Prostate Cancer最新文献

Background: Prostate cancer (PC) ranks as the third cause of cancer-related deaths among Iranian men. The age-period-cohort (APC) model helps identify critical ages, periods, and high-risk birth cohorts to prevent and control PC. Thus, this research aimed to evaluate the effect of APC on PC mortality in Iran from 1990 to 2021. Method: Our data include the number of PC deaths and population, collected by the Global Burden of Disease (GBD) and categorized by 5-year age groups. We computed average annual percentage changes (AAPCs) and relative risks by using joinpoint regression analysis and APC models, respectively. Results: Crude and age-standardized mortality rates for PC were increasing, with AAPC of 2.254% (95% CI: 2.099% and 2.410%; p < 0.001) and 0.257% (95% CI: 0.088% and 0.428%; p < 0.001), respectively. Furthermore, an increase occurred in both age effect from ages 20-24 years (RR = 0.033; 95% CI: 0.023 and 0.046) to over 95 years (RR = 16.183; 95% CI: 14.702 and 17.814) and the period from 1992 (RR = 0.542; 95% CI: 0.516 and 0.570) to 2021 (RR = 1.892; 95% CI: 1.809 and 1.979). While, the cohort effect demonstrated a lower mortality rate in later born than earlier born (Coef = 2.302 for the < 1901 cohort compared to Coef = -2.249 for the 2002-2006 cohort). Conclusion: Our study indicated that the trend of PC deaths in Iran increased during 1990-2021, and the period effect confirms this. Considering fewer deaths in high-income countries due to the widespread implementation of PSA testing, the occurrence of the aging phenomenon in our country, and the upward trend in deaths related to the age effect, sensitizing people and policymakers to conduct PSA screening seems necessary.

Background: A need exists for effective treatments for prostate cancer (PCA) due its re-emergence following androgen deprivation therapy, a major clinical problem. In a previous study, we presented evidence on the chemopreventive and chemotherapeutic potential of luteolin, a flavonoid, in PCA including castration-resistant PCA. In this single-arm phase I study, we clinically examined the safety of the oral intake of luteolin in patients under active surveillance (AS). Methods: Between March and September in 2022, five patients with low-intermediate risk PCA and under AS were treated daily with 50 mg of oral luteolin for six months. We investigated the efficacy of oral luteolin in oncological outcomes and any adverse events (AEs) and examined prostate and blood specimens. Results: The median age of patients was 68 years (range: 60-78), and the median initial prostate-specific antigen level was 9.5 ng/mL. All patients were under AS without rapid progression. After treatment with luteolin, AEs were not noted in any patients for six months. All patients underwent a protocol biopsy. Of these, two patients showed a favorable response, one patient had stable disease, and two patients showed disease progression; robot-assisted radical surgery was subsequently performed for the latter. Immunohistochemical analysis revealed decreased expression of androgen receptor and NKX3.1 in noncancerous lesions after luteolin treatment. In addition, quantitative reverse transcription-PCR revealed that serum micro(mi)RNA expression in serum and prostate gland, including miR-29 and miR-30, tended to be upregulated after luteolin treatment compared with during the pretreatment phase. Conclusions: Our small phase I study of men with PCA suggests that daily treatment with 50 mg of an oral supplement of luteolin is safe and effective with regard to oncological outcomes, particularly in patients under AS.

Prostate cancer is the most common noncutaneous malignancy among men worldwide, including in Sudan, where it represents a significant public health challenge. CD147, a transmembrane glycoprotein implicated in tumor progression, invasion, and metastasis, has shown potential as a prognostic biomarker in various cancers. This retrospective case-control study aimed to evaluate CD147 expression in prostate adenocarcinoma among Sudanese men and its association with tumor grade. A total of 80 paraffin-embedded tissue samples, including 40 cases of prostate adenocarcinoma and 40 benign prostatic hyperplasia (BPH) controls, were analyzed using immunohistochemistry. CD147 expression was observed in 22.5% of adenocarcinoma cases compared to 7% of controls; however, the association was not statistically significant (p=0.07). Low-grade tumors were predominant in the cohort, consistent with early-stage diagnoses. The findings revealed no clear link between CD147 expression and tumor grade, diverging from prior studies that associate CD147 with advanced tumor stages. The nonsignificant results may be attributed to the small sample size, emphasizing the need for future research with larger, more diverse cohorts, advanced molecular techniques, and functional studies to better elucidate the role of CD147 in prostate cancer pathogenesis and its potential as a therapeutic target.

Background: Assessment of comorbid diseases is essential to clinical research and may risk-stratify patients for mortality independent of established methods such as the Charlson Comorbidity Index (CCI). Methods: In a retrospective study of U.S. Veterans, we examined the association between the number of medications, 1-year mortality, and overall survival in Veterans being treated for metastatic castration-resistant prostate cancer (mCRPC) between 2011 and 2017. Results: Among 8855 Veterans, a median of 11 medications and 6 medication classes were filled in the year prior to initial treatment of mCRPC with abiraterone or enzalutamide. The median patient age was 74 years, 25.7% of patients were Black, and the median CCI was 3. Despite being associated with fewer medications, increasing age was associated with an increased CCI. After adjusting for patient, tumor, and treatment factors, both the number of medications and the number of medication classes were associated with increased 1-year mortality with adjusted OR (95% CI) of 1.03 (1.03, 1.04) and 1.08 (1.06, 1.11), respectively. Medications within Anatomic Therapeutic Class (ATC) N (nervous system) and ATC G (genitourinary and sex hormones) were associated with decreased OS, HR 1.18 (1.11, 1.25) and HR 1.15 (1.10, 1.20), respectively. Medications within ATC C (cardiovascular) were associated with increased OS, HR 0.91 (0.86, 0.97). Within a subgroup of patients with comparable age and CCI, the increased number of medications was associated with the increased risk of death. Conclusions: The number and type of medications were independently associated with survival in patients undergoing treatment for mCRPC. With new therapies for treatment of advanced prostate cancer, patients are living longer, which increases the need for better understanding of the impact of comorbid diseases. Simple methods to assess disease burden and prognosticate survival have the potential to guide treatment decisions and improve the quality of life in this patient population.

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.