Prostate cancer with elevated free prostate-specific antigen density:A case report

BACKGROUND Prostate cancer is the second most common cancer among men worldwide,and prostate-specific antigen(PSA)is often used in clinical practice to screen for prostate cancer.Normal total PSA(tPSA)level initially excludes prostate cancer.Here,we report a case of prostate cancer with elevated free PSA density(fPSAD).CASE SUMMARY A patient diagnosed with benign prostatic hyperplasia underwent prostatectomy,and the postoperative pathological results showed acinar adenocarcinoma of the prostate.The patient is currently undergoing endocrine chemotherapy.CONCLUSION We provide a clinical reference for diagnosis and treatment of patients with normal tPSA but elevated fPSAD.

The performance characteristics of prostate-specific antigen and prostate-specific antigen density in Chinese men

We investigated the performance characteristics of prostate-specific antigen （PSA） and PSA density （PSAD） in Chinese men. All Chinese men who underwent transrectal ultrasound-guided prostate biopsy （TRUS-PB） from year 2000 to 2013 were included. The receiver operating characteristic （ROC） curves for both PSA and PSAD were analyzed. The sensitivity, specificity, positive predictive value （PPV） and negative predictive value （NPV） at different cut-off levels were calculated. A total of 2606 Chinese men were included. For the ROC, the area under curve was 0.770 for PSA （P〈 0.001） and 0.823 for PSAD （P〈 0.001）. PSA of 4.5 ng ml^-1 had sensitivity of 94.4%, specificity of 14.1%, PPV of 29.5%, and NPV of 86.9%; PSAD of 0.12 ng ml^-1cc^-1 had sensitivity of 94.5%, specificity of 26.6%, PPV of 32.8%, and NPV of 92.7%. On multivariate logistic regression analyses, PSA cut-off at 4.5 ng ml^-1 （OR 1.61, 95% CI 1.05-2.45, P = 0.029） and PSAD cut-off at 0.12 ng ml^-1 cc^-1 （OR 6.22, 95% CI 4.20-9.22, P 〈 0.001） were significant predictors for prostate cancer detection on TRUS-PB. In conclusion, the performances of PSA and PSAD at different cut-off levels in Chinese men were very different from those in Caucasians. PSA of 4.5 ng ml^-1 and PSAD of O. 12 ng ml^-1 cc^-1 had near 95% sensitivity and were significant predictors of prostate cancer detection in Chinese men.

Prostate-specific antigen density predicts favorable pathology and biochemical recurrence in patients with intermediate-risk prostate cancer

This study was designed to identify clinical predictors of favorable pathology and biochemical recurrence （BCR） in patients with intermediate-risk prostate cancer （IRPCa）. Between 2006 and 2012, clinicopathological and oncological data from 203 consecutive men undergoing robot-assisted radical prostatectomy （RARP） for IRPCa were reviewed in a single-institutional retrospective study. Favorable pathology was defined as Gleason score 〈6 and organ-confined cancer as detected by surgical pathology. Logistic regression analysis was used to determine predictive variables of favorable pathology, and the Kaplan-Meier and multivariate Cox regression model were used to estimate BCR-free survival after RARP. Overall, 38 patients （18.7%） had favorable pathology after RARP. Lower quartile prostate-specific antigen density （PSAD） was associated with favorable pathology compared to the highest quartile PSAD after adjusting for preoperative PSA, clinical stage and biopsy Gleason score （odds ratio, 5.42; 95% confidence interval, 1.01-28.97; P = 0.048）. During a median 37.8 （interquartile range, 24.6-60.2） months of follow-up, 66 patients experienced BCR. There were significant differences with regard to BCR free survival by PSAD quartiles （log rank, P = 0.003）. Using a multivariable Cox proportion hazard model, PSAD was found to be an independent predictor of BCR in patients with IRPCa after RARP （hazard ratio, 4.641; 95% confidence interval, 1.109-19.417; P = 0.036）. The incorporation of the PSAD into risk assessments might provide additional prognostic information and identify some patients in whom active surveillance would be appropriate in patients with IRPCa.

The role of prostate-specific antigen density and negative multiparametric magnetic resonance imaging in excluding prostate cancer for biopsynaive men:clinical outcomes from a high-volume center in China

This study aimed to assess the role of prostate-specific antigen density(PSAD)and negative multiparametric magnetic resonance imaging(mpMRI)in predicting prostate cancer for biopsy-naive men based on a large cohort of the Chinese population.From a prostate biopsy database between March 2017 and July 2021,we retrospectively identified 240 biopsy-naive patients with negative prebiopsy mpMRI(Prostate Imaging Reporting and Data System version 2[PI-RADS v2]score<3).Logistic regression analysis was performed to select the potential predictors for clinically significant prostate cancer(csPCa).Receiver operating characteristic(ROC)curve analysis and area under the ROC curve(AUC)were performed to assess the diagnostic accuracy.The negative predictive values of mpMRI in excluding any cancer and csPCa were 83.8%(201/240)and 90.8%(218/240),respectively.R0C curve analysis indicated that PSAD was the most promising predictor,with an AUC value of 0.786(95%confidence interval[CI]:0.699-0.874),and multiparametric logistic regression analysis confirmed that higher PSAD remained a significant marker for predicting csPCa(odds ratio[0R]:10.99,95%CI:2.75-44.02,P<0.001).Combining negative mpMRI and PSAD below 0.20 ng ml^(-2)obviously increased the predictive value in excluding PCa(91.0%,101/111)or csPCa(100.0%,111/111).If a PSAD below 0.20 ng ml^(-2)was set as the criterion to omit biopsy,nearly 46.3%of patients(463 per 1000)with negative mpMRI could safely avoid unnecessary biopsy,with approximately 4.2%of patients(42 per 1000)at risk of missed diagnosis of PCa and no patients with csPCa missed.A PI-RADS v2 score<3 and a PSAD<0.20 ng ml^(-2)could be potential criteria for the Chinese population to omit prompt biopsy safely.

Diagnostic value comparison of the combination of prostate-specific membrane antigen-body PET/MR and the prostate health index with each alone in early diagnosis of prostate cancer

ObjectiveThis study aimed to figure out whether the combination of the prostate health index(PHI)and prostate-specific membrane antigen(PSMA)-PET/MR could improve the diagnostic accuracy for prostate cancer(PCa)than that of each individual method used alone.MethodsIn this prospective,observational study,41 patients who underwent the systematic prostate biopsy between June 2019 and September 2022 were enrolled.Both the PHI test and ^(18)F-PSMA-1007-PET/MR were performed prior to biopsies.The diagnostic accuracy of different models was compared by logistic regression,areas under the curve(AUCs)of the receiver operating characteristic,and net reclassification index(NRI).ResultsAmong the 41 patients,14(34.1%)were pathologically diagnosed with PCa.The PHI in the PCa group was significantly higher than that in the benign group(44.4 vs.35.0,p=0.048).Similarly,all the patients in the PCa group received positive results of ^(18)F-PSMA-1007-PET/MR,of which the positive rate was significantly higher than that in benign group(100%vs.62.96%,p=0.025).The ^(18)F-PSMA-1007-PET/MR provided additional diagnostic values to the PHI(AUC:0.802 vs.0.692,p=0.025).However,there was no significant difference between the combination model and the ^(18)F-PSMA-1007-PET/MR alone(AUC 0.802 vs.0.685,p=0.071).The optimal PHI cutoff of the combination model is 32,with which the model could significantly reduce unnecessary biopsies(NRI:22.22%,95%confidence interval:6.54%–37.90%,p=0.005).However,among patients with the PHI of≥43.5,there was no significant difference between the combination model and the PHI alone(NRI:11.11%,95%confidence interval:−0.74%–22.97%,p=0.066).ConclusionThe combination of the PHI and ^(18)F-PSMA-1007-PET/MR outperforms the PHI alone for predicting PCa,especially in avoiding unnecessary biopsies.However,for patients with the PHI of≥43.5,the addition of ^(18)F-PSMA-1007-PET/MR to the PHI does not yield additional benefits.

Technetium-99m-methylene diphosphonate single photon emission computed tomography/computed tomography combined with prostate-specific antigen/free prostate-specific antigen ratio for bone metastasis of prostate cancer

BACKGROUND Prostate cancer(PC)is one of the most common malignant tumors in men,and bone metastasis is one of its common complications,which seriously affects the quality of life and prognosis of patients.AIM To investigate the diagnostic value of technetium-99m-methylene diphosphonate(99mTc-MDP)single photon emission computed tomography(SPECT)/CT imaging combined with the serum prostate-specific antigen(PSA)/free PSA ratio for PC bone metastasis(PCBM).METHODS One hundred patients with PC who visited the Hospital of Chengdu University of Traditional Chinese Medicine from January 2020 to January 2022 were recruited as the experimental(Exp)group,while 30 patients with benign prostatic lesions(BPLs)were recruited as the control(Ctrl)group.All patients underwent 99mTc-MDP SPECT/CT imaging and serum PSA/fPSA testing.The SPECT/CT imaging results and serum PSA/fPSA ratios of patients were analyzed to evaluate their diagnostic values for PCBM.RESULTS The difference in general information of the patients was not obvious,showing comparability.The two methods showed no visible differences in negative predictive value and sensitivity for patients with PCBM,but had great differences in positive predictive value and specificity(P<0.05).The PSA/fPSA ratio of patients with PC in the Exp group was lower than those with BPLs,and patients with PCBM had a much lower PSA/fPSA ratio than those without PC(P<0.05).The results confirmed that the combined use of 99mTc-MDP SPECT/CT imaging and serum PSA/fPSA ratio achieved a detection rate of 95%for PCBM.CONCLUSION The combination of 99mTc-MDP SPECT/CT and PSA/fPSA ratio is accurate and reliable for the diagnosis of PCBM,which provides an important reference for clinical practice.

Prostate-specific Antigen Density Variation Rate as a Potential Guideline Parameter for Second Prostate Cancer Detection Biopsy

Background： The diagnostic value of current prostate-specific antigen （PSA） tests is challenged by the poor detection rate of prostate cancer （PCa） in repeat prostate biopsy. In this study, we proposed a novel PSA-related parameter named PSA density variation rate （PSADVR） and designed a clinical trial to evaluate its potential diagnostic value for detecting PCa on a second prostate biopsy. Methods： Data from 184 males who underwent second ultrasound-guided prostate biopsy 6 months after the first biopsy were included in the study. The subjects were divided into PCa and non-PCa groups according to the second biopsy pathological results. Prostate volume, PSA density （PSAD）, free-total PSA ratio, and PSADVR were calculated according to corresponding formulas at the second biopsy. These parameters were compared using t-test or Mann-Whitney U-test between PCa and non-PCa groups, and receiver operating characteristic analysis were used to evaluate their predictability on PCa detection. Results： PCa was detected in 24 patients on the second biopsy. Mean values of PSA, PSAD, and PSADVR were greater in the PCa group than in the non-PCa group （8.39 μg/L vs. 7.16 μg/L, 0.20 vs. 0.16, 14.15% vs. 1.36%, respectively）. PSADVR had the largest area trader the curve, with 0.667 sensitivity and 0.824 specificity when the cutoff was 10%. The PCa detection rate was significantly greater in subjects with PSADVR 〉10% than PSADVR _〈10% （28.6% vs. 6.5%, P 〈 0.001 ）. In addition, PSADVR was the only parameter in this study that showed a significant correlation with mid-to-high-risk PCa （r = 0.63, P = 0.03）. Conclusions： Our results demonstrated that PSADVR improved the PCa detection rate on second biopsies, especially for mid-to-high-risk cancers requiring prompt treatment.

Measurement of Serum Total and Free Prostate-Specific Antigen for Breast Cancer Diagnosis in Women

Objective: To investigate the diagnostic value and the relationship between the clinicopathological features and the levels of total and free prostate-specific antigen (PSA) in women with breast cancer.Methods: Using the microparticle enzyme immunoassay system, we measured the concentrations of these markers in the sera of 85 women with breast cancer and in 30 healthy women.Rseults: The lowest detection level for both markers was 0.01 ng/ml. Free PSA levels were significantly higher in women with breast cancer than that in healthy women (P<0.05). The percentage of free PSA predominant subjects was 37.6% in breast cancer patients and 3.3% in healthy women. Cut-off values were 0.36 ng/ml for total PSA and 0.02 ng/ml for free PSA. In women with breast cancer, total PSA positivity was 23.5% and free PSA positivity was 27.1%. Compared to negatives, total PSA positive patients had a higher percentage of lymph node involvement tumours (P>0.05). However, patients with predominant free PSA had a higher percentage of early stage than patients with predominant PSA-ACT.Conclusion: Although the sensitivity of free PSA predominance is low (37.6%) in distinguishing women with breast cancer from healthy women, its specificity is high (97.0%).Free PSA predominance tends to be present in early stage tumours. These findings may indicate clinical significance of preoperative measurement of serum total and free PSA in women with breast cancer.

Prostate-specific antigen half-life： a new predictor of progression- free survival and overall survival in Chinese prostate cancer patients

We investigated the potential value of prostate-specific antigen half-life （PSAHL） and decreasing velocity （PSAVd） to predict progression-free survival （PFS） and overall survival （OS） in Chinese patients with prostate cancer. A total of 153 patients treated with hormonal therapy were included in the study. Of these, 78 patients progressed to hormone- refractory prostate cancer （HRPC） and 24 patients died by the end of follow-up. PSAHL was defined as the time during which prostate-specific antigen （PSA） concentration became half of the initial value during the first hormonal therapy. PSAVd reflected the decreasing velocity of PSA during the first hormonal therapy. PFS was defined as the interval from the beginning of hormonal therapy to HRPC. Cox proportional hazards regression analysis was used to evaluate whether PSAHL and PSAVd were significantly associated with PFS and OS. The median PSAHL and PSAVd were 0.50 months and 33.8 ng mL^-1 per month. The median PFS and OS were 22.7 months （95% confidence interval [CI], 22.0-29.6 months） and 43.5 months （95% CI, 37.9-48.4 months）, respectively. On univariate and multivariate analysis, long PSAHL （〉 0.5 months）, metastatic disease, high biopsy Gleason scores （〉 8） and high nadir PSA （〉 0.4 ng mL^-1） were all found to be significantly associated with short PFS. Long PSAHL, high nadir PSA and short PSA doubling time （PSADT 〈 2.0 months） were significantly associated with short OS. There were no significant relationships between PSAVd and either PFS or OS. Thus, PSAHL is a promising new independent predictor of survival. Patients with long PSAHL were identified as those at high risk for a relatively short PFS and OS.

A nomogram based on age, prostate-specific antigen level, prostate volume and digital rectal examination for predicting risk of prostate cancer

Nomograms for predicting the risk of prostate cancer developed using other populations may introduce sizable bias when applied to a Chinese cohort. In the present study, we sought to develop a nomogram for predicting the probability of a positive initial prostate biopsy in a Chinese population. A total of 535 Chinese men who underwent a prostatic biopsy for the detection of prostate cancer in the past decade with complete biopsy data were included. Stepwise logistic regression was used to determine the independent predictors of a positive initial biopsy. Age, prostate-specific antigen （PSA）, prostate volume （PV）, digital rectal examination （DRE） status, % free PSA and transrectal ultrasound （TRUS） findings were included in the analysis. A nomogram model was developed that was based on these independent predictors to calculate the probability of a positive initial prostate biopsy. A receiver-operating characteristic curve was used to assess the accuracy of using the nomogram and PSA levels alone for predicting positive prostate biopsy. The rate for positive initial prostate biopsy was 41.7% （223/535）. The independent variables used to predict a positive initial prostate biopsy were age, PSA, PV and DRE status. The areas under the receiver-operating characteristic curve for a positive initial prostate biopsy for PSA alone and the nomogram were 79.7% and 84.8%, respectively. Our results indicate that the risk of a positive initial prostate biopsy can be predicted to a satisfactory level in a Chinese population using our nomogram. The nomogram can be used to identify and counsel patients who should consider a prostate biopsy, ultimately enhancing accuracy in diagnosing prostate cancer.

Percent free prostate-specific antigen for prostate cancer diagnosis in Chinese men with a PSA of 4.0-10.0 ng/mL:Results from the Chinese Prostate Cancer Consortium

Objective:To test the diagnostic performance of percent free prostate-specific antigen(%fPSA)in predicting any prostate cancer(PCa)and high-grade prostate cancer(HGPCa)in a retrospective multi-center biopsy cohort with a PSA level of 4.0e10.0 ng/mL in China.Methods:Consecutive patients with a PSA of 4.0-10.0 ng/mL who underwent transrectal ultrasound-guided biopsy were enrolled at 16 Chinese medical centers from January 1st,2010 to December 31st,2013.Total and free serum PSA determinations were performed using three types of electro-chemiluminescence immunoassays recalibrated to the World Health Organization(WHO)standard.The diagnostic accuracy of PSA,%fPSA,and %fPSA in combination with PSA(%fPSA t PSA)was determined using the area under the receiver operating characteristic(ROC)curve(AUC).Results:A total of 2310 consecutive men with PSA levels between 4.0 and 10.0 ng/mL were included,and the detection rate of PCa was 25.1%.The AUC of%fPSA and %fPSA t PSA in predicting any PCa was superior to PSA alone in men aged≥60 years(0.623 vs.0.534,p<0.0001)but not in men aged 40e59 years(0.517 vs.0.518,p=0.939).Similar result was yield in predicting HGPCa.Conclusion:In a clinical setting of Chinese men with 4.0e10.0 ng/mL PSA undergoing initial prostate biopsy,adding %fPSA to PSA can moderately improve the diagnostic accuracy for any PCa and HGPCa compared with PSA alone in patients≥60 but not in patients aged 40-59 years.

Radioiodine therapy for castration-resistant prostate cancer following prostate-specific membrane antigen promoter-mediated transfer of the human sodium iodide symporter

Radioiodine therapy, the most effective form of systemic radiotherapy available, is currently useful only for thyroid cancer because of the thyroid-specific expression of the human sodium iodide symporter （hNIS）. Here, we explore the efficacy of a novel form of gene therapy using prostate-specific membrane antigen （PSMA） promoter-mediated hNIS gene transfer followed by radioiodine administration for the treatment of castration-resistant prostate cancer （CRPC）. The androgen-dependent C33 LNCaP cell line and the androgen-independent C81 LNCaP cell line were transfected by adenovirus. PSMA promoter-hNIS （Ad.PSMApro-hNIS） or adenovirus.cytomegalovirus-hNIS containing the cytomegalovirus promoter （Ad.CMM-hNIS） or a control virus. The iodide uptake was measured in vitro. The in vivo iodide uptake by C81 cell xenografts in nude mice injected with an adenovirus carrying the hNIS gene linked to PSMA and the corresponding tumor volume fluctuation were assessed. Iodide accumulation was shown in different LNCaP cell lines after Ad.PSMApro-hNIS and Ad.CMV-hNIS infection, but not in different LNCaP cell lines after adenovirus.cytomegalovirus （Ad.CMV） infection. At each time point, higher iodide uptake was shown in the C81 cells infected with Ad.PSMApro-hNIS than in the C33 cells （P 〈 0.05）. An in vivo animal model showed a significant difference in 1311 radioiodine uptake in the tumors infected with Ad.PSMApro-hNIS, Ad.CMV-hNIS and control virus （P 〈 0.05） and a maximum reduction of tumor volume in mice infected with Ad.PSMApro-hNIS. These results show prostate-specific expression of the hNIS gene delivered by the PSMA promoter and effective radioiodine therapy of CRPC by the PSMA promoter-driven hNIS transfection.

Body mass index and serum lipid profile influence serum prostate-specific antigen in Chinese men younger than 50 years of age

This study is to assess the potential factors that could affect the serum prostate-specific antigen （PSA） level in healthy younger men. We evaluated the associations of age, body mass index （BMI） and serum lipid profile with serum PSA level in 6774 Chinese men （aged 20-49 years） who received a routine health examination. Eligible men were classified into 10-year age groups, BMI was categorized as underweight （〈18.5）, normal （18.5-22.9）, overweight （23.0-24.9）, obese （25.0-29,9） and very obese （〉30） according to the redefined World Health Organization （WHO） criteria for the Asia-Pacific region. PSA levels were compared among groups as well, In multiple linear regression analysis, PSA was positively correlated with age （P〈0.0001）. Negative correlations existed between PSA and BMI （P〈0.0001） and triglyceride level （P=0.01）. No relationship could be found between PSA and serum cholesterol （P=0.711） or high-density lipoprotein （HDL; P =0.665）. In addition, we found that serum PSA levels increased with age and decreased with BMI. Our study demonstrates that age, BMI and triglyceride levels influence the PSA level in men 〈50 years of age.

Serum prostate-specific antigen as a predictor of prostate volume and lower urinary tract symptoms in acommunity-based cohort： a large-scale Korean screening study

The aim of this study is to assess the ability of serum prostate-specific antigen （PSA） to predict prostate volume （PV） and lower urinary tract symptoms （LUTS） represented by the international prostate symptom score （IPSS）. From January 2001 to December 2011, data were collected from men who first enrolled in the Korean Prostate Health Council Screening Program. Patients with a serum PSA level of 10 ng ml^-1 or age 〈40 years were excluded. Accordingly, a total of 34 857 men were included in our study, and serum PSA, PV and the IPSS were estimated in all patients. Linear and age-adjusted multivariate logistic analyses were used to assess the potential association between PSA and PV or IPSS. The predictive value of PSA for estimating PV and IPSS was assessed based on the receiver operating characteristics-derived area under the curve （AUC）. The mean PV was 29.9 ml, mean PSA level was 1.49 ng ml^-1 and mean IPSS was 15.4. A significant relationship was shown between PSA and PV, and the IPSS and PSA were also significantly correlated after adjusting by age. The AUCs of PSA for predicting PV ~20 ml, 〉25 ml and 〉35 ml were 0.722, 0.728 and 0.779, respectively. The AUCs of PSA for predicting IPSS 〉 7, 〉 13 and 〉 19 were 0. 548, 0.536 and 0. 537, respectively. Serum PSA was a strong predictor of PV in a community-based cohort in a large-scale screening study. Although PSA was also significantly correlated with IPSS, predictive values of PSA for IPSS above the cutoff levels were not excellent. Further investigations are required to elucidate the exact interactions between PSA and LUTS and between PSA and PV in prospective controlled studies. Such studies may suggest how PSA can be used to clinically predict PV and the IPSS.

Relationship between insulin resistance, obesity and serum prostate-specific antigen levels in healthy men

The purpose of this study was to determine the relationship between insulin resistance, obesity and serum prostate-specific antigen （PSA） levels in healthy men with serum PSA level below 4 ng mL-1. The men included in the study cohort were 11 827 healthy male employees of the Korea Hydro and Nuclear Power Co., LTD who had undergone medical checkups including fasting glucose, fasting insulin and serum PSA between January 2003 and December 2008. Insulin resistance was calculated by homeostasis model assessment （HOMA [fasting glucose × fasting insulin]/22.5） and quantitative insulin sensitivity check index （QUICK/; 1/[log （fasting insulin） ＋ log （fasting glucose）]）. Age-adjusted body mass index （BMI） was significantly increased according to increasing quartile of insulin resistance as determined by HOMA and QUICKI, respectively, in analysis of variance （ANOVA） test and Duncan＇s multiple comparison test （P 〈 0.001）, but age-adjusted serum PSA concentration was significantly decreased according to increasing quartile of insulin resistance as determined by HOMA and QUICK/（P 〈 0.001）. Age, BMI, insulin resistance by HOMA or QUICK/were significantly independent variables to serum PSA level in a multivariate linear regression analysis （P 〈 0.001）. Insulin resistance was a significant independent variable to serum PSA level along with BMI. Insulin resistance and BMI were negatively correlated with serum PSA level in healthy men. Insulin resistance was positively correlated with BMI.

Prostate-specific membrane antigen expression in hepatocellular carcinoma,cholangiocarcinoma,and liver cirrhosis

BACKGROUND Primary liver cancer includes three subtypes:Hepatocellular carcinoma(HCC),intrahepatic cholangiocarcinoma(CCA),and combined hepatocellular carcinoma.Patients with primary liver cancer experienced poor prognosis and high mortality,so early detection of liver cancer and improved management of metastases are both key strategies to reduce the death toll from liver cancer.Prostate-specific membrane antigen(PSMA)expression in the tumor-associated neovasculature of nonprostate malignancies including liver cancer has been reported recently,but conclusive evidence of PSMA expression based on the pathological type of liver cancer remains limited.AIM To study the expression of PSMA in HCC,CCA,and liver cirrhosis.METHODS A total of 446 formalin-fixed paraffin-embedded(FFPE)liver tumor and liver cirrhosis tissue samples were obtained retrospectively from the Pathology Department of Tongji Hospital.Immunohistochemistry was used to detect PSMA expression in these 446 FFPE liver biopsy specimens(213 HCC,203 CCA,and 30 liver cirrhosis).The tumor compartment and the associated neovascular endothelium were separately analyzed.PSMA expression was examined by two certified pathologists,and the final results were presented in a 4-point scoring system(0-3 points).Correlation between PSMA expression and clinicopathological information was also assessed.RESULTS PSMA was expressed primarily in the neovascular endothelium associated with tumors.The positive rate of PSMA staining in HCC was significantly higher than that in CCA(86.8%vs 79.3%;P=0.001)but was only 6.6%in liver cirrhosis(P=0.000).HCC cases had more 3-score PSMA staining than CCA had(89/213,41.8%vs 35/203,17.2%;P=0.001).PSMA expression correlated positively with the stage and grade of HCC and CCA.In both liver cancer subtypes,there were more PSMA+cases in stages III–V diseases than in stages I and II.High staining intensity of PSMA was more frequently observed in liver cancers at high grade and advanced stage.There was no significant association of PSMA expression with sex,age,region,α-fetoprotein,hepatitis B surface antigen,or tumor size in both tumor subtypes.CONCLUSION Neovascular PSMA may be a promising marker to differentiate HCC from liver cirrhosis and a prognostic marker for anti-tumor angiogenesis therapy for HCC.

Decreasing trend in prostate cancer with high serum prostate-specific antigen levels detected at first prostate-specific antigen-based population screening in Japan

To clarify the recent trends in prostate-specific antigen （PSA） distribution in men in Japan, we analyzed the PSA distributions of men undergoing PSA-based population screening. We summarized the annual individual data of PSA-based population screening in Kanazawa, Japan, from 2000 to 2011, and analyzed baseline serum PSA values of the participants at the first population screening. Serum PSA distributions were estimated in all participants and those excluding prostate cancer patients according to age. From 2000 to 2011, 19 620 men participated aged 54-69 years old in this screening program. Mean baseline serum PSA level of all participants at the first screening was 2.64 ng m1-1 in 2000, and gradually decreased to approximately 1.30 ng ml-I in 2006. That of participants excluding prostate cancer patients was 1.46 ng m1-1 in 2000, and there was no remarkable change during the study period. The 95t＂ percentiles in the participants excluding prostate cancer patients detected at the first population screening of men aged 54-59, 60-64, and 65-69 years old were 2.90, 3.60, and 4.50 ng m1-1, respectively. After the commencement of population screening, the proportion of prostate cancer patients with high serum PSA levels decreased. However, there were no changes in serum PSA levels in men without prostate cancer. Age-specific PSA reference level of men without prostate cancer in Japan was similar to that in China and Korea.

Serum testosterone and prostate-specific antigen levels are major risk factors for prostatic volume increase among benign prostatic hyperplasia patients

Objective:Benign prostatic hyperplasia(BPH)is one of the most common diseases found among elderly men.Even though multiple risk factors of BPH have been identified in the past,the risk factors which have a direct impact on prostate volume have not been identified.In this study,we aim to determine the most significant contributing risk factors to prostate volume enlargement by analyzing possible associated risk factors previously studied.Methods:This is a quantitative study with an analytical observational design,performed using a retrospective cohort approach.Total sampling was performed on 83 patients who underwent transurethral resection of the prostate(TURP)in Sanglah General Hospital from January to February 2019.Bivariate analysis is performed to examine each variable's association with prostate volume followed by a multivariate analysis.All variables were reassessed with path analysis to measure the direct effects,indirect effects,and total effects on prostate volume.Results:Bivariate analysis shows that serum testosterone(R=0.208;p=0.059)and prostate-specific antigen(PSA)level(R=0.626;p=0.001)have a significant association with prostate volume.Multivariate analysis shows that serum PSA(B=1.4;p=0.001;95%confidence interval[95%CI]=1.039-1.770)and testosterone(B=0.024;p=0.005;95%CI=0.008-0.041)levels are significant among all the analyzed risk factors.There is a significant and strong effect of PSA to prostate volume(c=0.636;p=0.001)whereas testosterone has a significant albeit weak effect to prostate volume(c=0.246;p=0.009)based on the total effect of the path analysis.Conclusion:Serum testosterone and PSA levels are significantly associated with prostatic volume increase among BPH patients.

Blood and urine biomarkers in prostate cancer:Are we ready for reflex testing in men with an elevated prostate-specific antigen?

Objective:There is no consensus on the role of biomarkers in determining the utility of prostate biopsy in men with elevated prostate-specific antigen(PSA).There are numerous biomarkers such as prostate health index,4Kscore,prostate cancer antigen 3,ExoDX,SelectMDx,and Mi-Prostate Score that may be useful in this decision-making process.However,it is unclear whether any of these tests are accurate and cost-effective enough to warrant being a widespread reflex test following an elevated PSA.Our goal was to report on the clinical utility of these blood and urine biomarkers in prostate cancer screening.Methods:We performed a systematic review of studies published between January 2000 and October 2020 to report the available parameters and cost-effectiveness of the aforementioned diagnostic tests.We focus on the negative predictive value,the area under the curve,and the decision curve analysis in comparing reflexive tests due to their relevance in evaluating diagnostic screening tests.Results:Overall,the biomarkers are roughly equivalent in predictive accuracy.Each test has additional clinical utility to the current diagnostic standard of care,but the added benefit is not substantial to justify using the test reflexively after an elevated PSA.Conclusions:Our findings suggest these biomarkers should not be used in binary fashion and should be understood in the context of pre-existing risk predictors,patient’s ethnicity,cost of the test,patient life-expectancy,and patient goals.There are more recent diagnostic tools such as multi-parametric magnetic resonance imaging,polygenic single-nucleotide panels,IsoPSA,and miR Sentinel tests that are promising in the realm of prostate cancer screening and need to be investigated further to be considered a consensus reflexive test in the setting of prostate cancer screening.

Prostate-specific antigen kallikrein and the heart

Currently,there is growing interest regarding prostatespecific antigen(PSA) and the cardiovascular system.Increased PSA serum levels have been reported after prolonged cardiopulmonary resuscitation,cardiac surgery,extracorporeal cardiopulmonary bypass,acute myocardial infarction(AMI) and coronary artery stenting.The possible role of PSA in cardiac events has been questioned due to the finding of PSA decrease during AMI and by the correlation of variation in PSA levels with coronary lesions and occurrence of major adverse cardiac events.Complexed PSA forms and uncomplexed PSA forms are observed in the bloodstream but the increasing formation of irreversible bound PSA seems to be a crucial finding during AMI.Large studies need to be carried out to confirm these preliminary results and to elucidate unclear aspects.These findings present many potential directions for future research including the role of uncomplexed forms of PSA,the possible distribution of PSA in the heart,the relative expression levels in heart disease states,the mode of expression regulation and other potential specific substrates.The journey of PSA investigation could be longer than initially expected.