Determinants Of Prostate Cancer Research Articles

MRI-Derived Apparent Diffusion Coefficient of Peri-Prostatic Adipose Tissue Is a Potential Determinant of Prostate Cancer Aggressiveness in Preoperative Setting: A Preliminary Report.

Background: The aim of this study was to test the association between periprostatic adipose tissue (PPAT)—apparent diffusion coefficient (ADC) value recorded at multiparametric magnetic resonance imaging (mpMRI) and determinants of prostate cancer (PCa) aggressiveness in the preoperative setting. Methods: Data from 219 consecutive patients undergoing prostate biopsy (PBx) for suspicion of PCa, between January 2020 and June 2022, at our institution were retrospectively evaluated. Only patients who had mpMRI performed before PBx were included. The distribution of demographics and clinical features among PPAT-ADC values up to vs. above the median was studied using both parametric and non-parametric tests, according to variables. Linear and logistic regression models tested the association between PPAT-ADC values and determinants of PCa aggressiveness and the presence of intermediate-high risk PCa, respectively. Results: Of 132 included patients, 76 (58%) had PCa. Median PPAT-ADC was 876 (interquartile range: 654 − 1112) × 10−6 mm2/s. Patients with PPAT-ADC up to the median had a higher rate of PIRADS (Prostate Imaging—Reporting and Data System) 5 lesions (41% vs. 23%, p = 0.032), a higher percentage of PBx positive cores (25% vs. 6%, p = 0.049) and more frequently harbored ISUP (International Society of Urological Pathology) > 1 PCa (50% vs. 28%, p = 0.048). At univariable linear regression analyses, prostate-specific antigen (PSA), PSA density, PIRADS 5, and percentage of PBx positive cores were associated with lower PPAT-ADC values. PPAT-ADC up to the median was an independent predictor for intermediate-high risk PCa (odds ratio: 3.24, 95%CI: 1.17−9.46, p = 0.026) after adjustment for age and body mass index. Conclusions: Lower PPAT-ADC values may be associated with higher biopsy ISUP grade group PCa and a higher percentage of PBx-positive cores. Higher-level studies are needed to confirm these preliminary results.

Strain Elastography-Targeted Biopsy: Does Prostate Volume Affect Prostate Cancer Detection?

BackgroundThe present study aimed to assess the correlation between prostate volume and prostate cancer (PCa) detection by strain elastography (SE)-guided targeted biopsy (TB) compared with conventional transrectal ultrasound (TRUS)-guided systematic biopsy (SB).Material/MethodsThis retrospective study enrolled 357 patients suspected to have PCa. All patients received TRUS-guided 10-core SB and SE-guided TB. The sensitivity for PCa detected by SE-guided TB was compared with that by TRUS-guided SB, in combination with prostate biopsy pathology. The correlation between the prostate volume and the detection rate of SE-guided TB was investigated.ResultsPCa was pathologically confirmed in 151 out of 357 patients. The by-patient detection rate of TRUS-guided SB was 72.8% (110/151). Subsequently, a further increase of 6.6% (10/151) in PCa determination was obtained by the SE-guided TB. The sensitivity of SE-guided TB for patients with prostate volume <30 ml, 30–50 ml, 51–80 ml, and >80 ml was 91.7% (44/48), 80.3% (53/66), 70.4% (19/27), and 40.0% (4/10), respectively (p=0.002). For patients with a prostate volume less than 30 ml, SE-guided TB (91.7%) had a higher sensitivity than SB (62.5%) (p<0.007).ConclusionsSE-guided TB has a higher detection rate of PCa in comparison with TRUS-guided SB. There was also a negative correlation between prostate volume and SE-guided TB. Therefore, use of SE-guided TB may complement use of conventional SB, especially for patients with smaller prostate volume.

Placing prostate cancer disparities within a psychosocial context: challenges and opportunities for future research.

Black men are more likely to be diagnosed with prostate cancer compared with White men. Despite advances in prevention and treatment strategies, disparities in prostate cancer among Black men persist. While research on the causes of higher incidence and mortality is ongoing, there is limited evidence in the existing literature that clearly speaks to the potential psychological or social factors that may contribute to disparities in prostate cancer incidence. Given the lack of attention to this issue, we review scientific evidence of the ways in which social factors, including socioeconomic status and racial segregation, as well as psychological factors, like depression and anxiety, are related to subsequent prostate cancer risk, which could occur through behavioral and biological processes. Our objective is to illuminate psychosocial factors and their context, using a racial disparity lens, which suggests opportunities for future research on the determinants of prostate cancer. Ultimately, we aim to contribute to a robust research agenda for the development of new prostate cancer prevention measures to reduce racial disparities.

FUSION PROSTATE BIOPSY IN PATIENTS WITH PREVIOUS NEGATIVE STANDARD PROSTATE BIOPSY

Introduction . Prostate cancer is one of the common oncological diseases in men. Standard prostate biopsy with subsequent histological verification is now an integral part of the diagnosis of prostate cancer; however, the number of false-negative results and cases of underestimation of the degree of tumor aggressiveness remain excessively high. Advances in multiparametric magnetic resonance imaging have lead to improved detection of prostate tumors. Objective . Disclosure of the main advantages of prostate biopsy under the magnetic resonance imaging control, consideration of technical aspects of its implementation. Materials and methods . The fusion of magnetic resonance imaging data with transrectal ultrasound enables the targeted biopsy of suspicious areas. 136 consecutively selected patients were examined, mean age of 62 years, mean prostate volume was 53 cm3, the average prostate-specific antigen 11.3 ng/ml. All the patients underwent at least 1 transrectal prostate biopsy. We assigned patients into 3 groups: group 1 (n=43) underwent repeated standard transrectal biopsy of the prostate; in group 2 (n=39) patients had transperineal biopsy of the prostate; in group 3 there were patients (n=39) in whom a targeted fusion biopsy with magnetic resonance imaging and transrectal ultrasound - navigation has been performed. An average number of biopsy cores in each group was 12, 26.6 and 25.3, respectively. Results . Prostate cancer was diagnosed in 30.2%, 53.7 % and 56.4 % respectively. Better prostate cancer detectability during fusion biopsy generally occurred due to the localized forms of the disease (93.3 %). Conclusion . Fusion biopsy using magnetic resonance imaging and transrectal ultrasound and perineal biopsy allows precise determination of prostate cancer pathological stage, Gleason grade of a tumor and its exact localization. Most tumors detectable by saturation perineal biopsy and fusion biopsy using magnetic resonance imaging and transrectal ultrasound were clinically significant, which makes it possible to recommend these methods of biopsy to patients with a high level of suspicion for prostate cancer.

Does Core Length Taken per cc of Prostate Volume in Prostate Biopsy Affect the Diagnosis of Prostate Cancer?

IntroductionThe aim of this study was to determine the minimal core length to be taken per cc of prostate volume for an effective prostate biopsy. Patients and MethodsA retrospective analysis was performed on the records of 379 patients who underwent a first prostate biopsy with 12 to 16 cores under transrectal ultrasound guidance between September 2012 and April 2015. For each patient, the core length per cc of the prostate and the percentage of sampled prostate volume were calculated, and these values were compared between the patients with and without prostate cancer. ResultsA total of 348 patients were included in the study. Cancer was determined in 26.4% of patients. The mean core length taken per cc of prostate and the percentage of sampled prostate volume were determined to be 3.40 ± 0.15 mm/cc (0.26%; range, 0.08-0.63 cc) in patients with cancer and 2.75 ± 0.08 mm/cc (0.20%; range, 0.04-0.66 cc) in patients without cancer (P = .000 and P = .000), respectively. Core length taken per cc of prostate of > 3.31 mm/cc was found to be related to an increase in the rates of prostate cancer diagnosis (odds ratio, 2.84; 95% confidence interval, 1.68-4.78). The rate of cancer determination for core length taken per cc of prostate of < 3.31 mm/cc was 19.9% and of > 3.31 mm/cc, 41.1%. ConclusionsCore length taken per cc of prostate and the percentage of sampled prostate volume are important morphometric parameters in the determination of prostate cancer. The results of study suggest a core length per cc of the prostate of > 3.31 mm/cc as a cutoff value for quality assurance.

Comparison of 8, 10, 12, 16, 20 cores prostate biopsies in determination of prostate cancer and importance of prostate volume

In this study, we evaluate the relationship between increasing core numbers and cancer detection rate. We included 1120 patients with prostate-specific antigen levels ≤20 ng/mL and/or suspicious digital rectal examination findings in this study. All patients had a first-time prostate biopsy and 8, 10, 12, 16, and 20 core biopsies were taken and examined in different groups during the study. Multiple logistic regression analysis was made to reach the factor affecting the cancer detection rate between the patients with and without cancer. A p < 0.05 was considered statistically significant. Out of 1120 patients, 221 (19.7%) had prostate cancer. Again of the total 1120 patients, 8 core biopsies were taken from 229 (20.4%); 10 core biopsies from 473 (42.2%); 12 core biopsies from 100 (8.9%); 16 core biopsies from 140 (12.5%); and 20 core biopsies from 178 (15.9%) patients. The increase in the core number increased the cancer detection rate by 1.06 times (p = 0.008). As long as prostate volume increases, increasing the core number elevates the cancer detection rate. Thus, the rate of missed cancer will be reduced and the rates of unnecessary repetitive biopsy decreases.

Abstract 2618: Chemokine-associated loci and prostate cancer among men of African descent

Abstract Recent research efforts have focused on the identification of genetic determinants of prostate cancer (PCA). Emphasis has been placed on genes that encode chemokines and their receptors, since they play an essential role in tumorigenesis. This study seeks to evaluate the individual and combined effects of 42 single nucleotide polymorphisms (SNPs) in chemokine associated genes in relation to PCA outcomes among 814 African-American, African and Jamaican men. We hypothesized individuals inheriting chemokine-associated loci (linked to increased inflammation, immune response, metastasis and cell survival) will have an increased risk of developing PCA and/or aggressive disease relative to individuals expressing the referent genotypes. Forty-two SNPs detected in chemokine-associated genes were evaluated in germ-line DNA samples collected from 279 PCA cases and 535 controls using Illumina's Veracode genotyping system. Study participants were recruited from cancer screening programs, hospitals, or cancer centers located in the D.C., South Carolina, and Kingston, Jamaica. Genotyping was performed by Expression Analysis, Inc. Main effects were evaluated using logistic regression analysis (LR). Among US men, inheritance of one or more CCL5 rs2280789G (OR= 0.60; 95% CI=0.40, 0.90), CCL5 rs3817655A (OR = 0.56; 95%CI = 0.39, 0.81), CCL5 rs2107538G (OR = 0.66; 95%CI = 0.46, 0.96), and CCL25 rs2032887G (OR= 0.66; 95% CI=0.46, 0.96) alleles were significantly associated with a 32-56% reduction in the risk of developing PCA with P-values ranging from 0.027-0.0001. For Jamaican men, there was a two-fold increase in PCA susceptibility associated with CCR5 rs1799988 under the recessive genetic model (OR=1.96; 95% CI=1.04, 3.70) as well as the CCR7 rs3136685 TC+CC (OR=2.3; 95% CI=1.05, 5.07) and CCR5 rs1799987 AA genotypes (OR=2.18; 95% CI=1.04, 4.58). However, the CCR9 rs1488371 CA+AA genotype (OR=0.6; 95% CI=0.23, 0.94) was related to a 40% reduction in PCA among Jamaicans. With the exception of CCR5 rs1799987 and CCL25 rs2032887, the aforementioned relationships persisted after adjusting for potential confounders (i.e., age, family history of prostate cancer). In summary, polymorphisms in chemokine-associated genes modify PCA susceptibility among men of African descent in the current study. In larger ongoing studies, we will evaluate main and joint modifying effects in relation to high tumor grade, biochemical/disease recurrence, and disease-specific/overall mortality. Such efforts will help to identify genetic markers capable of explaining disproportionately high prostate cancer incidence, mortality, and morbidity rates among men of African descent. [[Unsupported Character - &amp;#8195;]] Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2618. doi:1538-7445.AM2012-2618

Abstract A70: Chemokine-associated genetic variants as predictors of prostate cancer outcomes among men of African descent

Abstract Background: African-American men in the U.S. are 1.6 and 2-fold more likely to receive a prostate cancer (PCA) diagnosis and die from the disease relative to their Caucasian counterparts, respectively. This health disparity extends beyond the U.S. For instance, men from Kingston, Jamaica have higher cancer mortality and morbidity rates compared to African-Americans. Reasons for these disparities may be attributed to differences in cancer screening practices, lifestyle factors, clinical management of the disease, detection of aggressive/advance tumors that are not responsive to available treatments, and genetic susceptibilities. Recent research efforts have focused on the identification of genetic determinants of PCA. Emphasis has been placed on genes that encode chemokines and their receptors, since they play an essential role in tumorigenesis. For instance, over expression of CCR6 is associated with lung, pancreatic, and PCA, presumably by triggering leukocyte production and promoting cell survival and metastasis. Moreover sequence variants detected in CCL5 (rs2280078, rs2107538 at positions −28 and −403, respectively) and CCR6 (rs9459883, rs3798315) were significantly associated with oral cancer, lymphoma or brain cancer in three independent studies. Research Goal and Objective: With the ultimate goal of improving PCA detection/prognosis predictions and clinical management practices, this study seeks to systematically evaluate the individual and combined effects of 41 single nucleotide polymorphisms (SNPs) in chemokine associated genes in relation to PCA risk and disease progression among 1,237 African-American, African and Caribbean men. Hypothesis: We hypothesized that individuals inheriting one or multiple chemokine associated loci (linked to increased inflammation, immune response surveillance, metastasis and cell survival) will have an increased risk of developing PCA relative to those of referent genotypes. Materials and Methods: Forty-one sequence variants detected in chemokine associated genes will be evaluated in germ-line DNA samples collected from 420 PCA cases and 735 controls using Illumina's Veracode genotyping system. Study participants were recruited from cancer screening programs, hospitals, or cancer centers located in the Washington D.C., South Carolina, and Kingston, Jamaica. Main effects and complex SNP interactions will be evaluated using logistic regression analysis and multi-factor dimensionality reduction (MDR), respectively. All risk models will be adjusted for potential confounders (i.e., age and West African Ancestry) and multiple hypothesis testing. Results: In a pilot study, four SNPs detected in CCR6, CCL5, and CCR4 were significantly associated with PCA among 230 men of African Descent from the United States (124 PCA cases, 106 controls). Inheritance of at least one minor CCR6 rs2023305 A allele was associated with a 1.92 fold increase in the risk of developing PCA. However, a 48–63% decrease in PCA was observed among carriers of the CCL5 (rs2107538 AG+AA, rs3817655 AT+AA) and CCR4 rs6550178 AG. With the exception of the CCR4 marker, these markers remained statistically after adjusting for age and West African ancestry. Discussion: In summary, polymorphisms in chemokine associated genes modify PCA susceptibility among men of African descent in the current study. Our findings will undergo further evaluation and validation in a larger and ethnically diverse study population, including 420 PCA cases and 735 controls from the U.S. and Jamaica. Such efforts will help to identify genetic markers capable of explaining disproportionately high prostate cancer incidence, mortality, and morbidity rates among men of African descent. Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):A70.

Modifiable risk factors for prostate cancer mortality in London: forty years of follow-up in the Whitehall study

The determinants of prostate cancer--aside from established but non-modifiable risk factors of increased age, black ethnicity, and a positive family history--are poorly understood. We examined the association of a series of baseline socioeconomic, behavioral, and metabolic characteristics with the risk of prostate cancer mortality in a 40-year follow-up of study members from the original Whitehall cohort study. During this period there were 578 prostate cancer deaths in 17,934 men. After adjustment for a series of baseline covariates, results from proportional hazards regression analyses indicated that marital status (hazard ratio; 95% confidence interval: widowed/divorced vs. married: 1.44; 0.95, 2.18), raised blood cholesterol (tertile 3 vs. 1: 1.35; 1.11, 1.65), and increased physical stature (tertile 3 vs. 1: 1.37; 1.09, 1.74) were associated with death from prostate cancer, although statistical significance at conventional levels was not apparent in all analyses. There was no evidence that physical activity, smoking habit, socio-economic status, component of either blood pressure or diabetes predicted the risk of death from this malignancy herein. In the present study, there was a suggestion that marital status, blood cholesterol, and height were risk indices for death from prostate cancer.

The effect of warfarin on the risk of prostate cancer

14524 Background: The anticancer activity of oral anticoagulants has been a matter of debate for several years. Recent evidence suggests that prolonged treatment with warfarin may be associated with a reduced incidence of newly diagnosed urogenital cancer during long-term follow-up of patients with venous thromboembolism. The aim of this study was to assess whether exposure to warfarin was associated with reduced risk of prostate cancer in a large population-based cohort. Methods: We conducted a matched case-control study nested within the population of beneficiaries of the Saskatchewan Prescription Drug Plan aged 50 years and older from 1981–2002 with no history of cancer since 1967. New cases of prostate cancer diagnosed between 1981 and 2002 were identified using the linked Saskatchewan Cancer Agency registry. Six controls per case matched on age, gender, and sampling time were randomly selected. The cumulative exposure to warfarin in the five years preceding the cancer diagnosis was assessed. Prescription counts were used to define warfarin exposure. Exposure in the year immediately preceding the cancer diagnosis was excluded to control for detection bias. Conditional logistic regression analysis was used to assess confounding by other drugs such as nonsteroidal anti-inflammatory medications. Results: Among 11502 cases and 69012 controls, 7.4% of cases and 7.1% of controls had a history of any warfarin use. Compared to men who had never used warfarin, adjusted odds ratio (OR) for prostate cancer among ever-users in the 5 year period was 0.94 (95% confidence interval (CI), 0.86–1.03). In those who accumulated 1, 2, 3 and 4 years of warfarin use, the adjusted ORs were 1.01 (95% CI, 0.89–1.16), 1.00 (95% CI, 0.82–1.23), 0.81 (95% CI, 0.60–1.09), and 0.80 (95% CI, 0.65–0.99), respectively (p-trend=0.03). Conclusion: Our results suggest that cumulative use of warfarin of at least 4 years may be associated with a reduced risk of prostate cancer. However, confounding by other determinants of prostate cancer associated with warfarin use is possible. Nonetheless, confirmation of these findings by prospective studies may provide the evidence necessary to consider the use of warfarin in prostate cancer prevention. No significant financial relationships to disclose.