T. Van Den Broeck

The role of TET-mediated DNA hydroxymethylation in prostate cancer

Ten-eleven translocation (TET) proteins are recently characterized dioxygenases that regulate demethylation by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine and further derivatives. The recent finding that 5hmC is also a stable and independent epigenetic modification indicates that these proteins play an important role in diverse physiological and pathological processes such as neural and tumor development. Both the genomic distribution of (hydroxy)methylation and the expression and activity of TET proteins are dysregulated in a wide range of cancers including prostate cancer. Up to now it is still unknown how changes in TET and 5(h)mC profiles are related to the pathogenesis of prostate cancer. In this review, we explore recent advances in the current understanding of how TET expression and function are regulated in development and cancer. Furthermore, we look at the impact on 5hmC in prostate cancer and the potential underlying mechanisms. Finally, we tried to summarize the latest techniques for detecting and quantifying global and locus-specific 5hmC levels of genomic DNA.

The survival impact of neoadjuvant hormonal therapy before radical prostatectomy for treatment of high-risk prostate cancer.

Background:Several randomized controlled trials assessed the outcomes of patients treated with neoadjuvant hormonal therapy (NHT) before radical prostatectomy (RP). The majority of them included mainly low and intermediate risk prostate cancer (PCa) without specifically assessing PCa-related death (PCRD). Thus, there is a lack of knowledge regarding a possible effect of NHT on PCRD in the high-risk PCa population. We aimed to analyze the effect of NHT on PCRD in a multicenter high-risk PCa population treated with RP, using a propensity-score adjustment.Methods:This is a retrospective multi-institutional study including patients with high-risk PCa defined as: clinical stage T3–4, PSA >20 ng ml−1 or biopsy Gleason score 8–10. We compared PCRD between RP and NHT+RP using competing risks analysis. Correction for group differences was performed by propensity-score adjustment.Results:After application of the inclusion/exclusion criteria, 1573 patients remained for analysis; 1170 patients received RP and 403 NHT+RP. Median follow-up was 56 months (interquartile range 29–88). Eighty-six patients died of PCa and 106 of other causes. NHT decreased the risk of PCRD (hazard ratio (HR) 0.5; 95% confidence interval (CI) 0.32–0.80; P=0.0014). An interaction effect between NHT and radiotherapy (RT) was observed (HR 0.3; 95% CI 0.21–0.43; P<0.0008). More specifically, of patients who received adjuvant RT, those who underwent NHT+RP had decreased PCRD rates (2.3% at 5 year) compared to RP (7.5% at 5 year). The retrospective design and lack of specific information about NHT are possible limitations.Conclusions:In this propensity-score adjusted analysis from a large high-risk PCa population, NHT before surgery significantly decreased PCRD. This effect appeared to be mainly driven by the early addition of RT post-surgery. The specific sequence of NHT+RP and adjuvant RT merits further study in the high-risk PCa population.

Treatment-induced changes in the androgen receptor axis: Liquid biopsies as diagnostic/prognostic tools for prostate cancer

Prostate cancer progression and treatment relapse is associated with changes in the androgen receptor axis, and analysis of alternations of androgen receptor signaling is valuable for prognostics and treatment optimization. The profile of androgen receptor axis is currently obtained from biopsy specimens, which are not always easy to obtain. Moreover, the information acquired only provides a snapshot of the tumor biology, with strict spatial and temporal limitations. On the other hand, circulation is easily accessible source of both circulating tumor cells and circulating tumor DNA, which can be sampled at numerous time points. This Review will explore the potential use of androgen receptor axis alternations detectable in the blood in therapeutic decision-making and precision medicine for advancing metastatic castration-resistant prostate cancer.

The benefits and harms of different extents of lymph node dissection during radical prostatectomy for prostate cancer: A systematic review

Nicola Fossati , Peter-Paul M. Willemse , Thomas Van den Broeck , Roderick C.N. van den Bergh , Cathy Yuhong Yuan , Erik Briers , Joaquim Bellmunt , Michel Bolla , Philip Cornford , Maria De Santis , Ekelechi MacPepple , Ann M. Henry , Malcolm D. Mason , Vsevolod B. Matveev , Henk G. van der Poel , Theo H. van der Kwast , Olivier Rouvière , Ivo G. Schoots , Thomas Wiegel , Thomas B. Lam , Nicolas Mottet , Steven Joniau *