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Background: The majority of men referred with a raised PSA for suspected prostate cancer will receive unnecessary tertiary investigations including MRI and biopsy. Here, we compared different types of biomarkers to refine tertiary referrals and when different definitions of clinically significant cancer were used. Methods: Data and samples from 798 men referred for a raised PSA (≥ 3 ng/mL) and investigated through an MRI-guided biopsy pathway were accessed for this study. Bloods were acquired pre-biopsy for liquid biomarkers and germline DNA. Variables explored included PSA + Age (base model), free/total PSA (FTPSA), Prostate Health Index (phi), PSA density (PSAd), polygenic risk score (PRS) and MRI (≥ LIKERT 3). Different diagnostic endpoints for significant cancer (≥ grade group 2 [GG2], ≥ GG3, ≥ Cambridge Prognostic Group 2 [CPG2], ≥ CPG3) were tested. The added value of each biomarker to the base model was evaluated using logistic regression models, AUC and decision curve analysis (DCA) plots. Results: The median age and PSA was 65 years and 7.13 ng/mL respectively. Depending on definition of clinical significance, ≥ grade group 2 (GG2) was detected in 57.0% (455/798), ≥ GG3 in 27.5% (220/798), ≥ CPG2 in 61.6% (492/798) and ≥ CPG3 in 42.6% (340/798). In the pre-MRI context, the PSA + Age (base model) AUC for prediction of ≥ GG2, ≥ GG3, ≥ CPG2 and ≥ CPG3 was 0.66, 0.68, 0.70 and 0.75 respectively. Adding phi and PSAd to base model improved performance across all diagnostic endpoints but was notably better when the composite CPG prognostic score was used: AUC 0.82, 0.82, 0.83, 0.82 and AUC 0.74, 0.73, 0.79, 0.79 respectively. In contrast, neither FTPSA or PRS scores improved performance especially in detection of ≥ GG3 and ≥ CPG3 disease. Combining biomarkers did not alter results. Models using phi and PSAd post-MRI also improved performances but again benefit varied with diagnostic endpoint. In DCA analysis, models which incorporated PSAd and phi in particular were effective at reducing use of MRI and/or biopsies especially for ≥ CPG3 disease. Conclusion: Incorporating phi or PSAd can refine and tier who is referred for tertiary imaging and/or biopsy after a raised PSA test. Incremental value however varied depending on the definition of clinical significance and was particularly useful when composite prognostic endpoints are used. [ABSTRACT FROM AUTHOR]

Abstract Background The majority of men referred with a raised PSA for suspected prostate cancer will receive unnecessary tertiary investigations including MRI and biopsy. Here, we compared different types of biomarkers to refine tertiary referrals and when different definitions of clinically significant cancer were used. Methods Data and samples from 798 men referred for a raised PSA (≥ 3 ng/mL) and investigated through an MRI-guided biopsy pathway were accessed for this study. Bloods were acquired pre-biopsy for liquid biomarkers and germline DNA. Variables explored included PSA + Age (base model), free/total PSA (FTPSA), Prostate Health Index (phi), PSA density (PSAd), polygenic risk score (PRS) and MRI (≥ LIKERT 3). Different diagnostic endpoints for significant cancer (≥ grade group 2 [GG2], ≥ GG3, ≥ Cambridge Prognostic Group 2 [CPG2], ≥ CPG3) were tested. The added value of each biomarker to the base model was evaluated using logistic regression models, AUC and decision curve analysis (DCA) plots. Results The median age and PSA was 65 years and 7.13 ng/mL respectively. Depending on definition of clinical significance, ≥ grade group 2 (GG2) was detected in 57.0% (455/798), ≥ GG3 in 27.5% (220/798), ≥ CPG2 in 61.6% (492/798) and ≥ CPG3 in 42.6% (340/798). In the pre-MRI context, the PSA + Age (base model) AUC for prediction of ≥ GG2, ≥ GG3, ≥ CPG2 and ≥ CPG3 was 0.66, 0.68, 0.70 and 0.75 respectively. Adding phi and PSAd to base model improved performance across all diagnostic endpoints but was notably better when the composite CPG prognostic score was used: AUC 0.82, 0.82, 0.83, 0.82 and AUC 0.74, 0.73, 0.79, 0.79 respectively. In contrast, neither FTPSA or PRS scores improved performance especially in detection of ≥ GG3 and ≥ CPG3 disease. Combining biomarkers did not alter results. Models using phi and PSAd post-MRI also improved performances but again benefit varied with diagnostic endpoint. In DCA analysis, models which incorporated PSAd and phi in particular were effective at reducing use of MRI and/or biopsies especially for ≥ CPG3 disease. Conclusion Incorporating phi or PSAd can refine and tier who is referred for tertiary imaging and/or biopsy after a raised PSA test. Incremental value however varied depending on the definition of clinical significance and was particularly useful when composite prognostic endpoints are used.

Aim: Pathological discordance between biopsy and radical prostatectomy (RP) remains a critical issue in determining appropriate treatment for prostate cancer (PCa). With this study, we aimed to evaluate the role of prostate specific antigen (PSA) density in predicting pathological discordance in low-risk PCa. Methods: Data from 95 patients who underwent RP for low-risk PCa with Prostate Imaging Reporting and Data System 1-2 on multiparametric magnetic resonance imaging (MRI) were retrospectively analyzed in this cross-sectional study conducted between January and December 2023. The patients were divided into two groups according on biopsy and robotic-assisted laparoscopic prostatectomy pathology. The “compatible group” was defined as patients with no difference in International Society of Urological Pathology grade and tumor stage, other patients were defined as “incompatible group”. The cut-off value for PSA density to predict the presence of pathological discordance was calculated by receiver operating-characteristic curve. Results: Thirty eight (40%) patients were in the compatible group. No difference was found in serum PSA value between the groups (p=0.440), and a significant difference was found in prostate volume and PSA density (p=0.04 and p=0.001, respectively). The predictive cut-off value of PSA density was calculated as 0.088 ng/mL/cc (area under the curve: 0.729) (p

Background: MRI fusion prostate biopsy has improved the detection of clinically significant prostate cancer (CSC). Continued refinements in predicting the pre-biopsy probability of CSC are essential for optimal patient counseling. We investigated potential factors related to improved cancer detection rates (CDR) of CSC in patients with PI-RADS ≥ 3 lesions. Methods: The pathology of 980 index lesions in 980 patients sampled by transrectal mpMRI-targeted prostate biopsy across four medical centers between 2017–2020 was reviewed. PI-RADS lesion distribution included 291 PI-RADS-5, 374 PI-RADS-4, and 315 PI-RADS-3. We compared CDR of index PI-RADS ≥ 3 lesions based on location (TZ) vs. (PZ), PSA density (PSAD), and history of prior negative conventional transrectal ultrasound-guided biopsy (TRUS). Results: Mean age, PSA, prostate volume, and level of prior negative TRUS biopsy were 66 years (43–90), 7.82 ng/dL (5.6–11.2), 54 cm3 (12–173), and 456/980 (46.5%), respectively. Higher PSAD, no prior history of negative TRUS biopsy, and PZ lesions were associated with higher CDR. Stratified CDR highlighted significant variance across subgroups. CDR for a PI-RADS-5 score, PZ lesion with PSAD ≥ 0.15, and prior negative biopsy was 77%. Conversely, the CDR rate for a PI-RADS-4 score, TZ lesion with PSAD < 0.15, and prior negative biopsy was significantly lower at 14%. Conclusions: For index PI-RADS ≥ 3 lesions, CDR varied significantly based on location, prior history of negative TRUS biopsy, and PSAD. Such considerations are critical when counseling on the merits and potential yield of prostate needle biopsy.

Aim: Pathological discordance between biopsy and radical prostatectomy (RP) remains a critical issue in determining appropriate treatment for prostate cancer (PCa). With this study, we aimed to evaluate the role of prostate specific antigen (PSA) density in predicting pathological discordance in low-risk PCa. Methods: Data from 95 patients who underwent RP for low-risk PCa with Prostate Imaging Reporting and Data System 1-2 on multiparametric magnetic resonance imaging (MRI) were retrospectively analyzed in this cross-sectional study conducted between January and December 2023. The patients were divided into two groups according on biopsy and robotic-assisted laparoscopic prostatectomy pathology. The "compatible group" was defined as patients with no difference in International Society of Urological Pathology grade and tumor stage, other patients were defined as "incompatible group". The cut-off value for PSA density to predict the presence of pathological discordance was calculated by receiver operating-characteristic curve. Results: Thirty eight (40%) patients were in the compatible group. No difference was found in serum PSA value between the groups (p=0.440), and a significant difference was found in prostate volume and PSA density (p=0.04 and p=0.001, respectively). The predictive cut-off value of PSA density was calculated as 0.088 ng/mL/cc (area under the curve: 0.729) (p<0.001). The sensitivity, specificity, positive and negative predictive values for this 0.088 ng/mL/cc value were 75.4%, 63.2%, 67.2% and 70.3%, respectively. Conclusion: Prostate specific antigen density was found to have good performance in predicting pathological discordance in low-risk PCa patients with no pathological lesions detected by multiparametric MRI. [ABSTRACT FROM AUTHOR]

Purpose: Despite advancements in prostate multiparametric magnetic resonance imaging (mpMRI) and fusion biopsy (FB), the management of incidental prostate cancer (IPCa) after surgery for benign prostatic obstruction (BPO) remains unclear. The aim of this retrospective study is to determine the prevalence of IPCa in our cohort and identify potential predictors for its occurrence. Methods: We enrolled patients underwent TURP or simple prostatectomy for BPO at our high-volume center between January 2020-December 2022. Data on age, pre-operative total PSA (tPSA) and PSA density (PSAd) levels, prostate volume, previous MRI, biopsies, specimen weight, rates of positive tissue slices, ISUP score and three-month tPSA were collected. Results: Of 454 patients with negative digital rectal examination who underwent BPO surgery, 74 patients (16.3%) were found to have IPCa. Of these, 33 patients (44.6%) had undergone previous mpMRI. Among the patients who had mpMRI, 23 had negative mpMRI results for suspected prostate cancer, while 10 had positive mpMRI findings (PIRADS ≥ 3) but no evidence of tumor upon FB. KW analysis indicates that PSAd was statistically associated with higher ISUP score, while at univariable regression analysis negative mpMRI (p = 0.03) was the only potential predictor for IPCa. Conclusions: Among the ISUP groups, PSAd showed a correlation with the tumor, while negative mpMRI was protective against clinically significant PCa. In the era of mpMRI and FB, the IPCa rates found at our center is higher than reported in existing literature and if it were confirmed with further studies, maybe there is a need for expansion in urology guidelines. [ABSTRACT FROM AUTHOR]

Background: MRI fusion prostate biopsy has improved the detection of clinically significant prostate cancer (CSC). Continued refinements in predicting the pre-biopsy probability of CSC are essential for optimal patient counseling. We investigated potential factors related to improved cancer detection rates (CDR) of CSC in patients with PI-RADS ≥ 3 lesions. Methods: The pathology of 980 index lesions in 980 patients sampled by transrectal mpMRI-targeted prostate biopsy across four medical centers between 2017–2020 was reviewed. PI-RADS lesion distribution included 291 PI-RADS-5, 374 PI-RADS-4, and 315 PI-RADS-3. We compared CDR of index PI-RADS ≥ 3 lesions based on location (TZ) vs. (PZ), PSA density (PSAD), and history of prior negative conventional transrectal ultrasound-guided biopsy (TRUS). Results: Mean age, PSA, prostate volume, and level of prior negative TRUS biopsy were 66 years (43–90), 7.82 ng/dL (5.6–11.2), 54 cm3 (12–173), and 456/980 (46.5%), respectively. Higher PSAD, no prior history of negative TRUS biopsy, and PZ lesions were associated with higher CDR. Stratified CDR highlighted significant variance across subgroups. CDR for a PI-RADS-5 score, PZ lesion with PSAD ≥ 0.15, and prior negative biopsy was 77%. Conversely, the CDR rate for a PI-RADS-4 score, TZ lesion with PSAD < 0.15, and prior negative biopsy was significantly lower at 14%. Conclusions: For index PI-RADS ≥ 3 lesions, CDR varied significantly based on location, prior history of negative TRUS biopsy, and PSAD. Such considerations are critical when counseling on the merits and potential yield of prostate needle biopsy. [ABSTRACT FROM AUTHOR]

Objective: In the diagnosis of prostate cancer, only digital rectal examination and prostate-specific antigen (PSA) testing cause unnecessary prostate biopsies, excessive cost, and treatment burden. Therefore, PSA density (PSAD) and multiparametric magnetic resonance imaging (mp-MRI) of the prostate are becoming common. In this study, we aimed to investigate the predictiveness of PSAD and mp-MRI of the prostate in the diagnosis of prostate cancer, which are non-invasive diagnostic methods. Materials and Methods: The files of 193 patients who applied to the urology outpatient clinic for approximately 5 years were reviewed and evaluated retrospectively. Serum PSAD values and prostate imaging reporting and data system (PIRADS) scores were recorded. Prostate biopsies were performed. The cut-off value for PSAD was 0.15 ng/mL/cc. Patients with <0.15 were divided into group 1, and those with ≥0.15 were divided into group 2. Patients with a PIRADS score of 3 were divided into the suspicious group, and patients with a PIRADS score of 4 or 5 were divided into the risky group. Results: Prostate volume, PSA, and PSAD were significantly different between the benign and malignant groups. PSAD was positively correlated with the PIRADS score. Of the 123 patients with a PIRADS score of 3, 82.9% had benign prostatic enlargement (BPE) and 17.1% had prostate cancer. Of the 70 patients with a PIRADS score of 4 or 5, 45.7% had BPE and 54.3% had prostate cancer (p<0.001). Clinically significant prostate cancer rates were significantly different between the PSA score groups and were also different for PIRADS (p<0.001). The sensitivity and specificity of PSAD in the diagnosis of prostate cancer were 67.8% and 64.9%, respectively. The sensitivity and specificity of the PIRADS score in the diagnosis of prostate cancer were 64.4% and 76.1%, respectively. When these two parameters were used in combination, the specificity was 87.3% and the sensitivity was 81.4% in the presence of at least one. Conclusion: According to the data of the study, it was concluded that PSAD and PRIDAS scores are complementary diagnostic methods in the diagnosis of prostate cancer and are indispensable elements in the diagnosis. PSAD and PRIDAS scores are important diagnostic parameters in making the biopsy decision in the diagnosis of prostate cancer and help to prevent unnecessary prostate biopsies. [ABSTRACT FROM AUTHOR]

PURPOSEThe present study aims to evaluate whether perfusion parameters in prostate magnetic resonance imaging (MRI), (68)Ga-prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT), prostate-specific antigen (PSA), and PSA density can be used to predict the lesion grade in patients with prostate cancer (PCa).METHODSThe study included a total of 137 PCa cases in which 12-quadrant transrectal ultrasound-guided prostate biopsy (TRUSBx) was performed, the Gleason score (GS) was determined, and pre-biopsy multiparametric prostate MRI and (68)Ga-PSMA PET/CT examinations were undertaken. The patient population was evaluated in three groups according to the GS: (1) low risk; (2) intermediate risk; (3) high risk. The PSA, PSA density, pre-TRUSBx (68)Ga-PSMA PET/CT maximum standardized uptake value (SUVmax), perfusion MRI parameters [maximum enhancement, maximum relative enhancement, T0 (s), time to peak (s), wash-in rate (s-1), and wash-out rate (s-1)] were retrospectively evaluated.RESULTSThere was no significant difference between the three groups in relation to the PSA, PSA density, and (68)Ga-PSMA PET/CT SUVmax (P > 0.05). However, the values of maximum enhancement, maximum relative enhancement (%), T0 (s), time to peak (s), wash-in rate (s-1), and wash-out rate (s-1) significantly differed among the groups. A moderate positive correlation was found among the prostate volume, PSA (r = 0.490), and (68)Ga-PSMA SUVmax (r = 0.322) in the patients. The wash-out rate (s-1) and wash-in rate (s-1) had the best diagnostic test performance (area under the curve: 89.1% and 78.4%, respectively).CONCLUSIONNo significant correlation was found between the (68)Ga-PSMA PET/CT SUVmax and the GS. The wash-out rate was more successful in estimating the pretreatment GS than the (68)Ga-PSMA PET/CT SUVmax.

Background: Prostate cancer screening with prostate-specific antigen (PSA) can result in unnecessary biopsies and overdiagnosis. Alternately, PSA density (PSAD) calculation may help support biopsy decisions; however, evidence of its usefulness is not concrete. Objective: To evaluate the predictive value of PSAD for clinically significant prostate cancer detection by systematic and MRI-targeted biopsies. Methods: This prospective study was conducted at two tertiary hospitals in Riyadh, Saudi Arabia, between December 2018 and November 2021. Patients suspected of prostate cancer were subjected to multi-parametric MRI, and for those with positive findings, systematic and targeted biopsies were performed. Clinically non-significant and significant prostate cancer cases were classified based on histopathology-defined ISUP grade or Gleason score. The PSAD was measured using the prostate volume determined by the MRI and categorized into ≤0.15, 0.16–0.20, and >0.20 ng/ml2 subgroups. Results: Systematic and targeted biopsies were carried out for 284 patients. The discriminant ability of PSAD is higher in MRI-targeted biopsy compared with systematic biopsy (AUC: 0.77 vs. 0.73). The highest sensitivity (97%) and specificity (87%) were detected at 0.07 ng/ml2 in targeted biopsy. More than half of the clinically significant cases were detected in the >0.2 ng/ml2 PSAD category (systematic: 52.4%; targeted: 51.1%). The CHAID methodology found that the probability of having clinically significant cancer (CSC) in patients with PSAD >0.15 ng/ml2 was more than threefold than that in patients with PSAD ≤0.15 ng/ml2 (64% vs. 20.2%). When considered by age, in PSAD ≤0.15 ng/ml2 subgroup, the percentage of CSC detection rate increased from 20.2% to 24.6% in patients aged ≥60 years. Conclusion: PSAD has good discriminant power for predicting clinically significant prostate cancer. A cutoff of 0.07 ng/ml2 should be adopted, but should be interpreted with caution and by considering other parameters such as age. [ABSTRACT FROM AUTHOR]

PURPOSE The present study aims to evaluate whether perfusion parameters in prostate magnetic resonance imaging (MRI), (68)Ga-prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT), prostate-specific antigen (PSA), and PSA density can be used to predict the lesion grade in patients with prostate cancer (PCa). METHODS The study included a total of 137 PCa cases in which 12-quadrant transrectal ultrasound-guided prostate biopsy (TRUSBx) was performed, the Gleason score (GS) was determined, and pre-biopsy multiparametric prostate MRI and (68)Ga-PSMA PET/CT examinations were undertaken. The patient population was evaluated in three groups according to the GS: (1) low risk; (2) intermediate risk; (3) high risk. The PSA, PSA density, pre-TRUSBx (68)Ga-PSMA PET/CT maximum standardized uptake value (SUVmax), perfusion MRI parameters [maximum enhancement, maximum relative enhancement, T0 (s), time to peak (s), wash-in rate (s-1), and wash-out rate (s-1)] were retrospectively evaluated. RESULTS There was no significant difference between the three groups in relation to the PSA, PSA density, and (68)Ga-PSMA PET/CT SUV (P > 0.05). However, the values of maximum enhancement, max- max imum relative enhancement (%), T0 (s), time to peak (s), wash-in rate (s-1), and wash-out rate (s-1) significantly differed among the groups. A moderate positive correlation was found among the prostate volume, PSA (r = 0.490), and (68)Ga-PSMA SUVmax (r = 0.322) in the patients. The wash-out rate (s-1) and wash-in rate (s-1) had the best diagnostic test performance (area under the curve: 89.1% and 78.4%, respectively). CONCLUSION No significant correlation was found between the (68)Ga-PSMA PET/CT SUVmax and the GS. The washout rate was more successful in estimating the pretreatment GS than the (68)Ga-PSMA PET/CT SUVmax. [ABSTRACT FROM AUTHOR]

Introduction: Modern image-guided biopsy pathways at diagnostic centres have greatly refined the investigations of men referred with suspected prostate cancer. However, the referral criteria from primary care are still based on historical prostate-specific antigen (PSA) cut-offs and age-referenced thresholds. Here, we tested whether better contemporary pathways and biopsy methods had improved the predictive utility value of PSA referral thresholds. Methods: PSA referral thresholds, age-referenced ranges and PSA density (PSAd) were assessed for positive predictive value (PPV) in detection of clinically significant prostate cancer (csPCa – histological ⩾ Grade Group 2). Data were analysed from men referred to three diagnostics centres who used multi-parametric magnetic resonance imaging (mpMRI)-guided prostate biopsies for disease characterisation. Findings were validated in a separate multicentre cohort. Results: Data from 2767 men were included in this study. The median age, PSA and PSAd were 66.4 years, 7.3 ng/mL and 0.1 ng/mL2, respectively. Biopsy detected csPCa was found in 38.7%. The overall area under the curve (AUC) for PSA was 0.68 which is similar to historical performance. A PSA threshold of ⩾ 3 ng/mL had a PPV of 40.3%, but this was age dependent (PPV: 24.8%, 32.7% and 56.8% in men 50–59 years, 60–69 years and ⩾ 70 years, respectively). Different PSA cut-offs and age-reference ranges failed to demonstrate better performance. PSAd demonstrated improved AUC (0.78 vs 0.68, p < 0.0001) and improved PPV compared to PSA. A PSAd of ⩾ 0.10 had a PPV of 48.2% and similar negative predictive value (NPV) to PSA ⩾ 3 ng/mL and out-performed PSA age-reference ranges. This improved performance was recapitulated in a separate multi-centre cohort (n = 541). Conclusion: The introduction of MRI-based image-guided biopsy pathways does not appear to have altered PSA diagnostic test characteristics to positively detect csPCa. We find no added value to PSA age-referenced ranges, while PSAd offers better PPV and the potential for a single clinically useful threshold (⩾0.10) for all age groups. Level of evidence: IV [ABSTRACT FROM AUTHOR]

Abstract Purpose The study aimed to construct a predictive model for clinically significant prostate cancer (csPCa) and investigate its clinical efficacy to reduce unnecessary prostate biopsies. Methods A total of 847 patients from institute 1 were included in cohort 1 for model development. Cohort 2 included a total of 208 patients from institute 2 for external validation of the model. The data obtained were used for retrospective analysis. The results of magnetic resonance imaging were obtained using Prostate Imaging Reporting and Data System version 2.1 (PI-RADS v2.1). Univariate and multivariate analyses were performed to determine significant predictors of csPCa. The diagnostic performances were compared using the receiver operating characteristic (ROC) curve and decision curve analyses. Results Age, prostate-specific antigen density (PSAD), and PI-RADS v2.1 scores were used as predictors of the model. In the development cohort, the areas under the ROC curve (AUC) for csPCa about age, PSAD, PI-RADS v2.1 scores, and the model were 0.675, 0.823, 0.875, and 0.938, respectively. In the external validation cohort, the AUC values predicted by the four were 0.619, 0.811, 0.863, and 0.914, respectively. Decision curve analysis revealed that the clear net benefit of the model was higher than PI-RADS v2.1 scores and PSAD. The model significantly reduced unnecessary prostate biopsies within the risk threshold of > 10%. Conclusions In both internal and external validation, the model constructed by combining age, PSAD, and PI-RADS v2.1 scores exhibited excellent clinical efficacy and can be utilized to reduce unnecessary prostate biopsies.

Background: Prostate cancer screening with prostate-specific antigen (PSA) can result in unnecessary biopsies and overdiagnosis. Alternately, PSA density (PSAD) calculation may help support biopsy decisions; however, evidence of its usefulness is not concrete. Objective: To evaluate the predictive value of PSAD for clinically significant prostate cancer detection by systematic and MRI-targeted biopsies. Methods: This prospective study was conducted at two tertiary hospitals in Riyadh, Saudi Arabia, between December 2018 and November 2021. Patients suspected of prostate cancer were subjected to multi-parametric MRI, and for those with positive findings, systematic and targeted biopsies were performed. Clinically non-significant and significant prostate cancer cases were classified based on histopathology-defined ISUP grade or Gleason score. The PSAD was measured using the prostate volume determined by the MRI and categorized into ≤0.15, 0.16–0.20, and >0.20 ng/ml2 subgroups. Results: Systematic and targeted biopsies were carried out for 284 patients. The discriminant ability of PSAD is higher in MRI-targeted biopsy compared with systematic biopsy (AUC: 0.77 vs. 0.73). The highest sensitivity (97%) and specificity (87%) were detected at 0.07 ng/ml2 in targeted biopsy. More than half of the clinically significant cases were detected in the >0.2 ng/ml2 PSAD category (systematic: 52.4%; targeted: 51.1%). The CHAID methodology found that the probability of having clinically significant cancer (CSC) in patients with PSAD >0.15 ng/ml2 was more than threefold than that in patients with PSAD ≤0.15 ng/ml2 (64% vs. 20.2%). When considered by age, in PSAD ≤0.15 ng/ml2 subgroup, the percentage of CSC detection rate increased from 20.2% to 24.6% in patients aged ≥60 years. Conclusion: PSAD has good discriminant power for predicting clinically significant prostate cancer. A cutoff of 0.07 ng/ml2 should be adopted, but should be interpreted with caution and by considering other parameters such as age.

Background: Freehand transperineal prostate biopsy (TPPBx) using a coaxial needle technique offers an alternative to probe-mounted freehand or template-guided techniques in the diagnosis of prostate cancer (PCa). It only requires the same equipment used for transrectal ultrasound-guided (TRUS) biopsy. Our study is the first in Malaysia to report this experience and its outcomes. We aim to determine PCa detection rate and pain tolerability of freehand TPPBx utilizing a coaxial needle under local anesthesia (LA). Methods: Institutional review board approval was obtained from National Medical Research Register (NMRR ID-21-02052-VIL). We retrospectively reviewed the medical records of patients who underwent TPPBx between August 2020 and April 2022. Records were reviewed for patients’ characteristics, prostate volume, prostate-specific antigen (PSA) results, biopsy results and pain tolerability. Data was analyzed to determine PCa and clinically significant prostate cancer (csPCa) detection rate. LA was achieved using perineal skin infiltration and a periprostatic nerve block. The commonly used standard side-firing transrectal ultrasound with its Prostate Biplane Transducer was used as an imaging guide. The principles of the Ginsburg protocol were followed. Pain tolerability was assessed using a visual analog scale. Results: A total of 55 patients with elevated PSA levels underwent freehand TPPBx under LA. The mean age was 67.3 years, the median PSA was 14.2 ng/mL, and the median PSA density (PSAD) was 0.33 ng/mL/cc. The optimal PSAD cutoff for predicting csPCa was 0.35 ng/mL/cc (area under the curve [AUC], 0.792; sensitivity, 87.5%; specificity, 69.2%). PCa was detected in 24 patients (43.6%), of whom 16 (29.1%) had csPCa. The median pain scores during LA infiltration and biopsy were four and two, respectively, which were significant different (P

Abstract Background The PSAD calculating by the serum PSA level divided by prostate volume had more specificity and accuracy than the serum PSA level for detection of prostate cancer. Methods MRI examinations of 319 patients who had suspected prostate cancer between January 2014 and December 2019 were retrospectively reviewed. Prostate volumes were measured by MRI images and PSAD values were calculated. The accuracy and optimal cutoff points of MRI-based PSAD were evaluated using receiver operating characteristic curves (ROC curves). Correlations between the MRI-based PSAD and Gleason scores were also analyzed to predict prognosis of prostate cancer. Results Overall, of 154 patients were included in this study, 59 patients (38.31%) were diagnosed with prostate cancer. The optimal cutoff point of PSAD was 0.16 (81.40% sensitivity, 54.70% specificity, 52.70% PPV, 82.50% NPV), and the AUC was 0.680 (95% CI: 0.609–0.751). In subgroup analyses, the optimal cutoff point of PSAD in patients with serum PSA 4–10 ng/ml was 0.16 (61.10% sensitivity, 76.00% specificity) and for > 10 ng/ml was 0.30 (68.30% sensitivity, 64.30% specificity). Furthermore, there was a statistically significant correlation between PSAD and Gleason scores (p-value 0.014). Conclusions The optimal cutoff point of MRI-based PSAD was 0.16 which was relatively different from international consensus.

Purpose: The study aimed to construct a predictive model for clinically significant prostate cancer (csPCa) and investigate its clinical efficacy to reduce unnecessary prostate biopsies. Methods: A total of 847 patients from institute 1 were included in cohort 1 for model development. Cohort 2 included a total of 208 patients from institute 2 for external validation of the model. The data obtained were used for retrospective analysis. The results of magnetic resonance imaging were obtained using Prostate Imaging Reporting and Data System version 2.1 (PI-RADS v2.1). Univariate and multivariate analyses were performed to determine significant predictors of csPCa. The diagnostic performances were compared using the receiver operating characteristic (ROC) curve and decision curve analyses. Results: Age, prostate-specific antigen density (PSAD), and PI-RADS v2.1 scores were used as predictors of the model. In the development cohort, the areas under the ROC curve (AUC) for csPCa about age, PSAD, PI-RADS v2.1 scores, and the model were 0.675, 0.823, 0.875, and 0.938, respectively. In the external validation cohort, the AUC values predicted by the four were 0.619, 0.811, 0.863, and 0.914, respectively. Decision curve analysis revealed that the clear net benefit of the model was higher than PI-RADS v2.1 scores and PSAD. The model significantly reduced unnecessary prostate biopsies within the risk threshold of > 10%. Conclusions: In both internal and external validation, the model constructed by combining age, PSAD, and PI-RADS v2.1 scores exhibited excellent clinical efficacy and can be utilized to reduce unnecessary prostate biopsies. [ABSTRACT FROM AUTHOR]

• PIRADS 3 lesion represents a "gray zone" where further tools are needed for decision making for risk stratification and prostate biopsy. • 4k score has better performance in predicting clinically significant prostate cancer in patients with PIRADS 3 lesions and PSA density less than 0.15 ng/mL/cm3. • Using a threshold of PSA density of 0.1 ng/mL/cm3 or 4k score of 10% would help reduce unnecessary biopsy without missing a significant proportion of clinically significant prostate cancer. The recommendation to perform biopsy of PIRADS 3 lesions has not been adopted with strength as compared to higher scored lesions on multiparametric MRI. This represents a challenging scenario and an unmet need for clinicians to apply a risk adapted approach in these cases. In the present study, we examined clinical and radiologic characteristics in men with PI-RADS 3 index lesions that can predict csPCa on mpMRI-target biopsy. Revision of a prospective database with patients who underwent targeted and systematic biopsies from 2015 to 2023 for PI-RADS 3 lesions identified on mpMRI. Baseline variables were collected, such as PSA density (PSAd), 4Kscore, prostate size, and the apparent diffusion coefficient (ADC) value of the lesion on mpMRI. Logistic regression, receiver operating characteristic (ROC) and decision curve analyses (DCA) assessing the association between clinic-radiologic factors and csPCa were performed. Overall, 230 patients were included in the study and the median age was 65 years. The median prostate size and PSA were 50 g and 6.26 ng/mL, respectively. 17.4% of patients had csPCa, while 27.5% had Gleason group 1. In univariable logistic analyses, we found that age, BMI, prostate size, PSAd, ADC, and 4Kscore were significant csPCa predictors (P < 0.05). PSAd showed the best prediction performance in terms of AUC (= 0.679). On multivariable analysis, PSAd and 4Kscore were associated with csPCa. The net benefit of PSAd combined with clinical features was superior to those of other parameters. Within patients with PSAd < 0.15, 4Kscore was a statistically significant predictor of csPCa (OR = 3.25, P = 0.032). PSAd and 4Kscore are better predictors of csPCa in patients with PIRADS 3 lesions compared to ADC. The predictive role of 4Kscore is higher in patients with low PSAd. These results can assist practitioners in the risk stratification of patients with equivocal lesions to determine the need of biopsy. [ABSTRACT FROM AUTHOR]

Abstract Objective To predict prostate cancer using novel biomarker ratios and create a predictive scoring system. Materials and methods Data of a total of 703 patients who consulted Urology Department of Selayang Hospital between January 2013 and December 2017 and underwent prostate biopsy were screened retrospectively. Prostate specific antigen (PSA) levels, prostate volumes (PV), neutrophil and lymphocyte counts, neutrophil-to-lymphocyte ratio (NLR), Prostate specific antigen density (PSAD) and histopathology were evaluated. Results Ages ranged from 43 to 89 years, divided into 2 groups as per biopsy results; positive for prostate cancer (n = 290, 41.3%) and negative for malignancy (n = 413; 58.7%). Intergroup comparative evaluations were performed. Independent variables with p 0.4, Age > 70 and DRE. A score of 2 or more predicted prostate cancer with a Sensitivity of 83.8% and Specificity of 86.4%. Conclusions NLR is shown to be good predictor for prostate cancer its usage in this scoring system affords more disease specificity as compared to PSA alone.

To develop and evaluate a multimodal approach including clinical parameters and biparametric MRI-based artificial intelligence (AI) model for determining the necessity of prostate biopsy in patients with PI-RADS 3 lesions. This retrospective study included a prospectively recruited patient cohort with PI-RADS 3 lesions who underwent prostate MRI and MRI/US fusion-guided biopsy between April 2019 and February 2024 in a single institution. The study examined demographic data, PSA and PSA density (PSAD) levels, prostate volumes, prospective PI-RADS v2.1-compliant interpretations of a genitourinary radiologist, lesion characteristics, history of prior biopsies, and AI evaluations, focusing mainly on the detection of clinically significant prostate cancer (csPCa) (International Society of Urological Pathology grade group ≥2) on MRI/US fusion-guided biopsy. The AI model lesion segmentations were compared to manual segmentations and biopsy results. The statistical methods employed included Fisher's exact test and logistic regression. The cohort was comprised of 248 patients with 312 PI-RADS 3 lesions in total (n = 268 non-csPCa, n = 44 csPCa). The AI model's negative predictive value (NPV) was 89.2 % for csPCa in all lesions. In patient-level analysis, the NPV was 91.2 % for patients with a highest PI-RADS score of 3. PSAD was a significant predictor of csPCa (odds ratio = 5.8, p = 0.038). Combining AI and PSAD, where AI correctly mapped a lesion or PSAD ≥0.15 ng/mL2, achieved higher sensitivity (77.8 %) while maintaining a high NPV (93.1 %). Combining AI and PSAD has the potential to enhance biopsy decision-making for PI-RADS 3 lesions by minimizing missed csPCa occurrences and reducing unnecessary biopsies. • The high NPV of the AI model highlights consistency in ruling out non-cancerous lesions. • Combining AI and PSAD enhances diagnostic accuracy for PI-RADS 3 lesions. • A flexible AI-PSAD combination reduces missed csPCa cases and unnecessary biopsies. [ABSTRACT FROM AUTHOR]

Abstract Background Prostate disorders are among the leading causes of morbidity and mortality in men above the age of 40 years globally. Serum prostate-specific antigen (PSA) levels may be used to screen men at risk of prostate cancer and determine choice of medical treatment in benign prostatic hyperplasia (BPH) and evaluation of patients with prostatitis, while prostate sonography determines prostate volume (PV) and detects nodules. BPH may exhibit distinct hypoechoic, isoechoic, or hyperechoic nodules in the transition zone, whereas hypoechoic nodules in the peripheral zone are diagnostic for prostate cancer in over 50% of cases. In this study, we aimed at determining the relationship between serum PSA levels and transrectal prostate sonographic findings among asymptomatic Ugandan males. Methods Ugandan males above 30 years of age or older without lower urinary tract symptoms were cross-sectionally enrolled into the study. Serum PSA determination and transrectal ultrasound were performed. Association between PSA levels and PV was assessed using Spearman’s correlation coefficients (ρ). Results A total of 277 men were studied. The median serum PSA level was 1 (95% CI: 1–2). Most (n = 217, 78.3%) participants had serum PSA levels ≤ 4 ng/ml. The median sonographic PV was 26 (95% CI: 26–29) mls. One hundred and fifty-five (56.0%) participants had PV between 25 and 50 mls. Both PSA levels and PV progressively increased with age from 0.9 ng/ml and 22 mls in the 30–39 year age group to 7 ng/ml and 38 mls in the 60–69 year age group, respectively. PSA levels weakly correlated with PV (ρ = 0.27) (p

We assessed the impact of MRI and PSA density on the probability to pursue an active surveillance of prostate cancer. We found that the use of these characteristics could improve selection of patients at diagnosis, stratifying the delayed treatment risk. During follow-up, some biopsies could be avoided with a reasonably risk and higher MRI lesion were at high-risk of treatment. Introduction: A greater selection of candidates for active surveillance (AS) of prostate cancer (PCa) may decrease the rate of delayed treatment. We aimed to study: 1) the impact of MRI and PSA density (PSAd) at baseline on the final status, and 2) the impact of bio-clinical features during the follow-up on pursuing AS. Materials and Methods: This retrospective, monocentric study between June 2013 and July 2020, included 99 patients in AS (median follow-up: 19 months [18-92]). All MRI were reviewed by a single radiologist. Lost to follow-up were 17 patients and 6 patients chose treatment by themselves. Treatment was proposed in case of upgrading (= GG2) or increasing PCa volume. Results: Impact of MRI and PSAd at baseline: Combining PSAd = 0.15 and PIRADS = 3, the probability to remain in AS was 72%. This rate reached 83% when PSAd = 0.10 was associated to normal MRI. During follow-up: One hundred fiftyseven prostatic biopsies (PBx) were performed and 38 (24%) found PCa upgrading. The association between negative MRI and PSAd = 0.10, during follow-up, had an excellent NPV to predict treatment (95%). This combination concerned 25% (37/151) of surveillance biopsies that could have been avoided at the cost of delaying upgrading in 3% (1/37). In multivariate analysis, only PIRADS = 4 before PBx was associated to a risk of treatment during follow-up (OR, 10.4 [95% CI, 4.2-25.8]; P < .0001). Conclusion: Using PSAd and MRI at baseline to select patients showed excellent performances to predict the maintenance in AS. During follow-up, MRI PIRADS = 4 was associated to an increased risk of treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: The selection of proper candidates for prostate biopsy after magnetic resonance imaging (MRI) has usually been studied in the overall population with suspected prostate cancer (PCa). However, the performance of these tools can change regarding the Prostate Imaging-Reporting and Data System (PI-RADS) categories. We compared three different tools: PSA density, MRI-ERSPC risk calculator and Proclarix in 567 men with suspected PCa (PSA > 3 ng/mL and/or abnormal rectal examination) in one academic institution. All patients underwent multiple transrectal ultrasound guided biopsies after a multiparametric MRI was performed. We concluded that in the overall population, MRI-ERSPC RC outperformed PSA density and Proclarix, whereas in patients with lesions PI-RADS < 3 Proclarix was better than the other tools. However, no tool guaranteed 100% detection of clinically significant PCa in PI-RADS 4 and 5. Tools to properly select candidates for prostate biopsy after magnetic resonance imaging (MRI) have usually been analyzed in overall populations with suspected prostate cancer (PCa). However, the performance of these tools can change regarding the Prostate Imaging-Reporting and Data System (PI-RADS) categories due to the different incidence of clinically significant PCa (csPCa). The objective of the study was to analyze PSA density (PSAD), MRI-ERSPC risk calculator (RC), and Proclarix to properly select candidates for prostate biopsy regarding PI-RADS categories. We performed a head-to-head analysis of 567 men with suspected PCa, PSA > 3 ng/mL and/or abnormal rectal examination, in whom two to four core transrectal ultrasound (TRUS) guided biopsies to PI-RADS ≥ three lesions and/or 12-core TRUS systematic biopsies were performed after 3-tesla mpMRI between January 2018 and March 2020 in one academic institution. The overall detection of csPCa was 40.9% (6% in PI-RADS < 3, 14.8% in PI-RADS 3, 55.3% in PI-RADS 4, and 88.9% in PI-RADS 5). MRI-ERSPC model exhibited a net benefit over PSAD and Proclarix in the overall population. Proclarix outperformed PSAD and MRI-ERSPC RC in PI-RADS ≤ 3. PSAD outperformed MRI-ESRPC RC and Proclarix in PI-RADS > 3, although none of them exhibited 100% sensitivity for csPCa in this setting. Therefore, tools to properly select candidates for prostate biopsy after MRI must be analyzed regarding the PI-RADS categories. While MRI-ERSPC RC outperformed PSAD and Proclarix in the overall population, Proclarix outperformed in PI-RADS ≤ 3, and no tool guaranteed 100% detection of csPCa in PI-RADS 4 and 5. [ABSTRACT FROM AUTHOR]

• PSA density kinetics is a proxy endpoint of biochemical freedom from relapse. • 3-month PSA density is predictive of long-term freedom from biochemical relapse. • 3–6 months PSA density decay slope also predicts. • PSA outcome PSA density kinetics may serve as a tool to validate classifiers of radioresistance. The present study explores PSA density (PSA-D) as predictor of biochemical and local failure in organ-confined prostate cancer at 3–6 months after hypofractionated stereotactic ablative radiotherapy (SABR). A cohort of 219, hormone-naïve, NCCN intermediate-risk prostate cancer patients were derived from a phase 2 study of 5 × 9 Gy prostate cancer SABR. PSA-D was calculated at 3 and 6 months by dividing serum PSA by the MR-derived prostate CTV, while the slope of the 3–6 months curve was used to express the kinetics of PSA-D decay. The median follow-up was 60.3 (range 46–76) months, and the actuarial 7-year bRFS was 98.0% for intermediate-risk favorable (FIR) patients versus 84.5% for the unfavorable (UIR) subgroup (P = 0.02). Fourteen patients developed a Phoenix-defined biochemical PSA relapse (bRFS) at a median of 34.2 months, 11 confirmed with 68Ga-PSMA PET/CT scan that revealed tracer uptake at the site of dominant intraprostatic pretreatment lesion in 8 patients. The 3-month PSA-D concertation (cut-off 0.08 ng/ml2) and 3–6 months decay slope (cut-off −0.45) values were predictive of long-term bRFS. A dual adverse PSA-D permutation was detected in 25/148 UIR patients, exhibiting 47.5% 7-year bRFS compared with 94.1% for the remaining 123 UIR patients with favorable PSA-D kinetics (P = 0.0006). Intraprostatic local relapse in patients with a 3-month PSA-D > 0.080 ng/ml2 was 11.0% vs. 1.7% for patients with PSA-D ≤ 0.080 ng/ml2 (P = 0.01) and 2.3% vs. 4.3%, respectively, for nodal progression (P = 0.68). Early post-treatment PSA-D kinetics transcends pre-treatment risk stratification of tumor relapse and adds a nuance in the biological characterization of intermediate-risk prostate cancer phenotypes. The dual adverse PSA-D algorithm may serve as a tool to validate current search of classifiers of radioresistance in prostate cancer with therapeutic implications. [ABSTRACT FROM AUTHOR]

Background: We aimed to investigate the association between prostate specific antigen (PSA) density and Gleason score of the positive surgical (PSM) margin after radical prostatectomy with biochemical recurrence in patients with prostate cancer. Materials and Methods: In this retrospective cohort study, patients with prostate cancer referred to Hasheminejad Hospital in Tehran, Iran, during 2009-2019, who underwent radical prostatectomy were enrolled through the convenience sampling method. The follow-up period was determined as at least one year after radical prostatectomy to determine biochemical recurrence. Prostate-specific antigen density (PSAD) and the Gleason score of surgical specimen and positive surgical margins (PSM) were evaluated and their association with biochemical recurrences was investigated. Results: One hundred and three patients were assessed. The overall biochemical recurrence rate was 48.5% with a mean follow-up of 24 months (12-42 months) and an average time to biochemical recurrence of 18 months (16-20 months). BCR-free (Biochemical recurrence-free) survival rates of patients divided based on the PSAD cut-off point (0.205 ng/ml/cc) were significantly different using the log-rank test (P= 0.008) (85.7%, 57.1%, and 14.3% for values ≤ 0.205 ng/ml/c versus 55.8%, 20.9%, and 0% for values ˃ 0.205 ng/ml/cc, respectively for 1-, 2- and 3-year survival). Moreover, Cox regression showed that the Gleason score of PSM, the Gleason score of the surgical specimen, and the PSAD predicted biochemical recurrence more, respectively. Conclusion: PSAD and PSM Gleason scores were strong predictors of biochemical recurrence after radical prostatectomy and their use along with other common indicators including tumor grade and stage and PSA level can increase the accuracy of risk assessment in patients with prostate cancer.

Objective: To predict prostate cancer using novel biomarker ratios and create a predictive scoring system.Materials and Methods: Data of a total of 703 patients who consulted Urology Department of Selayang Hospital between January 2013 and December 2017 and underwent prostate biopsy were screened retrospectively. Prostate specific antigen (PSA) levels, prostate volumes (PV), neutrophil and lymphocyte counts, neutrophil-to-lymphocyte ratio (NLR), Prostate specific antigen density (PSAD) and histopathology were evaluated.Results: Ages ranged from 43 to 89 years, divided into 2 groups as per biopsy results; positive for prostate cancer (n = 290, 41.3%) and negative for malignancy (n = 413; 58.7%). Intergroup comparative evaluations were performed. Independent variables with p < 0.001 in the univariate analysis were age, DRE, PV, NLR, PSAD. A scoring system was modelled using NLR < 0.9, PSAD > 0.4, Age > 70 and DRE. A score of 2 or more predicted prostate cancer with a Sensitivity of 83.8% and Specificity of 86.4%.Conclusions: NLR is shown to be good predictor for prostate cancer its usage in this scoring system affords more disease specificity as compared to PSA alone. [ABSTRACT FROM AUTHOR]

Objectives: Multiparametric magnetic resonance imaging (mpMRI) is a useful tool to diagnose prostate cancer (PCa) but its cost is not negligible. In order to reduce costs and minimize time to diagnosis, it is necessary to establish which patients benefit the most from doing mpMRI prior to prostate biopsy (PB). Our aim was to test if mpMRI still predicts PCa and clinically significant PCa (csPCa) in patients with high clinical suspicion of cancer, defined as prostate specific antigen (PSA) > 10 ng/ml, PSA-Density (PSAD) > 0.15 ng/ml/cc or suspicious digital rectal examination (DRE). Materials and methods: We retrospectively collected data on 206 patients who underwent mpMRI before PB at our Department from January 2017 to July 2018. mpMRI results were classified using Prostate Imaging Reporting and Data System (PI-RADS) version 2. In primary analysis, we evaluated the association of mpMRI with PCa and csPCa and stratified this model for low and high clinical suspicion of cancer. In secondary analysis, we determined the rate of negative PB results in patients with high suspicion of cancer and compared theses rates with those obtained if only those with PI-RADS 3-5 would be biopsied. Results: In primary analysis and overall, mpMRI was predictive of PCa and csPCa. In stratified analysis, mpMRI was still significantly associated with csPC in patients with PSA > 10ng/ml and PSAD > 0.15 ng/ml/cc, but not in those with suspicious DRE. In secondary analysis, negative result rates were lower if only patients with PI-RADS 3-5 were biopsied, even in subgroups with high suspicion of cancer based on PSA and PSAD. In patients with suspicious DRE, however, the rate of negative results did not change significantly if only patients with PI-RADS 3-5 were biopsied. Conclusions: mpMRI is still useful in predicting csPCa in patients with PSA > 10 ng/mL and PSAD > 0.15 ng/ml/cc. If DRE is suspicious, though, mpMRI might be no longer useful in the prediction of PCa. [ABSTRACT FROM AUTHOR]

Objectives: Multiparametric magnetic resonance imaging (mpMRI) is a useful tool to diagnose prostate cancer (PCa) but its cost is not negligible. In order to reduce costs and minimize time to diagnosis, it is necessary to establish which patients benefit the most from doing mpMRI prior to prostate biopsy (PB). Our aim was to test if mpMRI still predicts PCa and clinically significant PCa (csPCa) in patients with high clinical suspicion of cancer, defined as prostate specific antigen (PSA) > 10 ng/ml, PSA-Density (PSAD) > 0.15 ng/ml/cc or suspicious digital rectal examination (DRE). Materials and methods: We retrospectively collected data on 206 patients who underwent mpMRI before PB at our Department from January 2017 to July 2018. mpMRI results were classified using Prostate Imaging Reporting and Data System (PI-RADS) version 2. In primary analysis, we evaluated the association of mpMRI with PCa and csPCa and stratified this model for low and high clinical suspicion of cancer. In secondary analysis, we determined the rate of negative PB results in patients with high suspicion of cancer and compared theses rates with those obtained if only those with PI-RADS 3-5 would be biopsied. Results: In primary analysis and overall, mpMRI was predictive of PCa and csPCa. In stratified analysis, mpMRI was still significantly associated with csPCa in patients with PSA > 10 ng/ml and PSAD > 0.15 ng/ml/cc, but not in those with suspicious DRE. In secondary analysis, negative result rates were lower if only patients with PI-RADS 3-5 were biopsied, even in subgroups with high suspicion of cancer based on PSA and PSAD. In patients with suspicious DRE, however, the rate of negative results did not change significantly if only patients with PI-RADS 3-5 were biopsied. Conclusions: mpMRI is still useful in predicting csPCa in patients with PSA > 10 ng/mL and PSAD > 0.15 ng/ml/cc. If DRE is suspicious, though, mpMRI might be no longer useful in the prediction of PCa.

Objective: Many men with non-clinically significant prostate cancer (N-CSPCa) will not progress to symptomatic forms within their lifetime. So, predicting clinically significant PCa (CSPCa) will prevent unnecessary biopsies, overdiagnoses, and overtreatment of patients. Thus, we aimed at demonstrating the predictive ability of prostate-specific antigen (PSA) density (PSAD) and f/t PSA in revealing CSPCa (Gleason score =7) in patients diagnosed with prostate cancer on biopsy with a PSA level of 2.5-10 ng/mL. Materials and Methods: We evaluated 78 patients with PSA 2.5-10.0 ng/mL who underwent transrectal ultrasound guided (TRUSG)-guided prostate biopsy in our clinic between March 2017 and August 2020 and whose histology reported as prostate adenocarcinoma. In addition to the demographic content of the patients, PSA, free PSA, prostate size (with TRUSG), rectal examination findings, and prostate biopsy results were recorded. Clinically significant prostate cancer was defined as a minimum Gleason score of 7. Results: The mean age of the patients was 66.9±8.4 years, PSA value was 6.9±1.8 ng/mL, free/total PSA ratio was 18±8.1%, and PSAD was 0.150±0.078. The p-values of PSA, free PSA, PSAD, f/t PSA, and prostate volume between CSPCa and N-CSPCa groups were 0.010, 0.780, 0.001, 0.084, and 0.030, respectively. The area under the curve of the PSAD for predicting CSPCa was 0.719 with a 95% Cl (0.604-0.835), and the standard errors were 0.062 and 0.059, respectively. When PSAD cut-off was 0.130 for predicting CSPCa, sensitivity and specificity rates were 75% and 63%, respectively. Conclusion: PSAD can be used in predicting CSPCa, but not f/t PSA. PSAD is not a strong stand-alone tool owing to its sensitivity and specificity, but can be a part of future nomograms for predicting CSPCa and future protocols for active surveillance. [ABSTRACT FROM AUTHOR]

Hui Wang,1–3 Sheng Tai,1,2 Li Zhang,1,3 Jun Zhou,1–3 Chaozhao Liang1–31Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 2Anhui Province Key Laboratory of Genitourinary Diseases, Anhui Medical University, Hefei, People’s Republic of China; 3The Institute of Urology, Anhui Medical University, Hefei, People’s Republic of ChinaPurposes: To develop a new predictor and update nomogram based on prostate imaging reporting and data system version 2 (PI-RADS V2) in predicting intermediate- and high-risk prostate cancer (IH-Pca) and reducing the overtreatment for low-risk Pca (L-Pca).Methods: All men that underwent trans-rectal ultrasound-guided 12+X-core prostate biopsy between January 2015 and June 2018 were collected and analyzed. The significant risks (SRs) of Pca were selected by univariate and multivariate analysis. All SRs were divided into four groups (0 to 3 points) based on the probability of PI-RADS. Each patient can obtain a total score (TS). The updated nomogram was established by R package version 3.0. The area under the curve (AUC), net reclassification index (NRI), calibration curves and decision curves were used to evaluate the diagnostic performance.Results: There were 1,078 patients, including 640 (59%) men with normal or L-Pca (N-LPca) and 438 (41%) men with IH-Pca. The scores of TS for IH-Pca and N-LPca were 16.13±3.11 and 10.52±3.32, respectively (P

Chao Peng, Jun Zhang, Jianquan Hou Department of Urology, First Affiliated Hospital of Soochow University, Suzhou 215006, China Background: Prognosis for intermediate-risk prostate cancer (PCa) remains variable; therefore, we aimed to investigate high-risk factors for biochemical recurrence (BCR), and intermediate-risk PCa using radical prostatectomy to identify patients having equivalent BCR-free survival rates when compared to high-risk PCa.Patients and methods: A total of 441 medical records were analyzed, including those of 169 intermediate-risk and 272 high-risk PCa patients. Risk factors for time to BCR were tested and analyzed using Kaplan–Meier survival analysis, log-rank tests, and Cox proportion hazards models.Results: In the intermediate-risk group, prostate-specific antigen density (PSAD) and primary Gleason pattern were significant preoperative risk factors for BCR. Moreover, BCR-free survival of patients in the intermediate-risk group with a higher PSAD (>0.5 ng/mL/cm3) was comparable with that of patients in the high-risk group (P=0.735). When combining primary Gleason pattern 4 and 3 with PSAD cut-offs 0.3–0.7 ng/mL/cm3, we found that BCR-free survival of patients in the intermediate-risk group with a primary Gleason pattern 4 and PSAD >0.3 ng/mL/cm3 was comparable with that of patients in the high-risk group (P=0.463).Conclusion: PSAD and primary Gleason pattern are potential risk factors associated with biochemical failure in intermediate-risk PCa patients after radical prostatectomy. Regarding significant differences in prognosis according to PSAD as well as primary Gleason pattern on biopsy, a subset of the intermediate-risk patients could be identified with outcomes that were equivalent to that of high-risk patients. Keywords: biochemical recurrence, Gleason grade, intermediate risk, prostate cancer, PSA density

The association between PSA density, prostate cancer (PCa) and BPH is well established. The aim of the present study was to establish whether PSA density can be used as a reliable parameter to predict csPCa and to determine its optimal cutoff to exclude increased PSA levels due to intraprostatic inflammation. This is a large prospective single-center, observational study evaluating the role of PSA density in the discrimination between intraprostatic inflammation and clinically significant PCa (csPCa). Patients with PSA ≥ 4 ng/ml and/or positive digito-rectal examination (DRE) and scheduled for prostate biopsy were enrolled. Prostatic inflammation (PI) was assessed and graded using the Irani Scores. Multivariable binary logistic regression analysis was used to assess if PSA density was associated with clinically significant PCa (csPCa) rather than prostatic inflammation. A total of 1988 patients met the inclusion criteria. Any PCa and csPCa rates were 47% and 24% respectively. In the group without csPCa, patients with prostatic inflammation had a higher PSA (6.0 vs 5.0 ng/ml; p=0.0003), higher prostate volume (58 vs 52 cc; p4 ng/ml) were 0.10 ng/ml2 in biopsy naïve patients and 0.15 ng/ml2 in patients with a previous negative biopsy. PSA density rather than PSA, should be used to evaluate patients at risk of prostate cancer who may need additional testing or prostate biopsy. This readily available parameter can potentially identify men who do not have PCa but have an elevated PSA secondary to benign conditions.

Purpose: To compare the ability of Prostate Health Index (PHI) to diagnose csPCa, with that of total PSA, PSA density (PSAD) and the multiparametric magnetic resonance (mpMRI) of the prostate. Methods: We analysed a group of 395 men planned for a prostate biopsy who underwent a mpMRI of the prostate evaluated using the PIRADS v1 criteria. All patients had their PHI measured before prostate biopsy. In patients with an mpMRI suspicious lesions, an mpMRI/ultrasound software fusion-guided biopsy was performed first, with 12 core systematic biopsy performed in all patients. A ROC analysis was performed for PCa detection for total PSA, PSAD, PIRADS score and PHI; with an AUC curve calculated for all criteria and a combination of PIRADS score and PHI. Subsequent sub-analyses included patients undergoing first and repeat biopsy. Results: The AUC for predicting the presence of csPCa in all patients was 59.5 for total PSA, 69.7 for PHI, 64.9 for PSAD and 62.5 for PIRADS. In biopsy naive patients it was 61.6 for total PSA, 68.9 for PHI, 64.6 for PSAD and 63.1 for PIRADS. In patients with previous negative biopsy the AUC for total PSA, PHI, PSAD and PIRADS was 55.4, 71.2, 64.4 and 69.3, respectively. Adding of PHI to PIRADS increased significantly (p = 0.007) the accuracy for prediction of csPCa. Conclusion: Prostate Health Index could serve as a tool in predicting csPCa. When compared to the mpMRI, it shows comparable results. The PHI cannot, however, help us guide prostate biopsies in any way, and its main use may, therefore, be in pre-MRI or pre-biopsy triage. [ABSTRACT FROM AUTHOR]

The association between PSA density, prostate cancer (PCa) and BPH is well established. The aim of the present study was to establish whether PSA density can be used as a reliable parameter to predict csPCa and to determine its optimal cutoff to exclude increased PSA levels due to intraprostatic inflammation. This is a large prospective single-center, observational study evaluating the role of PSA density in the discrimination between intraprostatic inflammation and clinically significant PCa (csPCa). Patients with PSA ≥ 4 ng/ml and/or positive digito-rectal examination (DRE) and scheduled for prostate biopsy were enrolled. Prostatic inflammation (PI) was assessed and graded using the Irani Scores. Multivariable binary logistic regression analysis was used to assess if PSA density was associated with clinically significant PCa (csPCa) rather than prostatic inflammation. A total of 1988 patients met the inclusion criteria. Any PCa and csPCa rates were 47% and 24% respectively. In the group without csPCa, patients with prostatic inflammation had a higher PSA (6.0 vs 5.0 ng/ml; p=0.0003), higher prostate volume (58 vs 52 cc; p<0.0001), were more likely to have a previous negative biopsy (29% vs 21%; p=0.0005) and a negative DRE (70% vs 65%; p=0.023) but no difference in PSA density (0.1 vs 0.11; p=0.2). Conversely in the group with csPCa, patients with prostatic inflammation had a higher prostate volume (43 vs 40 cc; p=0.007) but no difference in the other clinical parameters. At multivariable analysis adjusting for age, biopsy history, DRE and prostate volume, PSA density emerged as a strong predictor of csPCA but was not associated with prostatic inflammation. The optimal cutoffs of PSA density to diagnose csPCa and rule out the presence of prostatic inflammation in patients with an elevated PSA (>4 ng/ml) were 0.10 ng/ml2 in biopsy naïve patients and 0.15 ng/ml2 in patients with a previous negative biopsy. PSA density rather than PSA, should be used to evaluate patients at risk of prostate cancer who may need additional testing or prostate biopsy. This readily available parameter can potentially identify men who do not have PCa but have an elevated PSA secondary to benign conditions. [ABSTRACT FROM AUTHOR]

Aim: The present study aimed to investigate the predictive value of (F/T)/PSAD and Free PSA/PSAD in PCa detection in Turkish males. Patients and Methods: A retrospective analysis of patients' files, from January 2007 to December 2017, with prostate-specific antigen (PSA) values between 4-10 ng/ml was conducted. According to the prostate biopsy outcomes, data were collected from patients and divided into prostate cancer (PCa) and/or benign prostatic hyperplasia (BPH) groups. Among the groups, prostate volume (PV), Free PSA (FPSA), Total PSA (TPSA), free-to-total PSA ratio (F/T), PSA Density (PSAD), (F/T)/PSAD, and FPSA/PSAD values were evaluated and compared. The utilization of these values in PCa detection was examined. Results: The present study participants were 131 PCa and 196 BPH patients, 327 in total. Sensitivity and specificity values of (F/T)/PSAD and FPSA/PSAD were better than PSAD, PSA, F/T. According to the optimal cut-off value, the sensitivity of (F/T)/PSAD and FPSA/PSAD was similar. Likewise, NPV of F/T, (F/T)/PSAD, and FPSA/PSAD were also similar. The logistic regression model using a combination of age, PV, FPSA/PSAD, and (F/T)/PSAD displayed a higher AUC than each of these values per se. Conclusion: FPSA/PSAD and (F/T)/PSAD, the relatively new parameters, have similar predictive accuracy in PCa detection. They have higher sensitivity and specificity than F/T PSA and PSAD alone. However, more research is needed to evaluate the efficiency of predictive value of these parameters. [ABSTRACT FROM AUTHOR]

Traditionally, men referred for investigation of raised prostate specific antigen (PSA) could expect to be investigated via blind TRUS biopsy. In recent years, the availability of pre‐biopsy imaging with multi‐parametric magnetic resonance imaging (mp‐MRI) has allowed urology centres to improve their triage and care of this patient cohort. The ability to identify discrete lesions for more accurately targeted TRUS, stream patients with anterior lesions for trans‐perineal biopsy, and of course to prevent those with no evidence of clinically significant prostate cancer from being subjected to unnecessary procedures has proved pre‐biopsy mp‐MRI a valuable tool in the assessment and diagnosis of prostate cancer. Our service recently audited the impact of the introduction of mp‐MRI on our prostate cancer assessment pathway. An analysis of the outcomes of 1558 referrals over a 2‐year period, and found that pre‐biopsy imaging has resulted in a marked reduction in unnecessary procedures and more accurate targeting of lesions, leading to improved outcomes for patients. [ABSTRACT FROM AUTHOR]

Introduction: Free to total PSA proportion (f/t FPSA) and PSA density (PSAD) are mostly used PSA derivatives for better cancer detection. In this study, we aimed to evaluate whether or not f/t PSA and PSAD had any diagnostic contribution to prostate cancer (pCa) detection in patients that had prostate volumes >= 100 cc. Material and Methods: The medical records of transrectal ultrasound guided prostate biopsy performed patients were retrospectively evaluated and divided into two categories according to their prostate volumes (=100 cc). The diagnostic value of total PSA, PSAD and f/t PSA in prostate cancer detection for prostate volumes >= 100 cc were statistically evaluated. Results: Among 311 patients 51 and 260 had prostate volumes >=100 cc and =100 cc. Although larger and prospective studies are warranted to make better inferences, up to that time our results may guide clinicians in their daily practice. [Arch Clin Exp Surg 2018; 7(4.000): 166-170]

Objective: In this study, we tried to assess whether power Doppler ultrasonography (PDU) evaluation along with transrectal ultrasound (TRUS) has an additional benefit in the diagnosis of prostate cancer in patients with prostate-specific antigen (PSA) levels of 4-10 ng/mL, when combined with the other methods proposed for this range of PSA. Materials and Methods: Fifty-six patients with PSA values of 4-10 ng/mL were included in the study. Digital rectal examinations, evaluation of total and free PSA, and PDU assessments were done simultaneously with TRUS and eight-core systematic prostate biopsies. Along with the latter, additional biopsies were taken from the suspicious areas detected on PDU. The free/total PSA ratios, PSA density values, TRUS, PDU findings, and biopsy results of 56 patients were recorded and evaluated. Results: Specificity and positive predictive values in detecting prostate cancer in patients with PSA range of 4-10 ng/mL, calculated using the criteria of free/total PSA values <15%, PSA density values >15%, and PDU findings, were 94.87% and 75%, respectively. These values were significantly higher than those of 89.75% and 69.73%, respectively, defined for the criteria of free/total PSA values <15% and PSA density values >15%. Conclusion: The results of this study highlighted that PDU may be useful to detect prostate cancer, and decrease the number of unnecessary biopsy recommendations in patients with PSA values of 4-10 ng/mL, when used in combination with free/total PSA ratio and PSA density. [ABSTRACT FROM AUTHOR]

Little is known about the outcomes of off-protocol selected prostate cancer patients who opt for active surveillance. In our cohort of 1,000 patients, outcomes of PRIAS-eligible patients were compared with outcomes of PRIAS-ineligible patients. Unfavourable outcomes after radical prostatectomy (RP) and risk of metastasis were evaluated. 50% of patients on AS did not comply with the PRIAS criteria. PRIAS-ineligible patients discontinued active surveillance due to tumour progression significantly earlier than PRIAS-eligible patients; they also had a higher risk of positive surgical margins and unfavourable histology after deferred RP. PSA density ≥ 0.2 was the most important individual predictor and, in addition to a higher risk of tumour progression and unfavourable surgical outcomes, was also associated with a significantly higher risk of biochemical progression after deferred radical prostatectomy and a higher risk of metastasis. [ABSTRACT FROM AUTHOR]

• csCaP NPV of mpMRI was 85.1% with a csCaP prevalence 28.9%. • Median GPC in biopsy cores from nonsuspicious group was high, albeit significantly lower than those of suspicious group (40% vs. 50%, p = 0.005). • Only PSAD > 0.15 ng/ml/cc was identified as an independent and significant predictor of csCaP in nonsuspicious group. Multiparametric magnetic resonance imaging (mpMRI) of the prostate has excellent sensitivity in detecting clinically significant prostate cancer (csCaP). However, whether a negative mpMRI in patients with a clinical suspicion of CaP can omit a confirmatory biopsy remains less understood and without consensus. Transperineal (TP) standard template biopsy (SBx) provides an effective approach to CaP detection. Our aim is to provide a comprehensive understanding of the CaP characteristics detected through TP SBx that are systematically overlooked by mpMRI. We conducted a retrospective analysis of all men who underwent prebiopsy mpMRI and subsequent a 20-core TP SBx at our hospital from September 2019 to February 2021. Patients with suspicious mpMRI received a combined TP SBx and targeted biopsy (TBx) (suspicious group), while those without suspicious (negative) mpMRI and who proceeded to biopsy, received TP SBx only (nonsuspicious group). A negative mpMRI was defined as the absence of suspicious findings and/or the presence of low-risk areas with a PI-RADS score of ≤2. Subsequently, we compared and evaluated the clinical and biopsy characteristics between these 2 groups. We identified 301 men in suspicious group and 215 men in nonsuspicious group. The overall CaP detection rate and csCaP detection rate by TP SBx were 74.1%, 38.9% for suspicious group and 43.3%, 14.9% for nonsuspicious group, respectively. csCaP NPV of mpMRI was 85.1% with a csCaP prevalence 28.9%. The greatest percentage of cancer involvement (GPC) in biopsy core from nonsuspicious group was significantly lower than those of suspicious group (40% vs. 50%, p = 0.005), In multivariate logistic analysis, only PSAD > 0.15 ng/ml/cc was identified as an independent and significant predictor of csCaP in nonsuspicious group. Within our cohort, false-negative rates of mpMRI for csCaP are substantial, reaching 15%. Nonsuspicious cases may contain a large volume tumor since the high GPC of SBx. For cases with nonsuspicious imaging and higher PSAD, a confirmatory biopsy may be necessary due to the increased risk of missed csCaP by mpMRI. [ABSTRACT FROM AUTHOR]

Background: To identify the predictor factors, such as prostate-specific antigen (PSA), age, prostate volume (PV), and PSA density (PSAD) as indications to perform transrectal ultrasonography (TRUS)-guided prostate biopsy in reducing unnecessary biopsies and improving detection rate. Methods: A total of 1232 samples were obtained from the medical records of patients underwent prostate biopsy from January 2008 to December 2013 in Cipto Mangunkusumo Hospital Jakarta. Pre-biopsy data including age, PSA, prostate volume, and PSAD were obtained. The Mann-Whitney U-test and unpaired t-test were conducted on the quantitative variables; a chi-square test was used for qualitative variables. This study also conducted receiver operating characteristic (ROC) curve analysis to determine the cut-off point and the optimum specificity and sensitivity for each variable. Results: Among 1232 patients, 33.5% had a positive biopsy result. The median age and PSA (68 years and 57.45 ng/ml) in the positive biopsy group was higher than in the negative group (65 years and 11.69 ng/ml), p Conclusion: The incidence of PCa increased with higher PSA level, older age and lower PV. Utilization of PSAD 0.17 ng/ml/ml as a cut-off point in patients with PSA level between 4-10 ng/ml is recommended to improve PCa detection in Indonesian men.

Aim: The aim of this study is to compare prostate volumes and calculated PSA densities measured by transrectal ultrasound performed by urologists with different levels of experience, and prostate volumes calculated based on magnetic resonance measurements Methods: The study comprises patients who underwent transrectal needle biopsy between February 2015 and November 2018 All of these patients underwent a multiparametric prostate MR using 1,5T Signa HDXT GE with endorectal coil beforehand The ultrasound measurement, done using the Toshiba Applio 500 device with end-fire endorectal probe, was performed by three urologists with two, seven and 20 years of clinical experience Prostate volume was in all patients calculated by using the largest diameters in three perpendicular axes in the „width x height x length x 0 523“ formula PSA density was then calculated as total PSA/prostate volume in millilitres Results: A total of 582 were evaluated The mean age was 62 86 years (31-91), average PSA was 8 70 ng/ml (0 53-75 00) The mean difference between TRUS and MR measurement was +8 41 ml The difference was +3 66 ml for the examiner with twenty years of experience, +11 19 ml for the examiner with seven years of experience and +8 12 ml for the examiner with two years of experience The average difference in PSA density between TRUS and MR was -0 025 ng/ml/ml Using the PSA density cut-off value of 0 15 ng/ml/ml and 0 20 ng/ ml/ml to indicate prostate biopsy, 8 % or 6 % less patients would have undergone prostate biopsy when using TRUS than with MR respectively Conclusion: In this cohort, transrectal ultrasonography yielded larger prostate volume estimates than magnetic resonance imaging; subsequently 6 % or 8 % less biopsies would have been performed when using PSA density as the only criterion for prostate biopsy. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the characteristics and histological outcomes in patients with Prostate Imaging Reporting and Data System (PI-RADS) 3 lesions undergoing magnetic resonance imaging-guided fusion-targeted biopsy (MRIFTB). Methods: We retrospectively reviewed 138 patients with PI-RADS category 3 lesions classified using multiparametric MRI who underwent MRIFTB between May 2016 and March 2018. The study population included biopsy-naïve and patients with prior negative biopsy. Univariate and multivariate analyzes were performed to determine significant predictors of prostate cancer (PCa) and clinically significant prostate cancer (csPCa). The definition of csPCa was set at Gleason score ≥ 3 + 4. Results: Overall, 114 (82.6%) biopsied lesions were benign and 24 (17.4%) were identified as prostate cancer. Of these 24 lesions, 14 (58.3%) harbored csPCa. Peripheral zone (PZ) lesions were more likely to be associated with malignant disease than transition zone lesions (13.7 vs. 6.2%). Multivariate logistic analysis revealed that age, PZ location, and prostate-specific antigen (PSA) density (P < 0.05) were independent predictors of both PCa and csPCa. Conclusions: A non-negligible number of PI-RADS 3 patients harbor csPCa. Moreover, age, lesion location, and PSA density could be potential clinical predictors of PCa and csPCa. Physicians should be aware of the cancer prevalence of PI-RADS 3 lesions, as the use of the aforementioned factors can help in the decision-making process for these patients. [ABSTRACT FROM AUTHOR]

Objective · To investigate the value of prostate volume, free prostate-specific antigen (f-PSA)/total PSA (t-PSA) ratio, PSA density (PSAD), colour Doppler ultrasound and contrast-enhanced transrectal ultrasonography (CETRUS) in patients with PSA level of 4-10 ng/mL. Methods · Retrospective analysis were performed in 119 patients with serum prostate-specific antigen level of 4-10 ng/mL who suspected prostate cancer in Pudong Gongli Hospital Jan 2015 to Jul 2018. All patients received TRUS-guided rectal (8+n)-core method biopsy. According to the result of puncture, the prostate cancer detection rate in patients with different prostate volumes, f-PSA/t-PSA ratios, PSADs, colour Doppler blood flow signals and CETRUS examination results. Results · The detection rate of prostate cancer in biopsies was 56.3% (67/119). The incidence of benign prostatic hyperplasia was 43.7% (52/119). The detection rate of prostate cancer in patients with f-PSA/t-PSA ratio ≤0.15 was higher than that with f-PSA/t-PSA ratio>0.15 (73.6% vs 42.4%, P0.001). The detection rate of prostate cancer in the patients with PSAD>0.2 μg/L was higher than PSAD ≤0.2 μg/L（69.8% vs 48.7%, P0.026). The detection rate of prostate cancer in the patients with positive CETRUS results was higher than that with negative CETRUS results (72.4% vs 41.0%，P0.001). Conclusion · The f-PSA/t-PSA ratio, PSAD and CETRUS examination results have important clinical significance for diagnosis of prostate cancer in patients with serum PSA level of 4-10 ng/mL. [ABSTRACT FROM AUTHOR]

After skin cancer, prostate cancer (PC) is the most common cancer among men. The gold standard for PC diagnosis is based on the PSA (prostate-specific antigen) test. Based on this preliminary screening, the physician decides whether to proceed with further tests, typically prostate biopsy, to confirm cancer and evaluate its aggressiveness. Nevertheless, the specificity of the PSA test is suboptimal and, as a result, about 75% of men who undergo a prostate biopsy do not have cancer even if they have elevated PSA levels. Overdiagnosis leads to unnecessary overtreatment of prostate cancer with undesirable side effects, such as incontinence, erectile dysfunction, infections, and pain. Here, we used artificial neuronal networks to develop models that can diagnose PC efficiently. The model receives as an input a panel of 4 clinical variables (total PSA, free PSA, p2PSA, and PSA density) plus age. The output of the model is an estimate of the Gleason score of the patient. After training on a dataset of 190 samples and optimization of the variables, the model achieved values of sensitivity as high as 86% and 89% specificity. The efficiency of the method can be improved even further by training the model on larger datasets.