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.

New model of PIRADS and adjusted prostatespecific antigen density of peripheral zone improves the detection rate of initial prostate biopsy:a diagnostic study

This study explored a new model of Prostate Imaging Reporting and Data System(PIRADS)and adjusted prostate-specific antigen density of peripheral zone(aPSADPZ)for predicting the occurrence of prostate cancer(PCa)and clinically significant prostate cancer(csPCa).The demographic and clinical characteristics of 853 patients were recorded.Prostate-specific antigen(PSA),PSA density(PSAD),PSAD of peripheral zone(PSADPZ),aPSADPZ,and peripheral zone volume ratio(PZ-ratio)were calculated and subjected to receiver operating characteristic(ROC)curve analysis.The calibration and discrimination abilities of new nomograms were verified with the calibration curve and area under the ROC curve(AUC).The clinical benefits of these models were evaluated by decision curve analysis and clinical impact curves.The AUCs of PSA,PSAD,PSADPZ,aPSADPZ,and PZ-ratio were 0.669,0.762,0.659,0.812,and 0.748 for PCa diagnosis,while 0.713,0.788,0.694,0.828,and 0.735 for csPCa diagnosis,respectively.All nomograms displayed higher net benefit and better overall calibration than the scenarios for predicting the occurrence of PCa or csPCa.The new model significantly improved the diagnostic accuracy of PCa(0.945 vs 0.830,P<0.01)and csPCa(0.937 vs 0.845,P<0.01)compared with the base model.In addition,the number of patients with PCa and csPCa predicted by the new model was in good agreement with the actual number of patients with PCa and csPCa in high-risk threshold.This study demonstrates that aPSADPZ has a higher predictive accuracy for PCa diagnosis than the conventional indicators.Combining aPSADPZ with PIRADS can improve PCa diagnosis and avoid unnecessary biopsies.

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.

The Significance of PSA Modified Parameters (F/T)/PSAD for Diagnosing Prostatic Cancer in the Grey Zone of 4～10 ng/ml

OBJECTIVE To investigate the diagnostic value of modified prostate specific antigen(PSA)parameters in the diagnosis of prostate cancer(PCA) when the serum PSAis in a grey zone of 4~10 ng/ml. METHODS The results of serum PSA determinations of the patients receiving a transrectal ultrasound-guided multiphase prostatic biopsy,were retrospectively analyzed.In the 88 patients with a serum PSA value of 4-10 ng/ml,the final diagnosis of PCA was made in 21,and that of benign prostate hyperplasia(BPH)in 67 patients.The percentage of the free-serum PSA([FPSA]/total-serum PSA[TPSA],F/T),PSA density(PSAD)and the sensitivity and specificity of the new PSA modified parameter(F/T)/PSAD in diagnosing PCA,within a set threshold value,was compared. RESULTS In the 88 patients with serum PSA in the grey zone of 4.0-10.0 ng/ml,there was no significant difference in comparing the TPSA between the 21 PCA patients and 67 BPH patients(P>0.05).However, there was a significant difference in the value of modified PSA parameters, such as F/T,PSAD and(F/T)/PSAD,between the PCA and the BPH groups (P<0.001).As the cut off point-value of the F/T,PSAD and(F/T)/PSAD was set at 0.16,0.15 and 0.8,the diagnostic sensitivity for PCA was 66.7%, 76.2%and 85.7%,and the specificity was 41.8%,43.3%and 68.7%,respectively.There was no significant difference in the sensitivity comparing the modified parameters for diagnosing PCA(P>0.05),whereas an overt predominance was present in the specificity of(F/T)/PSAD for PCAdiagnosis (P<0.05). CONCLUSION In the serum PSA grey zone of 4-10 ng/ml,a modified PSA parameter can improve the PCA diagnostic accuracy rate.With a considerably high sensitivity,application of the(F/T)/PSAD may effectively enhance the diagnostic specificity,which is superior to the F/T and PSAD, and can be expected to be one of the new indices derived from the PSA.

The Relationship of PSA,PSAD and Clinicopathological Stage in Patients with Prostate Cancer

OBJECTIVE To investigate the relationship between the clinicopatho- logical stage and serum prostate specific antigen(PSA)concentration and PSAdensity(PSAD)in patients with prostate cancer. METHODS The clinicopathological stage was determined on the basis of a pathological examination and clinical data in 65 prostate cancer patients treated by radical prostatectomy.PSA and PSAD were measured before the operation.The Spearman rank correlation was applied to evaluate the relationship between the clinicopathological stage,serum PSAconcentration and PSAD. RESULTS Patients with higher PSA and PSAD were significantly more likely to have higher clinical stages,a higher Gleason score,positive surgical margins,capsular penetration,and seminal vesicle invasion(each P<0.05). But there was no significant association between PSA and lymph node metastasis(P=0.053).The levels of serum PSA concentration and PSAD were significantly correlated with the clinical stage(P<0.05)in the prostate cancer patients. CONCLUSION The level of both PSA and PSAD were significantly correlated with the clinical stage(P<0.05)in the prostate cancer patients.But PSAD may be a more powerful predictor of clinical stage and prognosis than PSA.

Developing a diagnostic model for predicting prostate cancer: a retrospective study based on Chinese multicenter clinical data

The overdiagnosis of prostate cancer(PCa)caused by nonspecific elevation serum prostate-specific antigen(PSA)and the overtreatment of indolent PCa have become a global problem that needs to be solved urgently.We aimed to construct a prediction model and provide a risk stratification system to reduce unnecessary biopsies.In this retrospective study,clinical data of 1807 patients from three Chinese hospitals were used.The final model was built using stepwise logistic regression analysis.The apparent performance of the model was assessed by receiver operating characteristic curves,calibration plots,and decision curve analysis.Finally,a risk stratification system of clinically significant prostate cancer(csPCa)was created,and diagnosis-free survival analyses were performed.Following multivariable screening and evaluation of the diagnostic performances,a final diagnostic model comprised of the PSA density and Prostate Imaging-Reporting and Data System(PI-RADS)score was established.Model validation in the development cohort and two external cohorts showed excellent discrimination and calibration.Finally,we created a risk stratification system using risk thresholds of 0.05 and 0.60 as the cut-off values.The follow-up results indicated that the diagnosis-free survival rate for csPCa at 12 months and 24 months postoperatively was 99.7%and 99.4%,respectively,for patients with a risk threshold below O.05 after the initial negative prostate biopsy,which was significantly better than patients with higher risk.Our diagnostic model and risk stratification system can achieve a personalized risk calculation of csPCa.It provides a standardized tool for Chinese patients and physicians when considering thenecessity of prostatebiopsy.

PSA density in the diagnosis of prostate cancer in the Chinese population: results from the Chinese Prostate Cancer Consortium

We performed this study to investigate the diagnostic performance of prostate-specific antigen density(PSAD)in a multicenter cohort of the Chinese Prostate Cancer Consortium.Outpatients with prostate-specific antigen(PSA)levels≥4.0 ng ml^(-1) regardless of digital rectal examination(DRE)results or PSA levels<4.0 ng ml^(-1)and abnormal DRE results were included from 18 large referral hospitals in China.The diagnostic performance of PSAD and the sensitivity and specificity for the diagnosis of prostate cancer(PCa)and high-grade prostate cancer(HGPCa)at different cutoff values were evaluated.A total of 5220 patients were included in the study,and 2014(38.6%)of them were diagnosed with PCa.In patients with PSA levels ranging from 4.0 to 10.0 ng ml^(-1),PSAD was associated with PCa and HGPCa in both univariate(odds ratio[OR]=45.15,P<0.0001 and OR=25.38,P<0.0001,respectively)and multivariate analyses(OR=52.55,P<0.0001 and OR=26.05,P<0.0001,respectively).The areas under the receiver operating characteristic curves(AUCs)of PSAD in predicting PCa and HGPCa were 0.627 and 0.630,respectively.With the PSAD cutoff of 0.10 ng ml^(-2),we obtained a sensitivity of 88.7%for PCa,and nearly all(89.9%)HGPCa cases could be detected and biopsies could be avoided in 20.2%of the patients(359/1776 cases).Among these patients who avoided biopsies,only 30 cases had HGPCa.We recommend 0.10 ng ml^(-2) as the proper cutoff value of PSAD,which will obtain a sensitivity of nearly 90%for both PCa and HGPCa.The results of this study should be validated in prospective,population-based multicenter studies.

Peripheral zone PSA density:a predominant variable to improve prostate cancer detection efficiency in men with PSA higher than 4 ng ml^(-1)

To improve the diagnostic efficiency of prostate cancer(PCa)and reduce unnecessary biopsies,we defined and analyzed the diagnostic efficiency of peripheral zone prostate-specific antigen(PSA)density(PZ-PSAD).Patients who underwent systematic 12-core prostate biopsies in Shanghai General Hospital(Shanghai,China)between January 2012 and January 2018 were retrospectively identified(n=529).Another group of patients with benign prostatic hyperplasia(n=100)were randomly preselected to obtain the PSA density of the non-PCa cohort(N-PSAD).Prostate volumes and transition zone volumes were measured using multiparameter magnetic resonance imaging(mpMRI)and were combined with PSA and N-PSAD to obtain the PZ-PSAD from a specific algorithm.Receiver operating characteristic(ROC)curve analysis was used to assess the PCa detection efficiency in patients stratified by PSA level,and the area under the ROC curve(AUC)of PZ-PSAD was higher than that of PSA,PSA density(PSAD),and transition zone PSA density(TZ-PSAD).PZ-PSAD could amend the diagnosis for more than half of the patients with inaccurate transrectal ultrasonography(TRUS)and mpMRI results.When TRUS and mpMRI findings were ambiguous to predict PCa(PIRADS score≤3),PZ-PSAD could increase the positive rate of biopsy from 21.7%to 54.7%,and help 63.8%(150/235)of patients avoid unnecessary prostate biopsy.In patients whose PSA was 4.0–10.0 ng ml^(−1),10.1–20.0 ng ml^(−1),and>20.0 ng ml^(−1),the ideal PZ-PSAD cut-off value for predicting clinically significant PCa was 0.019 ng ml^(−2),0.297 ng ml^(−2),and 1.180 ng ml^(−2),respectively(sensitivity>90%).Compared with PSA,PSAD,and TZ-PSAD,the efficiency of PZ-PSAD for predicting PCa is the highest,leading to fewer missed diagnoses and unnecessary biopsies.

Clinical and prostate multiparametric magnetic resonance imaging findings as predictors of general and clinically significant prostate cancer risk:A retrospective single-center study

Background:To evaluate the predictive values of Prostate Imaging Reporting and Data System version 2(PI-RADS v2),prostate-specific antigen(PSA)level,PSA density(PSAD),digital rectal examination findings,and prostate volume,individually and in combination,for the detection of prostate cancer(Pca)in biopsy-naïve patients.Methods:We retrospectively analyzed 630 patients who underwent transrectal systematic prostate biopsy following prostate multiparametric magnetic resonance imaging.A standard 12-core biopsy procedure was performed.Univariate and multivariate analyses were performed to determine the significant predictors of clinically significant cancer but not Pca.Results:The median age,PSA level,and PSAD were 70 years,8.6 ng/mL,and 0.18 ng/mL/mL,respectively.A total of 374(59.4%)of 630 patients were biopsy-positive for Pca,and 241(64.4%)of 374 were diagnosed with clinically significant Pca(csPCa).The PI-RADS v2 score and PSAD were independent predictors of Pca and csPCa.The PI-RADS v2 score of 5 regardless of the PSAD value,or PI-RADS v2 score of 4 plus a PSAD of<0.3 ng/mL/mL,was associated with the highest csPCa detection rate(36.1%-82.1%).Instead,the PI-RADS v2 score of<3 and PSAD of<0.3 ng/mL/mL yielded the lowest risk of csPCa.Conclusion:The combination of the PI-RADS v2 score and PSAD could prove to be a helpful and reliable diagnostic tool before performing prostate biopsies.Patients with a PI-RADS v2 score of<3 and PSAD of<0.3 ng/mL/mL could potentially avoid a prostate biopsy.

Using the Prostate Imaging Reporting and Data System version 2 （PI-RIDS v2） to detect prostate cancer can prevent unnecessary biopsies and invasive treatment

Prostate cancer （PCa） is one of the most common cancers among men globally. The authors aimed to evaluate the ability of the Prostate Imaging Reporting and Data System version 2 （PI-RADS v2） to classify men with PCa, clinically significant PCa （CSPCa）, or no PCa, especially among those with serum total prostate-specific antigen （tPSA） levels in the ＂gray zone＂ （4-10 ng ml-1）. A total of 308 patients （355 lesions） were enrolled in this study. Diagnostic efficiency was determined. Univariate and multivariate analyses, receiver operating characteristic curve analysis, and decision curve analysis were performed to determine and compare the predictors of PCa and CSPCa. The results suggested that PI-RADS v2, tPSA, and prostate-specific antigen density （PSAD） were independent predictors of PCa and CSPCa. A PI-RADS v2 score L≥4 provided high negative predictive values （91.39% for PCa and 95.69% for CSPCa）. A model of PI-RADS combined with PSA and PSAD helped to define a high-risk group （PI-RADS score = 5 and PSAD L≥0 15 ng ml-1 cm-3, with tPSA in the gray zone, or PI-RADS score L≥4 with high tPSA level） with a detection rate of 96.1% for PCa and 93.0% for CSPCa while a low-risk group with a detection rate of 6.1% for PCa and 2.2% for CSPCa. It was concluded that the PI-RADS v2 could be used as a reliable and independent predictor of PCa and CSPCa. The combination of PI-RADS v2 score with PSA and PSAD could be helpful in the prediction and diagnosis of PCa and CSPCa and, thus, may help in preventing unnecessary invasive procedures.