Prostate Cancer最新文献

Purpose: To investigate how pretreatment testosterone levels correlate with progression-free survival, metastasis-free survival, and overall survival in a propensity-adjusted localized prostate cancer population.

Methods: Men diagnosed with clinical NCCN-risk stratified very-low, low, intermediate, high, and/or very-high risk prostate cancer who had a baseline total serum testosterone level≥100 ng/dl measured within the 100 days preceding the first definitive therapy were identified from our prospectively gathered institutional database. Cohorts below (100-239 ng/dl), within (240-593 ng/dl), or above (594 + ng/dl) one standard deviation from the mean testosterone level (416 ng/dl) were used for comparison. Progression-free, metastasis-free, and overall survival were evaluated. A separate cohort of men not receiving ADT was used to evaluate testosterone recovery after various treatment modalities (surgery, external beam radiation, brachytherapy, or combined EBRT + Brachy).

Results: There was no statistically significant difference between the low, average, and high testosterone cohorts for PFS, MFS, or OS. In men not using ADT, there were no statistically significant changes in testosterone levels 1 year after therapy, regardless of therapy type.

Conclusion: In men with serum testosterone levels >=100 ng/dl at diagnosis, baseline testosterone does not impact PFS, MFS, or OS. Recovery of testosterone back to baseline is expected for men undergoing either surgery, external beam or brachytherapy, or combined modality radiation when not using ADT.

Background: Late diagnosis of prostate cancer is common in low and middle income countries and contributes to high morbidity and mortality of the disease. Utilization of prostate cancer screening services plays a major role in prevention of adverse outcomes. However, there is limited information on the knowledge about, the perceived risk of, and the utilization of prostate cancer screening in Tanzania.

Objective: To determine knowledge and perceived risk of prostate cancer, and the utilization of prostate cancer screening services, and associated factors, among men in Dar es Salaam, Tanzania.

Design: A population-based cross-sectional study involving men aged 40 years and above living in Dar es Salaam was conducted between May and August, 2018.

Methodology: Participants were recruited through multistage random sampling and took part in structured face-to-face interviews. Categorical variables were summarized using proportions while continuous variables were summarized as medians and inter-quarterly range (IQR). Chi square test was used to compare differences between proportions, and logistic regression modelling was used to determine factors associated with utilization of prostate cancer screening. Both crude and adjusted odds ratios (OR), with corresponding 95% confidence intervals, are reported. All analyses were two-tailed and the significance level set at 5%.

Results: A total of 388 men with a median age of 53 years (IQR 44-55) participated. Half (52.1%) had poor knowledge about prostate cancer and prostate cancer screening. A third (32.3%, n = 125) perceived the risk of prostate cancer to be low. Only 30 respondents (7.7%) had ever been screened for prostate cancer. Utilization of prostate cancer screening services was independently associated with age above 60 years [AOR = 21.46, 95% CI: 6.23, 73.93], monthly income above 305 US Dollars [AOR = 15.68, 95% CI: 4.60, 53.48], the perceived risk of prostate cancer [AOR = 16.34, 95% CI: 7.82, 14.92] and knowledge about prostate cancer [AOR = 67.71, 95% CI: 8.20, 559.57].

Conclusions: Knowledge about prostate cancer and prostate cancer screening services was low among men in Dar es Salaam with a third perceiving themselves to be at no risk for the disease. Utilization of screening services was low and associated with low income, younger age, low perceived risk of prostate cancer and low knowledge about the disease. Intervention measures aiming to increase knowledge about prostate cancer and screening services, and affordable provision of services, are urgently called for.

Prostate cancer is a major cause of cancer-related mortality in men. Even though current therapeutic management has contributed to reducing mortality, additional intervention strategies are warranted to further improve the outcomes. To this end, we have investigated the efficacy of dicaffeoylquinic acids, ingredients in Yerba Mate (Ilex paraguariensis), an evergreen cultivated in South America, the leaves of which are used to prepare a tea/coffee-like drink. Of the various analogs tested, 4,5-dicaffeoylquinic acid (4,5-diCQA) was the most active molecule against DU-145 prostate cancer cells with a 50% inhibitory concentration (IC₅₀) of 5 μM. 4,5-diCQA was active both under normoxic and hypoxic conditions. The effect of 72-hour treatment on DU-145 cells persisted for an extended time period as assessed by clonogenic assay. Mechanistic studies revealed that the toxic effect was not due to induction of programmed cell death but through cell cycle arrest at S phase. Additionally, 4,5-diCQA did not impact PI3K/MAPK signaling pathway nor did it affect the depolarization of the mitochondrial membrane. 4,5-diCQA-induced accumulation of cells in the S-phase also seems to negatively impact Bcl-2 expression. 4,5-diCQA also exhibited inhibitory activity on LNCaP and PC-3 prostate cancer cells suggesting that it has therapeutic potential on a broad range of prostate cancers. Taken together, the novel inhibitory activity and mechanism of action of 4,5-diCQA opens up potential therapeutic options for using this molecule as monotherapy as well as in combinatorial therapies for the clinical management of prostate cancer.

Background: Several anesthesiologic regimens can be used for open radical retropubic prostatectomy. The aim of this retrospective analysis was to compare the combined general epidural anesthesia and the combined spinal epidural anesthesia with regard to availability, efficacy, side effects, and perioperative time consumption in a high-volume center.

Methods: A retrospective analysis was performed by querying the electronic medical records of 1207 consecutive patients from the database of our online documentation software. All patients underwent open radical retropubic prostatectomy from 01/2008 to 08/2011 and met the study criteria. Linear and multivariate regression analyses were performed to identify differences in parameters such as time consumption in the operating unit, hemodynamic parameters, volume replacement, and catecholamine therapy.

Results: 698 (57.8%) patients have been undergoing open radical retropubic prostatectomy under combined spinal epidural anesthesia and 509 (42.2%) patients by combined general epidural anesthesia. Operating unit (p <0.0001) and post-anesthesia care unit stay (p <0.0001) as well as total hospital stay (p <0.0001) were significantly shorter in the combined spinal epidural anesthesia group. In addition, this group had reduced intraoperative volume need (p <0.0001) as well as lower need of catecholamines (p <0.0001).

Conclusions: This retrospective study suggests that the combined spinal epidural anesthesia seems to be a suitable and efficient anesthesia technique for patients undergoing open radical retropubic prostatectomy. This specific approach reduces time in the operation unit and length of hospital stay.

Purpose: To explore the burden of prostate biopsy at the time of its indication, procedure, and pathological report in the prostate cancer-screening scenario that is neglected and underestimated in the literature.

Methods: Prostate biopsy was offered to 47 consecutive patients with prostate-specific antigen (PSA) over 4 ng/dl or suspicious digital rectal examination (DRE) of whom 16 had undergone a biopsy. Comprehensive validated questionnaires at Time 0 (prebiopsy), Time 1 (before diagnosis, 20 days after biopsy), and Time 2 (after diagnosis, 40 days after biopsy) accessed patients' erectile (IIEF-5) and voiding (IPSS) functions, Beck scales measured anxiety (BAI), hopelessness (BHS), and depression (BDI), added to the emotional thermometers including five visual analog scales for distress, anxiety, depression, anger, and need for help. The Mann-Whitney or Friedman tests were obtained among times and studied variables.

Results: Prostate biopsy did not significantly impact patients' erectile and voiding functions while a higher Beck anxiety index (BAI) was observed at Time 0 (6.89 ± 6.33) compared to Time 1 (4.83 ± 2.87), p=0.0214, and to Time 2 (4.22 ± 4.98), p=0.0178. At Time 0, patients that experienced a previous biopsy presented higher distress (3.1 ± 3.0 vs. 1.6 ± 2.3), p=0.043, and emotional suffering thermometer scores (2.3 ± 3.3 vs. 0.9 ± 2.4) compared to those undergoing the first biopsy, p=0.036. At Time 2, patients with positive biopsies compared with those with negative ones showed no significant difference in outcome scores. The sample power was >90%.

Conclusions: To be considered in patients' counseling and care, the current study supports the hypothesis that the peak burden of prostate biopsy occurs at the time of its indication and might be higher for those experiencing rebiopsy, significantly impacting patients' psychosocial domains.

Trial approval:  This trial is registered under number NCT03783741.

Prostate cancer (PCa) is the most common diagnosed malignancy and the second leading cause of cancer-related deaths among men in the USA. Advances in high-throughput genotyping and next generation sequencing technologies have enabled discovery of germline genetic susceptibility variants and somatic mutations acquired during tumor formation. Emerging evidence indicates that germline variations may interact with somatic events in carcinogenesis. However, the possible oncogenic interactions and cooperation between germline and somatic variation and their role in aggressive PCa remain largely unexplored. Here we investigated the possible oncogenic interactions and cooperation between genes containing germline variation from genome-wide association studies (GWAS) and genes containing somatic mutations from tumor genomes of 305 men with aggressive tumors and 52 control samples from The Cancer Genome Atlas (TCGA). Network and pathway analysis were performed to identify molecular networks and biological pathways enriched for germline and somatic mutations. The analysis revealed 90 functionally related genes containing both germline and somatic mutations. Transcriptome analysis revealed a 61-gene signature containing both germline and somatic mutations. Network analysis revealed molecular networks of functionally related genes and biological pathways including P53, STAT3, NKX3-1, KLK3, and Androgen receptor signaling pathways enriched for germline and somatic mutations. The results show that integrative analysis is a powerful approach to uncovering the possible oncogenic interactions and cooperation between germline and somatic mutations and understanding the broader biological context in which they operate in aggressive PCa.

Aim: The measurement of the volume of the prostate gland can have an influence on many clinical decisions. Various imaging methods have been used to measure it. Our aim was to conduct the first systematic review of their accuracy.

Methods: The literature describing the accuracy of imaging methods for measuring the prostate gland volume was systematically reviewed. Articles were included if they compared volume measurements obtained by medical imaging with a reference volume measurement obtained after removal of the gland by radical prostatectomy. Correlation and concordance statistics were summarised.

Results: 28 articles describing 7768 patients were identified. The imaging methods were ultrasound, computed tomography, and magnetic resonance imaging (US, CT, and MRI). Wide variations were noted but most articles about US and CT provided correlation coefficients that lay between 0.70 and 0.90, while those describing MRI seemed slightly more accurate at 0.80-0.96. When concordance was reported, it was similar; over- and underestimation of the prostate were variably reported. Most studies showed evidence of at least moderate bias and the quality of the studies was highly variable.

Discussion: The reported correlations were moderate to high in strength indicating that imaging is sufficiently accurate when quantitative measurements of prostate gland volume are required. MRI was slightly more accurate than the other methods.

Background: New therapies for castration-resistant prostate cancer (CRPC) may be associated with increased risk of second primary malignancies (SPM). We therefore estimated the population-based incidence of SPM among patients with CRPC in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. We also estimated the proportion of men with CRPC with bone metastases and overall survival.

Methods: We conducted a retrospective cohort study of United States (US) men aged ≥ 65 years with CRPC. Cohort entry was from January 1, 2000, to December 31, 2011, with follow-up through December 31, 2013. Castration resistance was defined by treatment with second-line systemic therapy (after surgical or medical castration). SPM were diagnoses of primary cancers (other than prostate) in SEER or Medicare data.

Results: Altogether 2,234 patients met eligibility criteria. Most (1,887; 84.5%) had evidence of bone metastases in Medicare claims. SPM occurred in 172 patients (incidence rate 5.9 per 100 person-years; 95% confidence interval [CI], 5.0-6.8; standardized incidence ratio = 3.1, 95% CI, 2.8-3.6, based on SEER incidence rate of all malignancies except prostate cancer among men aged ≥ 65 years). The most common SPM were lung/bronchus (n = 29, 16.9%), urinary bladder (n = 22, 12.8%), and colon/rectum (n = 21, 12.2%). Median survival was 1.2 years (95% CI, 1.1-1.3); 5-year survival was 9% (95% CI, 7-11%).

Conclusions: This study provides the first estimate of SPM risk in older men with CRPC in the US. The incidence rate is approximately threefold higher than the population-based cancer incidence among men without prostate cancer.

Purpose. To further validate the prognostic power of the biomarker PDE4D7, we investigated the correlation of PDE4D7 scores adjusted for presurgical clinical variables with longitudinal postsurgical biological outcomes. Methods. RNA was extracted from biopsy punches of resected tumors (550 patients; RP cohort) and diagnostic needle biopsies (168 patients; DB cohort). Cox regression and survival were applied to correlate PDE4D7 scores with patient outcomes. Logistic regression was used to combine the clinical CAPRA score with PDE4D7. Results. In univariate analysis, the PDE4D7 score was significantly associated with PSA recurrence after prostatectomy in both studied patient cohorts' analysis (HR 0.53; 95% CI 0.41-0.67; p<1.0E-04 and HR 0.47; 95% CI 0.33-0.65; p<1.0E-04, respectively). After adjustment for the presurgical clinical variables preoperative PSA, PSA density, biopsy Gleason, clinical stage, percentage tumor in the biopsy (data only available for RP cohort), and percentage of positive biopsies, the HR was 0.49 (95% CI 0.38-0.64; p<1.0E-04) and 0.43 (95% CI 0.29-0.63; p<1.0E-04), respectively. The addition of the PDE4D7 to the clinical CAPRA score increased the AUC by 5% over the CAPRA score alone (0.82 versus 0.77; p=0.004). This combination model stratified 14.6% patients of the DB cohort to no risk of biochemical relapse (NPV 100%) over a follow-up period of up to 15 years. Conclusions. The PDE4D7 score provides independent risk information for pretreatment risk stratification. Combining CAPRA with PDE4D7 scores significantly improved the clinical risk stratification before surgery.