Who with suspected prostate cancer can benefit from Proclarix after multiparametric magnetic resonance imaging?

Proclarix is a new blood-based test to assess the likelihood of clinically significant prostate cancer (csPCa) defined as >2 grade group. In this study, we analyzed whether Proclarix and PSA density (PSAD) could improve the selection of candidates for prostate biopsy after multiparametric magnetic resonance imaging (mpMRI). Proclarix and PSAD were assessed in 567 consecutive men with suspected PCa in whom pre-biopsy 3 Tesla mpMRI, scoring with Prostate Imaging-Report and Data System (PI-RADS) v.2, and guided and/or systematic biopsies were performed. Proclarix and PSAD thresholds having csPCa sensitivity over 90% were found at 10% and 0.07 ng/(mL*cm3), respectively. Among 100 men with negative mpMRI (PI-RADS <3), csPCa was detected in 6 cases, which would have been undetected if systematic biopsies were avoided. However, Proclarix suggested performing a biopsy on 70% of men with negative mpMRI. In contrast, PSAD only detected 50% of csPCa and required 71% of prostate biopsies. In 169 men with PI-RADS 3, Proclarix avoided 21.3% of prostate biopsies and detected all 25 cases of csPCa, while PSAD avoided 26.3% of biopsies, but missed 16% of csPCa. In 190 men with PI-RADS 4 and 108 with PI-RADS 5, Proclarix avoided 12.1% and 5.6% of prostate biopsies, but missed 4.8% and 1% of csPCa, respectively. PSAD avoided 18.4% and 9.3% of biopsies, but missed 11.4% and 4.2% csPCa, respectively. We conclude that Proclarix outperformed PSAD in the selection of candidates for prostate biopsy, especially in men with PI-RADS <3.

The Efficacy of Proclarix to Select Appropriate Candidates for Magnetic Resonance Imaging and Derived Prostate Biopsies in Men with Suspected Prostate Cancer.

PURPOSE: To analyze how Proclarix is valuable to appropriately select candidates for multiparametric magnetic resonance imaging (mpMRI) and derived biopsies, among men with suspected prostate cancer (PCa). Proclarix is a new marker computing the clinically significant PCa (csPCa) risk, based on serum thosmbospondin-1, cathepsin D, prostate-specific antigen (PSA) and percent free PSA, in addition to age, that has been developed in men with serum PSA 2 to 10 ng/mL, prostate volume ≥35 mL, and normal digital rectal examination (DRE). MATERIALS AND METHODS: Proclarix score (0%-100%) is analyzed in a prospective frozen serum collection of 517 correlative men scheduled for guided and/or systematic biopsies after mpMRI. Outcome variables were csPCa detection (grade group ≥2), insignificant PCa (iPCa) overdetection and avoided mpMRIs. RESULTS: The area under the curve of Proclarix was 0.701 (95% CI 0.637-0.765) among 281 men with serum PSA 2 to 10 ng/mL, prostate volume ≥35 mL, and -normal DRE, and 0.754 (95% CI 0.701-0.807) in the others, p=0.038. Net benefit of Proclarix existed in all men. After selecting 10% threshold, Proclarix was integrated in an algorithm which also used the serum PSA level and DRE. A reduction of 25.4% of mpMRIs request was observed and 17.7% of prostate biopsies. Overdetection of iPCa was reduced in 18.2% and 2.6% of csPCa were misdiagnosed. CONCLUSIONS: Proclarix is valuable in all men with suspected PCa. An algorithm integrating Proclarix score, serum PSA, and DRE can avoid mpMRI requests, unnecessary prostate biopsies and iPCa overdetection, with minimal loss of csPCa detection.

The current recommendation for the management of isolated high-grade prostatic intraepithelial neoplasia.

OBJECTIVE: To analyse the current predictive value of isolated high-grade prostatic intraepithelial neoplasia (HGPIN) for clinically significant prostate cancer (csPCa) detection in repeat biopsies. PATIENTS AND METHODS: A cohort of 293 men with isolated HGPIN detected in previous biopsies performed without multiparametric magnetic resonance imaging (mpMRI), and who underwent repeat biopsy within 1 to 3 years, was analysed. Pre-repeat biopsy mpMRI and guided biopsies to suspicious lesions (Prostate Imaging - Reporting and Data System [PI-RADS] ≥3) and/or and systematic biopsies were performed. Persistent prostate cancer (PCa) suspicion, defined as sustained serum prostate-specific antigen level >4 ng/mL and/or abnormal digital rectal examination, was present in 248 men (84.6%), and was absent in 45 men (15.4%). A control group of 190 men who had no previous HGPIN, atypical small acinar proliferation or HGPIN with atypia who were scheduled to undergo repeat biopsy due to persistent PCa suspicion were also analysed. csPCa was defined as tumours of Grade Group ≥2. RESULTS: In the subset of 45 men with isolated HGPIN, in whom PCa suspicion disappeared, only one csPCa (2.2%) and one insignificant PCa (iPCa) were detected. csPCa was detected in 34.7% of men with persistent PCa suspicion and previous HGPIN, and in 28.4% of those without previous HGPIN (P =0.180). iPCa was detected in 12.1% and 6.3%, respectively (P =0.039). Logistic regression analysis showed that the risk of csPCa detection was not predicted by previous HGPIN: odds ratio (OR) 1.369 (95% confidence interval [CI] 0.894-2.095; P =0.149); however, previous HGPIN increased the risk of iPCa detection: OR 2.043 (95% CI 1.016-4.109; P =0.006). CONCLUSION: The risk of csPCa in men with isolated HGPIN, in whom PCa suspicion disappears, is extremely low. Moreover, in those men in whom PCa suspicion persists, the risk of csPCa is not influenced by the previous finding of HGPIN. However, previous HGPIN increases the risk of iPCa detection. Therefore, repeat prostate biopsy should not be recommended solely because of a previous HGPIN.

The position of urethrovesical anastomosis after robotic radical prostatectomy assessed by MRI predicts early functional recovery: A cohort analyses from a randomized clinical trial.

PURPOSE: Functional and anatomical changes associated with prostate removal coincide with alterations in pelvic structures. Posterior rhabdosphincter reconstruction was designed to improve urinary continence after radical prostatectomy. The aim of this study was to determine magnetic resonance anatomic predictors of urinary recovery after radical prostatectomy, and to assess their relation to the type of reconstruction. MATERIAL AND METHODS: Forty patients were randomly selected from a trial (NCT03302169). Two independent radiologists determined the situation of the anastomosis in the pelvis according to MRI performed a month after the radical prostatectomy: vertical situation assessed as the distance to the line coccyx-inferior pubic margin (ACPv) and anteroposterior situation as the distance from the pubis (Distance A), and from the coccyx (Distance B). RESULTS: The Pearson correlation of ACPv, Distance A, and B between readers were 0.975, 0.940, and 0.711, p < 0.001. Patients with the reconstruction presented more cephalic situation of the anastomosis (higher ACPv) than patients with standard reconstruction technique. A multivariate analysis was performed including age, BMI, prostate volume, PRRS, and the MRI parameters. ACPv and Distance B were the only two independent predictors of no need for any urinary protection at 6 months after the surgery. CONCLUSIONS: This is the first study that suggests positional differences according to the type of reconstruction after radical prostatectomy related to early urinary recovery. Magnetic resonance measurements to determine anastomosis positioning are reliable and have a strong correlation between readers. Anatomic MRI features are independent predictors of urinary recovery after robotic radical prostatectomy.

Prediction of clinically significant prostate cancer after negative prostate biopsy: The current value of microscopic findings.

OBJECTIVE: To assess the current ability of atypical small acinar proliferation (ASAP), multifocal high-grade prostatic intraepithelial neoplasia (mHGPIN), HGPIN with atypia (PINATYP) and other non-malignant lesions to predict clinically significant prostate cancer (csPCa) in repeat prostate biopsies. METHODS: This retrospective study analyzed 377 repeat prostate biopsies, carried out between 2.014 and 2.017, and excluding those with previous PCa or 5-alpha reductase inhibitors treatment. ASAP, mHGPIN, PINATYP, prostatic atrophy, prostatic hyperplastic atrophy, proliferative inflammatory atrophy (PIA), chronic prostatitis, acute prostatitis, or granulomatous prostatitis, were prospectively reported after 12-core transrectal ultrasound (TRUS) systematic negative previous biopsies. 3T-multiparametric magnetic resonance imaging (mpMRI) was performed previous repeat biopsies. At least 2-core TRUS targeted biopsies of Prostate Imaging-Reporting and Data Systemv2 lesions ≥3, and/or 12-core TRUS systematic biopsy were performed in repeat prostate biopsies. The main outcome measurements were csPCa detection, which was defined when the International Society of Uro-Pathology group grade >1 and avoided biopsies. After logistic regression analysis the most efficient model was selected, nomogram was designed with internal validation, and clinical utility was analyzed. RESULTS: Normal benign tissue alone was present in less than 2% of previous negative biopsies. mHGPIN (39.7%), ASAP (4.3%) and PINATYP (3.7%) failed to predict csPCa risk in repeat biopsies. The finding of PIA (38.2%) associated with a decreased the risk of csPCa with an Odd ratio of 0.54 (95% confidence interval: 0.31-0.95), P= 0.031. The area under the curve, to predict csPCa, of mpMRI was 0.736, increasing up to 0.860 (95% confidence internal:0.82-0.90) when PSA density, age, digital rectal examination, and differential PSA between biopsies and PIA finding were integrated in a predictive model. At 6% threshold, more than 20% of repeat prostate biopsies were saved without missing csPCa. CONCLUSION: Currently, mHGPIN in negative prostate biopsy seems not able to predict the risk of future csPCa. The low incidence of ASAP and PINATYP, in our series, did not allow us to draw conclusions. PIA finding associated with a reduced risk of csPCa, and it could be integrated in a useful based-mpMRI predictive nomogram.

Association between urinary biomarkers and disease progression in adults with autosomal dominant polycystic kidney disease.

BACKGROUND: Height-adjusted total kidney volume (htTKV) is considered as the best predictor of kidney function in patients with autosomal dominant polycystic kidney disease (ADPKD), but its limited predictive capacity stresses the need to find new biomarkers of ADPKD progression. The aim of this study was to investigate urinary biomarkers of ADPKD progression. METHODS: This observational study included ADPKD patients, and two comparator groups of ischaemic and non-ischaemic kidney injury: benign nephroangiosclerosis patients and non-ischaemic chronic kidney disease (CKD) patients. Proteinuria, htTKV and urinary levels of molecules are associated with ischaemia and/or tubular injury. The slope of estimated glomerular filtration rate (eGFR) was used as a dependent variable in univariate and multivariate models of kidney function decline. RESULTS: The study included 130 patients with ADPKD, 55 with nephroangiosclerosis and 40 with non-ischaemic CKD. All patients had increased urinary concentrations of biomarkers associated with tubular lesions (liver fatty acid-binding protein, kidney injury molecule-1, ß2-microglobulin) and molecules overexpressed under ischaemic conditions [hypoxia-inducible factor-1α, vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein-1 (MCP-1)]. These biomarkers correlated positively with htTKV and negatively with the eGFR slope. htTKV was the single best predictor of the eGFR slope variability in univariate analyses. However, a multivariate model including urinary levels of ß2-microglobulin, MCP-1 and VEGF improved the capacity to predict the decline of eGFR in ADPKD patients compared with htTKV alone. CONCLUSIONS: The urinary levels of molecules associated with either renal ischaemia (VEGF and MCP-1) or tubular damage (ß2-microglobulin) are associated with renal function deterioration in ADPKD patients, and are, therefore, candidates as biomarkers of ADPKD progression.

Prostatic-specific antigen density behavior according to multiparametric magnetic resonance imaging result.

OBJECTIVE: To analyze prostatic-specific antigen density (PSAD) according to the Prostate Imaging Reporting and Data System (PIRADSv.2) score, in order to determine how it should be used. METHODS: This correlative series considered 952 men with prostatic-specific antigen >3 ng/ml and/or abnormal digital rectal examination who were subjected to prostatic biopsy (PB) between 2016 and 2017. Of these men, 768 had no previous 5-α-reductase inhibitor use or history of prostate cancer (CaP) and had previously undergone 3-T multiparametric magnetic resonance imaging (mpMRI). In this sample, 549 men were biopsy-naïve and 219 had at least 1 previous negative PB. A 12-core transrectal ultrasound-guided PB was performed in all participants, as well as at least 2-core targeted biopsies of every detected lesion with a PIRADSv.2 score ≥3. Significant CaP (sCaP) was defined as an International Society of Uropathologist grade >1 or tumor length >4 mm. RESULTS: The overall CaP detection was 41.7%, with sCaP detected in 37.4%. sCaP was detected in 4.3% of PIRADSv.2 <3, 21.5% of PIRADSv.2 =3, 56.6% of PIRADSv.2 =4, and 78.5% of PIRADSv.2 =5, (P < 0.001). Insignificant CaP detection ranged from 6.5% to 1.5% respectively (P = 0.099). PSAD was an independent predictor of sCaP (odds ratios 1.971, 95% confidence interval [1.633, 2.378], P <0.001) and mpMRI (OR 3.179, 95%CI [2.593, 4.950], P < 0.001). Age (P = 0.013), family history of CaP (P = 0.021), and the type of PB (initial vs. repeated, P < 0.001) were also independent predictors of sCaP. PSAD was determined by PIRADSv.2 (P = 0.013) and the presence of sCaP (P < 0.001). PSAD increased with PIRADSv.2 score, even in men with CaP (P < 0.001) and slightly in men without CaP (P = 0.019). The area under the curve for mpMRI increased from 0.830 to 0.869 when PSAD was associated, (P < 0.001). The area under the curve of PSAD decreased from 0.727 in men with a PIRADSv.2 score <3 to 0.706 in those with a score of 5. CONCLUSIONS: The efficacy of PSAD to detect sCaP decreases with PIRADSv.2. Predictors other than mpMRI and PSAD exist. Considering these conditions, independent predictors should be integrated in a nomogram and risk-calculator to personalize PB recommendation.

How to implement magnetic resonance imaging before prostate biopsy in clinical practice: nomograms for saving biopsies.

PURPOSE: To combine multiparametric MRI (mpMRI) findings and clinical parameters to provide nomograms for diagnosing different scenarios of aggressiveness of prostate cancer (PCa). METHODS: A cohort of 346 patients with suspicion of PCa because of abnormal finding in digital rectal examination (DRE) and/or high prostate specific antigen (PSA) level received mpMRI prior to prostate biopsy (PBx). A conventional 12-core transrectal PBx with two extra cores from suspicious areas in mpMRI was performed by cognitive fusion. Multivariate logistic regression analysis was performed combining age, PSA density (PSAD), DRE, number of previous PBx, and mpMRI findings to predict three different scenarios: PCa, significant PCa (ISUP-group ≥ 2), or aggressive PCa (ISUP-group ≥ 3). We validate models by ROC curves, calibration plots, probability density functions (PDF), and clinical utility curves (CUC). Cut-off probabilities were estimated for helping decision-making in clinical practice. RESULTS: Our cohort showed 39.6% incidence of PCa, 32.6% of significant PCa, and 23.4% of aggressive PCa. The AUC of predictive models were 0.856, 0.883, and 0.911, respectively. The PDF and CUC showed 11% missed diagnoses of significant PCa (35 cases of 326 significant PCa expected in 1000 proposed Bx) when choosing < 18% as the cutoff of probability for not performing PBx; the percentage of saved PBx was 47% (474 avoided PBx in 1000 proposed). CONCLUSION: We developed clinical and mpMRI-based nomograms with a high discrimination ability for three different scenarios of PCa aggressiveness (https://urostatisticalsolutions.shinyapps.io/MRIfusionPCPrediction/). Specific clinical cutoff points allow us to save a high number of PBx with a minimum of missed diagnoses.

Who Benefits from Multiparametric Magnetic Resonance Imaging After Suspicion of Prostate Cancer?

BACKGROUND: Prostate cancer (PC) suspicion is based on prostate-specific antigen (PSA) and digital rectal examination (DRE). Multiparametric magnetic resonance imaging (mpMRI) increases prostate biopsy (PBx) specificity and sensitivity for detection of aggressive PC. OBJECTIVE: To identify who benefits from mpMRI according to biopsy scenario (initial biopsy [IBx] vs repeated biopsy [RBx]) and the risk of aggressive PC according to PSA-DRE groups (G1, PSA <10ng/ml and -DRE; G2, PSA <10ng/ml and +DRE; G3, PSA ≥10ng/ml and -DRE; G4, PSA ≥10ng/ml and +DRE). DESIGN, SETTING, AND PARTICIPANTS: We carried out a retrospective analysis for 768 consecutive men with PC suspicion and scheduled for PBx in a referral institution in 2016 and 2017. INTERVENTION: Pelvic 3-T mpMRI scanning, targeted biopsy (TBx) for suspicious lesions (Prostate Imaging-Reporting and Data System [PI-RADS] score >1), and 12-core systematic biopsy (SBx). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We measured the rate of PBx procedures that could be avoided and the rate of high-grade PC (HGPC) that would be missed among men with negative mpMRI, and the increase in HGPC detection due to TBx. Univariate and multivariate analyses were performed. RESULTS AND LIMITATIONS: The rate of avoidable biopsies (PI-RADS <3) was 24.2% overall, with 25.7% for IBx and 20.5% for RBx (p=0.057). The IBx and RBx rates were 31.2% and 19.8% in G1, 13.5% and 30.4% in G2, 23.7% and 21.9% in G3, and 2.5% and 0% in G4, respectively. The overall rate of missed HGPC was 1.0% for IBx and 6.5% for RBx (p=0.170), while the IBx and RBx rates were 1.1% and 5.2% for G1, 2.0% and 11.1% for G2, 0% and 7.7% for G3, and 0% and 0% for G4, respectively (p<0.001). The rate of HGPC (PI-RADS 3-5) diagnosed following TBx increased to 23.9% for IBx and to 32.6% for RBx overall (p<0.001), while the IBx and RBx rates were 29.0% and 45.5% for G1, 20.0% and 33.3% for G2, 40.0% and 38.9% for G3, and 0% and 0% for G4, respectively (p<0.001). Limitations are the single-institution design, the lack of randomisation, and small samples for subgroup analyses. CONCLUSIONS: mpMRI was of no benefit for men with PSA ≥10ng/ml and +DRE. Among the other men, mpMRI was of benefit in IBx and RBx as would reduce the biopsy rate by up to 25.7% and increase the net HGPC detection rate by up to 28.4%. PATIENT SUMMARY: All men with suspected prostate cancer could benefit from multiparametric prostate cancer and targeted biopsy except for those with prostate-specific antigen ≥10ng/ml and positive digital rectal examination. The benefits include avoiding unnecessary prostate biopsy procedures and increasing the detection of aggressive cancer.

The role of negative magnetic resonance imaging: can we safely avoid biopsy in P.I.-R.A.D.S. 2 as in P.I.-R.A.D.S. 1?

Purpose: It remains unclear whether patients with prostate cancer suspicion and negative magnetic resonance imaging (M.R.I.) can safely obviate biopsy. The purpose of this study was to assess the clinical negative predictive value (N.P.V.) of M.R.I. in excluding prostate cancer. The secondary end-point was to compare N.P.V. to detect significant prostate cancer of M.R.I.The secondary end-point was to compare N.P.V. to detect significant prostate cancer in M.R.I. classified as P.I.-R.A.D.S.1 and as P.I.-R.A.D.S.2 Methods: From December 2012 to January 2017, 1128 M.R.I.s were performed consecutively due to prostate cancer clinical suspicion. The absence of suspicious and presence of low-risk areas were considered as negative M.R.I., P.I.-R.A.D.S.1 and 2. Biopsy results were compared according to P.I.-R.A.D.S. classification. The clinically significant disease was defined as International Society of Urological Pathology group higher than 1. Results: Two hundred and twenty-two (20%) M.R.I.s didn't highlight targetable imaging suspicious areas, which were recorded as negative tests: 130 (59%) P.I.-R.A.D.S.1 and 92 (41%) P.I.-R.A.D.S.2. Detection of clinically significant prostate cancer in at least one biopsy core was higher in the P.I.-R.A.D.S.2 group, 9% (8/92) vs 3% (4/130), p = 0.047. The N.P.V. in biopsy-naïve men and P.I.-R.A.D.S.1 was 95% for significant disease, while in patients subjected to repeated biopsies and P.I.-R.A.D.S.1, the N.P.V. found was 99%. Those rates differ from the P.I.-R.A.D.S.2 group: N.P.V. in biopsy-naïve patients was 84%, and 95% in repeated biopsy. Conclusions: P.I.-R.A.D.S.2 shouldn't be considered as a negative M.R.I. A biopsy cannot be routinely omitted in biopsy-naïve men with clinical suspicion of cancer and a low-suspicious area in M.R.I., giving the possibility of missing clinically significant tumors.

Intravascular papillary endothelial hyperplasia (Masson tumor) mimicking a sarcoma and developing from an arteriovenous hemodialysis fistula.

Intravascular papillary endothelial hyperplasia (IPEH), also known as Masson's tumor, is a rare nonneoplastic vascular lesion caused by the abnormal proliferation of endothelial cells. Clinically and radiologically, IPEH presents as a soft tissue mass that may simulate and be mistaken for a sarcomatous tumor. There have been reports of this entity involving the skin or subcutaneous tissues in normal blood vessels and vascular malformations. Herein, we present the first reported case of Masson's tumor arising from an arteriovenous hemodialysis fistula. We emphasize the imaging features of this lesion and briefly discuss its pathophysiology.