Prostate Cancer最新文献

Introduction: Genetic and environmental factors are involved in prostate cancer. The current study was conducted to study the relationship between G-137C, C-607A, and A-1447G polymorphisms in the promoter of IL-18 and CXCL10 inflammatory genes with prostate cancer.

Methods: As a genetic association study with a case-control design, the genomes of people living in Khorasan, Iran, were compared in two groups of cases and controls. The genotype of the A-1447G polymorphism present in the CXCL10 gene promoter was investigated by the PCR-RFLP method. PCR-SSP was used to study the genotype of G-137C and C-607A polymorphisms present in the IL-18 gene promoter. Odds ratio (OR) and 95% confidence interval (CI) were reported.

Results: One mutant allele in CXCL10 A-1447G polymorphism (AG) increased the chance of cancer (OR = 4.902, 95% CI = 2.70-8.87) and two mutant alleles (GG) increased more (OR = 7.174, 95% CI = 2.48-20.68). One mutant allele in IL-18 G-137C polymorphism (CG) increased the chance of cancer (OR = 5.583, 95% CI = 3.04-10.22) and two mutant alleles (CC) increased more (OR = 9.571, 95% CI = 3.10-29.46). One mutant allele in IL-18 C607A polymorphism (CA) increased the chance of cancer (OR = 5.359, 95% CI = 2.95-9.70) and two mutant alleles (AA) increased more (OR = 7.083, 95% CI = 2.61-19.15) (P < 0.001).

Conclusion: According to the results, the mutant alleles in polymorphisms CXCL10 A-1447G, IL-18 G-137C, and IL-18 C-607A alleles were associated with an increased chance of prostate cancer in this population.

This study evaluated the effects of docetaxel and androgen receptor signaling inhibitors as second-line treatments in patients with castration-resistant prostate cancer after androgen receptor signaling inhibitors as first-line treatment. This study retrospectively evaluated the clinical outcomes of second-line treatment with docetaxel or androgen receptor signaling inhibitor in patients with castration-resistant prostate cancer who received first-line treatment with androgen receptor signaling inhibitors. Clinical backgrounds and outcomes were compared between docetaxel and androgen receptor signaling inhibitors as second-line treatment. Of 59 patients, 21 (35.6%) and 38 (64.4%) received docetaxel and androgen receptor signaling inhibitors as second-line treatment after first-line treatment with androgen receptor signaling inhibitors, respectively. In the second-line setting, the median progression-free survival was longer with androgen receptor signaling inhibitor than with docetaxel (17 versus 6 months, P=0.014). In the first-line setting, the median progression-free survival was longer with androgen receptor signaling inhibitors than with docetaxel (32 versus 25 months, P=0.014); however, no significant difference was found in the overall survival. Multivariate analysis revealed that there was no significant association between second-line treatment and survival, and first-line treatment with abiraterone was identified as a prognostic factor for progression-free survival. Subgroup analysis showed that the abiraterone-enzalutamide sequence was more effective than the other three sequences for progression-free survival and overall survival. This study suggests that second-line treatment with an androgen receptor signaling inhibitor for castration-resistant prostate cancer after androgen receptor signaling inhibitors as first-line treatment may be more beneficial, particularly with abiraterone as the upfront treatment.

Background: Androgen deprivation therapy (ADT) for prostate cancer is implicated as a possible cause of cognitive impairment (CI). CI in dementia and Alzheimer's disease is associated with neuroinflammation. In this study, we investigated a potential role of neuroinflammation in ADT-related CI.

Methods: Patients with prostate cancer on ADT for ≥3 months were categorized as having ADT-emergent CI or normal cognition (NC) based on self-report at interview. Neuroinflammation was evaluated using positron emission tomography (PET) with the translocator protein (TSPO) radioligand [¹¹C]-PBR28. [¹¹C]-PBR28 uptake in various brain regions was quantified as standardized uptake value (SUVR, normalized to cerebellum) and related to blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI) choice-reaction time task (CRT) activation maps.

Results: Eleven patients underwent PET: four with reported CI (rCI), six with reported NC (rNC), and one status unrecorded. PET did not reveal any between-group differences in SUVR regionally or globally. There was no difference between groups on brain activation to the CRT. Regardless of the reported cognitive status, there was strong correlation between PET-TSPO signal and CRT activation in the hippocampus, amygdala, and medial cortex.

Conclusions: We found no difference in neuroinflammation measured by PET-TSPO between patients with rCI and rNC. However, we speculate that the strong correlation between TSPO uptake and BOLD-fMRI activation in brain regions involved in memory and known to have high androgen-receptor expression mediating plasticity (hippocampus and amygdala) might reflect inflammatory effects of ADT with compensatory upregulated/increased synaptic functions. Further studies of this imaging readout are warranted to investigate ADT-related CI.

Aim: Prostate cancer (PCa) is the second most common nonskin malignancy and the second most common cause of cancer-related deaths in men. The most common site of metastasis in PCa is the axial skeleton which may lead to back pain or pathological fractures. Hematogenous spread to the brain and involvement of the central nervous system (CNS) are a rare occurrence. However, failed androgen deprivation therapy (ADT) may facilitate such a spread resulting in an advanced metastatic stage of PCa, which carries a poor prognosis.

Methods: In this systematic review, we searched the PubMed, Scopus, and Web of Science online databases based on the PRISMA guideline and used all the medical subject headings (MeSH) in terms of the following search line: ("Brain Neoplasms" OR "Central Nervous System Neoplasms") and ("Prostatic Neoplasms" OR "Prostate"). Related studies were identified and reviewed.

Results: A total of 59 eligible studies (902 patients) were included in this systematic review. In order to gain a deeper understanding, we extracted and presented the data from included articles based on clinical manifestations, diagnostic methods, therapeutic approaches, and prognostic status of PCa patients having BMs.

Conclusion: We have demonstrated the current knowledge regarding the mechanism, clinical manifestations, diagnostic methods, therapeutic approaches, and prognosis of BMs in PCa. These data shed more light on the way to help clinicians and physicians to understand, diagnose, and manage BMs in PCa patients better.

Background: Genetic factors are one of the significant contributors to prostate cancer (PCa) development, and hereditary prostate cancer 2 (HPC2) locus gene ELAC2 is considered a PCa susceptibility region. The HPC2/ELAC2 gene has been identified by linkage analysis in familial prostate cancer patients in the United States but has never been studied in Burkina Faso. The objective of the present study was to analyze the carriage of the C650T (Ser217Leu) and G1621A (Ala541Thr) mutations of the ELAC2 gene and the risk factors in prostate cancer patients in Burkina Faso.

Methods: This case-control study included 76 participants, including 38 histologically confirmed prostate cancer cases and 38 healthy controls without prostate abnormalities. PCR combined with restriction fragment length polymorphism (RFLP) was used to characterize the genotypes of the Ser217Leu and Ala541Thr polymorphisms of the ELAC2 gene. The correlations between the different genotypes and risk factors for prostate cancer were investigated.

Results: The C650T mutation was present in 44.73% of prostate cancer cases and 47.37% of controls. The G1621A mutation was present in 26.32% of prostate cancer cases and 15.79% of controls. We did not detect an association between prostate cancer risk and the Ser217Leu (p=0.972) and Ala541Thr (p=0.267) variants of the ELAC2 gene. Also, the two ELAC2 SNPs did not correlate with clinical stage, prostate-specific antigen (PSA) level at diagnosis, or the Gleason score on biopsies. However, we found that 100% of homozygous carriers of the T650 mutation have an A1621 mutation (p ≤ 0.001).

Conclusion: Ser217Leu and Ala541Thr polymorphisms of ELAC2, considered alone or in combination, are not associated with prostate cancer risk.

Purpose: This randomized phase 2 study sought to assess the treatment effect of a finite duration of apalutamide with and without androgen deprivation therapy (ADT) in biochemically recurrent prostate cancer (BCR PC). Materials and Methods. Patients with BCR PC after primary definitive therapy and prostate-specific antigen (PSA) doubling time ≤12 months were randomized to open-label apalutamide (240 mg/d) alone, apalutamide plus ADT, or ADT alone (1 : 1:1 ratio) for 12 months followed by a 12-month observation period (NCT01790126). Mean changes from baseline in Functional Assessment of Cancer Therapy-Prostate (FACT-P) at 12 months (primary endpoint) and other prespecified assessments of health-related quality of life (HRQoL), PSA nadir, time to PSA progression, time to testosterone recovery, recovered testosterone >150 ng/dL without PSA progression at 24 months, and molecular markers were evaluated.

Results: In 90 enrolled patients (apalutamide plus ADT (n = 31), apalutamide (n = 29), ADT (n = 30)), FACT-P at 12 months was not significantly different between apalutamide, ADT and apalutamide, and ADT groups. Addition of apalutamide to ADT prolonged time to PSA progression but this change did not reach statistical significance (hazard ratio (HR): 0.56, 95% confidence interval (CI): 0.23-1.36, P=0.196); time to testosterone recovery was similar in the ADT-containing groups. In apalutamide plus ADT, apalutamide, and ADT groups, 37.9%, 37.0%, and 19.2% of patients, respectively, had testosterone >150 ng/dL at 24 months without confirmed PSA progression. Of the few biomarkers expressed in blood, EPHA3 was significantly associated with shorter time to PSA progression (P=0.02) in the overall population.

Conclusions: HRQoL was similar in patients treated with apalutamide alone, ADT alone, or their combination, although apalutamide plus ADT did not demonstrate statistically significant noninferiority in change from baseline in overall HRQoL. The aggregated efficacy and safety outcomes support further evaluation of apalutamide plus ADT in BCR PC.

Introduction: Orchidectomy is the most cost-effective means of hormonal therapy for locally advanced or metastatic prostate cancer (LAMP). However, cost-effectiveness should not detract from health-related quality of life (HRQoL) considerations. Bilateral simple orchidectomy (BSO) has been linked to negative psychometric deficits from an empty scrotum. This study compared the HRQoL, therapeutic efficacy, and cosmetic appeal of BSO with endogenous pseudotesticular techniques of bilateral subcapsular orchidectomy (BSCO) and bilateral-epididymal-sparing orchidectomy (BESO). Research Design. Nigerian patients with LAMP were randomised into three surgical arms: BSO, BSCO, and BESO. Expanded Prostate Cancer Index Composite-26 HRQoL and sociodemographic questionnaires were administered before and three months after orchidectomy. Serum testosterone and PSA were measured at 0, 1, 2, and 3 hours; 7 days; and 3 months postoperatively. Pseudotesticular volumes and cosmetic appeal were assessed at 3 months.

Result: Sixty-three patients were recruited (24 BSO, 21 BSCO, 18 BESO), 73% of whom were low-income earners. There was no significant difference in the procedure cost nor the PSA or testosterone nadirs achieved over the three-month follow-up period (11.3, 12.6, 15.2 ng/ml (p=0.667) and 0.44, 0.64, 0.79 nmol/l (p=0.603) respectively). Those with pseudotesticles (BSCO, BESO) felt less emasculated (p=0.010). BSCO produced the least sexual bother, highest sexual function, and largest pseudotesticular volumes. The cosmetic appeal scores were similar between groups (77.9 ± 22.8, 81 ± 13.9, and 81.9 ± 22.5, respectively, p=0.858).

Conclusion: Endogenous pseudotesticular techniques, when compared with BSO, reduce the negative psychological impact experienced by patients without increasing costs. BSCO produced the best pseudotesticular volumes and postoperative sexual function. This study is registered with the ClinicalTrials.gov of the National Institute of Health U.S. National Library of Medicine as TEPSO study, NCT03744494: Comparison of the Therapeutic Efficacy and Patient Satisfaction of Three Techniques of Bilateral Orchidectomy in Prostate Cancer Patients of a Nigerian Sub-population. Registration completed on 16^th of November, 2018 (registered retrospectively) NCT03744494.

The diverse roles of cytokines as IL-6 and IL-8 have been studied in terms of their SNPs in many diseases but their role in prostate cancer (PCa) is still uncertain. Aim. To determine the relevance of IL-6 rs1800795 SNP and/or IL-8 rs2227306 SNP with prostate cancer's risk. Subjects and Methods. 40 PCa patients, 40 benign prostate hyperplasia (BPH) patients, and 40-age-matched-control group were enrolled in the study. Genotyping of IL-6 rs1800795 (G/C) SNP and IL-8 rs2227306 (C/T) SNP was determined using real-time PCR. Results. High frequency of IL-6 rs1800795GG and IL-8 rs2227306CC genotypes was noticed among PCa patients with associated OR 10.091 and 8.143, respectively. Comparisons based on allele frequencies revealed that IL-6G and IL-8C alleles are more frequent among PCa patients than other groups. Presence of IL-6 rs1800795G and IL-8 rs2227306C alleles in the same patient increase PCa risk by 16.7 times. Statistical correlations between PSA ratio and both of IL-6 and IL-8 SNP did not show any significant relation among PCa patients. Conclusion. IL-6 rs1800795G and IL-8 rs2227306C alleles could be considered risk factors for PCa development, particularly if presented together. However, no relation was found between both cytokines SNP and severity of prostate cancer.

Objective: The study investigates the prostate-specific antigen threshold for adding targeted, software-based, magnetic resonance imaging-ultrasound fusion biopsy during a standard 12-core biopsy in biopsy-naïve patients. It secondarily explores whether the targeted biopsy is necessary in setting of abnormal digital rectal examination.

Methods: 260 patients with suspected localized prostate cancer with no prior biopsy underwent prostate magnetic resonance imaging and were found to have Prostate Imaging Reporting and Data System score ≥ 3 lesion(s). All 260 patients underwent standard 12-core biopsy and targeted biopsy during the same session. Clinically significant cancer was Gleason ≥3 + 4.

Results: Percentages of patients with prostate-specific antigen 0-1.99, 2-3.99, 4-4.99, 5-5.99, 6-9.99, and ≥10 were 3.0%, 4.7%, 20.8%, 16.9%, 37.7%, and 16.9%, respectively. Cumulative frequency of clinically significant prostate cancer increased with the addition of targeted biopsy compared with standard biopsy alone across all prostate-specific antigen ranges. The difference in clinically significant cancer detection between targeted plus standard biopsy compared to standard biopsy alone becomes statistically significant at prostate-specific antigen >4.3 (p=0.031). At this threshold, combination biopsy detected 20 clinically significant prostate cancers, while standard detected 14 with 88% sensitivity and 20% specificity. Excluding targeted biopsy in setting of a positive digital rectal exam would save 12.3% magnetic resonance imaging and miss 1.8% clinically significant cancers in our cohort.

Conclusions: In biopsy-naïve patients, at prostate-specific antigen >4.3, there is a significant increase in clinically significant prostate cancer detection when targeted biopsy is added to standard biopsy. Obtaining standard biopsy alone in patients with abnormal digital rectal examinations would miss 1.8% clinically significant cancers in our cohort.