News & Views in 2018

The extent of pelvic lymph node dissection at the time of radical cystectomy is debated as it might affect oncological outcomes in patients with bladder cancer. Gschwend et al. now demonstrate that the survival benefit is small and that the study might need to be repeated with a larger cohort.

Preliminary results from TRITON2 demonstrate efficacy of the poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib in ~50% of patients with metastatic castration-resistant prostate cancer and inactivation of BRCA1/BRCA2. However, those with ATM and CDK12 mutations do not seem to benefit. An improved homologous recombination deficiency test must be developed and alternative treatments defined for these subsets of patients.

Matta et al. report that men with prostate cancer who underwent surgery or radiotherapy, but not active surveillance, had greater odds of receiving antidepressants than controls. However, methodological limitations preclude the interpretation of a psychological benefit for men on active surveillance. Screening for distress and referral to evidence-based intervention should be a priority.

A recently published study has evaluated metabolism in human clear cell renal carcinomas (ccRCCs) using intraoperative [¹³C]glucose infusion during surgical procedures. The findings demonstrate aerobic glycolysis and repression of the Krebs cycle, confirming the existence of the Warburg effect in ccRCC tumours in vivo.

The results of the RAZOR trial of robot-assisted radical cystectomy versus open radical cystectomy in patients with bladder cancer show that robotic surgery is noninferior. However, care must be taken before widespread adoption of this modality, as superiority has not yet been established.

A recently published cohort study of 650 men undergoing prostate biopsy showed no association between current alcohol intake and overall prostate cancer risk, but did report an association between regular drinking during adolescence and early adulthood and high-grade prostate cancer.

A polygenic risk score (PRS) analysis reported that familial testicular germ cell tumours (TGCTs) were significantly enriched for TGCT risk alleles and that ≥84% were attributable to polygenic enrichment, supporting the polygenic aetiological basis of familial TGCT. Clinical application will first require improved TGCT screening and early detection tools.

The FDA recently expanded the indication for enzalutamide for the treatment of all men with metastatic and nonmetastatic castration-resistant prostate cancer on the basis of the PROSPER trial. Now that both disease states can have the same treatment, the need to thoroughly identify metastatic lesions is questioned.

Applying the principles of ‘omics’ to urinary tract infection opens up exciting diagnostic and management avenues. Urinary cell-free DNA can be used to gain new insight not only into the spectrum of pathogens present in host urine but also their likelihood to cause disease.

With the emergence of increasingly potent androgen deprivation therapy, rates of treatment-emergent small-cell neuroendocrine prostate cancer are increasing. In a recent prospective study, Aggarwal and colleagues defined the frequency and clinical and genomic characteristics of these tumours.

Platinum-based chemotherapy continues to be linked with the subsequent development of various solid tumours. In a large analytical study of >5,800 survivors of testicular cancer, Groot and colleagues observed statistically significant dose-dependent increases in gastrointestinal cancer incidence after platinum-based chemotherapy, providing evidence for a potential dose-dependent relationship.

A recent study has shown a decline in testosterone prescriptions since media reports of potential increased cardiovascular risk in 2014. The phenomenon of medical hysteria accounts for this reduced prescribing, as numerous subsequent studies provide substantial evidence of reduced cardiovascular risk and other important benefits with testosterone therapy for men with testosterone deficiency.

Immune checkpoint inhibitors targeting programmed cell death 1 (PD-1) or programmed cell death 1 ligand 1 (PD-L1) have had limited clinical impact in prostate cancer. To find a niche for immune checkpoint inhibition in this disease, future strategies might require improved biomarker-based patient selection or combination strategies to enhance in vivo immune activity.

The European Medicines Agency (EMA) and FDA have recently restricted the indications for first-line pembrolizumab and atezolizumab to patients with programmed cell death 1 ligand 1 (PD-L1)-high advanced urothelial carcinoma, a decision made following interim analyses from the ongoing Keynote-361 and IMvigor130 phase III trials. Questions remain on the magnitude of inferior survival and standardized implementation of PD-L1 testing.

New data have confirmed the genomic diversity of low-risk prostate cancer. Improved understanding of the heterogeneity of this disease has implications for disease management and has the potential to change treatment for patients in the future.

Cytoreductive nephrectomy, a standard approach for de novo metastatic renal cell carcinoma in the era of cytokine therapy, has been upheld during the age of targeted therapy on the basis of retrospective data. Now, the first level I prospective data from the CARMENA and SURTIME trials challenge this standard.

A recent study reports widespread decreases in PSA screening, prostate cancer diagnoses, and use of active treatment modalities since the 2011–2012 United States Preventive Services Task Force (USPSTF) recommendation against PSA screening. The updated 2017 USPSTF guideline, which embraces individualized decision-making, suggests the pendulum swung too far, but must not prompt a return to indiscriminate screening.

Use of multiparametric MRI for detection of prostate cancer has been increasing and two recent studies have provided high-quality evidence advocating its integration into the diagnostic protocol. A new paradigm for detection of prostate cancer in the era of PROMIS and PRECISION should be adopted globally.

The Guttmacher–Lancet Commission’s report on Sexual and Reproductive Health and Rights for All coincides with raised awareness of this topic as a result of global movements such as #metoo. However, weak political leadership, increasing fragmentation of services, and sustained underfunding pose a threat to sexual and reproductive health globally.

The detection of 78 bacterial species in the urinary tracts of 77 catheterized female patients further emphasizes that the urinary tract is not sterile. However, many questions arise from these findings, not the least of which is what these organisms are doing in the urinary tract.