Clinical utility of MR/ultrasound fusion-guided biopsy in patients with lower suspicion lesions on active surveillance for low-risk prostate cancer

BackgroundThe utility of Multiparametric magnetic resonance imaging (mpMRI) guided prostate biopsy among patients with prostate cancer (CaP) managed with active surveillance (AS) with low-suspicion lesions remains unsettled.MethodsWe performed a retrospective analysis of 415 men with low-risk CaP managed with active surveillance. We selected men with mpMRI visible index lesions scored as 2 or 3 according to Prostate Imaging Reporting and Data System (PI-RADS) version 2. The primary outcome was detection of clinically significant prostate cancer (csCaP) was defined as Gleason grade group ≥ 2. We assessed the diagnostic accuracy of biopsy approaches using area under the receiver operator characteristic (ROC) curve and evaluated factors associated with csCaP in these patients using multivariate logistic regression.ResultsCsCaP was identified in 22 of 125 patients (17.6%) with PI-RADS 2 or 3 index lesions during surveillance prostate biopsies. These included 10 (45.5%) diagnosed by systematic biopsy alone, 9 (40.9%) by targeted alone, and 3 (13.6%) by both approaches. On multivariable analysis, the only significant variable predicting the detection of csCaP in men with low-risk imaging mpMRI characteristics was higher PSAD (OR per 0.1 unit=2.26, 95% CI 1.25–4.06, P = 0.007. A PSAD cutoff of 0.1, 0.12 and 0.15 resulted in a negative predictive value (NPV) of 90.9%, 87.1% and 86.2%, respectively. When stratified by PI-RADS score, a PSAD cutoff of 0.1, 0.12 and 0.15 resulted in NPV of 96.2%, 90.6% and 89.7% and 86.2%, 84.2% and 83.3% for detection of csCaP in PI-RADS 2 and 3 lesions, respectively. In patients with PIRDAS 2 lesions, using a PSAD of 0.1 would potentially allow 51% of patients to avoid biopsy with only a 3.8% chance of missing csCaP.ConclusionIn men with clinical low-risk prostate cancer on active surveillance with PI-RADS 2 and 3 lesions, there is an almost 18% risk of upgrade to csCaP. Integration of PSAD may be a useful adjunctive tool in identifying patients at highest risk for upgrade despite favorable imaging findings. In men with PIRADS 2 lesions with PSAD ≤0.12 biopsy can be avoided. For men with PIRADS 2 lesions with PSAD ≤0.15 informed decision making regarding the AS intensity should include that these patients have a low risk (>10%) of developing csCaP. In men with PIRADS 3 lesions with PSAD >0.1, shared decision making should include discussion of a >10% miss rate of csCaP.     

The utility of in-bore multiparametric magnetic resonance-guided biopsy in men with negative multiparametric magnetic resonance-ultrasound software-based fusion targeted biopsy

ObjectivesTo evaluate the utility of in-bore multiparametric magnetic resonance-guided biopsy of the prostate (IB) in patients with visible lesion/s and previous negative software-based multiparametric magnetic resonance imaging/ultrasonography fusion-targeted biopsy of the prostate (FTB).Patients and methodsWe retrospectively analysed prospectively maintained database including consecutive men undergoing IB from March 2013 to October 2017 in 2 European centres expert in this procedure. We selected men with the following criteria: No previous treatment for prostate cancer (CaP), multiparametric magnetic resonance imaging (mpMRI) lesion(s) PIRADS score ≥ 3, FTB showing no clinically significant cancer (csCaP), and subsequent IB. Patient's characteristics, mpMRI findings, biopsy technique, and histopathological results were extracted. The primary outcome was to determine the detection rate of csCaP, defined as any Gleason pattern ≥ 4. A multivariable analysis was performed to identify predictors of positive findings at IB.ResultsFifty-three men were included. Median age was 68 years (interquartile range [IQR] 64–68), median Prostate-Specific Antigen (PSA) was 7.6 ng/ml (IQR 5.2–10.9), and median prostate volume was 59 ml (IQR 44–84). Fifty-six lesions with PIRADS score 3 in 9 cases (16%), 4 in 30 cases (54%), and 5 in 17 cases (30%) were detected. FTB was performed in all cases using a transrectal approach with 3 different platforms (Toshiba, Koelis, and Artemis). Median time between FTB and IB was 3 months (IQR 1–7). A median of 2 cores per lesion were collected with IB (IQR 2–3). No cancer, clinically insignificant and clinically significant cancer were found in 33 (59%), 9 (16%), and 14 (25%) targeted lesions, respectively. Median maximum cancer core length and maximum positive percentage were 9 mm (3–13) and 55% (21%–80%). The only predictor of csCaP on IB was prostate volume (P = 0.026) with an ideal cut-off at 70 ml.ConclusionOne in 4 patients with previous negative FTB, IB was able to detect csCaP. According to this study, IB would be of particularly useful in patients with large glands.     

PI-RADS 3 lesions: Does the association of the lesion volume with the prostate-specific antigen density matter in the diagnosis of clinically significant prostate cancer?

IntroductionCurrently, a new subclassification of the Pi-RADS 3 lesions and subgroups is being used: 3a (indolent or low-risk lesions with volume <0.5 ml) and 3b (significant or high-risk lesions with volume ≥0.5 ml). The prostate-specific antigen density (PSAd) has been identified as a diagnostic tool that helps to predict clinically significant prostate cancer (csCaP). The aim of this study is to evaluate the association of the volume of the Pi-RADS 3 lesions and the PSAd in the diagnosis of csCaP.Material and MethodsWe conducted a retrospective study that included prostate biopsies performed using a transperineal approach and guided by ultrasound between 2015 and 2020. csCaP was defined as Gleason score ≥3 + 4. The population was divided into groups according to the Pi-RADS 3 subclassification and the PSAd value. We calculated sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) of 3b lesions for the detection of high-grade prostate cancer, alone and combined with PSAD groups.ResultsIn total, 99 patients with Pi-RADS 3 lesions were included. Forty-three patients were in group 3a and 56, in 3b. Mean PSA was 7.28 ± 2.6 ng/ml. Pi-RADS 3a lesion did not present csCaP but 17.8% of Pi-RADS 3b lesion did. In group 3b with PSAd > 0.15, 62.5% presented csCaP. In those Pi-RADS 3b with PSAd ≤ 0.15, all biopsies were insignificant prostate cancer (isCaP) and 40 biopsies could have been avoided. Considering 3b as positive for csCaP detection, sensitivity was 100%, specificity 48.3%, NPV 17.8%, and PPV 100%. When adding PSAd to group 3b, sensitivity was 100%, specificity was 86.9%, NPV was 62.5%, PPV was 100%. In total, only the subgroup 3b with PSAd > 0.15 presented csCaP and 83.8% biopsies could be avoided.ConclusionsIn this series, the association of the volume of PIRADS 3 lesion and the PSAd improves specificity and PPV contributing to improve the management of csCaP.     

A magnetic resonance imaging-based nomogram for predicting clinically significant prostate cancer at radical prostatectomy

PurposeTo develop a nomogram incorporating clinical and multiparametric magnetic resonance imaging (mpMRI) parameters for the detection of clinically significant prostate cancer (csCaP) at radical prostatectomy (RP).Materials and MethodsWe retrospectively analyzed all consecutive patients who underwent robotic RP between 2016 and 2020. All patients underwent a 1.5-T mp-MRI according to the PI-RADS-v2 scoring system. RP specimens were examined with the whole-mount technique. csCaP definition: any tumor with a volume larger than 0.5 cm³ or with a Gleason score ≥7. Univariable logistic regression models explored the association between clinical and imaging data and the risk of csCaP. Significant variables (P < 0.05) were selected into multivariable regression models to identify independent predictors. A nomogram was designed to select the significant relevant predictors. The nomogram was internally validated in terms of discrimination and calibration. Receiver operating characteristics of the area under the curve was used to assess the discrimination ability of the nomogram. To assess the predictive performance of mpMRI, the accuracy of the mpMRI-based nomogram was compared with that excluding either PI-RADS score or mpMRI IL size.ResultsThe analysis involved 393 patients. The median age was 65(9) years. The median prostate specific antigen was 5.81(3.76) ng/ml. 363 had csCaP. PI-RADS v2 score of 4-5, prostate specific antigen density of 0.15 or more, and mpMRI index lesion (IL) size were significantly associated with csCaP in the multivariable regression analyses. Based on these variables, a diagnostic model was developed. The full model yielded an area under the curve of 0.77 (95%CI:0.75–0.80) which was significantly better than those excluding mpMRI findings (P = 0.02) Decision curve analysis showed a slight but significant net benefit associated with the use of the mp-MRI based nomograms compared with those excluding either PI-RADS score (Delta net benefit 0.0278) or mpMRI maximum IL size (Delta net benefit 0.0111).ConclusionsThe nomogram constructed in this study can assist urologists in assessing an individual's risk of csCaP at RP.     

Multiparametric MRI with in-bore targeted biopsy in the diagnostic pathway of prostate cancer: Data from a single institution experience

BackgroundAccuracy of multiparametric MRI (mpMRI) for the detection of significant prostate cancer (CaP) varies in the literature as only few studies use radical prostatectomy specimens as their gold standard. On another hand, MRI-targeted prostate biopsy is emerging as an alternative to the traditional randomized biopsy, with a higher detection rate of high-grade cancers. However, data on MRI guided in bore biopsy is lacking.Material and methodsWe reviewed every patient that had his mpMRI, MRI guided in bore biopsy and radical prostatectomy performed in our hospital between November 2015 and December 2020. The diagnostic performances of both mpMRI and MRI targeted biopsy in sampling PIRADS index lesions were studied, using radical prostatectomy specimens as the gold standard. Sensitivity, specificity, positive predictive value and negative predictive value of mpMRI for detecting T3 stage, extra-capsular extension, seminal vesicles involvement and lymph node disease were also evaluated.ResultsSixty-two met our inclusion criteria. For PIRADS≥3 lesions, sensitivity and positive predictive value for detecting clinically significant CaP were of 83.5% and 94.7%. A total of 32.2% prostate cancers on targeted biopsy were upgraded on final pathology, with an upgrading to ISUP≥2 in 3.2% and to ISUP≥3 in 14.5%. A total of 20.9% of cancers were downgraded but without any downgrading to ISUP 1. When final pathology is taken as a gold standard, sensitivity of mpMRI was 31.8% for T3 staging prediction, 30.0% for extra-capsular extension, 28.7% for seminal vesicles involvement and 66.7% for lymph node disease prediction. Specificity was 89.3%, 93.1%, 95.3%, and 92.7%, respectively.ConclusionmpMRI has an acceptable accuracy for the prediction of significant CaP and index lesion detection but is unreliable for CaP staging. Comparison between pathology and biopsy results revealed that the in-bore biopsy technique has an upgrading and downgrading rate comparable in the literature to fusion biopsy, but higher than the combined biopsy approach.     

A novel nomogram combined PIRADS v2 and neutrophil-to-lymphocyte ratio to predict the risk of clinically significant prostate cancer in men with PSA < 10 ng/ml at first biopsy

ObjectiveTo determine whether Prostate Imaging-Reporting and Data System version 2 (PIRADS v2) and neutrophil-to-lymphocyte ratio(NLR) improve the detection of clinically significant prostate cancer(csCaP) in men with prostate-specific antigen (PSA) <10 ng/ml at first biopsy.MethodsUnivariable and multivariable binary logistic regression analysis were used to screen for independent risk factors of csCaP. The multivariable model based on the risk factors was to build the nomogram predicting csCaP and assessed by receiver operator characteristic curve analysis, calibration plot, and decision curve analysis.ResultsThis retrospective study included 335 men with PSA < 10 ng/ml who underwent initial biopsy. A total of 78 (23.3%) men had csCaP. The nomogram was built based on the multivariable model including age, digital rectal examination, free prostate-specific antigen, PIRADS v2, and NLR. It had high area under the curve of 0.876 and was well calibrated in internal validation. Decision curve analysis also demonstrated that it would improve the prediction of csCaP.ConclusionPIRADS v2 and NLR improve the detection of csCaP in men with PSA < 10 ng/ml at first biopsy. Due to lack of external validation, relatively small cohort and homogenous population, the study has several limitations. Despite of this, the nomogram based on our study is a promising tool for patients to understand their risk of csCaP and for urologists to make clinical decisions.     

Prostate zonal anatomy correlates with the detection of prostate cancer on multiparametric magnetic resonance imaging/ultrasound fusion–targeted biopsy in patients with a solitary PI-RADS v2–scored lesion

PurposeTo evaluate the positive predictive value (PPV) of the Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) assessment method in patients with a single suspicious finding on prostate multiparametric magnetic resonance imaging (mpMRI).Patients and methodsA total of 176 patients underwent MRI/ultrasound fusion–targeted prostate biopsy after the detection of a single suspicious finding on mpMRI. The PPV for cancer detection was determined based on PI-RADS v2 assessment score and location.ResultsFusion biopsy detected prostate cancer in 60.2% of patients. Of these patients, 69.8% had Gleason score (GS) ≥7 prostate cancer. Targeted biopsy detected 90.5% of all GS≥7 prostate cancer. The PPV for GS≥7 detection of PI-RADS v2 category 5 (P5) and category 4 (P4) lesions was 70.2% and 37.7%, respectively. This increased to 88% and 38.5% for P5 and P4 lesions in the peripheral zone (PZ), respectively. Targeted biopsy did not miss GS≥7 disease compared with systematic biopsy in P5 lesions in the PZ and transition zone.ConclusionThe PPV of PI-RADS v2 for prostate cancer in patients with a single lesion on mpMRI is dependent on PI-RADS assessment category and location. The highest PPV was for a P5 lesion in the PZ.     

Serial prostate magnetic resonance imaging fails to predict pathological progression in patients on active surveillance

IntroductionLimited data guide urological practice when employing prostate magnetic resonance imaging (MRI) in active surveillance (AS) protocols. To determine the ability of prostate MRI to predict pathological progression in AS patients, we correlated findings of serial MRI with results of surveillance biopsies.MethodsPatients on AS with ≥2 prostate MRI and ≥2 prostate biopsies were included. Prostate Imaging-Reporting and Data System (PI-RADS) score upgrade, as assigned by experienced radiologists, was used to assess the ability of imaging to predict pathological biopsy progression. Imaging test statistics and the odds ratio of pathological progression according to MRI upgrade were calculated.ResultsOf 121 patients meeting criteria, 36 (30%) demonstrated MRI upgrade. Biopsy progression was noted in 55 patients (46%). Of these, 20 patients (37%) had biopsy progression predicted by MRI upgrade, while the remaining (n=35) had no lesion upgrade on prostate MRI. Conversely, among those with no biopsy progression (n=66), 16 patients (24%) had a false-positive upgrade on serial MRI. We report a sensitivity and specificity of MRI change for pathological progression of 36% and 76%, respectively. Although MRI change was associated with a positive predictive value of 56% for pathological progression, patients with a high-suspicion lesion (PI-RADS >3) at any time were more likely to experience disease progression, (odds ratio 3.3, 95% confidence interval 1.6–8.0, p<0.01).ConclusionsGiven its modest sensitivity/specificity, serial prostate MRI should be used judiciously as a surveillance tool. However, when prostate MRI demonstrates a PI-RADS >3 lesion, a high index of suspicion should be maintained, as these patients are more likely to progress on AS.     

The effect of multiplicity of PI-RADS 3 lesions on cancer detection rate of confirmatory targeted biopsy in patients diagnosed with prostate cancer and managed with active surveillance

Background and ObjectiveTo determine the effect of multiplicity of prostate imaging reporting and data system assessment category 3 (PI-RADS 3) lesions on cancer detection rate (CDR) of confirmatory targeted biopsy of such lesion in patients diagnosed with prostate cancer and managed with active surveillance.MethodsThis study was conducted at a single academic institution. There were 91 men with ≥ 1 PI-RADS 3 lesion detected through magnetic resonance imaging (MRI) after systematic prostate biopsy in the course of management of patients diagnosed with prostate cancer with active surveillance. We compared the CDRs based on targeted biopsy of PI-RADS 3 lesions that occurred (1) as solitary lesions, (2) as 1 of multiple PI-RADS 3 only lesions, or (3) with ≥ 1 higher grade lesion.ResultsMedian age was 65.0 years (interquartile range 59.5–70.0), median prostate specific antigen was 5.95 ng/ml (interquartile range 4.30–8.83), and median prostate specific antigen density was 0.161 ng/ml² (0.071–0.194). Forty-three men had solitary PI-RADS 3 lesions, 22 had multiple PI-RADS 3 only lesions, and 26 had multiple lesions with ≥ 1 higher grade lesion. The overall CDR (Gleason score ≥ 3 + 3) based on confirmatory MRI targeted biopsy in a given PI-RADS 3 lesion in each group was 23%, 45%, and 54%, respectively (P = 0.0274). The CDRs for clinically significant disease (Gleason score ≥ 3 + 4) were 16%, 32%, and 35%, respectively (P = 0.1701).ConclusionsCoexisting lesions increase the CDR of confirmatory MRI targeted biopsy of PI-RADS 3 lesions in patients managed with active surveillance. Risk stratification algorithms for PI-RADS 3 lesion to guide biopsy and management decisions may consider including multiplicity of lesions.     

Magnetic resonance imaging radiomic features for recurrent prostate cancer following proton radiation therapy–A pilot study

ObjectiveThe role of multiparametric MRI (mp-MRI) for postproton radiation evaluation is unclear. In this pilot study, we characterize the mp-MRI features using the Prostate Imaging-Reporting and Data System (PI-RADS) for recurrent prostate cancer (PCa) following proton radiation therapy.MethodsAfter obtaining IRB approval, we identified 163 consecutive cases who underwent MRI-fusion prostate biopsy at our institution from November 2017 to May 2020. This study evaluated patients with prostate cancer (PCa) with biochemical recurrence following proton radiation. Patients were excluded if they had grossly metastatic disease, metal fragments, implanted devices, or with surgically removed prostates. The mpMRI studies were reviewed in depth and scored by 2 fellowship-trained radiologists. Following MRI-fusion biopsy of lesions of interest (LOI), slides were read by fellowship-trained pathologists.ResultsWe found 14 patients with 16 lesions who met the study inclusion criteria. The median age was 69 years (range 57–79) and median time to biochemical recurrence was 7.3 years (range 3–13). On post-treatment imaging, decreases in prostate size and diffusely decreased T2 signal intensity were observed, making the use of apparent diffusion coefficient (ADC) and early enhancement at dynamic contrast enhanced (DCE) imaging often necessary for diagnosis of disease recurrence. We identified a total of 16 lesions with PIRADS scores of 3 or higher. Of these lesions, there were 5 PIRADS 3 lesions (4/5 (80%) without prostate cancer), 7 PIRADS 4-5 lesions (6 (86%) had high risk Pca), and 4 lesions with unassigned PIRADS scores (100% had high risk cancers). Among the MRI variables, diffusion weighted imaging (DWI) heterogeneity had the strongest association with recurrence of PCa (P < 0.001).ConclusionsResults of our pilot study showed that the PIRADS scoring system in the postproton radiation therapy setting has some correlations with prostate cancer recurrence; However, the clinical value of these findings are unclear. While definitive PIRADS categorization of lesions demonstrated expected frequency of cancer consistent with the scoring system, all unassigned lesions also harbored malignancy suggesting a cautious approach to PIRADS scoring system in postproton radiation setting. The findings from this study may be validated using a larger cohort.     

Multicenter analysis of clinical and MRI characteristics associated with detecting clinically significant prostate cancer in PI-RADS (v2.0) category 3 lesions

ObjectivesWe sought to identify clinical and magnetic resonance imaging (MRI) characteristics in men with the Prostate Imaging - Reporting and Data System (PI-RADS) category 3 index lesions that predict clinically significant prostate cancer (CaP) on MRI targeted biopsy.Materials and MethodsMulticenter study of prospectively collected data for biopsy-naive men (n = 247) who underwent MRI-targeted and systematic biopsies for PI-RADS 3 index lesions. The primary endpoint was diagnosis of clinically significant CaP (Grade Group ≥2). Multivariable logistic regression models assessed for factors associated with clinically significant CaP. The probability distributions of clinically significant CaP based on different levels of predictors of multivariable models were plotted in a heatmap.ResultsMen with clinically significant CaP had smaller prostate volume (39.20 vs. 55.10 ml, P < 0.001) and lower apparent diffusion coefficient (ADC) values (973 vs. 1068 μm²/s, P = 0.013), but higher prostate-specific antigen (PSA) density (0.21 vs. 0.13 ng/ml², P = 0.027). On multivariable analyses, lower prostate volume (odds ratio [OR]: 0.95, 95% confidence interval [CI]: 0.92–0.97), lower ADC value (OR: 0.99, 95% CI: 0.99–1.00), and Prostate-specific antigen density >0.15 ng/ml² (OR: 3.51, 95% CI 1.61–7.68) were independently associated with significant CaP.ConclusionHigher PSA density, lower prostate volume and ADC values are associated with clinically significant CaP in biopsy-naïve men with PI-RADS 3 lesions. We present regression-derived probabilities of detecting clinically significant CaP based on various clinical and imaging values that can be used in decision-making. Our findings demonstrate an opportunity for MRI refinement or biomarker discovery to improve risk stratification for PI-RADS 3 lesions.     

Intercenter reproducibility of software-based fusion biopsies for grade group prediction when targeting suspicious MRI lesions

PurposeTo assess the intercenter reproducibility of software-based fusion targeted biopsy (TB) for grade-group assessment and pretherapeutic evaluation of highly suspicious MRI lesions.Patients and methodsIn this study, were included 380 consecutive patients who underwent radical prostatectomy (RP) after prostate cancer diagnosis and a prebiopsy MRI showing Prostate Imaging-Reporting and Data System (PIRADS) score 4 or 5 lesions. All patients underwent systematic biopsies (SB) combined with software-based fusion TB in the 2 centers. Biopsies were only performed by expert urologists or radiologists in a contemporary time frame. The primary endpoint was the center difference of concordance/upgrading rates between biopsy and RP specimens.ResultsPathological features on biopsy and RP specimens were significantly different among centers with more unfavourable disease in center 1. The rate of TB upgrading was 33.6% in center 1 vs. 35.4% (P = 0.860) in center 2. Grading concordance was also comparable among centers (50.0% vs. 47.1%) as well as the SB upgrading rate. Regression analysis did not find any baseline characteristics (Age, prostate-specific antigen, MRI lesions, center) predictive for TB upgrading. These findings were achieved by using fewer TB per lesion in center 1 (2.3 vs. 5.0, P < 0.001), at the expense of more SB cores (14.4 vs. 8.5, P < 0.001). The influence of MRI characteristics (lesion size and number, PIRADS score) on upgrading rates was consistent among centers.ConclusionsSoftware-based fusion TB technique leads to comparable outcomes in terms of grade group prediction accuracy in PIRADS 4 to 5 lesions, insignificant between centers, in spite of different non imaging-based aggressiveness features.     

Do patients with a PI-RADS 5 lesion identified on magnetic resonance imaging require systematic biopsy in addition to targeted biopsy?

IntroductionMagnetic Resonance Imaging (MRI)-targeted prostate biopsy (MRI-TB) improves the detection of prostate cancer. These biopsies typically involve both a 12-core systematic biopsy (SB) and MRI-TB of the lesion. Since the majority of PI-RADS 5 lesions represent clinically significant cancers, the utility of SB in addition to MRI-TB is unclear. We evaluate the utility of SB in the setting of PI-RADS 5 lesions in biopsy naïve and active surveillance patients.MethodsPatients undergoing MRI-TB+SB with a PI-RADS 5 lesion were retrospectively reviewed in a prospectively collected database. Pathology obtained from the MRI-TB was then compared to that of the SB, and each was reported based on the highest Gleason Grade from the sample. In patients with a prior biopsy, we identified instances in which the MRI-TB+SB resulted in upgraded pathology and further subdivided these patients based on whether the pathology upgrade was a result of the TB or the SB.ResultsWe identified PI-RADS 5 lesions in 97 patients. All lesions biopsied were found to be prostate cancer, and 86.9% were clinically significant. Gleason Grade from the MRI-TB of the PI-RADS 5 lesions was the same or higher to that of the SB in all but 3 cases (3.1%). Among 59 patients with a prior prostate biopsy, 54 had upgraded pathology from MRI-TB+SB (91.5%). Of these 54 patients, MRI-TB pathology of the PI-RADS 5 lesion was the same or higher to that of the SB in 52 patients (96.3%). In all patients with higher Gleason Grade on SB than MRI-TB, the MRI-TB demonstrated GG3 or higher and SB did not change subsequent clinical management.ConclusionIn the presence of a PI-RADS 5 lesion, SB offers minimal additional clinical value and could potentially be omitted when performing MRI-TB.     

Combined magnetic resonance spectroscopy and dynamic contrast-enhanced imaging for prostate cancer detection

BackgroundThe use of magnetic resonance spectroscopy imaging (MRSI) and dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) have emerged as a valid diagnostic tools for prostate cancer (CaP).MethodsMen with PSA levels below 10 ng/ml were enrolled in a prospective cohort study and underwent combined MRSI and DCE-MRI and transrectal ultrasound-guided prostate biopsy. Imaging was performed using a 1.5 T MR scanner (Symphony TIM; Siemens, Erlangen, Germany) with an endorectal coil (Medrad; Pittsburg, PA), inflated with 60 cc of air. Three-dimensional magnetic resonance spectroscopic data were acquired by using water and a lipid-suppressed double-spin-echo point-resolved spectroscopy sequence, which was optimized for quantitative detection of both choline and citrate. Dynamic contrast-enhanced MRI sequences were obtained with 3D T1-weighted FLASH images before and during rapid bolus administration of intravenous paramagnetic contrast medium gadoteric acid. Specificity, sensitivity, positive predictive value, negative predictive value, and accuracy were computed considering patients, each of the 2 lobes, each of the 6 sextants, and each 12th part of the prostate gland as single measurements.ResultsOverall, 106 patients were included in the analysis. Median age was 65.9 years (range, 61.2–70.5 years) and median PSA level at study entry was 7.1 ng/ml (range, 2.5–9.9). CaP was detected at biopsy in 24 patients (22.6 % of the population) with a median Gleason score of 8 (range 4–10). Diagnostic accuracy of combined MRSI and DCE-MRI was 85%, sensitivity was 71%, and specificity was 48%, considering patients as single measurements, with a negative predictive value of 91%, but a positive predictive value of only 19%. Positive predictive value of the examination improved to 25% for patients who repeated biopsy.ConclusionsAlthough this study confirms the potential usefulness of MRI for the diagnosis of CaP, the positive predictive value obtained was unacceptably low due to the high number of false positives recorded. Nevertheless, the high negative predictive value of the examination may serve to avoid unnecessary biopsies. Future research should be directed at assessing the value of combining MRI-based techniques with novel biochemical markers for the diagnosis of CaP in patients with low PSA levels.     

The additive value of mpMRI on prostate cancer detection: Comparison between patients with and without a suspicious digital rectal examination (DRE)

PurposeDiagnosis of prostate cancer (CaP) is based on digital rectal examination (DRE) and/or elevated prostate specific antigen (PSA) level. This approach lacks sensitivity and specificity and is associated with many negative biopsies, high rate of diagnosing clinically insignificant disease and lacks accuracy to predict clinically significant (CS) cancer. The addition of multiparametric magnetic resonance imaging (mpMRI) before prostate biopsy reduces the detection of low-grade tumors while improving the detection of CS CaP. Most studies that evaluated mpMRI performance did not separate the DRE status of the examined patients. Therefore, the aim of our study is to investigate whether mpMRI provides similar advantages in detection of CaP according to the DRE findings.Materials and MethodsThis prospective study included patients with clinically suspected CaP that were referred to MRI-fusion biopsy from 2014 to 2019. All patients had mpMRI of the prostate with an index lesion of PIRADS ≥3. Analysis was done comparing systemic and targeted biopsy. Patients were divided into two groups according to the DRE findings (positive or negative DRE) and the primary outcomes were compared between the 2 study groups: detection rate of CaP and the detection rate of CS disease defined as Gleason score ≥ 7.ResultsThe final study cohort included 86 patients: 47 with negative DRE and 39 with positive DRE. Overall cancer detection rate was higher in patients with a positive DRE (70.3% vs 48.9%, P <0.05). In the region of interest a higher overall detection rate and of CS disease was found in those with abnormal DRE (51.3% vs. 40.4% and 48.6% vs. 34.0% respectively). The systematic biopsy analysis showed an overall lower detection rate in the negative DRE group (8.5% vs. 18.9 %). The targeted biopsies detected more cancer and significant tumors per core in patients with positive DRE (29.2% vs. 18.5% and 22.1% vs. 14.5% respectively).ConclusionsPatients submitted to fusion biopsy and have a positive DRE are diagnosed more often with CaP, have higher grade disease and larger tumors. In patients suspicious for CaP and having a significant lesion on mpMRI one should combine targeted and systematic biopsy regardless of the DRE status.     

The value of magnetic resonance imaging-ultrasound fusion targeted biopsies for clinical decision-making among patients with previously negative transrectal ultrasound biopsy and persistent prostate-specific antigen elevation

IntroductionTargeted biopsy approaches have been shown to increase the detection of clinically significant prostate cancer (csPCa) within index prostate lesions. We report our initial experience with magnetic resonance imaging-ultrasound fusion biopsies (MRI-TB) in a population of men who had a previously negative transrectal ultrasound (TRUS) biopsy, persistent prostate-specific antigen (PSA) elevation, and ongoing suspicion of PCa. Patients were followed prospectively to assess for changes in clinical management following targeted biopsy.MethodsWe prospectively followed the first 122 patients undergoing MRI-TB at our institution. All men had clinical suspicion of PCa, prior negative TRUS biopsies, and persistent PSA elevation. A total of 177 index lesions were identified on multiparametric MRI and reviewed using the Prostate Imaging Reporting and Data System (PI-RADS) v2 scoring system. Lesions classified as PI-RADS ≥3 received targeted biopsy. Biopsy-naive patients and those on active surveillance were excluded. The primary outcome was detection rate of csPCa, defined as International Society of Urological Pathology (ISUP) Grade Group (GG) ≥2. Multivariate analysis was used to determine predictors of csPCa on fusion biopsy.ResultsPrior to fusion biopsy, patients had a mean of 17.9±8.6 negative core biopsies per patient and a median PSA of 9.5 (standard deviation [SD] 6.2) ng/nl. MRI-TB resulted in diagnosis of csPCa in 42/122 (34.4%) patients. Clinically significant PCa was found in eight (13.1%), 14 (21.9%), and 25 (48.1%) of PI-RADS 3, 4, and 5 lesions, respectively. The location of csPCa was within the peripheral zone (55.3%), transitional zone (40.4%), and central zone (8.5%). Clinical outcomes of patients with newly diagnosed csPCa show 4.8%, 57.1%, and 38.1% receiving active surveillance, radiation treatment, and radical prostatectomy, respectively. Predictors for csPCa were presence of PI-RADS 5 lesions, age, length of time from MRI to biopsy, and smaller prostate volumes.ConclusionsMRI-TB yields high detection rates for csPCa in men with elusive PSA elevation and frequently guides a change in clinical management. Clinical decision-making based on MRI findings and PI-RADS lesion scores are best informed by an understanding of institutional reporting patterns.     

Factors associated with higher prostate biopsy yield: when is software-assisted fusion MRI-targeting necessary?

ObjectiveTo evaluate the addition of software-assisted fusion magnetic resonance imaging (MRI) targeted biopsy to systematic biopsy and determine clinical and imaging factors associated with improved prostate cancer (PCa) detection.MethodsWe analyzed 454 patients who had prostate MRI and underwent combined systematic and software-assisted fusion MRI-targeted biopsy at 2 academic centers between July 2015 and December 2017. For our analysis, we compared the Gleason grade group of cores obtained systematically to cores obtained using MRI-targeting. Using multivariable analysis, we examined clinical and imaging factors associated with higher grade group disease in MRI-targeted cores.ResultsSoftware assisted fusion MRI-targeted biopsy detected higher grade group disease in 18.3% of patients. Factors associated with higher grade group disease in MRI-targeted cores included anterior MRI lesion location (odds ratio [OR] 3.15, P< 0.01) and multiple lesions on MRI (OR 2.47, P = 0.01). Increasing prostate volume per cubic centimeter was noted to be negatively associated (OR 0.98, P = 0.02). Notably, factors not found to be associated with improved detection included PIRADS classification 5 compared to 3 (OR 2.47, P = 0.08), PIRADS classification 4 compared to 3 (OR 1.37, P = 0.50), previous negative biopsy (OR 1.48, P = 0.29), inclusion on an active surveillance protocol (OR 1.36, P = 0.48), transitional zone lesion location (OR 0.72, P = 0.45), and institution at which biopsy was performed (OR 1.81, P = 0.16).ConclusionAdding software-assisted fusion MRI-targeting to systematic prostate biopsy offers benefit for men with an anterior and multiple MRI lesions. In absence of these factors, systematic biopsy alone or with cognitive fusion may be considered.     

Number of cores needed to diagnose prostate cancer during MRI targeted biopsy decreases after the learning curve

IntroductionWe hypothesized that the number of cores needed to detect prostate cancer would decrease with increasing MRI-targeted biopsy (TBx) experience.MethodsAll patients undergoing TBx at our institution from May 2017 to August 2019 were enrolled in a prospectively maintained database. Five biopsy cores were obtained from each lesion ≥3 on PI-RADS v2.0 followed by a systematic 12-core biopsy. To assess learning curve, the study population was divided into quartiles by sequential biopsies. Clinically significant prostate cancer (csPC) was defined as Gleason Grade Group 2 or higher.Results377 patients underwent prostate biopsy (533 lesions); 233 lesions (44%) were positive for prostate cancer and 173 lesions (32%) were csPC. There was a significant decline in the number of cores required for diagnosing any cancer (P < 0.001) and csPC (P < 0.05) after the first quartile. There was no difference when stratifying by PI-RADS score or lesion volume. Within the first quartile, limiting the biopsy to 3 cores would miss 16.2% of csPC, decreasing to 6.6% after approximately 100 patients.ConclusionMRI TBx is associated with a learning curve of approximately 100 cases. Four or 5 cores should be considered during the initial experience, but thereafter, 3 cores per lesion is sufficient to detect csPC.     

Clinical utility of PSAD combined with PI-RADS category for the detection of clinically significant prostate cancer

PurposeThe goal of this study was to determine the predictive value of prostate-specific antigen density (PSAD) plus Prostate Imaging Reporting and Data System (PI-RADS) category for the detection of clinically significant prostate cancer.Materials and MethodsThis retrospective study included 526 men without known prostate cancer (initial diagnosis group) and 133 men with prostate cancer grade group 1 (active surveillance group) who underwent magnetic resonance imaging–guided and/or systematic prostate biopsy procedures between August 2014 and October 2018. Prostate specific antigen (PSA), PSAD, and PI-RADS category were entered into logistic regression models for predicting clinically significant prostate cancer (grade group ≥2) at biopsy. Receiver operating characteristic curve analysis was performed to assess model accuracy.ResultsThe area under the curve (AUC) increased when PSAD was combined with PI-RADS in the initial diagnosis group (difference in AUC = 0.031; 95% confidence interval: 0.012, 0.050; P = 0.002) but not in the active surveillance group (difference in AUC = 0.016; 95% confidence interval: –0.040, 0.071; P = 0.579). When a PSAD threshold of 0.15 was applied, the frequency of clinically significant prostate cancer in patients with a PI-RADS score of 3 or lower decreased from 9.8% to 5.6% in the initial diagnosis group and from 10.7% to 2.7% in the active surveillance group.ConclusionsThe addition of PSAD improves the predictive performance of PI-RADS in men without known prostate cancer. A PSAD threshold of 0.15 can help to minimize the number of missed clinically significant prostate cancer cases in men with a PI-RADS score of 3 or lower who decide to defer biopsy.     

Clinical validation of IsoPSA,a single parameter,structure-focused assay for improved detection of prostate cancer: A prospective,multicenter study

BackgroundIsoPSA is a blood-based test that assesses prostate cancer (CaP) risk by partitioning and detecting cancer-specific structural isoforms of prostate specific antigen (PSA) with an aqueous 2- phase system.ObjectiveTo validate the diagnostic performance of IsoPSA for High-Grade CaP and Any CaP risk on biopsy in men age ≥ 50 with total PSA ≥ 4 ng/ml.Design, Setting, and ParticipantsProspective, multicenter study of 888 men scheduled for prostate biopsy at 8 academic and community sites between August 2015 and August 2020.InterventionIsoPSA test.Outcome Measurements and Statistical AnalysisReceiver operating characteristic and likelihood ratio analysis used to validate diagnostic performance for previously established IsoPSA Index cutoffs for High-Grade CaP (Gleason Score ≥ 7) and Any CaP (Gleason Score ≥ 6), compare IsoPSA to total PSA and % free PSA, and evaluate subgroups (total PSA 4–10 ng/ml, total PSA > 10 ng/ml, biopsy naïve, prior negative biopsy).Results and LimitationsThe disease prevalence was 35.6% (High-Grade CaP) and 58.9% (Any CaP). The area under the receiver operating characteristic curve was 0.783 (High-Grade CaP) and 0.770 (Any CaP). IsoPSA outperformed total PSA and % free PSA on area under the receiver operating characteristic curve, specificity, positive and negative predictive value at similar sensitivity. Using selected IsoPSA Index cutoffs, an estimated 46% (High-Grade CaP) and 42% (Any CaP) of biopsies could be avoided in low-risk patients. IsoPSA displayed statistically informative likelihood ratio-based predictive characteristics. IsoPSA maintained accuracy in clinically relevant subgroups.ConclusionsIsoPSA diagnostic performance and predictive value is validated for High-Grade CaP and Any CaP in men age ≥ 50 with total PSA ≥ 4 ng/ml undergoing diagnostic biopsy. IsoPSA outperforms total and % free PSA in discriminating the risk of prostate cancer on biopsy.Patient SummaryIsoPSA has the potential to reduce unnecessary biopsies and improve the risk-benefit ratio for CaP early detection.