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.
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 castrationresistant 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
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. Keywords context; preventing forgetting; central information; peripheral information; repeated testingAccurately remembering past events can be a major concern in everyday life. This includes more trivial events, such as remembering where we put our keys, and more significant events, such as remembering the details of a criminal event. Research has examined many factors that influence the accuracy of such episodic memories. One such factor is the time
243 Background: Lutetium-177- PSMA-617 (Lu-177) is a radioligand therapy that delivers radiation to PSMA-expressing cells in patients with advanced prostate cancer. In this study, we aimed to analyze ctDNA in responders and non-responders after Lu-177 treatments. Methods: Data was retrospectively collected on 31 heavily pre-treated metastatic CRPC patients who received Lu-177 treatment at Tulane Cancer Center. All patients fulfilled VISION criteria for treatment and all had ctDNA assessment with Guardant 360 within 30 days prior to first treatment with Lu-177. Of the 31 patients, 7 had paired ctDNA assessment both prior initiation of treatment and at the end of treatment. Clinical data such as PSA response (PSA decline 50% or more) to Lu-177, initial diagnosis, pathology, treatment history, and relevant germline genetic data were collected. Results: Of the 31 patients who received Lu-177 treatment, 18 had PSA response to Lu-177 (responders) and 13 did not (non-responders). In ctDNA mutational analyses, there were no significant differences detected prior to treatment between responders and non-responders. There was, however, a significant increase in the presence of copy number amplifications in non-responders (n= 11/13) when compared to responders (n= 7/18) (OR= 8.64, 95% C.I. [1.46, 51.25)], p = 0.0250). Amplification was detected in 10 genes in non-responders, whereas responders only had amplifications in AR (7/18) and EGFR (1/18). The most frequently amplified genes in non-responders were AR (8/13), CCNE1 (6/13), EGFR (4/13), and FGFR1 (4/13). Furthermore, in analysis of the 7 patients with paired ctDNA assessments, amplifications increased during treatment with Lu-177. Conclusions: Radioligand therapy with Lu-177 has been shown to prolong life and reduce disease progression. Our analysis of the cohort of Lu-177 treated patients showed that the presence of gene amplifications in ctDNA may play a role in predicting resistance to treatment with Lu-177.
248 Background: mCRPC patients with liver metastases have a poor prognosis and often progress rapidly on a variety of treatments. Previously, preliminary ctDNA analyses of mCRPC patients with liver metastases showed a range of commonly altered genes in patients with liver metastases (Ranasinghe et al; 2019). In this follow-up, we evaluated ctDNA alterations in an expanded cohort of mCRPC patients with liver metastases. Methods: From Tulane Cancer Center, retrospective review of mCRPC patients was used to identify patients with confirmed liver metastasis. All liver metastases were confirmed based on imaging data. All patients included had ctDNA evaluated with a multi-gene cancer panel via Guardant 360 assay (Guardant Health, Inc). Additional clinical annotation including family history, germline testing, staging, imaging, and laboratory values. Statistical analyses were performed with Fisher’s Exact and Wilcoxon Rank Sum tests. Results: 158 mCRPC patients with appropriate diagnostic imaging as well as ctDNA testing. From this group, 8% (n= 12) had confirmed liver metastases. Among the patients with liver metastasis, the most common alterations detected were in AR (50%; 6/12) and PIK3CA (25%; 3/12). Patients with liver metastasis were more likely to have amplifications in FGFR1 detected in their ctDNA (OR= 14.40; 95% C.I. (1.83, 113.22); p= 0.03). In addition to ctDNA, germline data was assessed, and it was found that patients with liver metastasis were more likely to have a pathogenic germline mutation (OR= 7.61; 95% C.I. (2.85, 20.31); p<.0001). The most common germline mutations detected in patients with liver metastasis were in BRCA2 (n= 3) and TP53 (n= 2). Conclusions: Though liver metastasis are less common in prostate cancer, it often occurs following extensive treatment and results in a poor prognosis for patients. In patients with liver metastasis, FGFR1 amplification was more often detected in ctDNA. Importantly, patients with liver metastasis were significantly more likely to have a pathogenic germline alteration.
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