Prostate Cancer Prostate-specific Antigen Research Articles

Pattern, Clinical Characteristics, and Impact of Family History on Prostate-Specific Antigen in Prostate Cancer: A Multicenter Study.

Prostate cancer (PCa) is a major cause of illness and death in men of Sub-Sahara African origin. The study assessed the pattern of PCa, the effect of family history on PSA at diagnosis, and clinical characteristics of PCa in Nigeria. A cross-sectional survey of 200 participants was performed within a 12-month period in Nigeria. Data were collected through patients' interview and hospital records and analyzed using SPSS version 25. Descriptive and inferential statistics were performed. P values <.05 were significant. Mean age of 68.5 years was observed among the 200 study participants. Only 64 (32.0%) had a positive immediate family history of PCa, and 61 (30.5%) were not aware of their family cancer history. Most patients 140 (70.0%) had lower urinary tract symptom (LUTS)/lower back pain/leg pain, and the average Gleason score was 7.55 (±0.876). Symptoms of LUTS/lower back pain mostly occurred in patients between 58 and 79 years, while LUTS/leg pain was more common in persons between 60 and 84. Average PSA differed among participants; persons with no family cancer history (M = 143.989; 95% confidence interval [CI] = 114.849-173.129), family history of PCa (M = 165.463; 95% CI = 131.435), family history of cervical cancer (M = 133.456; 95% CI = 49.335-217.576), and persons with no knowledge of their family cancer history (M = 121.546; 95% CI = 89.234-153.857). Univariate one-way (F-Tests) showed that family history of cancer had no significant impact on patients' PSA (R2 = 0.017; adjusted R2 = 0.002; df = 3; F = 1.154; p = .329) at diagnosis. PCa mostly occurred in men within 60 to 70 years of age, and family history of cancer did not predict PSA at diagnosis. Patients presented to health facilities at advanced or metastatic stages. These findings highlight the need for policies and strategies that encourage early PCa screening.

Potential diagnostic value of multiple indicators combined with total prostate-specific antigen in prostate cancer.

We aimed to investigate the diagnostic value of different laboratory indicators in combination with total prostate-specific antigen (TPSA) for prostate cancer (PCa). In this retrospective study, we selected 291 patients who underwent prostate biopsy. Patients were divided into the benign prostatic hyperplasia group and the PCa group. In both groups, patients were again divided into a group with TPSA 4.0-10.0 ng/mL and a group with TPSA >10.0 ng/mL. Clinical data including age, pre-puncture TPSA, free prostate-specific antigen (FPSA), and prostate volume (PV) were collected from all patients. We calculated the metrics PSA/PV (prostate-specific antigen density, PSAD), age/PV (AVR), age × PV/TPSA (PSA-AV), and (FPSA/TPSA)/PSAD [(F/T)/PSAD]). We plotted receiver operating characteristic (ROC) curves and calculated the area under the ROC curve (AUC). We found statistically significant differences in PV, PSAD, AVR, PSA-AV, and (F/T) PSAD for patients with TPSA 4.0-10.0 ng/mL and TPSA >10 ng/mL. We further plotted the ROC of individual or combined indices in different subgroups and calculated the AUC. We found that the diagnostic efficacy of the combined indices was higher with TPSA >10 ng/mL. The combination of TPSA with multiple indicators may improve diagnostic accuracy for PCa.

Indocyanine green dye and its application in gastrointestinal surgery: The future is bright green.

Indocyanine green (ICG) is a water-soluble fluorescent dye that is minimally toxic and widely used in gastrointestinal surgery. ICG facilitates anatomical identification of structures (e.g., ureters), assessment of lymph nodes, biliary mapping, organ perfusion and anastomosis assessment, and aids in determining the adequacy of oncological margins. In addition, ICG can be conjugated to artificially created antibodies for tumour markers, such as carcinoembryonic antigen for colorectal, breast, lung, and gastric cancer, prostate-specific antigen for prostate cancer, and cancer antigen 125 for ovarian cancer. Although ICG has shown promising results, the optimization of patient factors, dye factors, equipment, and the method of assessing fluorescence intensity could further enhance its utility. This review summarizes the clinical application of ICG in gastrointestinal surgery and discusses the emergence of novel dyes such as ZW-800 and VM678 that have demonstrated appropriate pharmacokinetic properties and improved target-to-background ratios in animal studies. With the emergence of robotic technology and the increasing reporting of ICG utility, a comprehensive review of clinical application of ICG in gastrointestinal surgery is timely and this review serves that aim.

Diagnostic Efficiency of Pan-Immune-Inflammation Value to Predict Prostate Cancer in Patients with Prostate-Specific Antigen between 4 and 20 ng/mL.

To evaluate the predictive value of the pan-immune-inflammation value (PIV) and other systemic inflammatory markers, including the neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII), for prostate cancer (PCa) and clinically significant prostate cancer (CSPCa) in patients with a prostate-specific antigen (PSA) value between 4 and 20 ng/mL. The clinical data of 319 eligible patients who underwent prostate biopsies in our hospital from August 2019 to June 2022 were retrospectively analyzed. CSPCa was defined as a "Gleason grade group of ≥2". A univariable logistic regression analysis and multivariable logistic regression analysis were conducted to analyze the association between the PIV, SII, MLR, and PCa/CSPCa. For the inflammatory indicators included in the multivariable logistic regression analysis, we constructed models by combining the separate inflammatory indicator and other significant predictors and compared the area under the curve (AUC). A nomogram based on the PIV for PCa was developed. We included 148 PCa patients (including 127 CSPCa patients) and 171 non-PCa patients in total. The patients with PCa were older, had higher MLR, SII, PIV, and total PSA (TPSA) values, consumed more alcohol, and had lower free/total PSA (f/T) values than the other patients. Compared with the non-CSPCa group, the CSPCa group had higher BMI, MLR, PIV, TPSA values, consumed more alcohol, and had lower f/T values. The univariable regression analysis showed that drinking history, higher MLR, PIV, and TPSA values, and lower f/T values were independent predictors of PCa and CSPCa. The AUC of the PIV in the multivariable logistic regression model was higher than those of the MLR and SII. In addition, the diagnostic value of the PIV + PSA for PCa was better than the PSA value. However, the diagnostic value for CSPCa was not significantly different from that of using PSA alone, while the AUC of the PIV + PSA was higher than the individual indicator of the PSA value. Our study suggests that for the patients who were diagnosed with PSA values between 4 and 20 ng/mL, the PIV and MLR are potential indicators for predicting PCa and CSPCa. In addition, our study indicates that the new inflammatory index PIV has clinical value in the diagnosis of PCa and CSPCa.

Prostate Cancer Screening Behavior Based on the Health Belief Model in Men Aged Over 40 Years

Background: Prostate cancer is the second most commonly diagnosed cancer and the fifth leading cause of cancer death among men worldwide. The early detection of prostate cancer with prostate-specific antigen (PSA) increases the disease treatment in the early stages. Moreover, knowledge and screening for PSA for prostate cancer in men decreases the mortality rate. Objectives: The present study aimed to screen prostate cancer behaviors according to the Health Belief Model in Men Aged above 40 in Dezful. Methods: This cross-sectional study encompassed 120 male employees aged above 40 years working at the Dezful University of Medical Sciences in 2018. The participants were selected using a random cluster sampling method. Data collection tools were a researcher-made, three-section questionnaire with questions on demographic characteristics, awareness, Health Belief Model (HBM) constructs, and prostate cancer screening behaviors. Results: The participants’ mean age was 46.22 ± 4.56 years (ranging from 40 to 60 years). Total awareness of prostate cancer and screening behavior among men was acceptable (5.59 ± 4.13). The performance of PSA was 20.8%. There was no significant difference between the mean age and PSA (P = 0.39). In the logistic regression analysis, perceived sensitivity to prostate cancer yielded a psychological predictor of prostate cancer screening behaviors (OR = 0.92, P value = 0.01). Conclusions: The findings showed a relationship between perceived sensitivity and the frequency of PSA. Moreover, the participants’ poor knowledge and performance indicated an urgent need for formal training programs to promote their sensitivity to the significance of prostate cancer screening. Factors affecting prostate cancer screening behaviors should be included in these training programs.

Mean Platelet Volume Enhances the Diagnostic Specificity of PSA for Prostate Cancer.

Mean platelet volume (MPV) is an indicator of platelet activation and has been proposed as a diagnostic marker for several kinds of cancers. We investigated the value of MPV as a diagnostic marker for prostate cancer (PCa) and examined whether MPV in combination with prostate-specific antigen (PSA) could increase the sensitivity or specificity of PSA for PCa diagnosis. For this study, 107 pathologically confirmed PCa and 177 non-PCa patients who underwent prostate biopsy were retrospectively studied. Clinical data and pre-biopsy hematological parameters were collected. The above parameters were compared between PCa and non-PCa patients. The correlation between MPV and clinical characteristics was analyzed. Receiver operating characteristic (ROC) analysis was used to explore the diagnostic value of MPV for PCa. Among all parameters analyzed, the difference was only found in MPV, platelet distribution width (PDW), and PSA between PCa and non-PCa patients. MPV was significantly decreased and PDW increased in PCa than that of non-PCa among men. ROC analysis identified MPV ≤ 9.05 fl as a cut-off value for potential PCa with area under the ROC curve (AUC) = 0.783, 95% CI = 0.733–0.833, sensitivity = 0.746, and specificity = 0.708. AUC and the sensitivity of MPV were comparable with total PSA (TPSA) or free PSA (FPSA). However, the specificity of MPV was larger than that of TPSA (0.461) or FPSA (0.561). Furthermore, MPV combined with TPSA or FPSA further enhanced the specificity of TPSA (0.844) or FPSA (0.927), but PDW did not. These findings suggested that MPV could have a predictive value for the diagnosis of PCa. MPV in combination with TPSA or FPSA could enhance the specificity of PSA and may reduce the rate of unnecessary biopsy for patients with high levels of PSA.

Systematic review and meta-analysis of the diagnostic accuracy of prostate-specific antigen (PSA) for the detection of prostate cancer in symptomatic patients

BackgroundProstate-specific antigen (PSA) is a commonly used test to detect prostate cancer. Attention has mostly focused on the use of PSA in screening asymptomatic patients, but the diagnostic accuracy of PSA for prostate cancer in patients with symptoms is less well understood.MethodsA systematic database search was conducted of Medline, EMBASE, Web of Science, and the Cochrane library. Studies reporting the diagnostic accuracy of PSA for prostate cancer in patients with symptoms were included. Two investigators independently assessed the titles and abstracts of all database search hits and full texts of potentially relevant studies against the inclusion criteria, and data extracted into a proforma. Study quality was assessed using the QUADAS-2 tool by two investigators independently. Summary estimates of diagnostic accuracy were calculated with meta-analysis using bivariate mixed effects regression.ResultsFive hundred sixty-three search hits were assessed by title and abstract after de-duplication, with 75 full text papers reviewed. Nineteen studies met the inclusion criteria, 18 of which were conducted in secondary care settings with one from a screening study cohort. All studies used histology obtained by transrectal ultrasound-guided biopsy (TRUS) as a reference test; usually only for patients with elevated PSA or abnormal prostate examination. Pooled data from 14,489 patients found estimated sensitivity of PSA for prostate cancer was 0.93 (95% CI 0.88, 0.96) and specificity was 0.20 (95% CI 0.12, 0.33). The area under the hierarchical summary receiver operator characteristic curve was 0.72 (95% CI 0.68, 0.76). All studies were assessed as having a high risk of bias in at least one QUADAS-2 domain.ConclusionsCurrently available evidence suggests PSA is highly sensitive but poorly specific for prostate cancer detection in symptomatic patients. However, significant limitations in study design and reference test reduces the certainty of this estimate. There is very limited evidence for the performance of PSA in primary care, the healthcare setting where most PSA testing is performed.

Contributions of Social Factors to Disparities in Prostate Cancer Risk Profiles among Black Men and Non-Hispanic White Men with Prostate Cancer in California.

Black men are more likely than Non-Hispanic White (NHW) men to be diagnosed with high-risk prostate cancer. We examined the extent to which social factors were associated with differences in prostate cancer risk profiles between Black men and NHW men [using a modification to the original D'Amico risk groups based on prostate specific antigen (PSA), Gleason score (GS), and TNM stage (stage)], based on individual and combined clinicopathologic characteristics. We conducted a cross-sectional population-based study of 23,555 Black men and 146,889 NHW men diagnosed with prostate cancer in the California Cancer Registry from 2004 to 2017. We conducted multivariable logistic regression to examine the association of year of diagnosis, block group-level neighborhood socioeconomic status (nSES), marital status, and insurance type on differences in prostate cancer risk profiles between Black and NHW men. High PSA (>20 ng/mL), GS, stage, individually and combined prostate cancer risk profiles were more common among Black men versus NHW men. In fully adjusted models, relative to NHW men, we observed a persistent 67% increased odds of high PSA among Black men. nSES was the factor most strongly associated with racial disparity in high PSA, accounting for 25% of the difference. Marital status was the factor that was second most associated with a racial disparity. nSES was the factor most strongly associated with racial disparities in high PSA prostate cancer. The influence of nSES on racial disparities in PSA, GS, stage, and prostate cancer risk profiles warrants further consideration.

Recent advances in glycopeptide enrichment and mass spectrometry data interpretation approaches for glycoproteomics analyses

蛋白质糖基化是生物体内最重要的翻译后修饰之一,在蛋白质稳定性、细胞内和细胞间信号转导、激素活化或失活和免疫调节等生理过程和病理进程中发挥重要作用。而异常的蛋白质糖基化往往和多种疾病的发生发展密切相关,目前应用于临床检测的多种肿瘤生物标志物大多属于糖蛋白或者糖抗原。因此在组学层次系统分析蛋白质糖基化的变化对阐明生物体内糖基化修饰的调控机理和发现新型疾病标志物都非常重要。基于质谱的蛋白质组学技术为全面分析蛋白质及其修饰提供了有效的分析手段。在自下而上的蛋白质组学研究中,由于完整糖基化肽段同时存在性质各异的肽段骨架和糖链结构、糖肽的相对丰度和离子化效率较低以及糖基化修饰有高度异质性等特点,完整糖肽的分析比其他翻译后修饰更加困难。近年来,为了更全面、系统地分析蛋白质糖基化,研究人员发展了一些新技术,包括完整糖肽的富集技术、质谱的碎裂模式和数据采集模式、质谱数据的解析方法和定量策略等等,大力推进了该领域的研究水平,也为研究蛋白质糖基化相关的生物标志物提供了技术支持。该篇综述主要关注近年来基于质谱的糖蛋白质组学研究中的新进展,重点介绍针对完整N-和O-糖基化肽段的富集新技术和谱图解析新方法,并讨论其在肿瘤早期诊断方面的应用潜力。

Study on individualized prostate biopsy guided by prostate specific antigen at different ranges

Background: Prostate specific antigen (PSA) is the most commonly used indicator for screening of prostate cancer(PCa), and the studies on PSA in PCa are very extensive at present. How to effectively use this indicator is worth for further study which this article wish to address. Objective: The aim of this study is to explore how PSA in different ranges can better guide the individualized prostate biopsy. Methods: A total of 117 patients with suspected PCa admitted to the Affiliated Hospital of Chengde Medical College from October 2018 to July 2020 were selected as the research subjects. PSA level and ratio of free and total PSA (F/TPSA) value of each patient were measured, and ultrasound-guided transrectal prostate biopsy was conducted for each patient, and then the PSA measurement results were compared with the prostate biopsy results. Results: The result of biopsy was PCa in 40 cases, BPH in 77 cases. The positive expression rates of Group I in BPH and PCa patients were 25.97% and 87.50%, respectively, and the difference was statistically significant (P &lt; 0.05).The positive expression rates of Group II in BPH and PCa patients were 10.39% and 75.00%, respectively, and the difference was statistically significant (P &lt; 0.05). The sensitivity, specificity, positive predictive value and diagnostic coincidence rates of Group I and Group II were 87.50%, 74.03%, 63.63%, 78.63% and 75.00%, 89.61%, 78.94% and 84.62%, respectively. Conclusion: Under different TPSA intervals, F/T &lt; 0.16 has different diagnostic efficacy for PCa. Group I is more sensitive and suitable for early screening. Group II has stronger specificity in the diagnosis of PCa, Higher diagnostic coincidence rate, and has more diagnostic advantages before biopsy. Selecting Group II can help clinicians make more patient-friendly decisions and reduce the incidence of complications related to biopsy. According to patients’ aspiration for biopsy, auxiliary examinations such as magnetic resonance scan of prostate and bone scan should be performed actively for patients who meet the criteria I if they refuse to undergo biopsy. On the premise of not affecting PCa secondary prevention as much as possible, a more individualized biopsy plan was developed for patients.

Influence of Tumor Burden on Serum Prostate-Specific Antigen in Prostate Cancer Patients Undergoing Radical Prostatectomy.

ObjectiveWe aimed to assess the correlation between serum prostate-specific antigen (PSA) and tumor burden in prostate cancer (PCa) patients undergoing radical prostatectomy (RP), because estimation of tumor burden is of high value, e.g., in men undergoing RP or with biochemical recurrence after RP.Patients and MethodsFrom January 2019 to June 2020, 179 consecutive PCa patients after RP with information on tumor and prostate weight were retrospectively identified from our prospective institutional RP database. Patients with preoperative systemic therapy (n=19), metastases (cM1, n=5), and locally progressed PCa (pT4 or pN1, n=50) were excluded from analyses. Histopathological features, including total weight of the prostate and specific tumor weight, were recorded by specialized uro-pathologists. Linear regression models were performed to evaluate the effect of PSA on tumor burden, measured by tumor weight after adjustment for patient and tumor characteristics.ResultsOverall, median preoperative PSA was 7.0 ng/ml (interquartile range [IQR]: 5.41–10) and median age at surgery was 66 years (IQR: 61-71). Median prostate weight was 34 g (IQR: 26–46) and median tumor weight was 3.7 g (IQR: 1.8–7.1), respectively. In multivariable linear regression analysis after adjustment for patients and tumor characteristics, a significant, positive correlation could be detected between preoperative PSA and tumor weight (coefficient [coef.]: 0.37, CI: 0.15–0.6, p=0.001), indicating a robust increase in PSA of almost 0.4 ng/ml per 1g tumor weight.ConclusionPreoperative PSA was significantly correlated with tumor weight in PCa patients undergoing RP, with an increase in PSA of almost 0.4 ng/ml per 1 g tumor weight. This might help to estimate both tumor burden before undergoing RP and in case of biochemical recurrence.

Abstract 591: Circulating testosterone in modifying the association of BMI change rate with serum PSA in prostate cancer-free men with initial-PSA less than 4 ng/mL

Abstract Background: Body mass index (BMI)-adjusted prostate-specific antigen (PSA) model has been proposed to improve the predictive accuracy of serum PSA in prostate cancer (PCa) screening. However, how BMI change rate may influence PSA levels in PCa-free men has not been well studied. The current study is to examine the relationship between BMI change rate and serum PSA in PCa-free men and whether this relationship is modified by circulating testosterone. Methods: We conducted this study at a tertiary hospital in the Southeastern US using the Electronic Medical Records of PCa-free men with initial PSA less than 4 ng/mL (cutoff for prostate biopsy), at least 1 testosterone measurement and at least 2 BMI measurements during the study period. Time when the first BMI measurement was recorded served as the baseline, and the study period was defined from baseline to the most recent hospital visit. The included medical records ranged from Jun 2001 to Oct 2015. BMI change rate was created in two ways depending on the number of data points. For men with only 2 BMI measurements, it was calculated by firstly subtracting baseline BMI from the second BMI, then dividing the difference by time interval (months) between the two BMI measurements. For men with more than 2 BMI measurements, we firstly regressed BMI to time interval (months) between that measurement and baseline, then took the β regression coefficient (slope) as the BMI change rate for that men. Multivariable linear regression was used to assess the association of BMI change rate with three PSA measures, including peak, the most recent, and mean PSA during the study period. Effect modification by testosterone was assessed through stratified analysis by testosterone level of 280 ng/dL as cutoff. Results: A total of 470 men with a mean study period of 97.6 months were included. Median age at baseline was 62 years. After adjusting for covariates including baseline BMI, no significant association of BMI change rate was observed with peak PSA (β =0.416, P =0.078), the most recent PSA (β =0.360, P =0.139), or mean PSA (β =0.405, P =0.064) in the overall sample. However, testosterone-stratified analyses indicated that BMI change rate was positively associated with peak PSA (β =1.118, P =0.013), the most recent PSA (β =0.932, P =0.044), and mean PSA (β =1.034, P =0.013) in men with testosterone &amp;lt;280 ng/dL, but no significant association was observed in men with testosterone ≥280 ng/dL (for peak PSA, β =0.076, P =0.785; for the most recent PSA, β =0.072, P =0.802; for mean PSA, β =0.099, P =0.700). Conclusion: Accelerated BMI increase in middle-to-late adulthood might correlate with higher PSA level if a low circulating testosterone occurred concurrently. Further studies are needed to confirm this finding. Citation Format: Kai Wang, Mattia Prosperi, Peihua Qiu, Ting-Yuan David Cheng, Victoria Y. Bird, Xinguang Chen, Mingyang Song. Circulating testosterone in modifying the association of BMI change rate with serum PSA in prostate cancer-free men with initial-PSA less than 4 ng/mL [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 591.

MicroRNA-3162-5p-Mediated Crosstalk between Kallikrein Family Members Including Prostate-Specific Antigen in Prostate Cancer.

MicroRNAs mediate biological processes through preferential binding to the 3' untranslated region (3' UTR) of target genes. Studies have shown their association with prostate cancer (PCa) risk through single-nucleotide polymorphisms (SNPs), known as miRSNPs. In a European cohort, 22 PCa risk-associated miRSNPs have been identified. The most significant miRSNP in the 3' UTR of Kallikrein-related peptidase 3 (KLK3) created a binding site for miR-3162-5p. Here we investigated the miR-3162-5p-KLK interaction and the clinical implication of miR-3162-5p in PCa. We tested the role of miR-3162-5p in PCa etiology using IncuCyte live-cell imaging and anchorage-independent growth assays. The effect of miR-3162-5p on KLK and androgen receptor (AR) expression was measured by RT-quantitative (q)PCR and target pulldown assays. KLK3 proteolytic activity was determined by DELFIA® immunoassay. Mass spectrometry identified pathways affected by miR-3162-5p. miR-3162-5p expression was measured in clinical samples using RT-qPCR. miR-3162-5p affected proliferation, migration, and colony formation of LNCaP cells by regulating the expression of KLK2-4 and AR by direct targeting. KLK3 protein expression was regulated by miR-3162-5p consistent with lower KLK3 proteolytic activity observed in LNCaP-conditioned media. KLK/AR pulldown and mass spectrometry analysis showed a potential role of miR-3162-5p in metabolic pathways via KLK/AR and additional targets. Increased miR-3162-5p expression was observed in prostate tumor tissues with higher Gleason grade. Our study provides an insight into possible involvement of miR-3162-5p in PCa etiology by targeting KLKs and AR. It highlights clinical utility of miR-3162-5p and its interactive axis as a new class of biomarkers and therapeutic targets for PCa.

A Step Closer to Cancer Screening by Blood Test.

In January 2018 (1), researchers working primarily at Johns Hopkins University in Baltimore, MD, reported on a new cancer-screening blood test called CancerSEEK, which received much attention. Although most localized cancers can be cured by surgery alone, when they spread through the body producing metastases, surgery is not sufficient. One of the main challenges of cancer research, therefore, is to diagnose the disease before it spreads. Although there are some types of hereditary cancers that allow relatively early follow-up, as well as other types for which screening tests already exist, cancer is too often discovered only when the first symptoms occur. In many cases, the disease takes several years to develop and manifest itself symptomatically, thereby providing a window of opportunity during which time detection is potentially possible. The earlier the cancer is diagnosed, the greater the chances of remission, and the greater our chance of saving lives. Current detection tests such as colonoscopy or mammography are restricted to 1 type of cancer, and the only blood test currently used is prostate-specific antigen for prostate cancer. Effective screening techniques for early detection do not exist for many types of cancers, and many newly developed tests have proven ineffective in reducing cancer mortality. CancerSEEK is partially based on a remarkable discovery made a long time ago but developed only in recent years: Tumor DNA is found in the bloodstream and can be used for diagnostic and therapeutic purposes (2–4). However, the detection of this DNA bearing the signature of a nascent cancer remains difficult. Circulating tumor DNA (ctDNA)5 (4) analysis for diagnostics is currently limited as a routine clinical test to mutation detection, to guide the clinician toward the best therapeutic choice based on the patient's molecular profile. Recent improvements in ctDNA-based diagnostic tests are allowing us to …

Abstract 2702: Mutations of SPOP, FOXA1 and IDH1 are associated with prostate cancer metastasis and biochemical outcomes

Abstract Recent genomic studies have shed light on cataloging genomic alterations in prostate cancer. Mechanistic studies allow the use of this information to subclassify the heterogeneous prostate tumors for optimized treatment planning. Speckle-Type POZ Protein (SPOP), Forkhead Box Protein A1 (FOXA1) and Isocitrate Dehydrogenase 1 (IDH1) are among the genes that show frequent point mutations in primary prostate cancers. However, the clinical significance of these gene mutations in cancer patients is less clear. To determine the whether SPOP, FOXA1 and IDH1 mutations are associated with clinical outcomes in prostate cancer, we pyro-sequenced the three genes in prostate cancer patients and evaluated the clinical and prognostic significance. 198 patients from the first hospital of Xi’An Jiaotong University (China) were analyzed. All patients were newly diagnosed with prostate cancer from January 2010 to December 2015. No patient was lost to follow-up. The average follow-up time after the primary diagnosis was 27 months. The Fisher’s exact tests were used to compare categorical data. The risk of metastasis among patients with SPOP, FOXA1 and IDH1 mutations was evaluated using univariate and multivariate logistic regression models. The prognostic significance of clinical and gene mutations was determined using multivariate Cox regression analysis. SPOP mutations were found in 16 patients (8.1%), with all of the mutations clustered in the substrate-binding MATH domain. FOXA1 mutationswere found in nine patients (4.5%), and were clustered in the Forkhead domain. IDH1 mutations were detected in three patients (1.5%). Mutation frequencies of SPOP, FOXA1 and IDH1 were associated with prostate-specific antigen (PSA), a biochemical marker of prostate tumor presence/risk which is decided by Gleason Score, T stage and PSA level, along with prostate cancer PSA failure and metastasis. Among patients with SPOP mutation, 56.3% showed metastasis at the time of diagnosis of primary cancer, compared to only 11.5% of patients with wild-type SPOP. Similarly, the probabilities of FOXA1 and IDH1 mutations with metastasis were approximately 44.4% and 66.7% versus 13.8% and 14.4%, respectively, comparing to their wild-type counterparts. The metastasis risk for patients with SPOP mutation was 1.27 times of the SPOP wild-type patients (P = 0.003). We also found that patients with SPOP (P &amp;lt; 0.0001) and FOXA1 (P = 0.0403) mutations showed higher risk of PSA failure compared with wild-type. The PSA failure risk for patients with SPOP mutation was 35.49 times of the SPOP wild-type patients. In contrast, IDH1 mutation was not associated with PSA failure (P = 0.054). Multivariate analyses demonstrate that SPOP mutation is an independent factor that is associated with prostate cancer metastasis and PSA failure recurrence. These findings underscore the clinical significance for profiling SPOP, FOXA1 and IDH1. Note: This abstract was not presented at the meeting. Citation Format: Jinlu Ma, Suxia Han, Xin Sui, Wenyan Lu, Yonghe Li, Bo Xu. Mutations of SPOP, FOXA1 and IDH1 are associated with prostate cancer metastasis and biochemical outcomes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2702. doi:10.1158/1538-7445.AM2017-2702

Investigating the prostate specific antigen, body mass index and age relationship: is an age-BMI-adjusted PSA model clinically useful?

PurposePrevious studies indicate a possible inverse relationship between prostate-specific antigen (PSA) and body mass index (BMI), and a positive relationship between PSA and age. We investigated the associations between age, BMI, PSA, and screen-detected prostate cancer to determine whether an age–BMI-adjusted PSA model would be clinically useful for detecting prostate cancer.MethodsCross-sectional analysis nested within the UK ProtecT trial of treatments for localized cancer. Of 18,238 men aged 50–69 years, 9,457 men without screen-detected prostate cancer (controls) and 1,836 men with prostate cancer (cases) met inclusion criteria: no history of prostate cancer or diabetes; PSA < 10 ng/ml; BMI between 15 and 50 kg/m2. Multivariable linear regression models were used to investigate the relationship between log-PSA, age, and BMI in all men, controlling for prostate cancer status.ResultsIn the 11,293 included men, the median PSA was 1.2 ng/ml (IQR: 0.7–2.6); mean age 61.7 years (SD 4.9); and mean BMI 26.8 kg/m2 (SD 3.7). There were a 5.1% decrease in PSA per 5 kg/m2 increase in BMI (95% CI 3.4–6.8) and a 13.6% increase in PSA per 5-year increase in age (95% CI 12.0–15.1). Interaction tests showed no evidence for different associations between age, BMI, and PSA in men above and below 3.0 ng/ml (all p for interaction >0.2). The age–BMI-adjusted PSA model performed as well as an age-adjusted model based on National Institute for Health and Care Excellence (NICE) guidelines at detecting prostate cancer.ConclusionsAge and BMI were associated with small changes in PSA. An age–BMI-adjusted PSA model is no more clinically useful for detecting prostate cancer than current NICE guidelines. Future studies looking at the effect of different variables on PSA, independent of their effect on prostate cancer, may improve the discrimination of PSA for prostate cancer.

Evaluating serum insulin-like growth factor 1 and insulin-like growth factor binding protein 3 as markers in prostate cancer diagnosis.

Prostate-specific antigen (PSA) lacks specificity and sensitivity in discriminating prostate cancer (PCa) from benign prostatic hyperplasia (BPH) when the total PSA (tPSA) level is between 4 and 10 ng/mL. It remains to be investigated if additional tumor-associated molecules may improve the PCa diagnostic accuracy. The aim of the present study was to investigate whether serum levels of insulin-like growth factor 1 (IGF1), insulin-like growth factor binding protein 3 (IGFBP3) and their combinations with PSA may enhance the diagnosis of PCa. Serum tPSA and free PSA (fPSA) levels were measured using an automated chemiluminescence-based method. IGF1 and IGFBP3 levels were evaluated by radioimmunoassays in a prospectively and consecutively enrolled subset of 149 patients with tPSA ≤10 ng/mL made up of patients with benign prostatic hyperplasia (BPH; n = 113) and PCa (n = 36). IGF1 and IGFBP3 serum levels did not significantly differ between the PCa and BPH groups. No important correlation was found between the IGF molecules and PSA isoforms in both groups. Statistical analysis of the combination of markers indicated that only the free/total PSA ratio (f/tPSA%) was informative and independent in predicting the presence of PCa, considering that for high values of this percentage (17%) the probability of finding PCa decreased. Receiver operating characteristics areas under the curve (AUC) for IGF1 and IGFBP3 were not informative (AUC ~0.5 in both cases) contrary to the AUC for f/tPSA% (AUC = 0.689, p = 0.0002). The present study showed that neither IGF1 and IGFBP3 alone nor in combination with PSA enhance the diagnostic performance of PSA in PCa.

Evaluation of prostatic cancer prevalence in patients with prostatic-specific antigen between 4 and 10 and normal digital rectal examination

Background:Prostate cancer is one of the most common male cancers. The prevalence of prostate cancer is different due to genetic and environmental factors. Diagnosis of prostate cancer is by biopsy due to prostate-specific antigen (PSA) and Digital Rectal Examination (DRE). Controversy about decision making for prostate biopsy in PSA between 4 and 10 and normal DRE, is one of the problems in this time. In this study we evaluated the prevalence of prostate cancer in males with PSA between 4 and 10 and normal DRE. We also evaluated the PSA density and percent of free PSA in patients with prostate cancer.Materials and Methods:A total of 121 males with PSA between 4 and 10 and normal DRE, were evaluated. Then, transrectal ultrasonography (TRUS) andprostate biopsy from 12 points of peripheral zone, was done. These data were analyzed by Chi-square, t-test and ANOVA and Roc curve.Results:In this study, the prevalence of prostate cancer in PSA between 4 and 10 and normal DRE, was evaluated, 29.8%. With use of Roc curve, PSA density cutoff point was calculated 0.12 and percent of free PSA cutoff point, was calculated, 18%.Conclusion:In males with PSA between 4 and 10 and normal DRE, PSA density smaller than 0.12-0.15, and percent of free PSA greater than 18%, the prevalence of prostate cancer is very few and we can safely ignore the TRUS and prostate biopsy in these males and eliminate its costs and side effects.

Serum chemokine (CC motif) ligand 2 level as a diagnostic, predictive, and prognostic biomarker for prostate cancer.

Prostate-specific antigen (PSA) is regarded as the most sensitive biomarker for prostate cancer. Although androgen/androgen receptor (AR) signaling promotes prostate cancer progression, suppression of AR signaling induces chemokine (CC motif) ligand 2 (CCL2), which enables prostate cancer cells to gain metastatic potential. AR-controlled PSA alone may be an unreliable biomarker for patients receiving androgen deprivation therapy. Therefore, we investigated the validity of CCL2 as a complementary biomarker to PSA for prostate cancer. Our in vitro approach of enriching for prostate cancer cells with higher migration potential showed that CCL2 activated cellular migration. Importantly, we found that CCL2 levels were significantly different between men (n = 379) with and without prostate cancer. Patients with CCL2 ≥ 320 pg/mL had worse overall survival and prostate cancer -specific survival than those with CCL2 < 320 pg/mL. A novel risk classification was developed according to the risk factors CCL2 ≥ 320 pg/mL and PSA ≥ 100 ng/mL, and scores of 2, 1, and 0 were defined as poor, intermediate, and good risk, respectively, and clearly distinguished patient outcomes. CCL2 may serve as a novel biomarker for prostate cancer. The novel risk classification based on combining CCL2 and PSA is more reliable than using either alone.

Improving the value of PSA prostate cancer screening with “smarter” strategies and increased use of active surveillance.

6616 Background: Prostate-specific antigen (PSA) screening for prostate cancer is controversial. Epidemiological researchers and guideline groups have suggested many personalized and conservative s...