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Journal: Prostate Cancer and Prostatic Diseases

Prostate Cancer and Prostatic Diseases

The Role of Androgen Receptor (AR) in Liquid Biopsy to Predict Clinical Outcome to AR Signaling Inhibitors in Metastatic Castration Resistance Prostate Cancer Patients - Editorial

The ability to predict clinical outcomes prior to starting therapy is the hallmark of precision oncology. The detection of the androgen receptor splice variant 7 (AR-V7) in circulating tumor cells (CTCs) has now been externally and prospectively validated in the multicenter PROPHECY study using both the Hopkins mRNA and the Epic Sciences nuclear protein assays, demonstrating strong and significant associations with worse progression free and overall survival (PFS and OS) and a lack of responses in men with mCRPC,1 but such AR-V7 positive men can still have good outcomes with taxane chemotherapy.2 However, a limitation of CTC AR-V7 detection is that CTCs are required to be present, and nearly half of men with mCRPC have low to absent CTCs despite disease progression. In addition, AR-V7 likely only explains about 20-30% of AR therapy cross-resistance, meaning that other resistance mechanisms such as AR indifference and neuroendocrine transformation/lineage plasticity are also important.

Androgen Receptor Gain in Circulating Free DNA and Splicing Variant 7 in Exosomes Predict Clinical Outcome in CRPC Patients Treated with Abiraterone and Enzalutamide - Full-Text Article

Background - Androgen receptor (AR) signaling inhibitors represent the standard treatment in metastatic castration resistance prostate cancer (mCRPC) patients. However, some patients display a primary resistance, and several studies investigated the role of the AR as a predictive biomarker of response to treatment. This study is aimed to evaluate the role of AR in liquid biopsy to predict clinical outcome to AR signaling inhibitors in mCRPC patients.

Methods - Six milliliters of plasma samples were collected before first-line treatment with abiraterone or enzalutamide. Circulating free DNA (cfDNA) and exosome-RNA were isolated for analysis of AR gain and AR splice variant 7 (AR-V7), respectively, by digital droplet PCR.

Recommendation for the Use of Genomic Classifiers in Determining Patient Eligibility for Adjuvant Radiation Therapy - Editorial

Biomarkers and more complex integration of panels in so-called molecular or genomic classifiers have reached the level of clinical implication after careful standardization (LDT) and clinical validation. Whether these molecular classifiers are actually used and alter treatment decisions is studied in this manuscript.

A genomic classifier (GC) with prognostic indication, Decipher (Decipher Biosciences), aids in the decision for adjuvant radiotherapy (ART). In this study, the authors show that whereas the decision would have been "observation" in 39% of pre-genomic testing cases, the recommendation changed. The authors conclude that the use of GC substantially altered treatment decision-making, with a number needed to test of only 3.

Prospective Study to Define the Clinical Utility and Benefit of Decipher Testing in Men Following Prostatectomy - Full-Text Article

Background - Genomic classifiers (GC) have been shown to improve risk stratification post prostatectomy. However, their clinical benefit has not been prospectively demonstrated. We sought to determine the impact of GC testing on postoperative management in men with prostate cancer post prostatectomy.

Methods - Two prospective registries of prostate cancer patients treated between 2014 and 2019 were included. All men underwent Decipher tumor testing for adverse features post prostatectomy (Decipher Biosciences, San Diego, CA). The clinical utility cohort, which measured the change in treatment decision-making, captured pre- and postgenomic treatment recommendations from urologists across diverse practice settings (n = 3455). The clinical benefit cohort, which examined the difference in outcome, was from a single academic institution whose tumor board predefined “best practices” based on GC results (n = 135).

Preoperative Frailty Predicts Adverse Short-Term Postoperative Outcomes in Patients Treated with Radical Prostatectomy - Full-Text Article

Background - To investigate the effect of frailty on short-term postoperative outcomes in patients with prostate cancer treated with radical prostatectomy (RP).

Methods - Within the National Inpatient Sample database, we identified 91,618 RP patients treated between 2008 and 2015. The Johns Hopkins Adjusted Clinical Groups frailty-defining indicator was applied, and we examined the rates of frailty over time, as well as its effect on overall complications, major complications, nonhome-based discharge, length of stay (LOS), and total hospital charges (THCs). Time trends and multivariable logistic, Poisson and linear regression models were applied.

Adverse Short-Term Postoperative Outcomes in Patients Treated with Radical Prostatectomy Predicted by Preoperative Frailty - Editorial

The majority of urologists performing radical prostatectomy in developed populations are doing so with robotic platforms. Since adopting this approach, many of us have observed that our patients appear to have less pain and recover more rapidly. If we are brutally honest with ourselves, we have all probably lowered our bar for accepting patients for surgery on the basis of overall health because they seem to handle robotic-assisted surgery better than open surgery. In my own practice, for patients not willing to consider radiotherapy and were frail by my own subjective assessment, I would routinely send these patients for a review by one of my internal medicine colleagues who is by training a geriatrician and has developed a special interest in perioperative medicine. Almost always, these patients were then being cleared for surgery and gradually I have found that I am operating on more of these types of patients apart from just older patients.

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