BACKGROUND Prostate cancer(PC)is currently the most common malignant tumor of the genitourinary system in men.Radical prostatectomy(RP)is recommended for the treatment of patients with localized PC.Adjuvant hormonal t...BACKGROUND Prostate cancer(PC)is currently the most common malignant tumor of the genitourinary system in men.Radical prostatectomy(RP)is recommended for the treatment of patients with localized PC.Adjuvant hormonal therapy(AHT)can be administered postoperatively in patients with high-risk or locally advanced PC.Chemotherapy is a vital remedy for castration-resistant prostate cancer(CRPC),and may also benefit patients with PC who have not progressed to CRPC.CASE SUMMARY A 68-year-old male was admitted to our hospital because of urinary irritation and dysuria with increased prostate-specific antigen(PSA)levels.After detailed examination,he was diagnosed with PC and treated with laparoscopic RP on August 3,2020.AHT using androgen deprivation therapy(ADT)was performed postoperatively because of the positive surgical margin,extracapsular extension,and neural invasion but lasted only 6 mo.Unfortunately,he was diagnosed with rectal cancer about half a year after self-cessation of AHT,and was then treated with laparoscopic radical rectal resection and adjuvant chemotherapy using the capecitabine plus oxaliplatin(CapeOx)regimen.During the entire treatment process,the patient's PSA level first declined significantly after treatment of PC with laparoscopic RP and ADT,then rebounded because of self-cessation of ADT,and finally decreased again after CapeOx chemotherapy.CONCLUSION CapeOx chemotherapy can reduce PSA levels in patients with high-risk locally advanced PC,indicating that CapeOx may be an alternative chemotherapy regimen for PC.展开更多
The standard diagnostic modalities for Prostate Cancer (PC) include serum Prostate-Specific Antigen (PSA) assay, Digital Rectal Examination (DRE), and histological examination of prostate biopsy. They are limited by l...The standard diagnostic modalities for Prostate Cancer (PC) include serum Prostate-Specific Antigen (PSA) assay, Digital Rectal Examination (DRE), and histological examination of prostate biopsy. They are limited by low predictive potential and inability to predict which patients are at risk of developing metastatic disease. The aim of this study is to investigate the exon 4 of the KLK2 gene of subjects for changes in its nucleotide sequences (SNPs) and determine the correlation of these changes with serum PSA in an Igbo population of Nigeria. One hundred male subjects aged 40 years and above, who gave their consent, were used for the study. Their PSA determinations were done using ELISA technique while genetic studies were carried out using real-time PCR. tPSA, fPSA, and % fPSA of the subjects ranged between 0.8% - 18.30%, 0.10% - 1.60% and 0.0% - 0.7% respectively. Of the 100 subjects, 28 subjects had tPSA levels above 4.0 ng/ml with a mean of 7.10 (±3.30) ng/ml. Those with tPSA less than 4 ng/ml had a mean of 1.87 (±0.85) ng/m. 15 subjects showed SNPs with a mean tPSA of 6.87 (±4.82) ng/ml while the remaining 85 subjects without SNPs had a mean of 1.86 (±0.80) ng/ml. Results from direct DNA sequencing showed 11 SNPs. Ten subjects are curated in SNP database while one is uncurated. The Chi-square test showed significant association (p = 0.00) between tPSA levels and SNPs mutation (X<sup>2</sup> = 17.35, p = 0.00). A Kruskal-Wallis test demonstrated that the positional arrangement of the SNP mutations had no effect on PSA-total or free-values (H (10) = 10.92, p = 0.28;H (10) = 10.07, p = 0.38 respectively). Two SNPs: rs6072 and rs74478031 were associated with elevated PSA levels (p < 0.05). Their presence, therefore, has the potential to serve, in conjunction with raised PSA, as biomarkers of prostate cancer in the study population.展开更多
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 wit...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.展开更多
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 ...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.展开更多
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 ...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.展开更多
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). He...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.展开更多
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 p...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.展开更多
BACKGROUND Primary liver cancer includes three subtypes:Hepatocellular carcinoma(HCC),intrahepatic cholangiocarcinoma(CCA),and combined hepatocellular carcinoma.Patients with primary liver cancer experienced poor prog...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.展开更多
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 d...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.展开更多
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 impa...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.展开更多
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,ext...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.展开更多
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,4...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.展开更多
We report a case of metastatic castration-resistant prostate cancer, who received prior treatment with docetaxel and was then given cabazitaxel as salvage therapy. The patient was monitored by prostate-specific antige...We report a case of metastatic castration-resistant prostate cancer, who received prior treatment with docetaxel and was then given cabazitaxel as salvage therapy. The patient was monitored by prostate-specific antigen doubling time and prostate-specific antigen absolute value. The prostate-specific antigen doubling time was found to be a good response predictor in the patient.展开更多
Imaging has a central role in the context of focal therapy(FT)for prostate cancer(PCa).Prostate-specific membrane antigen(PSMA)positron emission tomography/magnetic resonance imaging(PET/MRI)is a novel imaging modalit...Imaging has a central role in the context of focal therapy(FT)for prostate cancer(PCa).Prostate-specific membrane antigen(PSMA)positron emission tomography/magnetic resonance imaging(PET/MRI)is a novel imaging modality that combines the morpho-functional information of MRI with the molecular characterization of PET.Some papers reported the potential advantages of PSMA PET/MRI in different clinical scenarios.Limited evidence on PSMA PET/MRI is available in the setting of FT.PSMA PET/MRI can be an effective imaging modality for detecting primary PCa and seems to provide accurate local staging of primary PCa.PSMA PET/MRI also shows high performance for restaging and detecting tumor recurrence.The higher soft-tissue contrast and the reduction of ionizing radiation are the main advantages reported in the literature compared to PET/computed tomography.PSMA PET/MRI could represent a turning point in the management of patients with PCa in the context of FT.Further studies are needed to confirm its applications in this specific clinical setting.展开更多
AIM: To investigate the relationship between prostatespecific antigen(PSA) levels and(1) bladder outlet obstruction(BOO) and(2) the severity of prostate inflammation.METHODS: Two hundred and twenty-two consecutive pat...AIM: To investigate the relationship between prostatespecific antigen(PSA) levels and(1) bladder outlet obstruction(BOO) and(2) the severity of prostate inflammation.METHODS: Two hundred and twenty-two consecutive patients undergoing transurethral resection of the prostate(TURP) were prospectively included. Patients with proven urinary tract infection and/or known prostate cancer were excluded. PSA levels, International Prostate Symptoms Score(IPSS), prostate weight, post residual volume and pressure flow parameters were determined. A histopathological assessment of the presence and severity of inflammation was also performed.RESULTS: Patients had a mean age of 69.1 ± 8.6 years(45-90 years), with mean preoperative PSA levels of 4.7 ± 5.4 ng/m L(0.2-32.5 ng/m L) and IPSS of 15.7 ± 6.9(0-32). Mean Pdet Q max was 96.3 ± 34.4 cm H2O(10-220 cm H2O). The mean resected prostate weight was 39.4 ± 27.3 g(3-189 g). Correlations were observed between PSA(logarithmic) and resected prostate weight(r = 0.54; P < 0.001), PSA(logarithmic) and Pdet Q max(r = 0.17; P = 0.032), and resected prostate weight and Pdet Q max(r = 0.39; P < 0.001). Furthermore, low correlations were observed between PSA(logarithmic) and active(r = 0.21; P < 0.0001) and chronic(r = 0.19; P = 0.005) inflammation. CONCLUSION: In this study we showed a correlation between BOO(Pdet Q max) and PSA(logarithmic). Furthermore, we demonstrated a weak correlation between PSA(logarithmic) and active as well as chronic prostatic inflammation.展开更多
Objective The aim of the study was to evaluate the efficiency of salvage treatments for prostate specific antigen(PSA)relapse of cT3N0M0 prostatic adenocarcinoma(PCa)after radical prostatectomy(RP)combined with neoadj...Objective The aim of the study was to evaluate the efficiency of salvage treatments for prostate specific antigen(PSA)relapse of cT3N0M0 prostatic adenocarcinoma(PCa)after radical prostatectomy(RP)combined with neoadjuvant androgen deprivation(ADT).Methods A total of 332 patients with cT3N0M0 PCa were enrolled in the prospective study and received RP and pelvic lymph node dissection with neoadjuvant ADT for 3 months.All patients with PSA relapse were treated with salvage external beam radiation therapy(RT)and ADT for 6 months.Results The 5-year postoperative PSA relapse rate was 40.96%(136/332).The patients have been divided into the PSA relapse and PSA relapse-free groups in order to compare patient characteristics.The ratio of patients with Gleason score≥8 and positive surgical margin in the PSA relapse group were significantly higher than those of in the PSA relapse-free group(P=0.01).The mean duration between the start of operative treatment and PSA relapse was 31 months.Salvage treatment to all 136 PSA relapse patients led to favorable outcomes.PSA relapse was not observed after salvage treatment by the end of follow-up.The 5-year overall survival rates of the PSA relapse and PSA relapse-free groups were 94.9%and 93.9%,respectively.Conclusion In pursuit of curative treatment,our study showed that RP combined with neoadjuvant ADT is an aggressive multimodality strategy associated with lower PSA relapse and better survival outcomes for stage cT3N0M0 PCa patients.Patients with PSA relapse after RP may benefit from early aggressive salvage RT combined with short-term ADT.展开更多
Prostate cancer (PCa) is most common diagnosed cancer in men and it is second most common cause of male cancer death. Many factors have been implicated in the pathogenesis of PCa. Although many papers have discussed t...Prostate cancer (PCa) is most common diagnosed cancer in men and it is second most common cause of male cancer death. Many factors have been implicated in the pathogenesis of PCa. Although many papers have discussed the prostate specific antigen (PSA) as biomarker of PCa, very few have addressed its rule in the carcinogenesis, metastasis and invasion of PCa. In this article we will review the pathological role of PSA, as a potential target in the therapeutics of PCa.展开更多
基金Supported by Jiaxing Science and Technology Foundation,No.2021AY30018.
文摘BACKGROUND Prostate cancer(PC)is currently the most common malignant tumor of the genitourinary system in men.Radical prostatectomy(RP)is recommended for the treatment of patients with localized PC.Adjuvant hormonal therapy(AHT)can be administered postoperatively in patients with high-risk or locally advanced PC.Chemotherapy is a vital remedy for castration-resistant prostate cancer(CRPC),and may also benefit patients with PC who have not progressed to CRPC.CASE SUMMARY A 68-year-old male was admitted to our hospital because of urinary irritation and dysuria with increased prostate-specific antigen(PSA)levels.After detailed examination,he was diagnosed with PC and treated with laparoscopic RP on August 3,2020.AHT using androgen deprivation therapy(ADT)was performed postoperatively because of the positive surgical margin,extracapsular extension,and neural invasion but lasted only 6 mo.Unfortunately,he was diagnosed with rectal cancer about half a year after self-cessation of AHT,and was then treated with laparoscopic radical rectal resection and adjuvant chemotherapy using the capecitabine plus oxaliplatin(CapeOx)regimen.During the entire treatment process,the patient's PSA level first declined significantly after treatment of PC with laparoscopic RP and ADT,then rebounded because of self-cessation of ADT,and finally decreased again after CapeOx chemotherapy.CONCLUSION CapeOx chemotherapy can reduce PSA levels in patients with high-risk locally advanced PC,indicating that CapeOx may be an alternative chemotherapy regimen for PC.
文摘The standard diagnostic modalities for Prostate Cancer (PC) include serum Prostate-Specific Antigen (PSA) assay, Digital Rectal Examination (DRE), and histological examination of prostate biopsy. They are limited by low predictive potential and inability to predict which patients are at risk of developing metastatic disease. The aim of this study is to investigate the exon 4 of the KLK2 gene of subjects for changes in its nucleotide sequences (SNPs) and determine the correlation of these changes with serum PSA in an Igbo population of Nigeria. One hundred male subjects aged 40 years and above, who gave their consent, were used for the study. Their PSA determinations were done using ELISA technique while genetic studies were carried out using real-time PCR. tPSA, fPSA, and % fPSA of the subjects ranged between 0.8% - 18.30%, 0.10% - 1.60% and 0.0% - 0.7% respectively. Of the 100 subjects, 28 subjects had tPSA levels above 4.0 ng/ml with a mean of 7.10 (±3.30) ng/ml. Those with tPSA less than 4 ng/ml had a mean of 1.87 (±0.85) ng/m. 15 subjects showed SNPs with a mean tPSA of 6.87 (±4.82) ng/ml while the remaining 85 subjects without SNPs had a mean of 1.86 (±0.80) ng/ml. Results from direct DNA sequencing showed 11 SNPs. Ten subjects are curated in SNP database while one is uncurated. The Chi-square test showed significant association (p = 0.00) between tPSA levels and SNPs mutation (X<sup>2</sup> = 17.35, p = 0.00). A Kruskal-Wallis test demonstrated that the positional arrangement of the SNP mutations had no effect on PSA-total or free-values (H (10) = 10.92, p = 0.28;H (10) = 10.07, p = 0.38 respectively). Two SNPs: rs6072 and rs74478031 were associated with elevated PSA levels (p < 0.05). Their presence, therefore, has the potential to serve, in conjunction with raised PSA, as biomarkers of prostate cancer in the study population.
文摘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.
文摘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.
文摘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.
文摘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.
文摘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.
基金National Natural Science Foundation of China,No.81873903,No.81671718,No.91959119 and No.81271600Natural Science Foundation of Hubei Province in China,No.2016CFB687.
文摘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.
文摘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.
文摘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.
文摘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.
文摘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.
文摘We report a case of metastatic castration-resistant prostate cancer, who received prior treatment with docetaxel and was then given cabazitaxel as salvage therapy. The patient was monitored by prostate-specific antigen doubling time and prostate-specific antigen absolute value. The prostate-specific antigen doubling time was found to be a good response predictor in the patient.
文摘Imaging has a central role in the context of focal therapy(FT)for prostate cancer(PCa).Prostate-specific membrane antigen(PSMA)positron emission tomography/magnetic resonance imaging(PET/MRI)is a novel imaging modality that combines the morpho-functional information of MRI with the molecular characterization of PET.Some papers reported the potential advantages of PSMA PET/MRI in different clinical scenarios.Limited evidence on PSMA PET/MRI is available in the setting of FT.PSMA PET/MRI can be an effective imaging modality for detecting primary PCa and seems to provide accurate local staging of primary PCa.PSMA PET/MRI also shows high performance for restaging and detecting tumor recurrence.The higher soft-tissue contrast and the reduction of ionizing radiation are the main advantages reported in the literature compared to PET/computed tomography.PSMA PET/MRI could represent a turning point in the management of patients with PCa in the context of FT.Further studies are needed to confirm its applications in this specific clinical setting.
基金the ‘Kwaliteitsfonds Jessa ZH’ for the financial support
文摘AIM: To investigate the relationship between prostatespecific antigen(PSA) levels and(1) bladder outlet obstruction(BOO) and(2) the severity of prostate inflammation.METHODS: Two hundred and twenty-two consecutive patients undergoing transurethral resection of the prostate(TURP) were prospectively included. Patients with proven urinary tract infection and/or known prostate cancer were excluded. PSA levels, International Prostate Symptoms Score(IPSS), prostate weight, post residual volume and pressure flow parameters were determined. A histopathological assessment of the presence and severity of inflammation was also performed.RESULTS: Patients had a mean age of 69.1 ± 8.6 years(45-90 years), with mean preoperative PSA levels of 4.7 ± 5.4 ng/m L(0.2-32.5 ng/m L) and IPSS of 15.7 ± 6.9(0-32). Mean Pdet Q max was 96.3 ± 34.4 cm H2O(10-220 cm H2O). The mean resected prostate weight was 39.4 ± 27.3 g(3-189 g). Correlations were observed between PSA(logarithmic) and resected prostate weight(r = 0.54; P < 0.001), PSA(logarithmic) and Pdet Q max(r = 0.17; P = 0.032), and resected prostate weight and Pdet Q max(r = 0.39; P < 0.001). Furthermore, low correlations were observed between PSA(logarithmic) and active(r = 0.21; P < 0.0001) and chronic(r = 0.19; P = 0.005) inflammation. CONCLUSION: In this study we showed a correlation between BOO(Pdet Q max) and PSA(logarithmic). Furthermore, we demonstrated a weak correlation between PSA(logarithmic) and active as well as chronic prostatic inflammation.
文摘Objective The aim of the study was to evaluate the efficiency of salvage treatments for prostate specific antigen(PSA)relapse of cT3N0M0 prostatic adenocarcinoma(PCa)after radical prostatectomy(RP)combined with neoadjuvant androgen deprivation(ADT).Methods A total of 332 patients with cT3N0M0 PCa were enrolled in the prospective study and received RP and pelvic lymph node dissection with neoadjuvant ADT for 3 months.All patients with PSA relapse were treated with salvage external beam radiation therapy(RT)and ADT for 6 months.Results The 5-year postoperative PSA relapse rate was 40.96%(136/332).The patients have been divided into the PSA relapse and PSA relapse-free groups in order to compare patient characteristics.The ratio of patients with Gleason score≥8 and positive surgical margin in the PSA relapse group were significantly higher than those of in the PSA relapse-free group(P=0.01).The mean duration between the start of operative treatment and PSA relapse was 31 months.Salvage treatment to all 136 PSA relapse patients led to favorable outcomes.PSA relapse was not observed after salvage treatment by the end of follow-up.The 5-year overall survival rates of the PSA relapse and PSA relapse-free groups were 94.9%and 93.9%,respectively.Conclusion In pursuit of curative treatment,our study showed that RP combined with neoadjuvant ADT is an aggressive multimodality strategy associated with lower PSA relapse and better survival outcomes for stage cT3N0M0 PCa patients.Patients with PSA relapse after RP may benefit from early aggressive salvage RT combined with short-term ADT.
文摘Prostate cancer (PCa) is most common diagnosed cancer in men and it is second most common cause of male cancer death. Many factors have been implicated in the pathogenesis of PCa. Although many papers have discussed the prostate specific antigen (PSA) as biomarker of PCa, very few have addressed its rule in the carcinogenesis, metastasis and invasion of PCa. In this article we will review the pathological role of PSA, as a potential target in the therapeutics of PCa.