Prostate Cancer最新文献

Objectives: To determine whether an alkaline phosphatase (ALP) flare after androgen deprivation therapy (ADT) is associated with the treatment response in castration-resistant prostate cancer (CRPC) and predicts the prognosis of metastatic prostate cancer (PCa) patients.

Methods: One hundred and nineteen patients diagnosed with metastatic PCa between 2008 and 2017 were retrospectively studied. The ALP flare ratio was calculated as the ratio of ALP levels 1 month after beginning ADT to ALP levels at diagnosis. The association of the ALP flare ratio with the prostate-specific antigen (PSA) response to CRPC treatment (second-generation androgen receptor targeted therapy (ART) or docetaxel), time to CRPC, and overall survival (OS) were investigated.

Results: The time to CRPC and OS was significantly longer in patients with an ALP flare ratio less than 1.33 compared to a ratio more than 1.33. No difference in PSA response was seen regarding the ALP flare ratio in both ART and docetaxel treatment. Second-generation ART-treated patients with a low ALP flare ratio showed longer OS than those with a higher ALP flare ratio (p=0.0367). However, no difference was seen between a high and low ALP flare ratio (p=0.8054) in docetaxel-treated patients. The ALP flare ratio was the most significant prognostic factor for OS (p < 0.0001).

Conclusions: A higher ALP flare ratio after first-line ADT was a significant prognostic factor in metastatic PCa, especially in patients treated with second-generation ART for CRPC. Chemotherapy for patients with a higher ALP flare ratio 1 month after induction of ADT may be a clinically relevant decision.

Lipocalin-2 has an important role in tumor progression, invasion, and metastasis. However, its role in prostate cancer remains unclear. The objective of this study is to determine the expression level of lipocalin-2 in human prostate cancer tissues and to evaluate the relationship between its expression level and clinicopathologic parameters including response to docetaxel treatment, Gleason score, progression-free survival (PFS), and overall survival (OS). We retrospectively analyzed paraffin-embedded tissue sections from 33 metastatic castrate-resistant prostate cancer (mCRPC) patients whose clinical outcomes had been tracked after docetaxel treatment. The expression status of lipocalin-2 was defined by immunohistochemistry (IHC) using the anti-lipocalin-2 antibody. Lipocalin-2 was highly expressed in 36% of the examined specimens. There was no significant correlation between high lipocalin-2 expression and docetaxel response (p : 0.09). High lipocalin-2 expression was significantly associated with a higher Gleason score (p=0.027). Kaplan-Meier survival analysis failed to show a significant correlation between expression levels of lipocalin-2 and both OS and PFS although patients with high lipocalin-2 levels had a numerically shorter PFS and OS time compared to patients with low levels. Consequently, it is clear that further studies are needed to evaluate the predictive and prognostic role of lipocalin-2 in prostate cancer patients.

Introduction: Prostate cancer is currently a public health problem with a frequency that varies from country to country. This study aims to describe the epidemiological, clinical, and histopathological and outcome features of prostate cancer in Lubumbashi in the Democratic Republic of Congo.

Materials and methods: This was a descriptive longitudinal study of patients diagnosed with prostate cancer at the University Clinics of Lubumbashi. The study period was 3 years (2017 to 2019). Parameters studied were age and clinical, biological (PSA level, prostatic specific antigen), histopathological, and outcome features.

Results: The mean age of patients was 68.7 years (range: 47 and 90 years). The 60 to 69 age group was the most affected (43.18%). Elderly subjects (≥60 years old) represented 89.77% of the cases (n = 79). Voiding disorders were the main reason for consultation in 55.68% of the cases. The mean PSA level was 133.7 ng/ml (range: 4 and 1564.5 ng/ml) at diagnosis and 125.4 ng/ml after 3 months of follow-up (range: 0.16 and 1782.1 ng/ml). Adenocarcinoma was the predominant histological type (100%). In prognosis, 31.82% of patients had a Gleason score greater than 7 and 59.10% had a high risk at the D'Amico risk classification for Prostate Cancer. Hormone therapy was administered alone in 75% of the cases and in combination with pulpectomy in 13.64% of the cases. The 3-year overall survival was 56.82%.

Conclusion: Prostate cancer is frequent and has a poor outcome in our country. The establishment of an individual screening policy would be an undeniable advantage in improving the prognosis.

Purpose: To evaluate the efficacy and safety of nanosomal docetaxel lipid suspension (NDLS, DoceAqualip) in patients with metastatic castration-resistant prostate cancer (mCRPC).

Materials and methods: In this multicenter, retrospective study, we analyzed the medical charts of mCRPC patients, who were treated with NDLS administered as 2-weekly (50 mg/m²) or 3-weekly regimens (75 mg/m²). The study endpoints were prostate-specific antigen (PSA) response (>50% PSA decline from baseline), PSA progression (PSA increase from baseline beyond 12 weeks: ≥25% and ≥2 ng/mL), median PSA decline, and time-to-treatment failure (TTF). Overall survival (OS) and safety were also evaluated.

Results: Data of 24 patients with mCRPC were analyzed in this study. NDLS was administered as a 2-weekly regimen in 37.5% (9/24; all first-line) patients and as a 3-weekly regimen in 62.5% patients (15/24; first-line: 20% (3/15), second-line: 80% (12/15)). Overall, PSA response was reported in 66.7% (16/24) patients. The PSA response was 77.8% (7/9 patients) in the 2-weekly group and 60% (9/15 patients) in the 3-weekly group. The median decline in PSA was 96.31% in the 2-weekly group and 83.29% in the 3-weekly group; the median TTF was 6.7 and 6.5 months in the 2 weekly group and 3-weekly group, respectively. The median OS was 14.6 months (follow-up: 5.5-25.8 months) in the 2-weekly group whereas it was not reached in the 3-weekly group (follow-up: 7.9-15.6 months). The most common hematological AEs were anemia, lymphopenia, thrombocytopenia, and neutropenia whereas nausea, weakness, constipation, vomiting, and diarrhea were the most common (≥10%) nonhematological AEs. Overall, NDLS treatment was well tolerated without any new safety concerns.

Conclusions: Nanosomal docetaxel lipid suspension (2-weekly or 3-weekly) was effective and well tolerated in patients with metastatic castration-resistant prostate cancer.

Primary prostate tumor heterogeneity is poorly understood, leaving research efforts with challenges regarding the initiation and advancement of the disease. The growth of tumor cells is accompanied by mutations in nuclear and in mitochondrial genomes. Thus, mitochondrial DNA mutations may be used as tumor cell markers. By the use of laser capture microdissection coupled with assays for mitochondrial point mutation detection, mtDNA mutations were used to trace mutated cells at a histological level. Point mutations in mtDNA were determined in 12 primary prostate cancers. The tumors represent different pathology-prognostic grade groups. Known mutational hotspots of the mtDNA were scanned for heteroplasmy. All specimens with mtDNA heteroplasmy were subsequently subsampled by laser capture microdissection. From a total number of 1728 microsamples, mitochondrial DNA target sequences were amplified and base substitutions detected by cycling temperature capillary electrophoresis. Real-time PCR was used as a quantitative assay to determine the relative mtDNA copy number of 12 tumors studied, represented by two samples from each (N = 24); a high degree (75%) demonstrated tumor specimen heterogeneity. A grid of 96 spots isolated by laser capture microdissection demonstrated interfocal sample heterogeneity and increased the limit of detection. The spots demonstrated a wide range of mutant fractions from 0 to 100% mutant copies. The mitochondrial DNA copy number in the samples was determined by real-time PCR. No correlation between copy number and pathology-prognostic grade groups was observed. Somatic mitochondrial DNA point mutations represent traceable biomarkers demonstrating heterogeneity in primary prostate cancer. Mutations can be detected in areas before changes in tissue histopathology are evident to the pathologist.

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.

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.

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 (p=0.052). 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.

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.

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).