Active Surveillance of Grade Group 1 Prostate Cancer: Long-term Outcomes from a Large Prospective Cohort

BackgroundActive surveillance (AS) is the preferred management option for most men with grade group (GG) 1 prostate cancer (PCa). Questions persist regarding long-term outcomes and the optimal approach to AS.ObjectiveTo determine survival and metastatic outcomes in AS patients. Secondary objectives were to measure the cumulative incidence and association of patient-level factors on biopsy grade reclassification.Design, setting, and participantsA prospective, active, open-enrollment cohort study was conducted from 1995 through July 2018 at a tertiary-care academic institution. Patients with very-low-risk or low-risk PCa were enrolled.InterventionAS with semiannual prostate-specific antigen (PSA) and digital rectal examination, serial prostate biopsy, and multiparametric magnetic resonance imaging (mpMRI).Outcome measurements and statistical analysisThe 10- and 15-yr cumulative incidences of primary and secondary outcomes were determined.Results and limitationsOverall, 1818 men were monitored on AS for a median of 5.0 yr (interquartile range 2.0–9.0). There were 88 non-PCa deaths, four PCa deaths, and one additional case of metastasis. The cumulative incidence of PCa-specific mortality or metastasis was 0.1% (95% confidence interval, 0.04–0.6%) at both 10 and 15 yr. The 5-, 10-, and 15-yr cumulative incidences of biopsy grade reclassification were 21%, 30%, and 32%, respectively. On multivariable analysis, biopsy grade reclassification was associated with older age, African-American race, PSA density, and increased cancer volume on biopsy, and men who underwent mpMRI prior to enrollment were less likely to undergo grade reclassification. Our selection and monitoring are more stringent than many other contemporary AS programs.ConclusionsIn a large, single-institution, prospective AS cohort, the risk of cancer death or metastasis was <1% over long-term follow-up. Consistent with clinical guidelines, these data support the use of AS for the management of most men diagnosed with GG1 PCa.Patient summaryThis study investigated long-term outcomes in patients with grade group 1 prostate cancer managed with active surveillance (AS). Ten years after enrolling in AS, the risk of metastasis or death from prostate cancer was <1%, while 48% of men switched to treatment. Patients who underwent multiparametric magnetic resonance imaging (mpMRI)/ultrasound-fusion targeted biopsy prior to enrollment were less likely to experience biopsy grade reclassification during follow-up, suggesting a role for mpMRI as part of a comprehensive risk assessment to confirm AS eligibility. These findings support the safety of AS in most men with grade group 1 prostate cancer, but specific outcomes may differ in programs with less intensive monitoring.     

Pathological findings at radical prostatectomy of biopsy naïve men diagnosed with MRI targeted biopsy alone without concomitant standard systematic sampling

ObjectivesTo test international society of urological pathology grade group (ISUP GG) concordance rates between multiparametric magnetic resonance imaging (mpMRI) targeted biopsies (TB) vs. standard systematic biopsies (SB) and radical prostatectomy (RP) specimens, in biopsy naïve patients.Materials and MethodsThis retrospective single center study included 80 vs. 500 biopsy naïve patients diagnosed with TB vs. SB and treated with RP between 2015 and 2018. First, we compared ISUP GG concordance rates and the percentages of undetected clinically significant prostate cancer (csPCa: ISUP GG ≥ 3), between TB vs. SB and RP. Second, multivariable logistic regression models tested predictors of concordance rates before and after 1:3 propensity score (PS) matching. Third, among TB patients, univariable logistic regression models tested variables associated with ISUP GG concordance at RP.ResultsOverall, ISUP GG concordance rates were, respectively, 55 vs. 41.4% for TB vs. SB (P = 0.02). However, no differences in concordance rates were observed in patients with biopsy ISUP GG1 (31 vs. 33.9% for TB vs. SB; P = 0.8). Moreover, 15 vs. 18.8% csPCa were missed by TB vs. SB, respectively (P = 0.4). In multivariable logistic regression models, TB were associated with higher concordance rates before (odds ratio [OR]: 1.13; P = 0.04) and after 1:3 PS matching (OR: 1.15; P 0.03), compared to SB. In TB patients, age (OR: 0.98; P = 0.04), maximum cancer core involvement (MCCI; OR: 1.02; P = 0.02) and maximum cancer core length (MCCL; OR: 1.01; P = 0.07) were associated with ISUP GG concordance. Moreover, a trend for lower concordance rates was observed with higher PSA-D (OR: 0.77; P = 0.1). Finally, intermediate lesion location at mpMRI was associated with lowest concordance rates (44%).ConclusionIn biopsy naïve patients treated with RP, TB achieved higher rates of ISUP GG concordance, but same percentages of csPCa missed, compared to SB. Moreover, only patients with ISUP GG ≥2, but not patients with ISUP GG1, exhibited higher concordance rates. Finally, age, MCCI, MCCL, PSA-D, and lesion location were associated with concordance between TB and RP.     

Prostate cancer detection with magnetic resonance imaging (MRI)/ cognitive fusion biopsy: Comparing standard and targeted prostate biopsy with final prostatectomy histology

IntroductionThe use of multiparametric magnetic resonance imaging (MRI) with targeted biopsies of the prostate improves the diagnosis of clinically significant prostate cancer. Recent studies have shown that targeted prostate biopsies also more accurately predict final histopathology after radical prostatectomy (RP). There are three broad techniques for performing MRI-targeted prostate biopsy: cognitive MRI/ultrasound (US) fusion, software MRI/US fusion, and in-bore MRI-guided. Current practices recommend that a standard systematic 12-core prostate biopsy be performed, as well as targeted biopsies in patients with positive MRI findings. This study aimed to evaluate the accuracy of histological grading of cognitive MRI/US fusion prostate biopsy by comparing the histology from the targeted biopsy specimens (TB), standard systematic specimens (SB), and the combination of both (CB) specimens with the final histological grade from subsequent prostatectomy.MethodsA retrospective, single-center review of 115 patients who underwent standard systematic and cognitive MRI/US-targeted biopsy of the prostate before undergoing a RP between 2016 and 2019 was performed. MRI findings, biopsy, final histology International Society of Urological Pathology (ISUP) grades, and patient demographics were collected. Cochran’s Q test and McNemar test were used to compare the differences in upgrading, downgrading, and concordance between each biopsy group.ResultsThe concordance between SB, TB, and CB biopsy were 28.7%, 49.6%, and 50.4%, respectively. There was no significant difference in concordance between TB and CB. Patients were more likely to be downgraded on the final histology when comparing CB with TB alone (26.1% vs. 16.5%, p<0.05). In cases where an ISUP grade 1 cancer was diagnosed on TB (n=24), there was a 62.5% chance that the final histology would be upgraded. In the same sample, when combined with a SB, the risk of upgrading on final histology was reduced to 37.5%.ConclusionsAlthough grading concordance between TB and CB were similar, the concomitant use of a SB significantly reduced the rate of upgrading in the final RP histopathology. CB may result in better decision-making regarding treatment options and also have implications for intraoperative planning.     

Randomized Study of Systematic Biopsy Versus Magnetic Resonance Imaging and Targeted and Systematic Biopsy in Men on Active Surveillance (ASIST): 2-year Postbiopsy Follow-up

BackgroundThe initial report from the ASIST trial showed little benefit from targeted biopsy for men on active surveillance (AS) for prostate cancer. Data after 2-yr follow-up are now available for analysis.ObjectiveTo determine if there was a difference in the AS failure rate in a 2-yr follow-up period among men undergoing magnetic resonance imaging (MRI) before initial confirmatory biopsy (CBx) compared to those who did not.Design, setting, and participantsThis is the 2-yr post-CBx follow-up for the ASIST trial, a prospective, randomized, multicenter, open-label study for men with Gleason grade group (GG) 1 cancer eligible for AS. Patients were randomized to CBx with 12-core systematic sampling or MRI with systematic and targeted sampling.Outcome measurements and statistical analysisPatients with GG ≤ 1 on CBx were followed for 2 yr and had MRI and biopsy at that time point. Patients failed AS if they were no longer under AS because of grade progression, clinical progression, subject choice, clinical judgment, treatment, or lost to follow-up. Clinically significant cancer (CSC) was defined as GG ≥ 2.Results and limitationsIn total, 259 men underwent CBx, 132 in the non-MRI and 127 in the MRI arm. After biopsy, 101 men in the non-MRI arm (76%) and 98 in the MRI arm (77%) continued AS. There were fewer men with AS failures in the MRI (19/98, 19%) compared to the non-MRI group (35/101, 35%; p = 0.017). At 2-yr biopsy there were fewer men with CSC in the MRI arm (9.9%, 8/81) than in the non-MRI arm (23%, 17/75; p = 0.048). Significant differences in AS failure rates were detected across the three centers in the MRI arm only (4.2% [2/48] vs 17% [4/24] vs 27% [7/26]; p = 0.019).ConclusionsBaseline MRI before CBx during AS results in 50% fewer AS failures and less grade progression over 2 yr. The center where MRI and targeted biopsy is performed may influence AS failure rates.Patient summaryThe ASIST trial randomized 273 men on active surveillance with low-grade prostate cancer diagnosed within the last year to systematic biopsy or magnetic resonance imaging (MRI) with systematic and targeted biopsy. The initial report showed little benefit from targeted biopsy. However, after 2 yr of follow-up we found that baseline MRI before confirmatory biopsy resulted in 50% fewer failures of surveillance and less progression to higher-grade cancer. This confirms the value of MRI in men on surveillance.This study is registered at ClinicalTrials.gov (NCT01354171).     

Assessing the diagnostic performance of systematic freehand PrecisionPoint transperineal prostate biopsy: Comparison of observed outcomes to PBCG nomogram predictions

ObjectiveWe assessed the diagnostic performance of freehand systematic transperineal biopsy (fTPb) by using the Prostate Biopsy Collaborative Group (PBCG) nomogram, which is a contemporary update to the PCPT nomogram.MethodsFrom 1/2012 to 12/2018, fTPb was performed on consecutive men with clinical suspicion of prostate cancer. Patients included in this study had no previous diagnosis of prostate cancer, PSA between 2.5 ng/ml and 20 ng/ml, and underwent at least 12 core biopsies. In addition, those men who underwent pre-biopsy multiparametric magnetic resonance imaging of the prostate were considered separately from those without prebiopsy imaging. Biopsies were performed by a single urologist who developed the needle guidance device used in the procedure. Clinical and pathological data were collected retrospectively. We compared observed biopsy outcomes with those predicted by PBCG nomogram utilizing chi-square statistical analysis.ResultsSystematic fTPb (without pre-biopsy MRI) was performed in 301 men (median age 67, mean PSA 6.9 ng/mL). These men had a median of 20 biopsy cores. Clinically significant cancer (ISUP 2 or greater) was found in 33.9% of men. In men without pre-biopsy MRI, using PBCG Nomogram, we found no significant difference between the expected and observed number of clinically significant cancer (96 vs. 102; P = 0.09). An additional 73 men (median age 67, mean PSA 7.8 ng/ml) underwent pre-biopsy MRI imaging. The addition of MRI targets to systematic sampling resulted in a median of 25 cores. Clinically significant cancer was found in 49.3%. Using the PBCG Nomogram, in the men with pre-biopsy MRI we found clinically significant cancer in significantly more men than was expected by PBCG nomogram predictions (36 vs. 20; P = <0.01). There were no biopsy-related infectious complications.ConclusionThe fTPb technique is a promising method to sample the prostate which provides cancer detection that is comparable to that expected from systematic TRUS biopsy. We found that pre-biopsy mpMRI resulted in greater than expected detection of clinically significant cancer when utilizing this technique.     

External Validation of a Multiparametric Magnetic Resonance Imaging–based Nomogram for the Prediction of Extracapsular Extension and Seminal Vesicle Invasion in Prostate Cancer Patients Undergoing Radical Prostatectomy

The nomogram reported by Gandaglia et al (The key combined value of multiparametric magnetic resonance imaging, and magnetic resonance imaging-targeted and concomitant systematic biopsies for the prediction of adverse pathological features in prostate cancer patients undergoing radical prostatectomy. Eur Urol 2020;77:733–41) predicting extracapsular extension (ECE) or seminal vesicle invasion (SVI) has been developed using multiparametric magnetic resonance imaging (MRI) parameters and MRI-targeted biopsy. We aimed to validate this nomogram externally by analyzing 566 patients harboring prostate cancer diagnosed on MRI-targeted biopsy followed by radical prostatectomy. At final pathology, 37% and 12% patients had ECE and SVI, respectively. Performance of the nomogram, in comparison with the Memorial Sloan Kettering Cancer Center (MSKCC) model and Partin tables, was evaluated using discrimination, calibration, and decision curve analysis. Regarding ECE prediction, the nomogram showed higher discrimination (71.8% vs 69.8%, p = 0.3 and 71.8% vs 61.3%, p < 0.001), and similar miscalibration and net benefit for probability threshold above 30% when compared with MSKCC model and Partin tables, respectively. Performance of the nomogram with regard to SVI was comparable in terms of discrimination (68.5% vs 70.4% vs 67.8%, p ≥ 0.6), presenting a slight overestimation on calibration plots and a net benefit for probability threshold above 7.5%. This is the first multicentric study that externally validates a nomogram predicting ECE and SVI in patients diagnosed with MRI-targeted biopsy. Its performance was less optimistic than expected, and implementation of MRI in this setting was not associated with a clear improvement in patient selection and clinical usefulness when compared with available models. We proposed an updated version of the nomogram predicting ECE using the recalibration method, which leads to an improvement in its performance and needs to be validated in another external set.Patient summaryWe validate a prediction tool based on multiparametric magnetic resonance imaging (MRI) parameters and MRI-targeted biopsy predicting extracapsular extension and seminal vesicle invasion at radical prostatectomy. An improvement of patient selection was not clearly demonstrated when compared with available models based on clinical parameters, and implementation of MRI in this setting still needs to be clarified.     

The accuracy of prostate cancer diagnosis in biopsy-naive patients using combined magnetic resonance imaging and transrectal ultrasound fusion-targeted prostate biopsy

BackgroundThis study aimed to estimate whether multiparametric magnetic resonance imaging (mpMRI)-transrectal ultrasound (TRUS) fusion biopsy (FUS-TB) increases the detection rates of clinically significant prostate cancer (csPCa) compared with TRUS-guided systematic biopsy (TRUS-GB).MethodsThis retrospective study focused on patients who underwent mpMRI before prostate biopsy (PB) with Prostate Imaging Reporting and Data System version 2 (PI-RADS v2) scores ≥3 and prostate-specific antigen (PSA) level between 2.5 and 20 ng/mL. Before FUS-TB, the biopsy needle position was checked virtually using three-dimensional mapping. After confirming the position of the target within the prostate, biopsy needle was inserted and PB was performed. Suspicious lesions were generally targeted with 2 to 4 cores. Subsequently, 10–12 cores were biopsied for TRUS-GB. The primary endpoint was the PCa detection rate (PCDR) for patients with PCa who underwent combined FUS-TB and TRUS-GB.ResultsAccording to PI-RADS v2, 76.7% of the patients with PI-RADS v2 score ≥3 were diagnosed with PCa. The PCDRs in patients with PI-RADS v2 score of 4 or 5 were significantly higher than those in patients with PI-RADS v2 score of 3 (3 vs. 4, P<0.001; 3 vs. 5, P<0.001; 4 vs. 5, P=0.073). According to PCDR, the detection rates of PCa and csPCa in the FUS-TB were significantly higher than that in the TRUS-GB.ConclusionsFollowing detection of suspicious tumor lesions on mpMRI, FUS-TB use detects a higher number of PCa cases compared with TRUS-GB.     

Use of serial multiparametric magnetic resonance imaging in the management of patients with prostate cancer on active surveillance

IntroductionWe evaluated the performance of multiparametric prostate magnetic resonance imaging (mp-MRI) and MRI/transrectal ultrasound (TRUS) fusion–guided biopsy (FB) for monitoring patients with prostate cancer on active surveillance (AS).Materials and methodsPatients undergoing mp-MRI and FB of target lesions identified on mp-MRI between August 2007 and August 2014 were reviewed. Patients meeting AS criteria (Clinical stage T1c, Gleason grade≤6, prostate-specific antigen density≤0.15, tumor involving≤2 cores, and≤50% involvement of any single core) based on extended sextant 12-core TRUS biopsy (systematic biopsy [SB]) were included. They were followed with subsequent 12-core biopsy as well as mp-MRI and MRI/TRUS fusion biopsy at follow-up visits until Gleason score progression (Gleason≥7 in either 12-core or MRI/TRUS fusion biopsy). We evaluated whether progression seen on mp-MRI (defined as an increase in suspicion level, largest lesion diameter, or number of lesions) was predictive of Gleason score progression.ResultsOf 152 patients meeting AS criteria on initial SB (mean age of 61.4 years and mean prostate-specific antigen level of 5.26 ng/ml), 34 (22.4%) had Gleason score≥7 on confirmatory SB/FB. Of the 118 remaining patients, 58 chose AS and had at least 1 subsequent mp-MRI with SB/FB (median follow-up = 16.1 months). Gleason progression was subsequently documented in 17 (29%) of these men, in all cases to Gleason 3+4. The positive predictive value and negative predictive value of mp-MRI for Gleason progression was 53% (95% CI: 28%–77%) and 80% (95% CI: 65%–91%), respectively. The sensitivity and specificity of mp-MRI for increase in Gleason were also 53% and 80%, respectively. The number needed to biopsy to detect 1 Gleason progression was 8.74 for SB vs. 2.9 for FB.ConclusionsStable findings on mp-MRI are associated with Gleason score stability. mp-MRI appears promising as a useful aid for reducing the number of biopsies in the management of patients on AS. A prospective evaluation of mp-MRI as a screen to reduce biopsies in the follow-up of men on AS appears warranted.     

The Key Combined Value of Multiparametric Magnetic Resonance Imaging,and Magnetic Resonance Imaging–targeted and Concomitant Systematic Biopsies for the Prediction of Adverse Pathological Features in Prostate Cancer Patients Undergoing Radical Prostatectomy

BackgroundThe combined role of multiparametric magnetic resonance imaging (mp-MRI), and magnetic resonance imaging (MRI)-targeted and concomitant systematic biopsies in the identification of prostate cancer (PCa) patients at a higher risk of adverse pathology at radical prostatectomy (RP) is still unclear.ObjectiveTo develop novel models to predict extracapsular extension (ECE), seminal vesicle invasion (SVI), or upgrading in patients diagnosed with MRI-targeted and concomitant systematic biopsies.Design, setting, and participantsWe included 614 men with clinical stage ≤ T2 at digital rectal examination who underwent MRI-targeted biopsy with concomitant systematic biopsy.Outcome measurements and statistical analysesLogistic regression analyses predicting ECE, SVI, and upgrading (ie, a shift from biopsy International Society of Urological Pathology grade group to any higher grade at RP) based on clinical variables with or without mp-MRI features and systematic biopsy information (the percentage of cores with grade group ≥2 PCa) were developed and internally validated. The area under the curve (AUC) was used to identify the models with the highest discrimination. Decision-curve analyses (DCAs) determined the net benefit associated with their use.Results and limitationsOverall, 333 (54%), 88 (14%), and 169 (27%) patients had ECE, SVI, and upgrading at RP, respectively. The inclusion of mp-MRI data improved the discrimination of clinical models for ECE (67% vs 70%) and SVI (74% vs 76%). Models including mp-MRI, and MRI-targeted and concomitant systematic biopsy information achieved the highest AUC at internal validation for ECE (73%), SVI (81%), and upgrading (73%) and represented the basis for three risk calculators that yield the highest net benefit at DCA.ConclusionsNot only mp-MRI and MRI-targeted sampling, but also concomitant systematic biopsies provide significant information to identify patients at a higher risk of adverse pathology. Although omitting systematic prostate sampling at the time of MRI-targeted biopsy might be associated with a reduced risk of detecting insignificant PCa and lower patient discomfort, it reduces the ability to accurately predict pathological features.Patient summaryThe combination of multiparametric magnetic resonance imaging (mp-MRI) with accurate biopsy information on MRI-targeted and systematic biopsies improves the accuracy of multivariable models based on clinical and mp-MRI data alone. Correct mp-MRI interpretation and proper extensive prostate sampling are both needed to predict adverse pathology accurately at radical prostatectomy.     

Detection of clinically significant prostate cancer by transperineal multiparametric magnetic resonance imaging-ultrasound fusion targeted prostate biopsy in smaller prostates

PurposeTransperineal (TP) multiparametric magnetic resonance imaging (mpMRI)-targeted biopsy (TBx) has been shown to detect more clinically significant (cs) prostate cancer (PCa) than standard template biopsies (SBx). Current data supports the inclusion of both TBx and SBx in obtaining an optimal csPCa detection rate. We compared csPCa detection rates in patients with different prostate volumes to examine the benefit of performing TBx in smaller prostates through the TP approach.MethodsWe identified all men who with suspicious lesions on mpMRI and underwent TP TBx (3-core) and concomitant SBx (20-core) in our single hospital from September 2019 to February 2021. Clinical, MRI and biopsy pathological characteristics were evaluated and compared between TBx and SBx. Grade group 2 or greater prostate adenocarcinoma was defined as csPCa.ResultsThree hundred and one (n = 301) men were included. The median prostate volume by MRI was 45 ml. The patients were divided by prostate volume into three groups: ≤30ml group (19.9%), >30 to ≤45 ml group (31.3%) and >45ml group (48.8%). Patients in the ≤30ml group showed significantly higher frequency of combined (both TBx and/or SBx) csPCa detection rate (65.0%) than patients in the >45ml group (39.5%) but similar frequency to the >30 to ≤45 ml group (54.2%,). By TBx only (55.0% vs 27.9%) or by SBx only (56.7% vs. 34.0%), patients in the ≤30ml group consistently showed significantly higher rates of csPCa detection than patients in the >45 ml group. In the ≤30ml group, the detection rate of csPCa was comparable by TBx, SBx or when combined. Four of 6 csPCa cases missed by TBx but detected by SBx were present at the base location.ConclusionOur data suggest that performing TBx with limited additional cores may potentially achieve the same csPCa detection rate as the combined SBx and TBx in smaller prostates.     

A novel nomogram predicting lymph node invasion among patients with prostate cancer: The importance of extracapsular extension at multiparametric magnetic resonance imaging

PurposeTo develop a novel risk tool that allows the prediction of lymph node invasion (LNI) among patients with prostate cancer (PCa) treated with robot-assisted radical prostatectomy (RARP) and extended pelvic lymph node dissection (ePLND).MethodsWe retrospectively identified 742 patients treated with RARP + ePLND at a single center between 2012 and 2018. All patients underwent multiparametric magnetic resonance imaging (mpMRI) and were diagnosed with targeted biopsies. First, the nomogram published by Briganti et al. was validated in our cohort. Second, three novel multivariable logistic regression models predicting LNI were developed: (1) a complete model fitted with PSA, ISUP grade groups, percentage of positive cores (PCP), extracapsular extension (ECE), and Prostate Imaging Reporting and Data System (PI-RADS) score; (2) a simplified model where ECE score was not included (model 1); and (3) a simplified model where PI-RADS score was not included (model 2). The predictive accuracy of the models was assessed with the receiver operating characteristic-derived area under the curve (AUC). Calibration plots and decision curve analyses were used.ResultsOverall, 149 patients (20%) had LNI. In multivariable logistic regression models, PSA (OR: 1.03; P= 0.001), ISUP grade groups (OR: 1.33; P= 0.001), PCP (OR: 1.01; P= 0.01), and ECE score (ECE 4 vs. 3 OR: 2.99; ECE 5 vs. 3 OR: 6.97; P< 0.001) were associated with higher rates of LNI. The AUC of the Briganti et al. model was 74%. Conversely, the AUC of model 1 vs. model 2 vs. complete model was, respectively, 78% vs. 81% vs. 81%. Simplified model 1 (ECE score only) was then chosen as the best performing model. A nomogram to calculate the individual probability of LNI, based on model 1 was created. Setting our cut-off at 5% we missed only 2.6% of LNI patients.ConclusionsWe developed a novel nomogram that combines PSA, ISUP grade groups, PCP, and mpMRI-derived ECE score to predict the probability of LNI at final pathology in RARP candidates. The application of a nomogram derived cut-off of 5% allows to avoid a consistent number of ePLND procedures, missing only 2.6% of LNI patients. External validation of our model is needed.     

Role of Changes in Magnetic Resonance Imaging or Clinical Stage in Evaluation of Disease Progression for Men with Prostate Cancer on Active Surveillance

BackgroundActive surveillance (AS) protocols rely on rectal examination, prostate-specific antigen, imaging, and biopsy to identify disease progression.ObjectiveTo evaluate whether an AS regimen based on magnetic resonance imaging (MRI) or clinical stage changes can detect reclassification to grade group (GG) ≥2 disease compared with scheduled systematic biopsies.Design, setting, and participantsWe identified a cohort of men initiated on AS between January 2013 and April 2016 at a single tertiary-care center. Patients completed confirmatory testing and prostate MRI prior to enrollment, then underwent laboratory and physical evaluation every 6 mo, MRI every 18 mo, and biopsy every 3 yr.Outcome measurements and statistical analysisMRI results were evaluated using composite Likert/Prostate Imaging Reporting and Data System v2 scoring. MRI and clinical changes were assessed for association with disease progression. Univariable and multivariable regression models were used to predict upgrading on 3-yr biopsy.Results and limitationsAt 3 yr, of 207 men, 66 (32%) had ≥ GG2 at biopsy: 55 (83%) with GG2, 10 (15%) with GG3, and one (1.5%) with GG4. Among patients with a 3-yr MRI score of ≥3, 41% had ≥ GG2 disease, compared with 15% with an MRI score of <3 (p = 0.0002). The MRI score increased in 48 men (23%), decreased in 27 (13%), and was unchanged in 132 (64%) men. Increases in MRI score were not associated with reclassification after adjusting for the 3-yr MRI score (p = 0.9). Biopsying only for an increased MRI score or clinical stage would avoid 681 biopsies per 1000 men, at the cost of missing ≥GG2 disease in 169 patients.ConclusionsAn AS strategy that uses MRI or clinical changes to trigger prostate biopsy avoids many biopsies but misses an unacceptable amount of clinically significant disease. Prostate biopsy for men on AS should be performed at scheduled intervals, regardless of stable imaging or examination findings.Patient summaryAn active surveillance strategy for biopsy based only on increases in magnetic resonance imaging score or clinical stage will avoid many biopsies; however, it will miss many patients with clinically significant prostate cancer.     

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.     

Systematic sampling during MRI-US fusion prostate biopsy can overcome errors of targeting—prospective single center experience after 300 cases in first biopsy setting

BackgroundMultiparametric magnetic resonance imaging (mpMRI) and targeted biopsy have become an integral part of the diagnosis of prostate cancer (PCa), as recommended by the European Association of Urology Guidelines. The aim of the current study was to evaluate the performance of MRI and MRI-transrectal ultrasound (TRUS) fusion prostate biopsy as first biopsy setting in a tertiary center.MethodsA cohort of 300 patients was included in the current analysis. All patients presented with clinical or biochemical suspicion of PCa and harbored at least one suspect lesion on mpMRI. MRI-TRUS fusion prostate biopsy, followed by 12 core systematic prostate biopsy were performed by the same operator using a rigid registration system.ResultsThe mean age of the patients was 64 years (IQR: 58–68.5 years) and the mean PSA was 6.35 ng/mL (IQR: 4.84–9.46 ng/mL). Overall cancer and csPCa diagnosis rates were 47% and 40.66%. Overall PCa/csPCa detection rates were 20.4%/11.1%, 52%/45% and 68.5%/66.7% for PI-RADS lesions 3, 4 and 5 (P<0.001/P<0.0001). Larger lesion diameter and lesion volume were associated with PCa diagnosis (P=0.006 and P=0.001, respectively). MRI-TRUS fusion biopsy missed PCa diagnosis in 37 cases (of whom 48.6% ISUP 1) in comparison with 9 patients missed by systematic biopsy (of whom 11.1% ISUP 1). In terms of csPCa, systematic biopsy missed 77.7% of the tumors located in the anterior and transitional areas. The rate of csPCa was highest when targeted biopsy was associated with systematic biopsy: 86.52% vs. 68.79% for targeted biopsy vs. 80.14% for systematic biopsy, P=0.0004. In 60.6% of cases, systematic biopsy was positive for PCa at the same site as the targeted lesion. Of these patients, eight harbored csPCa and were diagnosed exclusively on systematic biopsy.ConclusionsMRI-TRUS fusion prostate biopsy improves the diagnosis of csPCa. The main advantage of an MRI-guided approach is the diagnosis of anterior and transitional area tumors. The best results in terms of csPCa diagnosis are obtained by the combination of MRI-TRUS fusion with systematic biopsy. The systematic biopsy performed during MRI-targeted biopsy could have an important role in overcoming errors of MRI-TRUS fusion systems.     

3.0 T multiparametric prostate MRI using pelvic phased-array coil: Utility for tumor detection prior to biopsy

ObjectiveTo evaluate the role of multiparametric magnetic resonance imaging (MRI) performed in men without a biopsy-proven diagnosis of prostate cancer using follow-up biopsy as the reference standard.Materials and methodsForty-two patients without biopsy-proven cancer and who underwent MRI were included. In all patients, MRI was performed at 3T using a pelvic phased-array coil and included T2-weighted imaging, diffusion-weighted imaging, and dynamic contrast-enhanced imaging. Thirteen had undergone no previous biopsy, and 29 had undergone at least 1 previous negative biopsy. All patients underwent prostate biopsy following MRI. Two fellowship-trained radiologists in consensus reviewed all cases and categorized each lobe as positive or negative for tumor. These interpretations were correlated with findings on post-MRI biopsy.ResultsFollow-up biopsy was positive in 23 lobes in 15 patients (36% of study cohort). On a per-patient basis, MRI had a sensitivity of 100%, specificity of 74%, positive predictive value (PPV) of 68%, and negative predictive value (NPV) of 100%. On a per-lobe basis, MRI had a sensitivity of 65%, specificity of 84%, PPV of 60%, and NPV of 86%. There was a nearly significant association between Gleason score and tumor detection on MRI (P = 0.072).ConclusionsIn our sample, MRI had 100% sensitivity in predicting the presence of tumor on subsequent biopsy on a per-patient basis, suggesting a possible role for MRI in selecting patients with an elevated prostatic specific antigen (PSA) to undergo prostate biopsy. However, MRI had weaker specificity for prediction of a subsequent positive biopsy, as well as weaker sensitivity for tumor on a per-lobe basis, indicating that in patients with a positive MRI result, tissue sampling remains necessary for confirmation of the diagnosis as well as for treatment planning.     

Evaluation of post-ablation mpMRI as a predictor of residual prostate cancer after focal high intensity focused ultrasound (HIFU) ablation

PurposeTo evaluate the performance of multiparametric magnetic resonance imaging (mpMRI) and PSA testing in follow-up after high intensity focused ultrasound (HIFU) focal therapy for localized prostate cancer.MethodsA total of 73 men with localized prostate cancer were prospectively enrolled and underwent focal HIFU followed by per-protocol PSA and mpMRI with systematic plus targeted biopsies at 12 months after treatment. We evaluated the association between post-treatment mpMRI and PSA with disease persistence on the post-ablation biopsy. We also assessed post-treatment functional and oncological outcomes.ResultsMedian age was 69 years (Interquartile Range (IQR): 66–74) and median PSA was 6.9 ng/dL (IQR: 5.3–9.9). Of 19 men with persistent GG ≥ 2 disease, 58% (11 men) had no visible lesions on MRI. In the 14 men with PIRADS 4 or 5 lesions, 7 (50%) had either no cancer or GG 1 cancer at biopsy. Men with false negative mpMRI findings had higher PSA density (0.16 vs. 0.07 ng/mL², P = 0.01). No change occurred in the mean Sexual Health Inventory for Men (SHIM) survey scores (17.0 at baseline vs. 17.7 post-treatment, P = 0.75) or International Prostate Symptom Score (IPSS) (8.1 at baseline vs. 7.7 at 24 months, P = 0.81) after treatment.ConclusionsPersistent GG ≥ 2 cancer may occur after focal HIFU. mpMRI alone without confirmatory biopsy may be insufficient to rule out residual cancer, especially in patients with higher PSA density. Our study also validates previously published studies demonstrating preservation of urinary and sexual function after HIFU treatment.     

The 20-core prostate biopsy as an initial strategy: impact on the detection of prostatic cancer

Introduction:

To increase the detection rate of prostate cancer in recent years, we examined the increase in the number of cores taken at initial prostate biopsy. We hypothesized that an increasing number of cores may undermine the accuracy of models predicting the presence of prostate cancer at initial biopsy in patients submitted to 20-core initial biopsy.

Methods:

A total of 232 consecutive patients with prostate-specific antigen (PSA) between 4 and 20 ng/mL and/or abnormal digital rectal examination (DRE) underwent 12-core prostate biopsy protocol (group 1) or 20-core prostate biopsy protocol (group 2). The patients were divided into subgroups according to the results of their serum PSA and prostate volume. We evaluated the cancer detection rate overall and in each subgroup. Clinical data were analyzed using chi-square analysis and the unpaired t-test or 1-way ANOVA with significance considered at 0.05.

Results:

The 2 groups of patients were not significantly different with regard to parameters (age, abnormal DRE and serum PSA), although median prostate volume in group 1 (57.76 ± 26.94 cc) were slighter greater than in group 2. Cancer detection rate for patients submitted to 20 prostate biopsy was higher than patients submitted to 12 prostate biopsy (35.2% vs. 25%, p = 0.095). Breakdown to PSA level showed a benefit to 20 prostate biopsy for PSA <6 ng/mL (37.1% vs. 12.9%, p = 0.005). Stratifying results by prostate volume, we found that the improvement of cancer detection rate with 20 prostate biopsy was significant in patients with a prostate volume greater than 60 cc (55% in 20 prostate biopsy vs. 11.3% p < 0.05). Morbidity rates were identical in groups 1 and 2 with no statistically significant difference. There appeared to be no greater risk of infection and bleeding with 20 prostate biopsy protocol.

Conclusion:

The 20-core biopsy protocol was more efficient than the 12-core biopsy protocol, especially in patients with prostate specific antigen <6 ng/mL and prostate volume greater than 60 cc.     

Breast MRI assists in decision-making for surgical excision of atypical ductal hyperplasia

BackgroundAtypical ductal hyperplasia diagnosed on percutaneous breast biopsy typically undergoes surgical excision, upgrading to invasive breast cancer or ductal carcinoma in situ in 10% to 53%. In efforts to limit excision to those with highest upgrade risk, we sought to determine if breast magnetic resonance imaging has value in predicting upgrade. In this study, we will describe magnetic resonance imaging presentation of atypical ductal hyperplasia and assess magnetic resonance imaging accuracy in predicting upgrade.MethodsAll female patients ≥18 years with atypical ductal hyperplasia on percutaneous breast biopsy undergoing magnetic resonance imaging from 2008 to 2020 were included. Patient demographics, imaging presentation, magnetic resonance imaging enhancement kinetic curves, and pathology features were captured. Categorical variables were analyzed using Fisher exact to test for association between variables and upgrade. Continuous variables were analyzed using t tests.ResultsMagnetic resonance imaging was performed for 125 percutaneous breast biopsy with atypical ductal hyperplasia: 67 after and 58 before atypical ductal hyperplasia diagnosis. On magnetic resonance imaging, atypical ductal hyperplasia site had no enhancement in 45 (36%), nonmass enhancement in 50 (40%), and mass enhancement in 30 (24%). In total, 28% had atypical ductal hyperplasia diagnosed by magnetic resonance imaging–guided percutaneous breast biopsy. Surgical excision was performed for 96 (76.8%) and 15 (15.6%) upgraded (11 ductal carcinoma in situ, 4 invasive breast cancer). All 15 upgrades had enhancement. Any kinetic pattern enhancement was significantly associated with upgrade (P = .009) with upgrade most strongly associated with type III washout. The lowest risk for upgrade was pure atypical ductal hyperplasia and no magnetic resonance imaging enhancement (0%, n = 25).ConclusionsActive monitoring may be safely offered to women with pure atypical ductal hyperplasia on percutaneous breast biopsy when magnetic resonance imaging shows no enhancement. Any enhancement at atypical ductal hyperplasia site, particularly type III washout kinetics, should continue to undergo excision.     

Effects of “real life” prostate MRI inter-observer variability on total needle samples and indication for biopsy

PurposeProstate multiparametric magnetic resonance imaging (mpMRI) improves diagnosis of clinically significant cancer and reduces over-detection of nonsignificant cancer. Disagreement in the interpretation of mpMRI readings is well-known, with a reported discrepancy rate of 10% to 42%. We report the clinical repercussions of this variability on prostate biopsy candidates.Materials and MethodsMedical records of patients referred from 11 medical centers for MR-guided prostate biopsy (MRGpB) between October, 2017 and January, 2019 were retrospectively analyzed. Patients with at least one prostate imaging reporting and data system (PI-RADS) 3 or greater prostate lesion were selected, and the mpMRI studies (all read by others) were reviewed by our prostate mpMRI reader. Outcomes included changes in PI-RADS score and the subsequent effect on total needle samples and indication for biopsy.ResultsEighty-two patients with 128 lesions were suitable for analysis (mean age 66.5 ± 7.1 years, mean PSA 6.8 ± 8.5 ng/ml). Nine (11%) patients had suspicious rectal exams (T2a). Following our prostate mpMRI reader's imaging revisions, the PI-RADS score was downgraded in 66 (52%) lesions, upgraded in 15 (12%), and unchanged in 47 (37%), leaving a total of 84 suspected lesions (kappa = 0.17). Biopsy was deferred in 22 (27%) patients, and an estimated 136.4 (34.4%) samples were avoided (P = 0.0001 for both). There was a trend toward prostate size to correlate with imaging revision and abortion of biopsy (P = 0.06) while enrollment in active surveillance correlated with proof from such outcome (P = 0.007).ConclusionThese data suggest that high interobserver disagreement in prostate mpMRIs from diverse institutes significantly affects prostate biopsy practice. The clinical consequences of this discord are significant.     

The safety and effectiveness of low field intraoperative MRI guidance in frameless stereotactic biopsies of brain tumours—design and interim analysis of a prospective randomized trial

The aim of the study was to assess the safety and effectiveness of stereotactic brain tumour biopsy (STx biopsy) guided by low-field intraoperative magnetic resonance imaging (iMRI) in comparison with its frameless classic analogue based on a prospective randomized trial. A pilot group of 42 brain tumour patients was prospectively randomized into a low-field iMRI group and a control group that underwent a frameless STx biopsy. The primary endpoints of the analysis were postoperative complication rate and diagnostic yield, and the secondary endpoints were length of hospital stay and duration of operation. The iMRI group (21 patients) and the control group (21 patients) did not differ significantly according to demographic and epidemiological data. No major postoperative complications were noted in either group. In addition, no significant differences in the diagnostic yield (p?=?1.00) and length of hospital stay (p?=?0.16) were observed. The mean total OR time was 111?±?24 min in iMRI and 78?±?29 min in the control group (p?=?0.0001). Usage of iMRI may prolong the time of the procedure but seems to be comparable in safety and effectiveness to the standard frameless STx biopsy.