PSA-density, DRE, and PI-RADS 5: potential surrogates for omitting biopsy?

OBJECTIVE: In contrast to other malignancies, histologic confirmation prior treatment in patients with a high suspicion of clinically significant prostate cancer (csPCA) is common. To analyze the impact of extracapsular extension (ECE), cT-stage defined by digital rectal examination (DRE), and PSA-density (PSA-D) on detection of csPCA in patients with at least one PI-RADS 5 lesion (hereinafter, "PI-RADS 5 patients"). MATERIALS AND METHODS: PI-RADS 5 patients who underwent MRI/Ultrasound fusion biopsy (Bx) between 2016 and 2020 were identified in our institutional database. Uni- and multivariable logistic-regression models were used to identify predictors of csPCA-detection (GGG ≥ 2). Risk models were adjusted for ECE, PSA-D, and cT-stage. Corresponding Receiver Operating Characteristic (ROC) curves and areas under the curve (AUC) were calculated. RESULTS: Among 493 consecutive PI-RADS 5 patients, the median age and PSA was 69 years (IQR 63-74) and 8.9 ng/ml (IQR 6.0-13.7), respectively. CsPCA (GGG ≥ 2) was detected in 405/493 (82%); 36/493 patients (7%) had no cancer. When tabulating for PSA-D of > 0.2 ng/ml/cc and > 0.5 ng/ml/cc, csPCA was found in 228/253 (90%, PI-RADS5 + PSA-D > 0.2 ng/ml/cc) and 54/54 (100%, PI-RADS5 + PSA-D > 0.5 ng/ml/cc). Finally, a model incorporating PSA-D and cT-stage achieved an AUC of 0.79 (CI 0.74-0.83). CONCLUSION: In PI-RADS 5 patients, PSA-D and cT-stage emerged as strong predictors of csPCA at biopsy. Moreover, when adding the threshold of PSA-D > 0,5 ng/ml/cc, all PI-RADS 5 patients were diagnosed with csPCA. Therefore, straight treatment for PCA can be considered, especially if risk-factors for biopsy-related complications such as obligatory dual platelet inhibition are present.

Risk-Adapted Strategy Combining Magnetic Resonance Imaging and Prostate-Specific Antigen Density to Individualize Biopsy Decision in Patients With PI-RADS 3 ``Gray Zone'' Lesions.

INTRODUCTION: Recent guidelines suggest that biopsy may be omitted in some groups of patients with PI-RADS 3 lesions on mpMRI. In this study, we aimed to evaluate biopsy strategies involving prostate-specific antigen density (PSAd) to avoid unnecessary biopsy versus the risk of missing clinically significant prostate cancer (csPCa) in patients with PI-RADS 3 lesions. MATERIAL AND METHODS: Data of 616 consecutive patients who underwent PSAd and mpMRI before prostate biopsy between January 2017 and January 2022 at a single center were retrospectively assessed. All of these patients underwent combined cognitive or fusion targeted biopsy of suspicious lesions and transrectal ultrasonography guided systematic biopsy. PI-RADS 3 based strategies with PSAd and mpMRI combination were created. For each strategy, avoided unnecessary biopsy, reduced ISUP Grade 1, and missed ISUP Grade ≥ 2 ratios were determined. Decision curve analysis (DCA) was used to statistically compare the net benefit of each strategy. RESULTS: DCA revealed that patients who had PI-RADS 3 lesions with PSAd ≥ 0.2, and/or patients who had PI-RADS 4 and 5 lesions had the most benefit, under the threshold probability level between 10% and 50%, which avoided 48.2% unnecessary prostate biopsies and reduced 51% of ISUP grade 1 cases, while missed 17.5% of ISUP grade ≥ 2 cases. (22.1% for ISUP grade 2 and 8.8% for ISUP grade ≥ 3). Strategy 1 (PI-RADS 4-5 and/or PSAd ≥ 0.2), 3 (PI-RADS 4-5 and/or PI-RADS 3 if PSAd ≥ 0.15), and 7 (PI-RADS 4-5 and/or PI-RADS 3 if PSAd ≥ 0.15 and/or PI-RADS 2 if PSAd ≥ 0.2) were the next three best strategies. CONCLUSION: mpMRI combined with PSAd strategies reduced biopsy attempts in PI-RADS 3 lesions. Using these strategies, the advantage of avoiding biopsy and the risk of missing the diagnosis of csPCa can be discussed with the patient, and the biopsy decision can be made afterwards.

PI-RADS upgrading as the strongest predictor for the presence of clinically significant prostate cancer in patients with initial PI-RADS-3 lesions.

PURPOSE: Unclear lesions on multiparametric magnetic resonance tomography (mpMRI) are challenging for the indication of biopsy in patients with clinical suspicion of prostate cancer (PCa). The aim of this study is the validation of the detection rate of clinically significant PCa (csPCa) in patients with PI-RADS 3 findings and to determine the appropriate follow-up strategy. METHODS: In this retrospective single-center study, patients with maximum PI-RADS 3 lesions underwent targeted MRI/ultrasound-fusion biopsy (tPbx) combined with systematic 12-core biopsy (sPbx) and follow-up mpMRI with further control biopsy. We assessed the evolution of MRI findings (PI-RADS, volume of the lesion), clinical parameters and histopathology in follow-up MRI and biopsies. The primary objective is the detection rate of csPCa, defined as ISUP ≥ 2 findings. RESULTS: A total of 126 patients (median PSA 6.65 ng/ml; median PSA-density (PSAD) 0.13 ng/ml2) were included. The initial biopsy identified low-risk PCa in 24 cases (19%). During follow-up biopsy, 22.2% of patients showed PI-RADS upgrading (PI-RADS > 3), and 29 patients (23%) exhibited a tumor upgrading. Patients with PI-RADS upgrading had a higher risk of csPCa compared to those without PI-RADS upgrading (42.9% vs. 9.18%, p < 0.05). PI-RADS upgrading was identified as an independent predictor for csPCa in follow-up biopsy (OR 16.20; 95% CI 1.17-224.60; p = 0.038). CONCLUSION: Patients with stable PI-RADS 3 findings may not require a follow-up biopsy. Instead, it is advisable to schedule an MRI, considering that PI-RADS upgrading serves as an independent predictor for csPCa.

Clinical significance of prostate cancer identified by transperineal standard template biopsy in men with nonsuspicious multiparametric magnetic resonance imaging.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Prostate-specific Antigen Density as a Proxy for Predicting Prostate Cancer Severity: Is There Any Difference between Systematic and Targeted Biopsy?

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.

The Predictive Value of Prostate-Specific Antigen Density: A Retrospective Analysis of Likert 3 Multiparametric MRI of the Prostate.

Background Many international studies have covered the predictors of prostate cancer, but there is limited information pertaining to Likert 3 MRI scores and the diagnosis of clinically significant prostate cancer (cs-PCa). Therefore, this study aimed to assess the detection rate of significant prostate cancer in men with a Likert 3 score multiparametric MRI (mp-MRI) and the predictive value of prostate-specific antigen (PSA) density in detecting significant prostate cancer. Methods This is a retrospective analysis of patients referred for suspected confined prostate cancer. Inclusion criteria were patients with prostate mp-MRI score of Likert 3 and a prostate biopsy performed. Exclusion criteria included grossly abnormal feeling prostate, no biopsy performed, and an mp-MRI score (Prostate Imaging-Reporting and Data System/Likert) of 1, 2, 4, and 5. cs-PCa was defined as ≥ Gleason 3+4 prostate cancer. PSA density (PSAD) was calculated from MRI estimation of prostate volume. PSAD and histology results were subjected to receiver operating characteristic (ROC) curve analysis with the intention to assess the detection rate of significant prostate cancer in men with Likert 3 mp-MRI and the predictive value of PSAD in detecting significant prostate cancer. Results A total of 819 eligible men had a pre-biopsy mp-MRI scan taken between October 2019 and March 2022. A total of 177 men (21.6%, n = 819) were Likert 3 positive, and 31 did not proceed to take prostate biopsies. A total of 146 patients were included in the study. The median PSAD was 0.19 in men with cs-PCa. Prostate cancer was detected in 42 men (28.8% of the total included set), of which 27 (18.5%) had a Gleason 3+3 prostate cancer and 15 (10.3%) had Gleason ≥ 3+4 prostate cancer. Therefore, 35.7% (n = 42) of biopsy-positive men with Likert 3 mp-MRI had cs-PCa. The ROC curve analysis confirms that PSAD is a predictor of cs-PCa. The optimal PSAD threshold was 0.16 (95% CI: 0.14-0.19), which gives an accuracy of 0.7371, a sensitivity of 0.7333, and a specificity of 0.7375. Conclusion The specificity of PSAD is arguably insufficient for it to stand alone as a decision-making tool when counseling men with equivocal mp-MRI on whether or not to undergo prostate biopsy. A predictive model will need to incorporate other independent risk factors. These may include lesion size, multiplicity, location of lesion(s), and age.

Re-evaluating the diagnostic efficacy of PSA as a referral test to detect clinically significant prostate cancer in contemporary MRI-based image-guided biopsy pathways.

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.

Can the Gleason score be predicted in patients with prostate cancer? A dynamic contrast-enhanced MRI, (68)Ga-PSMA PET/CT, PSA, and PSA-density comparison study.

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 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). CONCLUSION: No 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.

Conditional survival of patients with low-risk prostate cancer: Temporal changes in active surveillance permanence over time.

PURPOSE: To determine risk categories for patients with prostate cancer (PCa) in active surveillance (AS) and to test the conditional survival (CS) that examined the effect of event-free survival since AS-entrance. MATERIALS AND METHODS: From January 2012 to December 2020 we analyzed 606 patients with PCa enrolled in our AS program. Kaplan-Meier (KM) plots depicted AS-exit rate. Multivariable Cox regression models (MCRMs) tested for AS-exit rate independent predictors to determine risk categories. CS estimates were used to calculate overall AS-exit rate after event-free survival intervals of 1, 2, 3, and 5 years, and after stratification according to risk categories. RESULTS: At MCRMs PSAd ≥ 0.15 (HR: 1.43; P-value 0.04), PI-RADS 4-5 (HR: 2.56; P-value <0.001) and number of biopsy positive cores ≥ 2 (HR: 1.75; P-value <0.001) were independent predictors of AS-exit. These variables were used to determine risk categories: low-, intermediate- and high-risk. Overall, according to CS-analyses, 5-year AS-exit free rate increased from 59.7% at baseline, to 67.3%, 74.7%, and 89.4% in patients who remained in AS respectively ≥1, ≥2, ≥3 and ≥5 years. After stratification according to risk categories, in those patients who remained in AS ≥ 5 years, 5-year AS-exit free rates increased from 76.3% to 100% in patients with a low-risk, from 62.7% to 83.7% in patients with an intermediate-risk and from 42.3% to 87.5% in patients with a high-risk. CONCLUSIONS: CS models showed a direct relationship between event-free survival duration and subsequent AS permanence in overall PCa patients and after stratification according to risk categories.

Developing a predictive model for clinically significant prostate cancer by combining age, PSA density, and mpMRI.

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.

Freehand transperineal prostate biopsy with a coaxial needle under local anesthesia: Experience from a single institution in Malaysia.

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 < 0.05). TPPBx exhibited an infection rate of zero. Conclusion: The PCa detection rate and patient tolerability of freehand TPPBx using a coaxial needle are similar to those of a contemporary published series. The use of existing equipment that is used for TRUS biopsy allows for widespread use and transition from TRUS biopsy.

Utility of PSA density in patients with PI-RADS 3 lesions across a large multi-institutional collaborative.

INTRODUCTION: Prostate MRI detecting PI-RADs = 3 lesions has low diagnostic utility for prostate malignancy. Use of PSA density has been suggested to further risk-stratify these men, to potentially avoid biopsies in favor of monitoring. We evaluate the ability of PSA density (PSAd) to risk-stratify PIRADs 3 lesions across patients who underwent a prostate biopsy in a large multi-institutional collaborative. MATERIALS AND METHODS: Pennsylvania Urology Regional Collaborative (PURC) is a voluntary quality improvement collaborative of 11 academic and community urology practices in Pennsylvania and New Jersey. A retrospective analysis was performed on all patients in the PURC database that had a prostate MRI with PI-RADs 3 lesions only. PSA just before the MRI and prostate size reported on MRI were used to calculate the PSA. Clinicopathologic data were evaluated. Univariable analysis using Chi-Square and Kruskal Wallis tests and multivariable logistic regression were used to identify predictors of any PCa, and clinically significant prostate cancer (csPCa) was defined as ≥ Grade Group 2 (GG2.) RESULTS: Between May 2015 and March 2021, 349 patients with PIRADs 3 lesions only were identified and comprised the cohort of interest. Median PSA was 5.0 with a prostate volume of 58cc and a median PSA density of 0.11, 10.6% of the cohort was African American with 81.4% being Caucasian. Significant prostate cancer was detected in 70/349 (20.0%) men. Smaller prostate volume, abnormal DRE, and higher PSAd were significantly associated with clinically significant prostate cancer on univariable analysis. In men with PSAd <0.15, 31/228 (13.6%) harbored csPCa. Multivariable analysis confirmed that men with PSAd >0.15 were more likely to harbor clinically significant prostate cancer (P < 0.001). CONCLUSION: Across a large regional collaborative, patients with PIRADs 3 lesions on mpMRI were noted to have clinically significant cancer in 20% of biopsies. Using a PSA density cut-off of 0.15 may result in missing clinically significant prostate cancer in 13.6%. This information is useful for prebiopsy risk stratification and counseling.

Should Targeted Biopsy be Performed in Patients Who Have Only Pi-rads 3 Lesions?

OBJECTIVE: To determine whether clinical or radiological parameters can predict clinically significant prostate cancer (csPC) in patients with the Prostate Imaging Reporting and Data System (PI-RADS) 3 lesions. PATIENTS AND METHODS: Data were obtained from 247 patients with PI-RADS 3 lesions on mpMRI and who had received a software guided transperineal/transrectal MRI/transrectal ultrasonography (MRI/TRUS) fusion prostate biopsy with concomitant standard systematic 12-core biopsy following mpMRI in the prostate cancer and prostate biopsy database of Turkish Urooncology Association, between 2016 and 2020. The cut-off values of clinical parameters were determined using receiver operating characteristic (ROC) curve analysis. Simple and multiple logistic regression analyses were performed to determine the clinical parameters in predicting csPC. RESULTS: A total of 56 patients (22.6%) had prostate cancer, 23 (9.3%) of whom had csPC. In the lesion- based analysis, cancer detection rates (CDRs) of each lesion in targeted biopsy were found to be 6% and 5% for ISUP GG 1 and ISUP GG ≥ 2, respectively. In the patient-based analysis, clinically insignificant CDRs were significantly higher in systematic biopsy compared with targeted biopsy, whereas no significant difference was found in terms of clinically significant CDRs (p = 0.020 and p=0.422, respectively). The cut-off values were determined as 48.3 mL (AUC [95% CI] = 0.68 [0.53-0.82]) for prostate volume, and 0.213 ng/mL/mL (AUC [95% CI] = 0.64 (0.51-0.77]) for PSAD in predicting csPC. In the multiple logistic regression analysis, only PSAD was found to be an independent risk factor in predicting csPC (OR [95% CI]: 3.56 [1.15-10.91], p = 0.024). CONCLUSION: Since PSAD > 0.20 ng/mL/mL was found to be positive independent risk factor in predicting csPC, in the absence of advanced radiological parameters, PSAD could be used for the biopsy decision in patients with PI-RADS 3 lesions.

PSA density is associated with BPH cellular composition.

BACKGROUND: Current AUA guidelines recommend 5 alpha reductase inhibitor (5ARI) treatment for patients with obstructive benign prostatic hyperplasia (BPH) that display prostate volume ≥30 cc and total prostate specific antigen (PSA) ≥1.5 ng/ml. However, BPH is highly pleomorphic and response to 5ARIs is highly variable. An understanding of cellular composition based on a noninvasive PSA density test could lead to improved clinical decision making. METHODS: The histological composition of 307 BPH specimens was scored by a pathologist for stromo-glandular content and associated with total PSA, prostate volume, PSA density and other clinical variables using univariate and multivariate linear regression. RESULTS: The percentage of glandular composition in prostates of 5ARI-naïve men was positively and independently associated with PSA and PSA density. It was determined through statistical modeling that a PSA density ≤0.05 ng/ml2 associated with a glandular composition of ≤30% with 76% sensitivity. CONCLUSIONS: PSA density could provide a decisive variable for estimating BPH cellular content and may eventually improve selection of patients for 5ARI treatment. Further work is needed to demonstrate that patients with higher glandular content are more responsive to 5ARI treatment.

Comparison of Proclarix, PSA Density and MRI-ERSPC Risk Calculator to Select Patients for Prostate Biopsy after mpMRI.

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.

Should Targeted Biopsy be Performed in Patients Who Have Only Pi-rads 3 Lesions?

Objective: To determine whether clinical or radiological parameters can predict clinically significant prostate cancer (csPC) in patients with the Prostate Imaging Reporting and Data System (PI-RADS) 3 lesions. Patients and Methods: Data were obtained from 247 patients with PI-RADS 3 lesions on mpMRI and who had received a software guided transperineal/transrectal MRI/transrectal ultrasonography (MRI/TRUS) fusion prostate biopsy with concomitant standard systematic 12-core biopsy following mpMRI in the prostate cancer and prostate biopsy database of Turkish Urooncology Association, between 2016 and 2020. The cut-off values of clinical parameters were determined using receiver operating characteristic (ROC) curve analysis. Simple and multiple logistic regression analyses were performed to determine the clinical parameters in predicting csPC. Results: A total of 56 patients (22.6%) had prostate cancer, 23 (9.3%) of whom had csPC. In the lesion- based analysis, cancer detection rates (CDRs) of each lesion in targeted biopsy were found to be 6% and 5% for ISUP GG 1 and ISUP GG ≥ 2, respectively. In the patient-based analysis, clinically insignificant CDRs were significantly higher in systematic biopsy compared with targeted biopsy, whereas no significant difference was found in terms of clinically significant CDRs (p = 0.020 and p=0.422, respectively). The cut-off values were determined as 48.3 mL (AUC [95% CI] = 0.68 [0.53–0.82]) for prostate volume, and 0.213 ng/mL/mL (AUC [95% CI] = 0.64 (0.51–0.77]) for PSAD in predicting csPC. In the multiple logistic regression analysis, only PSAD was found to be an independent risk factor in predicting csPC (OR [95% CI]: 3.56 [1.15–10.91], p = 0.024). Conclusion: Since PSAD > 0.20 ng/mL/mL was found to be positive independent risk factor in predicting csPC, in the absence of advanced radiological parameters, PSAD could be used for the biopsy decision in patients with PI-RADS 3 lesions (AU)

Predicting the diagnosis of prostate cancer with a scoring system based on novel biomarkers.

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.

Early PSA density kinetics predicts biochemical and local failure following extreme hypofractionated radiotherapy in intermediate-risk prostate cancer.

PURPOSE: 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). METHODS AND MATERIALS: 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. RESULTS: 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). CONCLUSIONS: 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.

Impact of Multiparametric MRI and PSA Density on the Initial Indication or the Maintaining in Active Surveillance During Follow-Up in low-Risk Prostate Cancer.

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 fifty-seven 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.

Unified model involving genomics, magnetic resonance imaging and prostate-specific antigen density outperforms individual co-variables at predicting biopsy upgrading in patients on active surveillance for low risk prostate cancer.

BACKGROUND: Active surveillance (AS) is the reference standard treatment for the management of low risk prostate cancer (PCa). Accurate assessment of tumor aggressiveness guides recruitment to AS programs to avoid conservative treatment of intermediate and higher risk patients. Nevertheless, underestimating the disease risk may occur in some patients recruited, with biopsy upgrading and the concomitant potential for delayed treatment. AIM: To evaluate the accuracy of mpMRI and GPS for the prediction of biopsy upgrading during active surveillance (AS) management of prostate cancer (PCa). METHOD: A retrospective analysis was performed on 144 patients recruited to AS from October 2013 to December 2020. Median follow was 4.8 (IQR 3.6, 6.3) years. Upgrading was defined as upgrading to biopsy grade group ≥2 on follow up biopsies. Cox proportional hazard regression was used to investigate the effect of PSA density (PSAD), baseline Prostate Imaging-Reporting and Data System (PI-RADS) v2.1 score and GPS on upgrading. Time-to-event outcome, defined as upgrading, was estimated using the Kaplan-Meier method with log-rank test. RESULTS: Overall rate of upgrading was 31.9% (n = 46). PSAD was higher in the patients who were upgraded (0.12 vs. 0.08 ng/ml2 , p = .005), while no significant difference was present for median GPS in the overall cohort (overall median GPS 21; 22 upgrading vs. 20 no upgrading, p = .2044). On univariable cox proportional hazard regression analysis, the factors associated with increased risk of biopsy upgrading were PSA (HR = 1.30, CI 1.16-1.47, p = <.0001), PSAD (HR = 1.08, CI 1.05-1.12, p = <.0001) and higher PI-RADS score (HR = 3.51, CI 1.56-7.91, p = .0024). On multivariable cox proportional hazard regression analysis, only PSAD (HR = 1.10, CI 1.06-1.14, p = <.001) and high PI-RADS score (HR = 4.11, CI 1.79-9.44, p = .0009) were associated with upgrading. A cox regression model combining these three clinical features (PSAD ≥0.15 ng/ml2 at baseline, PI-RADS Score and GPS) yielded a concordance index of 0.71 for the prediction of upgrading. CONCLUSION: In this study PSAD has higher accuracy over baseline PI-RADS score and GPS score for the prediction of PCa upgrading during AS. However, combined use of PSAD, GPS and PI-RADS Score yielded the highest predictive ability with a concordance index of 0.71.