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.

Background: The knowledge of risk factors and complications related to extended pelvic lymph node dissection (ePLND) during radical prostatectomy can help selecting patients who will benefit the most with lymph node dissection concomitant to radical prostatectomy.

Materials and methods: Retrospective cohort evaluating 135 patients with PC, with a high risk for lymph node metastasis, submitted to ePLND by a single surgeon between 2013 and 2019, performed either by the laparoscopic or laparoscopic robot-assisted approach. Data related to complications were properly recorded using the Martin's criteria and were classified by the Satava and Clavien-Dindo-Strasberg methods. Logistic regression was used to determine predictors of complications related to ePLND.

Results: The mean number of lymph nodes removed was 10.2 ± 4.9, and in 28.2%, they were positive for metastasis. There were five intraoperative complications (4%), all in patients operated by laparoscopic approach. There were nine severe postoperative complications (7.3%), four of which occurred after postoperative day 30. Three patients (2.4%) had thromboembolic complications and five patients (4.0%) had lymphocele that required treatment. There was a correlation between the American Society of Anesthesiologists (ASA) physical status classification and postoperative complications (p=0.06), but it was not possible to identify statistically significant predictors.

Conclusion: ePLND during radical prostatectomy has a low rate of intraoperative complications and may change prostate cancer staging. Postoperative complications, especially venous thromboembolism and lymphocele, need to be monitored even in the late postoperative period.

Background: The evaluation of tumour-infiltrating lymphocytes (TILs) in solid malignancies has yielded insights into immune regulation within the tumour microenvironment and has also led to the development and optimisation of adoptive T cell therapies.

Objectives: This study examined the in vitro expansion of TILs from prostate adenocarcinoma, as a preliminary step to evaluate the potential of TILs for adoptive T cell therapy. Design, Setting, and Participants. Malignant and adjacent nonmalignant tissues were obtained from fifteen men undergoing radical prostatectomy. Interventions. There were no study interventions. Outcome Measurements and Statistical Analysis. Expanded cells were analysed by flow cytometry, and the data was assessed for associations between cell subpopulations and expansion rate.

Results: Tumour-infiltrating lymphocytes could be expanded to numbers that would be needed to generate a therapeutic infusion product from nine of 15 malignant specimens (60%). The CD4⁺ T cells predominated over CD8⁺ T cells (median 56.8% CD4⁺, 30.0% CD8⁺), and furthermore, faster TIL expansion was associated with a higher proportion of CD4⁺ T cells (median 69.8% in faster-growing cultures; 36.8% in slower-growing cultures). A higher proportion of CD3^-CD56⁺ cells versus CD3⁺ cells was associated with slower TIL expansion in cultures from malignant specimens (median 13.3% in slower-growing cultures versus 2.05% in faster-growing cultures), but not from nonmalignant specimens.

Conclusions: The expansion of TILs for potential therapeutic use is feasible. Our findings also indicate that further examination of TILs from prostate adenocarcinomas may yield insights into mechanisms of regulation of T cells within the tumour microenvironment. Further research is required to evaluate their therapeutic potential.

Aim: Accurate diagnosis of prostate cancer (PCa) has a fundamental role in clinical and patient care. Recent advances in diagnostic testing and marker lead to standardized interpretation and increased prescription by clinicians to improve the detection of clinically significant PCa and select patients who strictly require targeted biopsies.

Methods: In this study, we present a systematic review of the overall diagnostic accuracy of each testing panel regarding the panel details. In this meta-analysis, using a structured search, Web of Science and PubMed databases were searched up to 23 September 2019 with no restrictions and filters. The study's outcome was the AUC and 95% confidence interval of prediction models. This index was reported as an overall and based on the WHO region and models with/without MRI.

Results: The thirteen final articles included 25,691 people. The overall AUC and 95% CI in thirteen studies were 0.78 and 95% CI: 0.73-0.82. The weighted average AUC in the countries of the Americas region was 0.73 (95% CI: 0.70-0.75), and in European countries, it was 0.80 (95% CI: 0.72-0.88). In four studies with MRI, the average weighted AUC was 0.88 (95% CI: 0.86-0.90), while in other articles where MRI was not a parameter in the diagnostic model, the mean AUC was 0.73 (95% CI: 0.70-0.76).

Conclusions: The present study's findings showed that MRI significantly improved the detection accuracy of prostate cancer and had the highest discrimination to distinguish candidates for biopsy.

Materials and methods: This prospective single-arm study enrolled 15 men treated with IG-IMRT for localized prostate cancer. All participants received a dedicated 3 Tesla MRI examination of the prostate in addition to a pelvic CT examination for treatment planning. Two volumetric modulated arc therapy (VMAT) plans with a prescription dose of 79.2 Gy were designed using identical constraints based on CT- and MRI-defined consensus volumes. The volume of rectum exposed to 70 Gy or more was compared using the Wilcoxon paired signed rank test.

Results: For CT-based treatment plans, the median volume of rectum receiving 70 Gy or more was 9.3 cubic centimeters (cc) (IQR 7.0 to 10.2) compared with 4.9 cc (IQR 4.1 to 7.8) for MRI-based plans. This resulted in a median volume reduction of 2.1 cc (IQR 0.5 to 5.3, P < .001).

Conclusions: Using MRI to plan prostate IG-IMRT to a dose of 79.2 Gy reduces the volume of rectum receiving radiation dose in excess of tolerance (70 Gy or more) and should be considered in men who are at high risk for late rectal toxicity and are not good candidates for other rectal sparing techniques such as hydrogel spacer. This trial is registered with NCT02470910.