Prostate Cancer and Prostatic Diseases - Results from #60

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Prostate Cancer and Prostatic Diseases

Prevalence of DNA Repair Gene Mutations in Localized Prostate Cancer According to Clinical and Pathologic Features: Association of Gleason Score and Tumor Stage - Full Text Article

Background - DNA repair gene mutations are present in 8–10% of localized prostate cancers. It is unknown whether this is influenced by clinicopathologic factors.

Methods - We interrogated localized prostate adenocarcinomas with tumor DNA sequencing information from the TCGA validated (n = 333) and Nature Genetics (n = 377) datasets. Homologous recombination repair genes included in our

The Association of Gleason Score and Tumor Stage in the Prevalence of DNA Repair Gene Mutations in Localized Prostate Cancer

To speak with Bob Dylan, ‘’..times they are a changing..’’, particularly when it comes to our insight in the genetic changes in prostate cancer. In the early days of molecular genetics studies of prostate cancer, scientists often referred to prostate cancer as being very different from other cancers, e.g. mutations in TP53 were rarely found in this malignancy. With the large scale introduction of next-generation sequencing and the impressive SU2C initiative, focusing on metastatic/advanced cancers, it was shown that prostate cancer was not that of a ‘’cancer genetic outlier’’. TP53-, Rb mutations ánd a rather high frequency of aberrations in genes encoding DNA repair proteins were found in advanced prostate cancer (metastatic CRPC).

A straight forward hypothesis is that these mutations have prognostic significance, i.e. mutations in pivotal cancer pathways are associated with clinical-, pathological stage, and grade, which in turn are a good proxy/surrogate for the outcome of the disease. Marshall and colleagues¹ focussed on DNA repair gene mutations and ‘mined’ existing DNA sequencing information (TCGA, NatureGenetics via cBioportal) to test this hypothesis. There appeared to be a clear correlation between pathological stage (pT3/4 versus pT2) and Gleason Grade groups (GG ≥ 3 versus GG 1-2). In the cT≥3 ánd GG ≥3 tumors in >20% DNA repair gene mutations were identified. Interestingly there appeared

Endoscopic Enucleation of the Prostate

It has now been over 20 years since holmium enucleation of the prostate was first described. Since then, several other energy sources have been described to perform endoscopic enucleation and more recently there has been a shift to performing the surgery using an enbloc resection technique instead of individual lobar resection. At the end of the day, it probably doesn’t make a great deal of difference as to which energy source is used to perform endoscopic enucleation of the prostate (EEP) and as to whether tissue removal was by individual lobes or enbloc. They are all achieving the same anatomical removal of tissue and are a basically similar principle of technique.

There have been systematic reviews and meta-analyses evaluating individual energy sources to perform EEP versus transurethral resection of the prostate (TURP). The study by Zhang and colleagues is novel in that for the first time, we have an analysis that takes the stance that all of the EEP techniques are essentially equivalent, and therefore creating a very powerful comparison with TURP.

Efficacy and Safety of Enucleation vs. Resection of Prostate for Treatment of Benign Prostatic Hyperplasia: A Meta-analysis of Randomized Controlled Trials - Full Text Article

The purpose of this study is to compare the efficacy and safety of transurethral enucleation and resection of the prostate for treatment of benign prostatic hyperplasia (BPH).

This meta-analysis was conducted through a systematic search before 1 September 2018. All included publications were randomized controlled trials (RCTs). Efficacy was evaluated based on International Prostate Symptom Score (IPSS), maximum urinary flow rate (Qmax), and quality of life (QoL).

Statin Use and Time to Progression in Men on Active Surveillance for Prostate Cancer - Full Text Article

Recent evidence suggests that statins may improve prostate cancer outcomes; however, their role in active surveillance (AS) is poorly characterized. We aimed to evaluate the association between statin use at diagnosis and time to progression on AS.

Data were obtained from a prospectively maintained cohort of men undergoing AS between 1995 and 2016 at our institution. All men satisfied the low-risk criteria: Gleason score <7, <4 positive cores, <50% involvement of any core, and prostate-specific antigen level <10.0 ng/dL. Kaplan–Meier curves and

Statins in Prostate Cancer and the Relationship in Men Undergoing Active Surveillance

The Fountain of Youth is thought to be a mystical spring that restores youth upon its drinkers. It has been searched for dating back to before the ancient Romans. Many people spent their lives chasing it – just ask Ponce De Leon! We now know the Fountain of Youth does not exist. In more recent times, the Fountain of Youth has been replaced by various remedies such as elixirs, oils, ointments, and herbs. More recently, people have turned to pharmaceuticals, of which statins has been one of the most touted. Statins are currently the most widely prescribed class of medicines. However, unlike various treatments of the past, statins are very effective. Specifically, they acutely block cholesterol production thereby lowering serum cholesterol levels typically by ~25%. In turn, this leads to dramatic reductions in heart disease risk.

Given the presumed importance of cholesterol in cancer pathways (it is the precursor for androgens as well as important in cell signaling pathways), there are multiple reasons to believe statins have anti-prostate cancer properties. While multiple studies have examined the role of statins in prostate cancer, often with mixed results, no prior study has examined this relationship in men undergoing active surveillance.

Prostatic Urethral Lift (PUL) for Treating Lower Urinary Tract Symptoms - Results of the MedLift Study

The Luminal Improvement Following Prostatic Tissue Approximation (L.I.F.T) study demonstrated the efficacy of prostatic urethral lift (PUL) to treat lower urinary tract symptoms (LUTS) secondary to bladder outlet obstruction (BOO)¹. One of the exclusion criteria for L.I.F.T. was the presence of an obstructing median or middle lobe (OML). The MedLift study was a non-randomized cohort analysis assessing the efficacy of PUL to improve symptoms of BOO in 45 patients with OML.

Other than OML status, the inclusion criteria for MedLift were identical to L.I.F.T.: ≥ 50 years of age, International Prostate Symptom Score (I-PSS) ≥ 13, and Qmax ≤ 12 ml/s. The primary endpoints were an improvement in I-PSS over baseline and incidence of post-procedure complications. Outcomes were compared to the L.I.F.T. historical cohort.

Prostatic Urethral Lift (PUL) for Obstructive Median Lobes: 12 Month Results of the MedLift Study - Full Text Article

Evidence indicating Prostatic Urethral Lift (PUL) delivers significant improvement in symptomatic BPH with low morbidity is based on subjects with lateral lobe (LL) enlargement only. MedLift was an FDA IDE extension of the L.I.F.T. randomized study designed to examine the safety and efficacy of PUL for the treatment of obstructive middle lobes (OML). Inclusion criteria for this non-randomized cohort were identical to the L.I.F.T. randomized study, except for requiring an OML: ≥ 50 years of age, IPSS ≥ 13, and Qmax ≤ 12 ml/s. Primary endpoint analysis quantified the improvement in IPSS over baseline and rate of postprocedure serious complications.

Thromboembolic Events Associated with ADT Treatment in Prostate Cancer Patients

Androgen deprivation therapy (ADT) is the mainstay of systemic therapy for men with metastatic or recurrent hormone-sensitive prostate cancer (mHSPC), as well as localized and PSA recurrent prostate cancer when radiation is indicated for higher risk disease. ADT is also continued indefinitely in men with mCRPC, and thus many men with aggressive forms of prostate cancer will be treated with years of ADT and face the cumulative risks of low testosterone.

Association of Androgen Deprivation Therapy with Thromboembolic Events in Patients with Prostate Cancer: a Systematic Review and Meta-analysis: Full-Text Article

Background: Whether androgen deprivation therapy (ADT) causes excess thromboembolic events (TEs) in men with prostate cancer (PCa) remains controversial and is the subject of the US Food and Drug Administration safety warning. This study aims to perform a systematic review and meta-analysis on previous studies to determine whether ADT is associated with TEs in men with PCa.

Prostate Cancer Risk by Lipid Parameters

Cholesterol is a key building block of cells. It provides crucial support to cell membranes allowing signaling between the inside and outside of cells. Cholesterol makes up ~ 1/3 of the cell membrane. Also, cholesterol is the precursor for many hormones – including testosterone. Without cholesterol, life as we know it could not exist. However, there is such a thing as too much of a good thing. Specifically, high serum cholesterol levels have been linked with numerous conditions such as cardiovascular disease, stroke, and many cancers.

Serum Cholesterol and Prostate Cancer Risk in the Finnish Randomized Study of Screening for Prostate Cancer - Full Text Article

Background: Hypercholesterolemia has been associated with advanced stage prostate cancer (PCa), but the role of lipid parameters such as HDL and triglycerides is unclear. We examined PCa risk by lipid parameters in a population nested within the Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC).

The Use of PET/CT in Prostate Cancer - Full Text Article

Background: Positron emission tomography/computed tomography (PET/CT) has recently emerged as a promising diagnostic imaging platform for prostate cancer. Several radiolabelled tracers have demonstrated efficacy for cancer detection in various clinical settings. In this review, we aim to illustrate the diverse use of PET/CT with different tracers for the detection of prostate cancer.

From the Desk of the Associate Editor: The Diverse Use of PET/CT Diagnostic Imaging for Prostate Cancer

This comprehensive review summarizes important clinical concepts in the rapidly advancing field of positron emission tomography/computed tomography (PET/CT) for prostate cancer. The authors reviewed 18F-NaF-, choline-, fluciclovine- and prostate-specific membrane antigen (PSMA)-based modalities in primary disease staging and assessment of biochemical recurrence. The most thoroughly studied modality to date is choline PET/CT.

Correlation of B7-H3 with Androgen Receptor, Immune Pathways and Poor Outcome in Prostate Cancer: An Expression-based Analysis – Full Text Article

BACKGROUND: B7-H3 (CD276), part of the B7 superfamily of immune checkpoint molecules, has been shown to have an immunomodulatory role. Its regulation, receptor and mechanism of action remain unclear. B7-H3 protein expression correlates with prostate cancer outcomes, and humanized monoclonal antibodies (that is, enoblituzumab) are currently being investigated for therapeutic use. Here we used genomic expression data to examine the relationship between B7-H3 mRNA expression and prostate cancer.

From the Desk of the Associate Editor: The Relationship of the B7H3 Immune Checkpoint to Prostate Cancer Outcomes

Prostate cancer is known to be an immune evasive tumor, often coexisting with areas of inflammation in the primary site, but without over-expression of the traditional PD-1/PD-L1 immune checkpoint, unlike many other cancer subtypes. While certain prostate cancer subsets like microsatellite high (MSI high) and CDK12 deleted disease may respond well to single agent PD-1 pathway inhibitors, in most (>90%) of prostateadenocarcinomas, other immunosuppressive molecules and pathways are likely to be of greater importance and have yet to be adequately targeted. Here is where B7-H3 may be relevant.

From the Desk of the Associate Editor: Utility of a PrCa Urinary Biomarker in Active Surveillance

The proof of concept for the utility of urinary biomarkers to predict biopsy outcome was published in 2003 by Hessels et al, which subsequently led to the launch of the PCA3 test in 2007. The test was mostly used for repeat biopsy decisions, to which also the FDA approval in 2012 was confined. The potential utility in active surveillance settings was suggested by many and in their recent paper Tosoain et al study the value of a first PCA3 outcome (fPCA3) and a subsequent PCA3 test (sPCA3) to predict Grade Reclassification (GR) in men on active surveillance.

Longitudinal Assessment of Urinary PCA3 for Predicting Prostate Cancer Grade Reclassification in Favorable-Risk Men During Active Surveillance - Full Text Article

BACKGROUND: To assess the utility of urinary prostate cancer antigen 3 (PCA3) as both a one-time and longitudinal measure in men on active surveillance (AS).

METHODS: The Johns Hopkins AS program monitors men with favorable-risk prostate cancer with serial PSA, digital rectal examination (DRE), prostate magnetic resonance imaging and prostate biopsy. Since 2007, post-DRE urinary specimens have also been routinely obtained. Men with multiple PCA3 measures obtained over ⩾3 years of monitoring were included. The utility of first PCA3

From the Desk of the Associate Editor: PSMA PET/CT in the Assessment of Intra-Prostatic Prostate Cancer

A large number of studies on ⁶⁸Ga PSMA PET/CT are coming out of Australia due to the ready access to this technology. To give some background, PET/CT imaging has long been registered with the Australian Therapeutic Goods Administration (TGA) and with this has come the approval to use any radionuclide tracer. With it being unnecessary to apply for additional registration to use new tracers, this has allowed uptake of 68Ga PSMA PET/CT into routine clinical practice throughout Australia and to the extent that it is rapidly replacing conventional radionuclide bone scans and CT scan of the abdomen and pelvis as imaging for the staging of prostate cancer.

Comparison of Multiparametric Magnetic Resonance Imaging and PSMA PET/CT to Prostatectomy Histopathology - Full Text Article

Background: Prostate-specific membrane antigen (PSMA) positron emission tomography (PET) can be used to locate lesions based on PSMA avidity, however, guidelines on its use are limited by its infancy. We aimed to compare multiparametric magnetic resonance imaging (mpMRI) and PSMA PET/CT to prostatectomy histopathology.

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