Clinically Significant Prostate Cancer Research Articles

A novel biopsy scheme for prostate cancer: targeted and regional systematic biopsy

PurposeTo explore a novel biopsy scheme for prostate cancer (PCa), and test the detection rate and pathological agreement of standard systematic (SB) + targeted (TB) biopsy and novel biopsy scheme.MethodsPositive needles were collected from 194 patients who underwent SB + TB (STB) followed by radical prostatectomy (RP). Our novel biopsy scheme, targeted and regional systematic biopsy (TrSB) was defined as TB + regional SB (4 SB-needles closest to the TB-needles). The McNemar test was utilized to compare the detection rate performance for clinical significant PCa (csPCa) and clinical insignificant PCa (ciPCa). Moreover, the accuracy, positive predictive value (PPV) and negative predictive value (NPV) were investigated. The agreement between the different biopsy schemes grade group (GG) and RP GG were assessed. The concordance between the biopsy and the RP GG was evaluated using weighted κ coefficient analyses.ResultsIn this study, the overall detection rate for csPCa was 83.5% (162 of 194) when SB and TB were combined. TrSB showed better NPV than TB (97.0% vs. 74.4%). Comparing to STB, the TB-detection rate of csPCa had a significant difference (p < 0.01), while TrSB showed no significant difference (p > 0.999). For ciPCa, the overall detection rate was 16.5% (32 of 194). TrSB showed better PPV (96.6% vs. 83.3%) and NPV (97.6% vs. 92.9%) than TB. Comparing to STB, the detection rate of both schemes showed no significant difference (p = 0.077 and p = 0.375). All three schemes GG showed poor agreement with RP GG (TB: 43.3%, TrSB: 46.4%, STB: 45.9%). Using weighted κ, all three schemes showed no difference (TB: 0.48, TrSB: 0.51, STB: 0.51). In our subgroup analysis (PI-RADS = 4/5, n = 154), all three schemes almost showed no difference (Weighted κ: TB-0.50, TrSB-0.51, STB-0.50).ConclusionOur novel biopsy scheme TrSB (TB + 4 closest SB needles) may reduce 8 cores of biopsy compared with STB (standard SB + TB), which also showed better csPCa detection rate than TB only, but the same as STB. The pathological agreement between three different biopsy schemes (TB/TrSB/STB) GG and RP GG showed no difference.

A nomogram to predict the absence of clinically significant prostate cancer in males with negative MRI

To create a nomogram to predict the absence of clinically significant prostate cancer (CSPCa) in males with non-suspicion multiparametric magnetic resonance imaging (mpMRI) undergoing prostate biopsy (PBx). We identified consecutive patients who underwent 3T mpMRI followed by PBx for suspicion of PCa or surveillance follow-up. All patients had Prostate Imaging Reporting and Data System score 1-2 (negative mpMRI). CSPCa was defined as Grade Group ≥2. Multivariate logistic regression analysis was performed via backward elimination. Discrimination was evaluated with area under the receiver operating characteristic (AUROC). Internal validation with 1,000x bootstrapping for estimating the optimism corrected AUROC. Total 327 patients met inclusion criteria. The median (IQR) age and PSA density (PSAD) were 64 years (58-70) and 0.10 ng/mL2 (0.07-0.15), respectively. Biopsy history was as follows: 117 (36%) males were PBx-naive, 130 (40%) had previous negative PBx and 80 (24%) had previous positive PBx. The majority were White (65%); 6% of males self-reported Black. Overall, 44 (13%) patients were diagnosed with CSPCa on PBx. Black race, history of previous negative PBx and PSAD ≥0.15ng/mL2 were independent predictors for CSPCa on PBx and were included in the nomogram. The AUROC of the nomogram was 0.78 and the optimism corrected AUROC was 0.75. Our nomogram facilitates evaluating individual probability of CSPCa on PBx in males with PIRADS 1-2 mpMRI and may be used to identify those in whom PBx may be safely avoided. Black males have increased risk of CSPCa on PBx, even in the setting of PIRADS 1-2 mpMRI.

Effectiveness of Magnetic Resonance Imaging/Ultrasound-guided Target Biopsy in Detecting Clinically Significant Prostate Cancer.

To evaluate the effectiveness of magnetic resonance imaging/ultrasound (MRI-US)-guided fusion biopsy in the detection of clinically significant prostate cancer (CSPC) and analyze the clinical features of patients highly suspected of having prostate cancer (PCa) but shown to be negative in target biopsies (TB) among patients with prostate imaging reporting and data system (PI-RADS) 4 or 5 lesions on multiparametric MRI (mpMRI) evaluations. We retrospectively evaluated all patients who underwent MRI/transrectal ultrasound (TRUS)-guided fusion biopsies at our institution between April 2018 and April 2022. All patients with at least one PI-RADS 3 or higher lesion and prostate-specific antigen (PSA) ≤20 ng/ml were enrolled in our study and subjected to TB in the region of interest (ROI). CSPC was defined as grade group (GG) ≥2 (equivalent to a Gleason score of 3+4). The detection rates of CSPC were higher in patients who underwent systematic biopsy (SB) and TB (54%; 177/328) than in those who underwent SB alone (39%; 128/328). Significant differences were noted in the detection of CSPC depending on age, prostate volume, PI-RADS score, PSA density (PSAD), number of biopsies obtained, lesion location, and ROI. MRI/TRUS-guided fusion prostate biopsy increased the detection rate of CSPC. PCa was less likely to be detected in patients with a low PSAD, large prostate volume and no family history among those with PI-RADS 4 or 5 lesions and should be considered in such patients and addressed by performing additional SB for improving CSPC detection rate.

Development and validation of a clinical decision support system based on PSA, microRNAs, and MRI for the detection of prostate cancer.

The aims of this study are to develop and validate a clinical decision support system based on demographics, prostate-specific antigen (PSA), microRNA (miRNA), and MRI for the detection of prostate cancer (PCa) and clinical significant (cs) PCa, and to assess if this system performs better compared to MRI alone. This retrospective, multicenter, observational study included 222 patients (mean age 66, range 46-75 years) who underwent prostate MRI, miRNA (let-7a-5p and miR-103a-3p) assessment, and biopsy. Monoparametric and multiparametric models including age, PSA, miRNA, and MRI outcome were trained on 65% of the data and then validated on the remaining 35% to predict both PCa (any Gleason grade [GG]) and csPCa (GG ≥ 2 vs GG = 1/negative). Accuracy, sensitivity, specificity, positive and negative predictive value (NPV), and area under the receiver operating characteristic curve were calculated. MRI outcome was the best predictor in the monoparametric model for both detection of PCa, with sensitivity of 90% (95%CI 73-98%) and NPV of 93% (95%CI 82-98%), and for csPCa identification, with sensitivity of 91% (95%CI 72-99%) and NPV of 95% (95%CI 84-99%). Sensitivity and NPV of PSA + miRNA for the detection of csPCa were not statistically different from the other models including MRI alone. MRI stand-alone yielded the best prediction models for both PCa and csPCa detection in biopsy-naïve patients. The use of miRNAs let-7a-5p and miR-103a-3p did not improve classification performances compared to MRI stand-alone results. The use of miRNA (let-7a-5p and miR-103a-3p), PSA, and MRI in a clinical decision support system (CDSS) does not improve MRI stand-alone performance in the detection of PCa and csPCa. • Clinical decision support systems including MRI improve the detection of both prostate cancer and clinically significant prostate cancer with respect to PSA test and/or microRNA. • The use of miRNAs let-7a-5p and miR-103a-3p did not significantly improve MRI stand-alone performance. • Results of this study were in line with previous works on MRI and microRNA.

Predictors of prostate cancer detection in MRI PI-RADS 3 lesions - Reality of a tertiary center.

The Prostate Imaging Reporting and Data System (PI-RADS) score reports the likelihood of a clinically significant prostate cancer (CsPCa) based on various multiparametric prostate magnetic resonance imaging (mpMRI) characteristics. The PI-RADS category 3 is an intermediate status, with an equivocal risk of malignancy. The PSA density (PSAD) has been proposed as a tool to facilitate biopsy decisions on PI-RADS category 3 lesions. The objective of this study is to determine the frequency of CsPCa, assess the diagnostic value of targeted biopsy and identify clinical predictors to improve the CsPCa detection rate in PI-RADS category 3 lesions. Between 1st January 2017 and 31st December 2022, a total of 1661 men underwent a prostate biopsy at our institution. Clinical and mpMRI data of men with PI-RADS 3 lesions was reviewed. The study population was divided into two groups: target group, including those submitted to systematic plus targeted biopsy versus non-target group when only systematic or saturation biopsy were performed. Patients with PI-RADS 3 lesions were divided into three categories based on pathological biopsy results: benign, clinically insignificant disease (score Gleason = 6 or International Society of Urologic Pathologic (ISUP) 1) and clinically significant cancer (score Gleason ≥ 7 (3+4) or ISUP ≥ 2) according to target and non-target group. Univariate and multivariate analyses were performed to identify clinical predictors to improve the CsPCa detection rate in PI-RADS category 3 lesions. A total of 130 men with PIRADS 3 index lesions were identified. Pathologic results were benign in 77 lesions (59.2%), 19 (14.6%) were clinically insignificant (Gleason score 6) and 34 (26.2%) were clinically significant (Gleason score 7 or higher). Eighty-seven of the patients were included in the target group (66.9%) and 43 in the non-target group (33.1%). The CsPCa detection was higher in the non-target group (32.6%, n = 14 vs 23.0%, n = 20 respectively). When systematic and target biopsies were jointly performed, if the results of systematic biopsies are not considered and only the results of target biopsies are taken into account, a CsPCa diagnosis would be missed on 9 patients. The differences of insignificant cancer and CsPCa rates among the target or non-target group were not statistically significant (p = 0.50 and p = 0.24, respectively). on multivariate analysis, the abnormal DRE and lesions localized in Peripheral zone (PZ) were significantly associated with a presence of CsPCa in PI-RADS 3 lesions (oR = 3.61, 95% CI [1.22,10.72], p = 0.02 and oR = 3.31, 95% CI [1.35, 8.11], p = 0.01, respectively). A higher median PSAD significantly predisposed for CsPCa on univariate analyses (p = 0.05), however, was not significant in the multivariate analysis (p = 0.76). In our population, using 0.10 ng/ml/ml as a cut-off to perform biopsy, 41 patients would have avoided biopsy (31.5%), but 5 cases of CsPCa would not have been detected (3.4%). We could not identify any statistical significance between other clinical and imagiological variables and CsPCa detection. PI-RADS 3 lesions were associated with a low likelihood of CsPCa detection. A systematic biopsy associated or not with target biopsy is essential in PI-RADS 3 lesions, and targeted biopsy did not demonstrate to be superior in the detection of CsPCa. The presence of abnormal DRE and lesions localized in PZ potentially predict the presence of CsPCa in biopsied PI-RADS 3 lesions.

Comparison of Targeted Biopsy and Combined Biopsy to Avoid Unnecessary Systematic Biopsy in Patients with PI-RADS 5 Lesions.

To evaluate the detection rates of prostate cancer (PCa) and clinically significant prostate cancer (CSPCa) detection via target biopsy (TB), systematic biopsy (SB), and combined biopsy (CB) in patients with PI-RADS 5 lesions. Patients with at least one PI-RADS 5 lesion were retrospectively enrolled in a prospectively collected database. The patients underwent multiparametric magnetic resonance imaging (mpMRI) followed by transrectal TB of PI-RADS 5 lesions and SB. The PCa and CSPCa detection rates and cores of TB and SB were compared with those of CB. In 585 patients, prostate biopsy revealed PCa in 560 cases (95.73%) and CSPCa in 549 cases (93.85%). PCa was detected in T2 patients (93.13%, 217/233) and in T3/4 patients (97.44%, 343/352). CSPCa was detected in T2 patients (89.27%, 208/233) and in T3/4 patients (96.87%, 341/352). The positive rates of TB for T2/3/4, T3/4, and T2 were 94.02%, 96.21%, and 90.56%, respectively. SB added 1.71% (10/585) PCa and 1.37% (8/585) CSPCa detection to TB. There was no difference between TB and SB in detecting different stages of cancer (p > 0.05). In the biopsy core analysis, TB had fewer biopsy cores and a higher detection rate than SB (all p < 0.05). In patients with PI-RADS score 5 lesions, TB can achieve the same detection rate as, with fewer biopsy cores than, CB. SB adds minimal clinical value and can be omitted for these patients.

Analysis of the relationship between PI-RADS scores and the pathological results of targeted biopsy based on MRI

Objective: To analyze the relationship between Prostate Imaging Reporting and Data System (PI-RADS) scores and the pathological results of transperineal magnetic resonance-ultrasound fusion guided biopsy. Methods: The clinical data, magnetic resonance imaging (MRI) results and prostate puncture biopsies of 517 patients who were assigned to PI-RADS score of 4 or 5 and underwent transperineal magnetic resonance-ultrasound fusion guided biopsy at The First Affiliated Hospital of Nanjing Medical University from June 2019 to March 2022 were retrospectively analyzed. Patients were divided into the PI-RADS 4 and PI-RADS 5 groups according to their PI-RADS scores and were stratified by their prostate specific antigen (PSA) values (PSA<10 ng/ml vs. PSA 10-20 ng/ml). The pathological negative rates from the biopsy, the distribution of the grade groups according to the grading system by World Health Organization/International Society of Urological Pathology (WHO/ISUP), the detection rates of prostate cancer (PCa) and clinically significant prostate cancer (CsPCa)between the groups were compared. Results: 369 patients with a PI-RADS score of 4 and 148 patients with a PI-RADS score of 5 were included in our research. The overall detection rates of PCa and CsPCa were 77.8% (402/517) and 66.7% (345/517), respectively. In the PI-RADS 4 group, patients with prostate negative biopsies or in WHO/ISUP 1, 2, 3, 4, or 5 grade groups accounted for 28.2%, 12.7%, 20.1%, 17.1%, 18.4% and 3.5%, respectively, whereas in the PI-RADS 5 group the rates were 7.4%, 6.8%, 22.3%, 22.3%, 26.4%, and 14.9%, respectively. The difference was statistically significant (P<0.001). The detection rates of PCa and CsPCa in the PI-RADS 4 group [71.8% (265/369) vs. 59.1% (218/369), P<0.001] were lower than those of the PI-RADS 5 group [92.6% (137/148) vs. 85.8% (127/148), P<0.001]. In the PI-RADS 4 group, the proportion of patients classified into WHO/ISUP 4-5 grade groups was lower than that of patients in the PI-RADS 5 group [22.0% (81/369) vs 41.2% (61/148) (P<0.001)]. The detection rates of PCa and CsPCa in the PSA<10 ng/ml stratification were less than that in the PSA 10-20 ng/ml stratification[74.1% (281/379) vs. 87.7% (121/138), P=0.001], and [60.9% (231/379) vs. 82.6% (114/138), P<0.001]. For patients with PSA<10 ng/ml, the detection rates of PCa and CsPCa in the PI-RADS 4 group were less than those in the PI-RADS5 group [70.9% (217/306) vs. 87.7% (64/73), P=0.003], and [56.2% (172/306) vs. 80.8% (59/73), P<0.001]. For those with a PSA value of 10-20 ng/ml, the detection rates of PCa and CsPCa in the PI-RADS 4 group were less than those in the PI-RADS 5 group [76.2% (48/63) vs. 97.3% (73/75), P<0.001], and [73.0% (46/63) vs. 90.7% (68/75), P=0.006]. There were statistically significant differences in the proportions of patients with prostate negative biopsy and those falling into WHO/ISUP grade groups 1, 2, 3, 4, or 5 (P<0.001) between the PI-RADS 4 group and the PI-RADS 5 group in both stratifications. Conclusions: In this study, the detection rates of CsPCa and PCa in the PI-RADS 4 group were less than those in the PI-RADS 5 group. With the increase of PI-RADS scores, the detection rate of high-grade PCa increased. The same results held for patients with PSA<10 ng/ml or with PSA 10-20 ng/ml.

The Value of Prostate-Specific Antigen Density in Combination with Lesion Diameter for the Accuracy of Prostate Cancer Prediction in Prostate Imaging-Reporting and Data System 3 Prostate Lesions

Introduction: The aim of the study was to investigate the value of prostate-specific antigen density (PSAD) and lesion diameter (LD) combination in prostate cancer (PCa) detection. Methods: 181 patients who were detected to have prostate imaging-reporting and data system (PI-RADS) 3 lesions in mpMRI and underwent prostate biopsies were included in the study. Demographic, clinical, and pathological data of all patients were evaluated. The patients were divided into four groups according to PSAD and LD status (PSAD <0.15 ng/mL/cc + LD <1 cm, PSAD <0.15 ng/mL/cc + LD ≥1 cm, PSAD ≥0.15 ng/mL/cc + LD <1 cm, and PSAD ≥0.15 ng/mL/cc + LD ≥1 cm). Diagnostic ability for PCa and clinical significant PCa (csPCa) was evaluated by PSAD and LD. Results: PSAD ≥0.15 ng/mL/cc (OR = 6; 95% Cl = 2.847–12.647; p < 0.001), LD ≥1 cm (OR = 7.341; 95% confidence interval [CI] = 2.91–18.52; p < 0.001), and combination of PSAD ≥0.15 ng/mL/cc and LD ≥1 cm (OR = 10.023; 95% CI = 4.32–23.252; p < 0.001) were associated with PCa detection rates. The most sensitivity, specificity, negative, and positive predictive values were found in PSAD ≥0.15 ng/mL/cc + LD ≥1 cm group for both PCa and csPCa detection (48.8%, 92%, 85.2%, and 65.6% for any PCa detection; 66.7%, 85.2%, 97.3%, and 24.2% for csPCa detection, respectively). Conclusion: The presence of PSAD ≥0.15 ng/mL/cc or LD ≥1 cm in mpMRI of patients with PI-RADS 3 lesions is associated significantly with the finding of PCa and particularly with the detection of csPCa.

Optimal size threshold for PIRADSv2 category 5 upgrade and its positive predictive value: is it predictive of “very high” likelihood of clinically-significant cancer?

To identify the optimal size metric and threshold for Prostate Imaging Reporting and Data System (PIRADS) 5 upgrade, calculate its positive predictive value (PPV) for clinically-significant prostate cancer (csPCA), and determine if it is indicative of a "very high" likelihood of csPCA. One hundred and forty-three PIRADS 4 or 5 lesions were evaluated. Lesion diameters were used to calculate lesion volume (LV). Pearson correlation between maximum lesion diameter (MLD) and LV was calculated. Area under the curve (AUC) for discriminating csPCA (Gleason grade ≥ 3+4) was calculated using MLD and LV. Optimal size thresholds (using Youden index) and highly predictive size thresholds were identified for the whole prostate (WP), peripheral zone (PZ), and transitional zone (TZ). There was high correlation between MLD and LV (r=0.77-0.81), with comparable AUCs for MLD and LV in the identification of csPCA in the WP (0.73, 0.72), PZ (0.73, 0.73), and TZ (0.79, 0.75). Optimal MLD thresholds were 1.4, 1.4, and 1.6 cm in the WP, PZ, and TZ respectively, with PPVs of 76%, 81%, and 69%, respectively. An MLD threshold of 2.7 cm would be needed in the WP to achieve a PPV approaching 90%, with sensitivity decreasing to 10%. There is high correlation between MLD and LV with comparable discrimination of csPCA using each. PIRADSv2's 1.5 cm MLD threshold is near the optimal threshold for PIRADS 5 upgrade but has moderate PPV. A much higher threshold would be needed to increase its PPV, with significant sacrifice in sensitivity.

Significant Prostate Cancer in Patients with PI-RADS Category 3 Lesions: A Single-Center, Retrospective Cohort Study.

The Prostate Imaging-Reporting and Data System (PI-RADS) category 3 is the most ambiguous lesion with a variable clinically significant prostate cancer (CsPCa) detection rate. Prostate-specific antigen density (PSAD) has been investigated as an adjunctive factor to improve the diagnostic efficiency of PI-RADS categories. This study aimed to investigate the utility of PSAD as an adjunctive factor in predicting CsPCA risk in patients with PI-RADS 3 lesions. The patients with an initial PI-RADS 3 category lesion (n=142) scheduled for systematic and magnetic resonance imaging-guided prostate biopsy between 2018 and 2022 were retrospectively evaluated. Demographic and clinical variables, including PSAD, were collected. The rate of CsPCa was the primary outcome. The impact of PSAD on the CsPCa detection rate was the secondary outcome. The median age was 62 years. The rate of CsPCa was 8.5% (n=12). The patients with CsPCa have significantly lower prostate volüme and higher PSAD levels than those without CsPCa (p=0.016 and p=0.012). The cut-off values of PSAD in predicting CsPCa in all PI-RADS 3 patients and patients with CsPCa and clinically insignificant prostate cancer (n=26) were ≥0.181 ng/ml2. The sensitivity and specificity values for PSAD ≥0.181 ng/ml2 were of 75% (95% CI: 42.8%-94.5%) and 81.5% (95% CI: 73.4%-88.0%) in predicting CsPCa among PI-RADS 3 category. Conclusion: PSAD values higher than 0.181 ng/ml2 can be used as an adjunctive clinical parameter in predicting CsPCa in patients with PI-RADS 3 lesions and differentiating CsPCa from clinically insignificant prostate cancer cases.

Relationship between Eccentricity and Volume Determined by Spectral Algorithms Applied to Spatially Registered Bi-Parametric MRI and Prostate Tumor Aggressiveness: A Pilot Study.

(1) Background: Non-invasive prostate cancer assessments using multi-parametric MRI are essential to the reliable detection of lesions and proper management of patients. While current guidelines call for the administration of Gadolinium-containing intravenous contrast injections, eliminating such injections would simplify scanning and reduce patient risk and costs. However, augmented image analysis is necessary to extract important diagnostic information from MRIs. Purpose: This study aims to extend previous work on the signal to clutter ratio and test whether prostate tumor eccentricity and volume are indicators of tumor aggressiveness using bi-parametric (BP)-MRI. (2) Methods: This study retrospectively processed 42 consecutive prostate cancer patients from the PI-CAI data collection. BP-MRIs (apparent diffusion coefficient, high b-value, and T2 images) were resized, translated, cropped, and stitched to form spatially registered BP-MRIs. The International Society of Urological Pathology (ISUP) grade was used to judge cases of prostate cancer as either clinically significant prostate cancer (CsPCa) (ISUP ≥ 2) or clinically insignificant prostate cancer (CiPCa) (ISUP < 2). The Adaptive Cosine Estimator (ACE) algorithm was applied to the BP-MRIs, followed by thresholding, and then eccentricity and volume computations, from the labeled and blobbed detection maps. Then, univariate and multivariate linear regression fittings of eccentricity and volume were applied to the ISUP grade. The fits were quantitatively evaluated by computing correlation coefficients (R) and p-values. Area under the curve (AUC) and receiver operator characteristic (ROC) curve scores were used to assess the logistic fitting to CsPCa/CiPCa. (3) Results: Modest correlation coefficients (R) (>0.35) and AUC scores (0.70) for the linear and/or logistic fits from the processed prostate tumor eccentricity and volume computations for the spatially registered BP-MRIs exceeded fits using the parameters of prostate serum antigen, prostate volume, and patient age (R~0.17). (4) Conclusions: This is the first study that applied spectral approaches to BP-MRIs to generate tumor eccentricity and volume metrics to assess tumor aggressiveness. This study found significant values of R and AUC (albeit below those from multi-parametric MRI) to fit and relate the metrics to the ISUP grade and CsPCA/CiPCA, respectively.

The Prevalence of Prostate Cancer in Biopsy Samples of Lesions with PI-RADS 2 Score in Multiparametric Magnetic Resonance Imaging: A Cross-sectional Study

Background: Prostate cancer (PC) is one of the most common cancers worldwide. Recently, multiparametric magnetic resonance imaging (mpMRI) has been used to diagnose PC in suspected patients. Prostate Imaging Reporting &amp; Data System (PI-RADS) was developed and applied as a criterion for detecting lesions suspicious of PC. Various studies have been conducted to determine the negative predictive value of non-suspicious mpMRI (PI-RADS 1 or 2). However, the results of these studies have been limited and different. Objectives: This study was conducted to determine the PC rate in patients with PI-RADS 2 lesions in mpMRI and the factors related to clinically significant prostate cancer (CsPC) diagnosis in these lesions. Methods: By referring to the archive department of Shahada-e-Tajrish, Rasul-e-Akram, Treata, and Payambaran hospitals, among the patients suspected of PC who underwent biopsy and had elevated prostate-specific antigen (PSA) serum levels, the prostate biopsy samples of 330 patients were consecutively included in the study. Frequency of samples diagnosed with PC and its histological characteristics, including mass location, Gleason score (GS), Gleason group (GG), percentage of G4 and G5 cells, sample size, percentage of involvement of sample with cancer tissue, and invasion to the surrounding tissues were examined. Adenocarcinoma samples were divided into low-risk, intermediate-to-high-risk groups based on D'Amico criteria and the relationship between age, PSA total (PSAt), PSA density (PSAd), prostate volume, and the presence of a PI-RADS 3 or 4 lesion at the same time with the rate of diagnosed CsPCs were reviewed. Results: The data from 709 tissue samples were collected, among which 249 were from the right inner part, 249 were from the left inner part, and 211 biopsy samples were from the peripheral portion of the prostate. Among these, 390 tissue samples in mpMRI studies were PI-RADS 2, and 319 were PI-RADS 3 or 4. The mean age of the patients was 64.78 ± 37.55. The mean PSAd, PSAt, and prostate volume were 0.15 ± 0.11, 8.73 ± 6.43, and 61.18 ± 25.76, respectively. Seventy-five samples were diagnosed with adenocarcinoma, of which 48% are in PI-RADS group 2, and 52% are in PI-RADS group 3 - 4 (P-value = 0.263). Comparing the histological characteristics of adenocarcinoma samples between the two groups showed that only the amount of GG was significantly higher in the samples with PI-RADS 3 and 4 (P-value = 0.035). Adenocarcinomas diagnosed in 72.2% of cases in PI-RADS 2 samples and 84.6% of PI-RADS 3 and 4 samples were clinically significant, and no significant difference was seen between the two groups (P-value = 0.38). The amount of PSAt in PI-RADS 2 adenocarcinoma samples was significantly higher in clinically significant carcinomas than in low-risk carcinomas (P-value = 0.045). Conclusions: The results of the present study showed that PI-RADS 2 lesions should be considered for biopsy when there is clinical suspicion of PC. PSA levels can effectively determine the need for biopsy in PI-RADS 2 lesions.

68Ga-PSMA PET/CT-based multivariate model for highly accurate and noninvasive diagnosis of clinically significant prostate cancer in the PSA gray zone

BackgroundThe prostate-specific antigen (PSA) has been widely used in screening and early diagnosis of prostate cancer (PCa). However, in the PSA grey zone of 4–10 ng/ml, the sensitivity and specificity for diagnosing PCa are limited, resulting in considerable number of unnecessary and invasive prostate biopsies, which may lead to potential overdiagnosis and overtreatment. We aimed to predict clinically significant PCa (CSPCa) by combining the maximal standardized uptake value (SUVmax) based on 68Ga‑PSMA PET/CT and clinical indicators in men with gray zone PSA levels.Methods81 patients with suspected PCa based on increased serum total PSA (TPSA) levels of 4 − 10 ng/mL who underwent transrectal ultrasound/magnetic resonance imaging (MRI)/PET fusion-guided biopsy were enrolled. Among them, patients confirmed by histopathology were divided into the CSPCa group and the non-CSPCa group, and data on PSA concentration, prostate volume (PV), PSA density (PSAD), free PSA (FPSA)/TPSA, Prostate Imaging-Reporting and Data System version 2.1 (PI-RADS v2.1) score, 68Ga-PSMA PET/CT imaging evaluation results and SUVmax were compared. Multivariate logistic regression analysis was performed to identify the independent predictors for CSPCa, thereby establishing a predictive model based on SUVmax that was evaluated by analyzing the receiver operating characteristic (ROC) curve and decision curve analysis.ResultsCompared to non-CSPCa, CSPCa patients had smaller PVs (median, 31.40 mL), lower FPSA/TPSA (median, 0.12), larger PSADs (median, 0.21 ng/mL2) and higher PI-RADS scores (P < 0.05). The prediction model comprising 68Ga-PSMA PET/CT maximal standardized uptake value, PV and FPSA/TPSA had the highest AUC of 0.927 compared with that of other predictors alone (AUCs of 0.585 for PSA, 0.652 for mpMRI and 0.850 for 68Ga-PSMA PET/CT). The diagnostic sensitivity and specificity of the prediction model were 86.21% and 86.54%, respectively.ConclusionGiven the low diagnostic accuracy of regular PSA tests, a new prediction model based on the 68Ga-PSMA PET/CT SUVmax, PV and FPSA/TPSA was developed and validated, and this model could provide a more satisfactory predictive accuracy for CSPCa. This study provides a noninvasive prediction model with high accuracy for the diagnosis of CSPCa in the PSA gray zone, thus may be better avoiding unnecessary biopsy procedures.

Yield of second-round MRI targeted ultrasound-guided fusion prostate biopsy after initial first-round targeted biopsy.

We aimed to determine the yield of second-round magnetic resonance imaging-ultrasound (MRI-US) fusion biopsy and factors that may predict eventual clinically significant (CS) prostate cancer (PCa) diagnosis. From 2013 to 2021, 85 men underwent second-round MRI-US fusion biopsy of 92 lesions (47.8% [44/92] peripheral zone and 52.2% [48/92] transition zone). Patient age, prostate-specific antigen (PSA), PSA density (PSAD), size/location of lesions, ADC value, Prostate Imaging-Reporting and Data System (PI-RADS), and PRECISE scores were recorded and compared to histopathological diagnosis (International Society of Urological Pathology [ISUP] grade-group 1 PCa, CS PCa=ISUP grade group ≥2 PCa) using logistic regression. Mean patient age, PSA, and PSAD were 64±7 years, 8.5±7.0 ng/ml, and 0.17±0.11, respectively. Results from first-round targeted biopsy were 63% (58/92) negative and 37% (34/92) clinically insignificant (grade group 1) PCa. Overall, second-round targeted biopsy identified 25% (23/92) CS PCa (grade group 2, n=19; grade group 3, n=4). Considering only lesions with initial negative targeted-biopsy results (n=58), 21% (12/58; grade group 2, n=8; grade group 3, n=4) CS PCa and 13 grade group 1 PCa were diagnosed at second-round biopsy. There was no difference in PSA (p=0.564), size (p=0.595), location (p=0.293), or PI-RADS score (p=0.342) of lesions by eventual CS PCa diagnosis. PSAD (0.2±1.4 vs. 0.16±0.10, p=0.167), ADC (0.748±0.199 vs. 0.833±0.257, p=0.151), and PRECISE score (p<0.01) showed a trend towards association or association with eventual CS PCa diagnosis. Repeat second-round targeted MRI-US fusion biopsy yielded CS PCa diagnosis in the targeted biopsy specimen in approximately 20% of patients in our study. PRECISE score may be a useful marker to help predict which patients require second-round biopsy.

The diagnostic effectiveness of serum sialic acid predicts both qualitative and quantitative prostate cancer in patients with prostate-specific antigen between 4 and 20 ng/mL.

This study aimed to evaluate the predictive value of the serum biochemical index, including alkaline phosphatase (AKP), lactate dehydrogenase (LDH), α-L-fucosidase (AFU), serum sialic acid (SA), and fibrinogen (FIB), for prostate cancer (PCa) and clinically significant prostate cancer (CSPCa) in patients with a prostate-specific antigen (PSA) value between 4 and 20 ng/mL. This study retrospectively examined the clinical data of 408 eligible patients who underwent prostate biopsies in our hospital between March 2015 and July 2022. CSPCa was defined as a "Gleason grade group of≥2". For analyzing the association between PCa/CSPCa and serum biochemical index, univariable logistic regression and multivariable logistic regression were conducted. Based on the multivariable logistic regression model, we constructed models and compared the area under the curve (AUC). We generated the nomogram, the ROC curve, the DCA curve, and the calibration curve for PCa. Overall, we studied 271 patients with PCa (including 155 patients with CSPCa) and 137 non-PCa patients. Patients with PCa were more likely to consume alcohol, have higher total PSA (TPSA) values, and have lower free PSA (FPSA) and free/total PSA (f/T) values. There were higher TPSA values and lower f/T values in the CSPCa group when compared with the non-CSPCa group. The univariate logistic regression analyses did not show significant results. However, AKP, AFU, SA, TPSA, and FPSA all retain significant significance when all factors are included in multifactor logistic regression analysis. This finding suggests that the exposure factor exhibited an independent effect on the outcome after controlling for other factors, including the potential confounding effects that may have been underestimated. Through ROC curves, we found that SA and TPSA levels are more powerful predictors. In contrast, there is a lack of excellent predictive value for PCA and CSPCa using Age, AFU, FIB, and FPSA. In our study, serum biochemical index is a potential prediction tool for PCa and CSPCa for patients with PSA values between 4 and 20 ng/mL. Additionally, the new serum biochemical index SA is also useful when diagnosing PCa and CSPCa, as we conclude in our study.

Transperineal US-MRI Fusion-Guided Biopsy for the Detection of Clinical Significant Prostate Cancer: A Systematic Review and Meta-Analysis Comparing Cognitive and Software-Assisted Technique

Introduction: We aimed to find potential differences in clinically significant prostate cancer (csPCa) detection rates between transperineal software-assisted fusion biopsy (saFB) and cognitive fusion biopsies (cFB). Methods: A systematic review of the literature was performed to identify comparative studies using PubMed, EMBASE, and Scopus according to the PICOS criteria. Cancer detection and complication rates were pooled using the Cochran–Mantel–Haenszel method with the random effect model and reported as odds ratios (ORs), 95% confidence intervals (CI), and p-values. A meta-analysis was performed using Review Manager (RevMan) 5.4 software by Cochrane Collaboration. The quality assessment of the included studies was performed using the Cochrane Risk of Bias tool, using RoB 2 for randomized studies and ROBINS-I for retrospective and nonrandomized ones. Results: Eight studies were included for the meta-analysis, including 1149 cases in software-based and 963 cases in cognitive fusion biopsy. The detection rates of csPCa were similar between the two groups (OR 1.01, 95% CI 0.74–1.37, p = 0.95). Study heterogeneity was low (I2 55%). Conclusion: There is no actual evidence of the superiority of saFB over cFB in terms of the csPCa detection rate. Operator experience and software availability can drive the choice of one fusion technique over the other.

Exploration of the diagnostic capacity of PSAMR combined with PI-RADS scoring for clinically significant prostate cancer and establishment and validation of the Nomogram prediction model.

The objective of this investigation was to explore the diagnostic capability of Prostate Specific Antigen Mass Ratio (PSAMR) combined with Prostate Imaging Reporting and Data System (PI-RADS) scoring for clinically significant prostate cancer (CSPC), develop and validate a Nomogram prediction model for the probability of prostate cancer occurrence in patients who have not undergone prostate biopsy. Initially, we retrospectively collected clinical and pathological data of patients who underwent trans-perineal prostate puncture at Yijishan Hospital of Wanan Medical College from July 2021 to January 2023. Through logistic univariate and multivariate regression analysis, independent risk factors for CSPC were determined. Receiver Operating Characteristic (ROC) curves were generated to compare the ability of different factors for diagnosis of CSPC. Then, we split the dataset into a training set and validation set, compared their heterogeneity, and developed a Nomogram prediction model based on the training set. Finally, we validated the Nomogram prediction model in terms of discrimination, calibration, and clinical usefulness. Logistic multivariate regression analysis illustrated that age [64-69 (OR = 2.736, P = 0.029); 69-75 (OR = 4.728, P = 0.001); > 75 (OR = 11.344, P < 0.001)], PSAMR [0.44-0.73 (OR = 4.144, P = 0.028); 0.73-1.64(OR = 13.022, P < 0.001); > 1.64(OR = 50.541, P < 0.001)], and PI-RADS score [4 points (OR = 7.780, P < 0.001); 5 points (OR = 24.533, P < 0.001)] were independent risk factors for CSPC. The Area Under the Curve (AUC) of the ROC curves of PSA, PSAMR, PI-RADS score, and PSAMR combined with PI-RADS score were respectively 0.797, 0.874, 0.889, and 0.928. The performance of PSAMR and PI-RADS score for diagnosis of CSPC was superior to PSA, but inferior to PSAMR combined with PI-RADS. Age, PSAMR, and PI-RADS were included in the Nomogram prediction model. The AUCs of the training set ROC curve and the validation set ROC curve were 0.943 (95% CI 0.917-0.970) and 0.878 (95% CI 0.816-0.940), respectively, in the discrimination validation. The calibration curve showed good consistency, and the decision analysis curve suggested the model had good clinical efficacy. We found that PSAMR combined with PI-RADS scoring had a strong diagnostic capability for CSPC, and provided a Nomogram prediction model to predict the probability of prostate cancer occurrence combined with clinical data.

Reconciling discordance between PI-RADS 4 lesions and targeted biopsy: Early experience of a multidisciplinary quality improvement protocol with PI-RADS 4 subcategorization

PurposePI-RADS 4 lesions are considered to have a “high” likelihood of clinically-significant prostate cancer (csPCa). However, patients undergoing targeted biopsy have a range of histologic findings. Understanding discordant cases is critical to improve diagnostic accuracy and inform subsequent management. We studied early findings from implementation of a multidisciplinary Quality Improvement (QI) protocol for reconciling discordance and evaluate the potential heterogeneity of PI-RADS 4. MethodsPatients with mpMRI PI-RADS 4 lesions undergoing fusion-targeted biopsy from January 2017 to May 2021 were retrospectively reviewed. The discordant targeted biopsy pathology (benign/GG1) was evaluated utilizing a QI protocol and all lesions were subcategorized based on ADC values. Positive Predictive Value (PPV) for PI-RADS 4 lesions overall and the Cancer Detection Rate (CDR) for subcategorized lesions were calculated. Results248 patients with 286 lesions were reviewed. Prior to re-review, PI-RADS 4 PPV for ≥ GG1 and ≥ GG2 lesions were 0.55 and 0.34, increasing to 0.67 and 0.43 following reconciliation. Lesion subcategorization based on ADC value as higher suspicion (4+) and lower suspicion (4-) resulted in 158 and 117 lesions, with reverse-fusion analysis revealing that 61% and 17% of lesions contained csPCa, respectively. Subgroup analysis among PI-RADS 4+ lesions led to an increase in the CDR to 75% and 61% for ≥ GG1 and ≥ GG2. ConclusionUse of multidisciplinary QI protocol to review discordance cases of PI-RADS 4 improves diagnostic accuracy and guides subsequent management. Our findings highlight the known heterogeneity of this category with reference to csPCa CDR, suggesting the potential value of PI-RADS 4 subcategorization.

Relationship between lower urinary tract symptoms (LUTS) and prostate cancer: A persistent myth

Background:The presence of lower urinary tract symptoms (LUTS) is described as an early symptom of prostate cancer in some patient guidelines; however, a statistical association has never been established.Methods:This study was conducted using a prospective electronic database at a single tertiary institution between January 2015 and November 2017. LUTS were assessed using the International Prostate Symptom Score (IPSS), and prostate cancer was graded according to the International Society of UroPathologists (ISUP) grading system. The association between IPSS and Grade Group was tested using parametric one-way analysis of variance (ANOVA) with post hoc analysis using Tukey’s honestly significant difference (Tukey’s HSD).Results:A total of 611 men attended the One-Stop Prostate Clinic (OSPC) and IPSSs were available for 557 men. Overall, 46% had mild LUTS (IPSS: 1–7), 38% had moderate LUTS (IPSS: 8–19) and 16% had severe LUTS (IPSS: 20–35). Almost 85% proceeded to have transrectal ultrasound (TRUS) prostate biopsies, and clinically significant prostate cancer (CSPC) was detected in 37% with mild LUTS, 35% with moderate LUTS and 42% with severe LUTS. Correlation between histopathology and IPSSs was assessed in all 78.8% of men who had IPSS data available and underwent prostate biopsies.Conclusion:This large series did not establish any correlation between LUTS and prostate cancer in men undergoing investigation for the suspicion of prostate cancer.Level of evidence:Not applicable

O044 The PI-RADS 3 lesion. Can we use a higher PSA density to reassure patients with MRI PI-RADS 3 score?

Abstract Introduction Prostate cancer has the second highest cancer incidence worldwide. Diagnosis of clinically significant prostate cancer (CSPC), defined as Gleason ≥3+4 or ≥ISUP 2, is underpinned by Prostate Imaging-Report and Data System (PI-RADS) scoring on MRI and serum PSA, with confirmation with prostate biopsy. Positive predictive value of PI-RADS 3 for CSPC is 13%. A PSA-density threshold of 0.15-0.18 ng/mL/cc is commonly utilised to justify biopsy vs PSA monitoring for PI-RADS 3. Methods Retrospective analysis of MRI, PSA and pathology results for consecutive patients undergoing diagnostic investigations for prostate cancer between November 2021 and March 2022. Results Average age of 200 males was 66.4 (SEM 0.62). MRIs reported 6% ≤PI-RADS 2, 61.5% PI-RADS 3 and 32.5% ≥PI-RADS 4. Among the PI-RADS 3 (n=123), average prostate volume was 70.0cc (SEM 3.21) and PSA density was 0.12 (SEM 0.01). 17.9% PI-RADS 3 patients underwent prostate biopsy although just 8.9% had PSA-density &amp;gt;0.18 ng/mL/cc. 40.9% biopsies identified CSPC with average PSA-density 0.23 (SEM 0.06). Conversely, for the 59.1% biopsies with no cancer or non-CSPC, average PSA-density was 0.14 (SEM 0.03) (p 0.078). Conclusion Almost 3/5 prostate biopsies carried out in patients with PI-RADS 3 lesions revealed non-CSPC or no cancer. There was a notable difference in PSA-density among PI-RADS 3 patients with biopsy-proven CSPC vs. non-CSPC or benign histology. Based on our institutions experience, we would propose a 0.2 ng/mL/cc PSA-density threshold when recommending biopsy over PSA monitoring for MRI reported PI-RADS 3 to improve patient selection for biopsy to identify CSPC.