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.
Key Advances in Urology
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.
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.
Bladder dysfunction in 2016: New insights into interstitial cystitis and chronic pelvic pain syndromes
In 2016, immunohistochemical evidence revealed major differences in the inflammatory characteristics of Hunner and non-Hunner interstitial cystitis/bladder pain syndrome (IC/BPS). Evidence has also emerged that an isomer of testosterone, etio-S, might be a urinary biomarker of IC/BPS. Intravesical botulinum toxin injections became a standard treatment of IC/BPS. Furthermore, the International Continence Society has published a new Standard for Terminology for Chronic Pelvic Pain Syndromes.
2016 was an important year for prostate cancer research. New clinical data highlight the need for personalized treatment across clinical disease states and have changed clinical practice for men with metastatic disease. Molecular studies have characterized tumour heterogeneity and informed biomarker development for advanced disease and research into mechanisms of treatment resistance.
The discovery and confirmation of the female urinary microbiota in 2012 provided opportunities to improve insight into lower urinary tract disorders in women, including UTI and urgency urinary incontinence. Now, research in 2016 has shown that expanded culture techniques enable improved uropathogen detection and confirm that bacteria detected by culture-independent methods are alive.
2016 has been a good year for research in non-muscle-invasive bladder cancer. Topics to see progress include risk assessment of patients treated with BCG maintenance, the role of repeat transurethral resection of the bladder (TURB), a prospective study of white-light versus narrow-band imaging, a meta-analysis regarding single instillation chemotherapy, and the effect of the use of fluorescence-guided TURB on progression.
Recent advances have been exciting in the genomics of and targeted therapeutics for renal cell carcinoma (RCC). New agents have been approved for advanced RCC, a novel agent targeting hypoxia-inducible factor 2α has shown considerable promise and molecular characterization of papillary RCC provides the foundation for development of targeted therapeutic approaches for this disease.
Current related Reviews
Lee and Gujar review the potential of virotherapy to increase the effectiveness of immunotherapies in prostate cancer. They discuss how oncolytic viruses can improve anticancer immunological responses and strategies for combining virotherapy with other immunotherapies to obtain improved patient outcomes.
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.
Survival of patients with muscle-invasive bladder cancer is poor and none of the targeted agents that are approved for cancer therapy have been approved for the treatment of bladder cancer. However, many novel targeted agents have been investigated in animal models of bladder cancer. This Review provides a comprehensive overview of targeted therapies for bladder cancer that have been investigated in animal models and have potential for clinical application.
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.
The low biomass of the urinary microbiota presents methodological challenges for studying their role in urological diseases. Here, the authors describe methods for urinary microbiota profiling, and discuss important technical considerations for sampling, DNA sequencing, data processing and downstream analysis.
Sfanos et al. discuss the potentially procarcinogenic role of prostatic infections and inflammation in prostate pathogenesis. They summarize findings that suggest that an aberrant microbiome together with an inflammatory microenvironment are involved in the initiation of prostate cancer precursor lesions.
Prostate-specific membrane antigen (PSMA) has gained increasing interest as target molecule for imaging. Several small compounds for labelling PSMA have been developed and are currently being investigated as imaging probes for PET. PSMA-based imaging has been reported to improve detection of metastatic disease compared with CT or multiparametric MRI and 68Ga-PSMA–PET imaging has been shown to increase detection of metastatic sites, therefore, it holds great promise to improve prostate cancer management.
In this Review, the authors describe technologies for image-guided surgery for managing lymphatic metastases in prostate cancer. Refining these technologies should increase precision in the surgical recognition of positive lymph nodes and reduce the morbidity of pelvic lymph node dissection.