Comparison of circulating tumor DNA between African American and Caucasian patients with metastatic castrate-resistant prostate cancer post-abiraterone and/or enzalutamide.

BACKGROUND: African American men are much more likely than Caucasian men to be diagnosed with and to die of prostate cancer. Genetic differences likely play a role. The cBioPortal database reveals that African American men with prostate cancer have higher rates of CDK12 somatic mutations compared to Caucasian men. However, this does not account for prior prostate cancer treatments, which are particularly important in the castrate-resistant setting. We aimed to compare somatic mutations based on circulating tumor DNA (ctDNA) in metastatic castration-resistant prostate cancer (mCRPC) between African American and Caucasian men after exposure to abiraterone and/or enzalutamide. METHODS: This single-institution retrospective study characterizes the somatic mutations detected on ctDNA for African American and Caucasian men with mCRPC who had progressed after abiraterone and/or enzalutamide from 2015 through 2022. We evaluated the gene mutations and types of mutations in this mCRPC cohort. RESULTS: There were 50 African American and 200 Caucasian men with CRPC with available ctDNA data. African American men were younger at the time of diagnosis (p = 0.008) and development of castration resistance (p = 0.006). African American men were more likely than Caucasian men to have pathogenic/likely pathogenic (P/LP) mutations in CDK12 (12% vs. 1.5%; p = 0.003) and copy number amplifications and P/LP mutations in KIT (8.0% vs. 1.5%; p = 0.031). African American men were also significantly more likely to have frameshift mutations (28% vs. 14%; p = 0.035). CONCLUSIONS: Compared to Caucasian men, African American men with mCRPC after exposure to abiraterone and/or enzalutamide had a higher incidence of somatic CDK12 P/LP mutations and KIT amplifications and P/LP mutations based on ctDNA. African American men also had more frameshift mutations. We hypothesize that these findings have potential implications for tumor immunogenicity.

Clinical and molecular determinants of PSA response to bipolar androgen therapy in prostate cancer.

BACKGROUND: Bipolar androgen therapy (BAT) is a novel therapy known to be effective in a subset of men with metastatic castrate resistant prostate cancer (mCRPC). A better understanding of responders and nonresponders to BAT would be useful to clinicians considering BAT therapy for patients. Herein we analyze clinical and genetic factors in responders/nonresponders to better refine our understanding regarding which patients benefit from this innovative therapy. METHODS: mCRPC patients were assessed for response or no response to BAT. Patients with PSA declines of greater than 50% from baseline after 2 or more doses of testosterone were considered to be responders. Whereas, nonresponders had no PSA decline after 2 doses of testosterone and subsequently manifest a PSA increase of >50%. Differences between these two groups of patients were analyzed using clinical and laboratory parameters. All patients underwent genomic testing using circulating tumor DNA (ctDNA) and germline testing pre-BAT. RESULTS: Twenty five patients were nonresponders and 16 were responders. Baseline characteristics between nonresponders and responders varied. Responders were more likely to have had a radical prostatectomy as definitive therapy and were more likely to have been treated with an androgen receptor (AR) antagonist (enzalutamide or apalutamide) immediately before BAT (compared to abiraterone). Duration of prior enzalutamide therapy was longer in responders. Nonresponders were more likely to have bone-only metastases and responders were more likely to have nodal metastases. Assays detected ctDNA AR amplifications more often in responding patients. Responders trended toward having the presence of more TP53 mutations at baseline. CONCLUSIONS: BAT responders are distinct from nonresponders in several ways however each of these distinctions are imperfect. Patterns of metastatic disease, prior therapies, duration of prior therapies, and genomics each contribute to an understanding of patients that will or will not respond. Additional studies are needed to refine the parameters that clinicians can utilize before choosing among the numerous treatment alternatives available for CRPC patients.

A narrative review of biparametric MRI (bpMRI) implementation on screening, detection, and the overall accuracy for prostate cancer.

Prostate cancer is the most common malignancy in American men following skin cancer, with approximately one in eight men being diagnosed during their lifetime. Over the past several decades, the treatment of prostate cancer has evolved rapidly, so too has screening. Since the mid-2010s, magnetic resonance imaging (MRI)-guided biopsies or 'targeted biopsies' has been a rapidly growing topic of clinical research within the field of urologic oncology. The aim of this publication is to provide a review of biparametric MRI (bpMRI) utilization for the diagnosis of prostate cancer and a comparison to multiparametric MRI (mpMRI). Through single-centered studies and meta-analysis across all identified pertinent published literature, bpMRI is an effective tool for the screening and diagnosis of prostate cancer. When compared with the diagnostic accuracy of mpMRI, bpMRI identifies prostate cancer at comparable rates. In addition, when omitting dynamic contrast-enhanced (DCE) protocol to the MRI, patients incur reduced costs and shorter imaging time while providers can offer more tests to their patient population.

Effects on Memory of Early Testing and Accuracy Assessment for Central and Contextual Content.

Memory for an event is influenced by many factors including retention interval, frequency of assessment, and type of information assessed concerning the event. We examined the usefulness of observer memory for contextual information in assessing accuracy of memory for central information. Participants viewed a video of a purse being stolen and were asked questions concerning the perpetrator and surrounding context of the event, including where and when the event occurred and who else was present. Participants tested immediately after seeing the video exhibited better memory than those tested for the first time 48-hour after the event. Additionally, testing immediately after viewing the video reduced forgetting over the 48-hour delay (i.e., early testing attenuated subsequent forgetting). Moreover, memory for the context of the event correlated positively with memory of the central information (i.e., perpetrator), and memory concerning other people at the event tended to have the highest correlation with perpetrator memory.