News & Views in 2017

Multiparametric MRI (mpMRI) findings are not always accurate in patients with a previous negative prostate biopsy. Truong et al. have developed a nomogram to identify patients with previous negative prostate biopsy who are at elevated risk of harbouring benign histology and should undergo repeat biopsy.

Cystine capacity is an assay for assessing urinary cystine saturation and risk of a stone episode in patients with cystinuria. Lowering the threshold for this test improves its sensitivity, potentially enabling relaxation of follow-up regimens for patients at lowest risk of stone episodes and dose modification of medications for those at highest risk.

Randomized trials of screening for localized prostate cancer on the basis of crude PSA thresholds and 6–12-core template biopsies had disappointing results. To improve patient outcomes, novel diagnostic tools with a high discriminative ability for clinically significant cancer are needed. The use of MRI can improve detection at biopsy without disproportionate increases in costs.

Current advances in the understanding of penile carcinogenesis provide the possibility for new personalized and actionable targeted therapeutic approaches to improve outcomes in men with advanced penile cancer. Targeting the human epidermal growth factor receptor pathway showed promising results in a recent phase II trial of first-line therapy with dacomitinib.

A new publication finds that varicocele repair might improve semen quality enough to enable couples who are awaiting in vitro fertilization or intrauterine insemination to attempt natural conception or less-invasive assisted reproductive techniques. The approach is interesting because it seeks to establish varicocele treatment as one step in a multimodal path to parenthood.

A new study provides a comprehensive catalogue of the genetic changes in Wilms tumour. Understanding the interplay between genetic and epigenetic aberrations during tumorigenesis and clonal evolution is fundamental to enabling prediction of who is at risk and which tumours will relapse when so many are curable.

Prostate-specific membrane antigen (PSMA) is expressed by prostate cancer cells as well as endothelial cells within the neovasculature of a number of malignancies including renal cell carcinoma (RCC). PET radiotracers that target PSMA have shown great promise for imaging RCC. Agents that target PSMA also have the potential to be used as therapeutics in patients with this malignancy.

Enhanced recovery after surgery (ERAS) pathways are increasingly used for patients undergoing radical cystectomy, but data on their benefits are still sparse. A new paper charts improvements in patient outcomes during a 10-year period. An optimized, defined ERAS protocol is certainly important, but the ERAS culture of consistency, performance measurement, and continual adoption of best practice are also crucial.

A recent systematic review on worldwide declining trends in sperm counts has fuelled alarming reports in national and international news media. However, methodological issues exist with data gathering and analysis precluding any conclusion and no solid data exist to indicate increasing frequency of couple infertility during past decades.

Antimicrobial resistance in Neisseria gonorrhoeae compromises gonorrhoea treatment globally and vaccines might be the only sustainable solution for gonorrhoea control. A new study for the first time provides a proof of principle for protection with ∼31% effectiveness against gonorrhoea, owing to cross-protection by the outer membrane vesicle Neisseria meningitidis serogroup B vaccine (MeNZB).

Galeterone is a steroid 17-α-hydroxylase/17,20 lyase and androgen receptor antagonist intended for patients with prostate cancer. Similar to abiraterone, galeterone has a steroid scaffold structure and mimics natural ligands; thus, these agents are metabolized by the same enzymes that synthesize or degrade naturally occurring steroids, which can result in attenuated efficacy.

Results of the STAMPEDE and LATITUDE trials, which investigated the addition of abiraterone and prednisone to androgen-deprivation therapy in advanced prostate cancer, have renewed interest in 'complete androgen blockade', a concept originally described by Fernand Labrie in the 1980s. However, whether this treatment regimen should become standard of care remains to be seen.

In clinical studies, mirabegron has been shown to cause a small increase in heart rate with a slight increase in QTc interval, as indicated on electrocardiograms. The mechanisms of these effects are unclear. The findings of a recent study might provide some new clues, although, the relevance of these new observations to the treatment of patients with overactive bladder syndrome have yet to be established.

The advent of molecular methods for the identification and characterization of the microbiome has led researchers to understand the role of the microbiota in various clinical conditions. Research by Cavarretta and colleagues has revealed the presence of microbial dysbiosis and its potential relationship with pathophysiology in the prostate tumour microenvironment. This finding could potentially enable future investigations that clarify the role of the microbiota in the development of prostate cancer and its future management, from a different perspective.

Life expectancy after primary treatment for localized prostate cancer is long, so the importance of functional outcomes and quality-of-life measures cannot be underestimated. Careful assessment of the data, with an emphasis on patient selection, definition of clinical significance, and length of follow-up duration, is essential.

Increased evidence that prostate-cancer-specific mortality can be reduced using serum PSA screening, in addition to the increasing role of active surveillance in reducing overtreatment underlies the revised USPSTF recommendation, which now supports selective use of PSA testing. However, this recommendation should not be interpreted as a license to return to the unthinking use of PSA testing of men between 50 to 70 years of age.

Sepsis is an infrequent but serious adverse risk of transrectal ultrasonography-guided prostate biopsy. A new study evaluated whether the use of single-dose ertapenem, a broad-spectrum antibiotic, resulted in increased carbapenem resistance following biopsy. However, physicians need to carefully consider the risks of antibiotic resistance when balancing the benefit of broad-spectrum antibiosis against a 1% risk of sepsis.

Despite a rapid increase in the use of anticancer immunotherapy, our understanding of the mechanisms of action and the patients' responses remains limited. The discovery of immune inhibitory markers in the tumour microenvironment following immunotherapy should improve our understanding and might enable us to better apply combination therapies.

The comparative efficacy of drugs for the management of overactive bladder syndrome (OAB) remains undefined. A new indirect treatment comparison demonstrates similar efficacy of mirabegron versus several antimuscarinic drugs and onabotulinum toxin A in a number of outcome measures. Head-to-head trials of these agents are still required to optimize the management of patients with OAB.

Advances in understanding of prostate cancer biology and improved treatment options have changed management of metastatic prostate cancer. Escape of the malignancy from the prostatic capsule no longer means that treatment is focused on limiting systemic spread, and data suggest that local treatment of the prostate is beneficial, even in men whose tumour has spread.