Somatic Mitochondrial DNA Point Mutations Used as Biomarkers to Demonstrate Genomic Heterogeneity in Primary Prostate CancerRead the full article
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Interleukin-10 Induces Expression of Neuroendocrine Markers and PDL1 in Prostate Cancer Cells
Interleukin-10 (IL10) is best studied for its inhibitory action on immune cells and ability to suppress an antitumour immune response. But IL10 also exerts direct effects on nonimmune cells such as prostate cancer epithelial cells. Elevated serum levels of IL10 observed in prostate and other cancer patients are associated with poor prognosis. After first-line androgen-deprivation therapy, prostate cancer patients are treated with androgen receptor antagonists such as enzalutamide to inhibit androgen-dependent prostate cancer cell growth. However, development of resistance inevitably occurs and this is associated with tumour differentiation to more aggressive forms such as a neuroendocrine phenotype characterized by expression of neuron specific enolase and synaptophysin. We found that treatment of prostate cancer cell lines in vitro with IL10 or enzalutamide induced markers of neuroendocrine differentiation and inhibited androgen receptor reporter activity. Both also upregulated the levels of PDL1, which could promote tumour survival in vivo through its interaction with the immune cell inhibitory receptor PD1 to suppress antitumour immunity. These findings suggest that IL10’s direct action on prostate cancer cells could contribute to prostate cancer progression independent of IL10’s suppression of host immune cells.
Understanding and Improving 18F-Fluciclovine PET/CT Reports: A Guide for Physicians Treating Patients with Biochemical Recurrence of Prostate Cancer
The positron emission tomography (PET) tracer 18F-fluciclovine has seen increasing use to localize disease in men with biochemical recurrence of prostate cancer, i.e., elevated prostate-specific antigen (PSA) levels post-treatment. 18F-Fluciclovine PET/computed tomography (CT) imaging reports now play central roles in many physician-patient discussions. However, because no standardized grading system or templates yet exist for 18F-fluciclovine image assessment, reports vary in format, comprehensiveness, and terminology and may be challenging to fully understand. To better utilize these documents, referring physicians should be aware of six key features of 18F-fluciclovine PET/CT. First, 18F-fluciclovine is a radiolabeled synthetic amino acid targeting the amino acid transporters ASCT2 and LAT1, which are ubiquitous throughout the body, but overexpressed in prostate cancer. Second, 18F-fluciclovine image interpretation is predominantly visual/qualitative: radiotracer uptake in suspicious lesions is compared with uptake in bone marrow or blood pool. Location of 18F-fluciclovine-avid lesions relative to typical recurrence sites and findings elsewhere in the patient are considered when evaluating lesions’ probability of malignancy, as is visibility on maximum intensity projection images when assessing bone lesions. Third, 18F-fluciclovine PET/CT detection rates increase as PSA levels rise. Fourth, detection rates may differ among centers, possibly due to equipment and reader experience. Fifth, since no diagnostic test is 100% accurate, scan data should not be used in isolation. Lastly, 18F-fluciclovine PET/CT findings frequently induce changes in disease management plans. In the prospective multicenter LOCATE and FALCON studies, scans altered management plans in 59% (126/213) and 64% (66/104) of patients, respectively; 78% (98/126) and 65% (43/66) of changes, respectively, involved modality switches. Referring physicians and imagers should collaborate to improve scan reports. Referrers should clearly convey critical information, including prescan PSA levels, and open clinical questions. Imagers should produce reports that read like consultations, avoid leaving open questions, and if needed, provide thoughts on next diagnostic steps.
Cancer Detection Rates of Systematic and Targeted Prostate Biopsies after Biparametric MRI
Objective. To compare prostate cancer detection rates (CDRs) and pathology results with targeted prostate biopsy (TB) and systematic prostate biopsy (SB) in biopsy-naive men. Methods. An in-patient control study of 82 men undergoing SB and subsequent TB in case of positive prostate MRI between 2015 and 2017 in the Jeroen Bosch Hospital, the Netherlands. Results. Prostate cancer (PCa) was detected in 54.9% with 70.7% agreement between TB and SB. Significant PCa (Gleason score ≥7) was detected in 24.4%. The CDR with TB and SB was 35.4% and 48.8%, respectively (). The CDR of significant prostate cancer with TB and SB was both 20.7%. Clinically significant pathology upgrading occurred in 7.3% by adding TB to SB and 22.0% by adding SB to TB. Conclusions. There is no statistically significant difference between CDRs of SB and TB. Both SB and TB miss significant PCas. Moreover, pathology upgrading occurred more often by adding SB to TB than vice versa. This indicates that the omission of SB in this study population might not be justified.
The Prospect of Identifying Resistance Mechanisms for Castrate-Resistant Prostate Cancer Using Circulating Tumor Cells: Is Epithelial-to-Mesenchymal Transition a Key Player?
Prostate cancer (PCa) is initially driven by excessive androgen receptor (AR) signaling with androgen deprivation therapy (ADT) being a major therapeutic approach to its treatment. However, the development of drug resistance is a significant limitation on the effectiveness of both first-line and more recently developed second-line ADTs. There is a need then to study AR signaling within the context of other oncogenic signaling pathways that likely mediate this resistance. This review focuses on interactions between AR signaling, the well-known phosphatidylinositol-3-kinase/AKT pathway, and an emerging mediator of these pathways, the Hippo/YAP1 axis in metastatic castrate-resistant PCa, and their involvement in the regulation of epithelial-mesenchymal transition (EMT), a feature of disease progression and ADT resistance. Analysis of these pathways in circulating tumor cells (CTCs) may provide an opportunity to evaluate their utility as biomarkers and address their importance in the development of resistance to current ADT with potential to guide future therapies.
Long-Term Follow-Up after Prostatectomy for Prostate Cancer and the Need for Active Monitoring
Background. Only truly long-term follow-up can determine the ultimate outcome in prostate cancer. Most studies have a median follow-up of less than 10 years and then project outcomes out to 15 and 20 years. We sought to follow patients for at least 20 years. Materials and Methods. We followed 754 prostate cancer patients treated with radical prostatectomy from 1988 to 1995 for a median follow-up (in survivors) of 23.9 years. We excluded lymph node and seminal vesicle positive patients and an additional 47 patients that did not have baseline prostate-specific antigen (PSA). This left 581 patients for analysis. Results. With the factors of PSA, Gleason score, and extraprostatic extension/margin positivity, we could partition patients into three risk groups for biochemical failure (low, intermediate, and high). In further analysis, we found that the risk of metastatic disease in the first two groups was almost identical (4% and 5%, respectively), while it was 19% in the high-risk group. High-risk patients were those with PSA >20 ng/ml and/or Gleason >7, or Gleason 7 + PSA 10–20 + epe (and or margin) positive. They had a 22% prostate cancer mortality. Conclusion. In patients with truly long-term follow-up after prostatectomy for prostate cancer, the risk of metastatic disease and cancer death is very low. Patients with the lower risk findings do not appear to benefit from routine follow-up after 10 years free of biochemical recurrence. With a higher risk of later failure, we recommend that the higher risk patients be followed at least intermittently for another 5 years (out to 15 years).
Synthetic Apparent Diffusion Coefficient for High b-Value Diffusion-Weighted MRI in Prostate
Purpose. It has been reported that diffusion-weighted imaging (DWI) with ultrahigh b-value increases the diagnostic power of prostate cancer. DWI with higher b-values is challenging as it commonly suffers from low signal-to-noise ratio (SNR), distortion, and longer scan time. The aim of our study was to develop a technique for quantification of apparent diffusion coefficient (ADC) for higher b-values from lower b-value DW images. Materials and Methods. Fifteen patients (7 malignant and 8 benign) were included in this study retrospectively with the institutional ethical committee approval. All images were acquired at a 3T MR scanner. The ADC values were calculated using a monoexponential model. Synthetic ADC (sADC) for higher b-value was computed using a log-linear model. Contrast ratio (CR) between prostate lesion and normal tissue on synthetic DWI (sDWI) was computed and compared with original DWI and ADC images. Results. No significant difference was observed between actual ADC and sADC for b-2000 in all prostate lesions. However, CR increased significantly (, paired t-test) in sDWI as compared to DWI. Malignant lesions showed significantly lower sADC as compared to benign lesions (, independent t-test). Mean (±standard deviation) of sADC of malignant lesions was 0.601 ± 0.06 and for benign lesions was 0.92 ± 0.09 (10−3 mm2/s). Discussion/Conclusion. Our initial investigation suggests that the ADC values corresponding to higher b-value can be computed using log-linear relationship derived from lower b-values (b ≤ 1000). Our method might help clinicians to decide the optimal b-value for prostate lesion identification.