Multiparametric magnetic resonance imaging and clinical variables: Which is the best combination to predict reclassification in active surveillance patients?

We tested the role of multiparametric magnetic resonance imaging (mpMRI) in disease reclassification and whether the combination of mpMRI and clinicopathological variables could represent the most accurate approach to predict the risk of reclassification during active surveillance. Three-hundred eighty-nine patients (pts) underwent mpMRI and subsequent confirmatory or follow-up biopsy according to the Prostate Cancer Research International Active Surveillance (PRIAS) protocol. Pts with negative (-) mpMRI underwent systematic random biopsy. Pts with positive (+) mpMRI [Prostate Imaging Reporting and Data System, version 2 (PI-RADS-V2) score ≥3] underwent targeted + systematic random biopsies. Multivariate analyses were used to create three models predicting the probability of reclassification [International Society of Urological Pathology ≥ Grade Group 2 (GG2)]: a basic model including only clinical variables (age, prostate-specific antigen density, and number of positive cores at baseline), an Magnetic resonance imaging (MRI) model including only the PI-RADS score, and a full model including both the previous ones. The predictive accuracy (PA) of each model was quantified using the area under the curve. mpMRI negative (-) was recorded in 127 (32.6%) pts; mpMRI positive (+) was recorded in 262 pts: 72 (18.5%) had PI-RADS 3, 150 (38.6%) PI-RADS 4, and 40 (10.3%) PI-RADS 5 lesions. At a median follow-up of 12 months, 125 pts (32%) were reclassified to GG2 prostate cancer. The rate of reclassification to GG2 prostate cancer was 17%, 35%, 38%, and 52% for mpMRI (-), PI-RADS 3, 4, and 5, respectively (P < 0.001). The PA was 69% and 64% in the basic and MRI models, respectively. The full model had the best PA of 74%: older age (P = 0.023; Odds ratio (OR) = 1.040), prostate-specific antigen density (P = 0.037; OR = 1.324), number of positive cores at baseline (P = 0.001; OR = 1.441), and PI-RADS 3, 4, and 5 (overall P = 0.001; OR = 2.458, 3.007, and 3.898, respectively) were independent predictors of reclassification. Disease reclassification increased according to the PI-RADS score increase, at confirmatory or follow-up biopsy. However, a no-negligible rate of reclassification was found also in cases of mpMRI (-). The combination of mpMRI and clinicopathological variables still represents the most accurate approach to pts on active surveillance.

Roscigno M ，Stabile A ，Lughezzani G ，Pepe P ，Dell'Atti L ，Naselli A ，Naspro R ，Nicolai M ，La Croce G ，Muhannad A ，Perugini G ，Guazzoni G ，Montorsi F ，Balzarini L ，Sironi S ，Da Pozzo LF ... -  《-》

The Use of Multiparametric Magnetic Resonance Imaging for Follow-up of Patients Included in Active Surveillance Protocol. Can PSA Density Discriminate Patients at Different Risk of Reclassification?

The objective of this study was to test Prostate Imaging Reporting and Data System (PI-RADS) classification on multiparametric magnetic resonance imaging (mpMRI) and MRI-derived prostate-specific antigen density (PSAD) in predicting the risk of reclassification in men in active surveillance (AS), who underwent confirmatory or per-protocol follow-up biopsy. Three hundred eighty-nine patients in AS underwent mpMRI before confirmatory or follow-up biopsy. Patients with negative (-) mpMRI underwent systematic random biopsy. Patients with positive (+) mpMRI underwent targeted fusion prostate biopsies + systematic random biopsies. Different PSAD cutoff values were tested (< 0.10, 0.10-0.20, ≥ 0.20). Multivariable analyses assessed the risk of reclassification, defined as clinically significant prostate cancer of grade group 2 or more, during follow-up according to PSAD, after adjusting for covariates. One hundred twenty-seven (32.6%) patients had mpMRI(-); 72 (18.5%) had PI-RADS 3, 150 (38.6%) PI-RADS 4, and 40 (10.3%) PI-RADS 5 lesions. The rate of reclassification to grade group 2 PCa was 16%, 22%, 31%, and 39% for mpMRI(-) and PI-RADS 3, 4, and 5, respectively, in case of PSAD < 0.10 ng/mL2; 16%, 25%, 36%, and 44%, in case of PSAD 0.10 to 0.19 ng/mL2; and 25%, 42%, 55%, and 67% in case of PSAD ≥ 0.20 ng/mL2. PSAD ≥ 0.20 ng/mL2 (odds ratio [OR], 2.45; P = .007), PI-RADS 3 (OR, 2.47; P = .013), PI-RADS 4 (OR, 2.94; P < .001), and PI-RADS 5 (OR, 3.41; P = .004) were associated with a higher risk of reclassification. PSAD ≥ 0.20 ng/mL2 may improve predictive accuracy of mpMRI results for reclassification of patients in AS, whereas PSAD < 0.10 ng/mL2 may help selection of patients at lower risk of harboring clinically significant prostate cancer. However, the risk of reclassification is not negligible at any PSAD cutoff value, also in the case of mpMRI(-).

Roscigno M ，Stabile A ，Lughezzani G ，Pepe P ，Galosi AB ，Naselli A ，Naspro R ，Nicolai M ，La Croce G ，Aljoulani M ，Perugini G ，Guazzoni G ，Montorsi F ，Balzarini L ，Sironi S ，Da Pozzo LF ... -  《-》

Value of 3-Tesla multiparametric magnetic resonance imaging and targeted biopsy for improved risk stratification in patients considered for active surveillance.

To evaluate the role of multiparametric magnetic resonance imaging (mpMRI) of the prostate and transrectal ultrasonography guided biopsy (TRUS-Bx) with visual estimation in early risk stratification of patients with prostate cancer on active surveillance (AS). Patients with low-risk, low-grade, localised prostate cancer were prospectively enrolled and submitted to a 3-T 16-channel cardiac surface coil mpMRI of the prostate and confirmatory biopsy (CBx), which included a standard biopsy (SBx) and visual estimation-guided TRUS-Bx. Cancer-suspicious regions were defined using Prostate Imaging Reporting and Data System (PI-RADS) scores. Reclassification occurred if CBx confirmed the presence of a Gleason score ≥7, greater than three positive fragments, or ≥50% involvement of any core. The performance of mpMRI for the prediction of CBx results was assessed. Univariate and multivariate logistic regressions were performed to study relationships between age, prostate-specific antigen (PSA) level, PSA density (PSAD), number of positive cores in the initial biopsy, and mpMRI grade on CBx reclassification. Our report is consistent with the Standards of Reporting for MRI-targeted Biopsy Studies (START) guidelines. In all, 105 patients were available for analysis in the study. From this cohort, 42 (40%) had PI-RADS 1, 2, or 3 lesions and 63 (60%) had only grade 4 or 5 lesions. Overall, 87 patients underwent visual estimation TRUS-Bx. Reclassification among patients with PI-RADS 1, 2, 3, 4, and 5 was 0%, 23.1%, 9.1%, 74.5%, and 100%, respectively. Overall, mpMRI sensitivity, specificity, positive predictive value, and negative predictive value for disease reclassification were 92.5%, 76%, 81%, and 90.5%, respectively. In the multivariate analysis, only PSAD and mpMRI remained significant for reclassification (P < 0.05). In the cross-tabulation, SBx would have missed 15 significant cases detected by targeted biopsy, but SBx did detect five cases of significant cancer not detected by targeted biopsy alone. Multiparametric magnetic resonance imaging is a significant tool for predicting cancer severity reclassification on CBx among AS candidates. The reclassification rate on CBx is particularly high in the group of patients who have PI-RADS grades 4 or 5 lesions. Despite the usefulness of visual-guided biopsy, it still remains highly recommended to retrieve standard fragments during CBx in order to avoid missing significant tumours.

Pessoa RR ，Viana PC ，Mattedi RL ，Guglielmetti GB ，Cordeiro MD ，Coelho RF ，Nahas WC ，Srougi M ... -  《-》

A novel nomogram to identify candidates for active surveillance amongst patients with International Society of Urological Pathology (ISUP) Grade Group (GG) 1 or ISUP GG2 prostate cancer, according to multiparametric magnetic resonance imaging findings.

To develop a novel nomogram to identify candidates for active surveillance (AS) that combines clinical, biopsy and multiparametric magnetic resonance imaging (mpMRI) findings; and to compare its predictive accuracy to, respectively: (i) Prostate Cancer Research International: Active Surveillance (PRIAS) criteria, (ii) Johns Hopkins (JH) criteria, (iii) European Association of Urology (EAU) low-risk classification, and (iv) EAU low-risk or low-volume with International Society of Urological Pathology (ISUP) Grade Group (GG) 2 classification. We selected 1837 patients with ISUP GG1 or GG2 prostate cancer (PCa), treated with radical prostatectomy (RP) between 2012 and 2018. The outcome of interest was the presence of unfavourable disease (i.e., clinically significant PCa [csPCa]) at RP, defined as: ISUP GG ≥ 3 and/or pathological T stage (pT) ≥3a and/or pathological N stage (pN) 1. First, logistic regression models including PRIAS, JH, EAU low-risk, and EAU low-risk or low-volume ISUP GG2 binary classifications (not eligible vs eligible) were used. Second, a multivariable logistic regression model including age, prostate-specific antigen density (PSA-D), ISUP GG, and the percentage of positive cores (Model 1) was fitted. Third, Prostate Imaging-Reporting and Data System (PI-RADS) score (Model 2), extracapsular extension (ECE) score (Model 3) and PI-RADS + ECE score (Model 4) were added to Model 1. Only variables associated with higher csPCa rates in Model 4 were retained in the final simplified Model 5. The area under the receiver operating characteristic curve (AUC), calibration plots and decision curve analyses were used. Of the 1837 patients, 775 (42.2%) had csPCa at RP. Overall, 837 (47.5%), 986 (53.7%), 348 (18.9%), and 209 (11.4%) patients were eligible for AS according to, respectively, the EAU low-risk, EAU low-risk or low-volume ISUP GG2, PRIAS, and JH criteria. The proportion of csPCa amongst the EAU low-risk, EAU low-risk or low-volume ISUP GG2, PRIAS and JH candidates was, respectively 28.5%, 29.3%, 25.6% and 17.2%. Model 4 and Model 5 (in which only PSA-D, ISUP GG, PI-RADS and ECE score were retained) had a greater AUC (0.84), compared to the four proposed AS criteria (all P < 0.001). The adoption of a 25% nomogram threshold increased the proportion of AS-eligible patients from 18.9% (PRIAS) and 11.4% (JH) to 44.4%. Moreover, the same 25% nomogram threshold resulted in significantly lower estimated risks of csPCa (11.3%), compared to PRIAS (Δ: -14.3%), JH (Δ: -5.9%), EAU low-risk (Δ: -17.2%), and EAU low-risk or low-volume ISUP GG2 classifications (Δ: -18.0%). The novel nomogram combining clinical, biopsy and mpMRI findings was able to increase by ~25% and 35% the absolute frequency of patients suitable for AS, compared to, respectively, the PRIAS or JH criteria. Moreover, this nomogram significantly reduced the estimated frequency of csPCa that would be recommended for AS compared to, respectively, the PRIAS, JH, EAU low-risk, and EAU low-risk or low-volume ISUP GG2 classifications.

Luzzago S ，de Cobelli O ，Cozzi G ，Peveri G ，Bagnardi V ，Catellani M ，Di Trapani E ，Mistretta FA ，Pricolo P ，Conti A ，Alessi S ，Marvaso G ，Ferro M ，Matei DV ，Renne G ，Jereczek-Fossa BA ，Petralia G ，Musi G ... -  《-》

Role of Multiparametric Prostate Magnetic Resonance Imaging before Confirmatory Biopsy in Assessing the Risk of Prostate Cancer Progression during Active Surveillance.

To evaluate the impact of multiparametric magnetic resonance imaging (mpMRI) before confirmatory prostate biopsy in patients under active surveillance (AS). This retrospective study included 170 patients with Gleason grade 6 prostate cancer initially enrolled in an AS program between 2011 and 2019. Prostate mpMRI was performed using a 1.5 tesla (T) magnetic resonance imaging system with a 16-channel phased-array body coil. The protocol included T1-weighted, T2-weighted, diffusion-weighted, and dynamic contrast-enhanced imaging sequences. Uroradiology reports generated by a specialist were based on prostate imaging-reporting and data system (PI-RADS) version 2. Univariate and multivariate analyses were performed based on regression models. The reclassification rate at confirmatory biopsy was higher in patients with suspicious lesions on mpMRI (PI-RADS score ≥ 3) (n = 47) than in patients with non-suspicious mpMRIs (n = 61) and who did not undergo mpMRIs (n = 62) (66%, 26.2%, and 24.2%, respectively; p < 0.001). On multivariate analysis, presence of a suspicious mpMRI finding (PI-RADS score ≥ 3) was associated (adjusted odds ratio: 4.72) with the risk of reclassification at confirmatory biopsy after adjusting for the main variables (age, prostate-specific antigen density, number of positive cores, number of previous biopsies, and clinical stage). Presence of a suspicious mpMRI finding (adjusted hazard ratio: 2.62) was also associated with the risk of progression to active treatment during the follow-up. Inclusion of mpMRI before the confirmatory biopsy is useful to stratify the risk of reclassification during the biopsy as well as to evaluate the risk of progression to active treatment during follow-up.

Salguero J ，Gómez-Gómez E ，Valero-Rosa J ，Carrasco-Valiente J ，Mesa J ，Martin C ，Campos-Hernández JP ，Rubio JM ，López D ，Requena MJ ... -  《-》