the management of all stages of upper tract urothelial carcinoma have been made in 2017. Radical nephroureterectomy can be valuable in patients with metastatic disease and adjuvant platinum-based chemotherapy can improve outcomes in those with advanced disease. Kidney-sparing surgery with early follow-up ureterorenoscopy has shown benefit in patients with low-grade tumours. Avoiding unnecessary ureterorenoscopy might decrease intravesical tumour recurrence.
Implementing a successful penile transplantation programme requires a multidisciplinary approach to overcome social, institutional, and patient-related obstacles. The literature in 2017 presents controversial ethical solutions, novel research models to evaluate immunosuppression, and long-term patient reports that help advance the field towards developing successful penile transplantation programmes.
In the past year, the results of three studies in the field of prostate cancer imaging — the prostate MR imaging study (PROMIS), an analysis of the cost-effectiveness of various diagnostic strategies based on PROMIS data, and a retrospective analysis of a prostate-specific membrane antigen (PSMA)-directed PET radiopharmaceutical — have been published that could have lasting effects on clinical practice.
Our biological understanding of TGCTs has been improved using sequencing, and molecular profiles associated with the genomic evolution and development of cisplatin resistance have been identified. The genomics of variants underpinning TGCT predisposition is being delineated. Studies of circulating microRNAs have demonstrated their potential for noninvasive diagnosis and disease monitoring.
A number of targetable molecular alterations and resistance mechanisms have been identified in metastatic castration-resistant prostate cancer (mCRPC). As our understanding of the genomic landscape of mCRPC increases, biomarker-driven clinical trials investigating targeted therapies will enable an increasingly personalized approach to its treatment.
In this Review, the authors discuss biomarker-driven prostate cancer molecular subtyping and the development of nanodiagnostic strategies to refine biomarker detection. They also describe the challenges of merging both aspects for precision prostate cancer management.
In this Review, the authors describe the pathogenesis of uncomplicated urinary tract infections (UTIs). They discuss the need for nonantibiotic treatments and explore the nonantibiotic management options for the prevention and management of recurrent UTI.
In this Review, the authors describe the current mechanistic understanding of infection stone formation and growth, including the influence of the organic matrix, microorganisms, and biofilms, highlighting the medical implications of these insights and the importance of multidisciplinary management approaches.
This Review by Ricketts and Linehan comprehensively summarizes the findings of The Cancer Genome Atlas analyses of renal cell carcinoma and their clinical implications. The authors highlight unique and shared features of the tumour histological subtypes, their predictive power and their possible utility as therapeutic targets.
Joosten et al. review the main epigenetic alterations involved in renal carcinogenesis and their effects on key signalling pathways. The authors also discuss the utility of epigenetic aberrations as renal cancer biomarkers and their potential as treatment targets.
The risk of pelvic nodal involvement in patients with high-risk prostate cancer has led to the development of whole-pelvis radiotherapy (WPRT); however, this approach remains controversial. In this Review, the authors discuss the mixed data surrounding WPRT and consider how advanced imaging techniques and ‘big data’ mining could improve patient selection and optimize WPRT by improving localization of subclinical disease.
Renal cell carcinomas (RCCs) harbour mutations in genes encoding chromatin modifiers, which have integral roles in genome maintenance and epigenetic regulation. Here, the authors review the mutational landscape and roles of chromatin modifiers as co-drivers in RCC, highlighting therapeutic opportunities.
Imber et al. summarize current knowledge of the risks of financial toxicity in patients with localized prostate cancer, proposing a framework of contributing factors, and discuss emerging assessment strategies to inform future research efforts.
Sexual arousal in women comprises two components: genital arousal and subjective arousal. For some women, genital arousal enhances subjective arousal; for others, the two types of arousal are desynchronous. In this Review, Meston and Stanton describe the mechanisms and the relationship between genital and subjective arousal and consider how they assist in diagnosis and treatment of sexual arousal dysfunction and development of treatments for female sexual arousal dysfunction.
An energetic interplay between tumour and immune cells leads to metabolic competition in the tumour ecosystem, an effect that could be targeted to boost immune checkpoint inhibition. In this Review, the authors discuss cancer cell and immune cell metabolism and consider the potential therapeutic targets within these processes.
The holmium:yttrium–aluminium–garnet (YAG) laser has been a standard of care for treating renal stones for the past 20 years. However, it is not without its limitations. In this Review, Fried and Irby discuss new laser technologies that offer an alternative to the holmium:YAG laser and consider fibre-optic approaches for delivery of the laser energy inside the urinary tract.
Felsenstein and Theodorescu discuss advances in therapy response prediction in patients with bladder cancer based on tumour genomics. They summarize current clinical approaches and future requirements in personalized precision medicine including targeted as well as immunotherapeutic strategies.
Large-scale, next-generation sequencing collaborations have identified drivers and vulnerabilities of urothelial carcinoma. In this Review, the authors discuss the mutational landscape of urothelial carcinoma, including specific mutations in pathways and driver genes and describe how the next generation of therapies will be based on patient-specific targetable mutations observed in individual tumours.
The management of advanced renal cell carcinoma (RCC) has dramatically changed over the past decade. In this Review, the authors discuss the development of novel immunotherapies to treat RCC, including inhibitors of checkpoint receptors, vaccines, T-cell agonists, and chimeric antigen receptor T cells.