Prospective assessment of AR splice variant and PSMA detection on circulating tumor cells of mCRPC patients: preliminary analysis of patients enrolled in PRIMERA trial (NCT04188275).

In our institution, a prospective observational trial testing micro-RNA (miRNA) and ARV7 mutational status in metastatic, castration resistant prostate cancer (mCRPC), is currently recruiting (PRIMERA trial, NCT04188275). A pre-planned interim analysis was performed when 50% of the planned accrual was reached. In this report, we explored the predictive value of Circulating Tumor Cell (CTC) detection in mCRPC patients undergoing 1st line therapy. Moreover, ARV7, ARFL, PSMA and PSA expression on CTC was reported to explore potential correlation with patient prognosis and response to therapy. PRIMERA is a prospective observational trial enrolling mCRPC patients undergoing standard treatment (ARTA + ADT) after I line ADT failure. Clinical and pathological features were collected. Outcomes selected for this preliminary analysis were time to castration resistance (TTCR), PSA at 8 weeks after ARTA therapy start, PSA drop at 8 weeks, Overall PSA drop, PSA nadir. Correlation between these outcomes and CTC detection was tested. Expression of ARV7, ARFL, PSA and PSMA was explored in CTC+ patients to assess their prevalence in this cohort and their impact on selected outcomes. Median TTCR was significantly shorter in CTC+ vs CTC- patients (32.3 vs 75 months, respectively, p = 0.03) and in ARFL+ vs ARFL- patients (30.2 vs 51.1 months, respectively, p = 0.02). ARV7, PSMA and PSA expression on CTC had no impact on median TTCR, nor on biochemical response to therapy. Patients in whom CTC and ARFL expression were detected had significant reduced TTCR. However, PSA response was not influenced by CTCs detection and specific biomarkers expression.

Evaluating determinants of receipt of molecular imaging in biochemical recurrent prostate cancer.

BACKGROUND: Molecular imaging with novel radiotracers is changing the treatment landscape in prostate cancer (PCa). Currently, standard of care includes either conventional and molecular imaging at time of biochemical recurrence (BCR). This study evaluated the determinants of and cost associated with utilization of molecular imaging for BCR PCa. METHODS: This is a retrospective observational cohort study among men with BCR PCa from June 2018 to May 2019. Multivariate logistic regression models were employed to analyze the primary outcome: receipt of molecular imaging (e.g. Fluciclovine PET and Prostate Specific Membrane Antigen PET) as part of diagnostic work-up for BCR PCa. Multivariate linear regression models were used to analyze the secondary outcome: overall healthcare cost within a 1-year time frame. RESULTS: The study sample included 234 patients; 79.1% White, 2.1% Black, 8.5% Asian/Pacific Islander, and 10.3% Other. The majority were 55 years or older (97.9%) and publicly insured (74.8%). Analysis indicated a one-unit reduction in PSA is associated with 1.3 times higher likelihood of receiving molecular imaging (p < 0.01). Analysis found that privately insured patients were associated with approximately $500,000 more in hospital reimbursement (p < 0.01) as compared to the publicly insured. Additionally, a one-unit increase in PSA is associated with $6254 increase in hospital reimbursement or an increase in total payments by 2.1% (p < 0.05). CONCLUSIONS: Higher PSA was associated with lower likelihood for molecular imaging and higher cost in a one-year time frame. Higher cost was also associated with private insurance, but there was no clear relationship between insurance type and imaging type.

A decision analysis comparing 3 active surveillance protocols for the treatment of patients with low-risk prostate cancer.

BACKGROUND: Active surveillance (AS) is a viable management option for approximately 50% of men who are newly diagnosed with prostate cancer. To the authors' knowledge, no direct comparisons between the different variants of AS protocols have been conducted to date. The authors developed a microsimulation decision model to evaluate which of 3 alternative AS protocols is optimal for men with low-risk prostate cancer, and compared each of these with immediate treatment. METHODS: Men who were diagnosed with low-risk prostate cancer at age 65 years were modeled as having been treated with either immediate therapy or via each of 3 AS protocols. Modeled AS protocols represent those in the literature; a modified AS protocol was included in a sensitivity analysis. Immediate therapy included radical prostatectomy, external-beam radiotherapy, or brachytherapy. Outcome measures were quality-adjusted life-years (QALYs) and costs. Cost-effectiveness analysis and deterministic and probabilistic sensitivity analyses were performed. RESULTS: Immediate therapy produced fewer QALYs than all variants of AS. Of the AS protocols evaluated, biennial biopsy was found to be the only efficient option, with an incremental cost-effectiveness ratio of $3490 per QALY compared with immediate therapy. It delayed the need for curative therapy by a mean of 56 months, and was found to be preferred in >86.9% of cases in probabilistic sensitivity analysis. A modified version of low-intensity AS dominated all other options. CONCLUSIONS: For a 65-year-old man with low-risk prostate cancer, AS with biennial biopsy appears to be highly cost-effective compared with common alternatives. An AS protocol using triennial biopsy was found to dominate all other strategies and should be considered for men who are comfortable with a longer period between biopsies. The optimal strategy depends on a patient's tolerance for periodic biopsies and comfort with delaying radical treatment. Physicians should incorporate these patient preferences into decision making.