Comparing Micro-Ultrasound to mpMRI in Detecting Clinically Significant Prostate Cancer

Objectives To compare the performance of micro-ultrasound (mUS) with multi-parametric magnetic resonance imaging (mpMRI) in detecting clinically significant prostate cancer. Materials and Methods Retrospective data from consecutive patients with any indication for prostate biopsy in 2 academic institutions were included. The operator, blinded to mpMRI, would first scan the prostate and annotate any mUS lesions. All mUS lesions were biopsied. Any mpMRI lesions that did not correspond to mUS lesion upon unblinding were additionally biopsied. Grade group (GG) ≥ 2 was considered clinically significant cancer. The Jeffreys interval method was used to compare performance of mUS with mpMRI with the non-inferiority limit set at −5%. Results Imaging and biopsy were performed in 82 patients with 153 lesions. mUS had similar sensitivity to mpMRI (per-lesion analysis: 78.4% versus 72.5%), but lower specificity, positive predictive value, negative predictive value, and area under the curve. Micro-ultrasound found GG ≥ 2 in 13% of cases missed by mpMRI, while mpMRI found GG ≥ 2 in 11% of cases missed by mUS. The difference 0.020 (95% CI −0.070 to 0.110) was not statistically significant (P = 0.33). Conclusion The sensitivity of mUS in detecting GG ≥ 2 disease was similar to that of mpMRI, but the specificity was lower. Further evaluation with a larger sample size and experienced operators is warranted.

DWI-related texture analysis for prostate cancer: differences in correlation with histological aggressiveness and data repeatability between peripheral and transition zones

Background We investigated the correlation between texture features extracted from apparent diffusion coefficient (ADC) maps or diffusion-weighted images (DWIs), and grade group (GG) in the prostate peripheral zone (PZ) and transition zone (TZ), and assessed reliability in repeated examinations. Methods Patients underwent 3-T pelvic magnetic resonance imaging (MRI) before radical prostatectomy with repeated DWI using b-values of 0, 100, 1,000, and 1,500 s/mm2. Region of interest (ROI) for cancer was assigned to the first and second DWI acquisition separately. Texture features of ROIs were extracted from comma-separated values (CSV) data of ADC maps generated from several sets of two b-value combinations and DWIs, and correlation with GG, discrimination ability between GG of 1–2 versus 3–5, and data repeatability were evaluated in PZ and TZ. Results Forty-four patients with 49 prostate cancers met the eligibility criteria. In PZ, ADC 10% and 25% based on ADC map of two b-value combinations of 100 and 1,500 s/mm2 and 10% based on ADC map with b-value of 0 and 1,500 s/mm2 showed significant correlation with GG, acceptable discrimination ability, and good repeatability. In TZ, higher-order texture feature of busyness extracted from ADC map of 100 and 1,500 s/mm2, and high gray-level run emphasis, short-run high gray-level emphasis, and high gray-level zone emphasis from DWI with b-value of 100 s/mm2 demonstrated significant correlation, excellent discrimination ability, but moderate repeatability. Conclusions Some DWI-related features showed significant correlation with GG, acceptable to excellent discrimination ability, and moderate to good data repeatability in prostate cancer, and differed between PZ and TZ.

Limited Adenocarcinoma of the Prostate on Needle Core Biopsy

Context.— Grading small foci of prostate cancer on a needle biopsy is often difficult, yet the clinical significance of accurate grading remains uncertain. Objective.— To assess if grading of limited adenocarcinoma on prostate biopsy specimen is critical. Design.— We studied 295 consecutive patients undergoing extended-sextant biopsy with only 1-core involvement of adenocarcinoma, followed by radical prostatectomy. Results.— The linear tumor lengths on these biopsy specimens were: less than 1 mm (n = 114); 1 mm or more or less than 2 mm (n = 82); 2 mm or more or less than 3 mm (n = 35); and 3 mm or more (n = 64). Longer length was strongly associated with higher Grade Group (GG) on biopsy or prostatectomy specimen, higher risk of extraprostatic extension/seminal vesicle invasion and positive surgical margin, and larger estimated tumor volume. When cases were compared based on biopsy specimen GG, higher grade was strongly associated with higher prostatectomy specimen GG, higher incidence of pT3/pT3b disease, and larger tumor volume. Outcome analysis further showed significantly higher risks for biochemical recurrence after radical prostatectomy in patients with 1 mm or more, 2 mm or more, 3 mm or more, GG2-4, GG3-4, GG4, less than 1 mm/GG2-4, less than 1 mm/GG3-4, less than 2 mm/GG3-4, 3 mm or more/GG2-4, or 3 mm or more/GG3-4 tumor on biopsy specimens, compared with respective control subgroups. In particular, 3 mm or more, GG3, and GG4 on biopsy specimens showed significance as independent prognosticators by multivariate analysis. Meanwhile, there were no significant differences in the rate of upgrading or downgrading after radical prostatectomy among those subgrouped by biopsy specimen tumor length (eg, <1 mm [44.7%] versus ≥1/<2 mm [41.5%] versus ≥2/<3 mm [45.7%] versus ≥3 mm [46.9%]). Conclusions.— These results indicate that pathologists still need to make maximum efforts to grade relatively small prostate cancer on biopsy specimens.

The Clinical Significance of Perineural Invasion by Prostate Cancer on Needle Core Biopsy

Context.— Perineural invasion (PNI) by prostate cancer has been associated with adverse pathology, including extraprostatic extension. However, the significance of PNI quantification on prostate biopsy (PBx) remains unclear. Objective.— To compare radical prostatectomy (RP) findings and long-term outcomes in patients whose PBx had exhibited PNI. Design.— We assessed 497 consecutive patients undergoing sextant (6-site/≥12-core) PBx showing conventional adenocarcinoma followed by RP. Results.— PNI was found in 1 (n = 290)/2 (n = 132)/3 (n = 47)/4 (n = 19)/5 (n = 5)/6 (n = 4) of the sites/regions of PBx. Compared with a single PNI site, multiple PNIs were significantly associated with higher preoperative prostate-specific antigen, higher Grade Group (GG) on PBx or RP, higher pT or pN category, positive surgical margin, and larger estimated tumor volume. When compared in subgroups of patients based on PBx GG, significant differences in RP GG (GG1–3), pT (GG1–2/GG1–3/GG2/GG3), surgical margin status (GG1–3/GG3/GG5), or tumor volume (GG1–2/GG1–3/GG2/GG3) between 1 versus multiple PNIs were observed. Moreover, there were significant differences in prostate-specific antigen (PNI sites: 1–2 versus 3–6/1–3 versus 4–6/1–4 versus 5–6), RP GG (1–3 versus 4–6/1–4 versus 5–6), pT (1–2 versus 3–6/1–3 versus 4–6), pN (1–3 versus 4–6), or tumor volume (1–2 versus 3–6/1–4 versus 5–6). Outcome analysis revealed significantly higher risks of disease progression in the entire cohort or PBx GG1–2/GG1–3/GG2/GG3/GG5 cases showing 2 to 6 PNIs, compared with respective controls with 1-site PNI. In multivariate analysis, multisite PNI was an independent predictor for progression (hazard ratio = 1.556, P = .03). Conclusions.— Multiple sites of PNI on PBx were associated with worse histopathologic features in RP specimens and poorer prognosis. PNI may thus need to be specified, if present, in every sextant site on PBx, especially those showing GG1–3 cancer.

Diagnostic significance of reassessment of prostate biopsy specimens by experienced urological pathologists at a high-volume institution

In prostate cancer, accurate diagnosis and grade group (GG) decision based on biopsy findings are essential for determining treatment strategies. Diagnosis by experienced urological pathologists is recommended; however, their contribution to patient benefits remains unknown. Therefore, we analyzed clinicopathological information to determine the significance of reassessment by experienced urological pathologists at a high-volume institution to identify factors involved in the agreement or disagreement of biopsy and surgical GGs. In total, 1325 prostate adenocarcinomas were analyzed, and the GG was changed in 452/1325 (34.1%) cases (359 cases were upgraded, and 93 cases were downgraded). We compared the highest GG based on biopsy specimens, with the final GG based on surgical specimens of 210 cases. The agreement rate between the surgical GG performed and assessed in our institute and the highest biopsy GG assessed by an outside pathologist was 34.8% (73/210); the agreement rate increased significantly to 50% (105/210) when biopsy specimens were reevaluated in our institute (chi-square test, P < 0.01). Multivariate logistic regression analysis showed that only the length of the lesion in the positive core with the highest GG in the biopsy was a significant factor for determining the agreement between biopsy GG and surgical GG, with an odds ratio of 1.136 (95% confidence interval: 1.057–1.221; P < 0.01). Thus, reassessment by experienced urological pathologists at high-volume institutions improved the agreement rate. However, it should be noted there is a high probability of discordance between a small number of lesions or short lesions and surgical GG.

MRI-based nomogram for the prediction of prostate cancer diagnosis: A multi-centre validated patient–physician decision tool

Objective: To update and externally validate a magnetic resonance imaging (MRI)-based nomogram for predicting prostate biopsy outcomes with a multi-centre cohort. Materials and methods: Prospective data from five UK-based centres were analysed. All men were biopsy naïve. Those with missing data, no MRI, or prostate-specific antigen (PSA) > 30 ng/mL were excluded. Logistic regression analysis was used to confirm predictors of prostate cancer outcomes including MRI-PIRADS (Prostate Imaging Reporting and Data System) score, PSA density, and age. Clinically significant disease was defined as International Society of Urological Pathology (ISUP) Grade Group ⩾ 2 (Gleason grade ⩾ 7). Biopsy strategy included transrectal and transperineal approaches. Nomograms were produced using logistic regression analysis results. Results: A total of 506 men were included in the analysis with median age 66 (interquartile range (IQR) = 60–69). Median PSA was 6.6 ng/mL (IQR = 4.72–9.26). PIRADS ⩾ 3 was reported in 387 (76.4%). Grade Group ⩾ 2 detection was 227 (44.9%) and 318 (62.8%) for any cancer. Performance of the MRI-based nomogram was an area under curve (AUC) of 0.84 (95% confidence interval (CI) = 0.81–0.88) for Grade Group ⩾ 2% and 0.85 (95% CI = 0.82–0.88) for any prostate cancer. Conclusion: We present external validation of a novel MRI-based nomogram in a multi-centre UK-based cohort, showing good discrimination in identifying men at high risk of having clinically significant disease. These findings support this risk calculator use in the prostate biopsy decision-making process. Level of evidence: 2c

Early detection of sublexical and lexical processing in beginning readers: evidence from Steady-State Visual Evoked Potentials (SSVEPs)

There are multiple levels of processing relevant to reading that vary in their visual, sublexical and lexical orthographic processing demands. Segregating distinct cortical sources for each of these levels has been challenging in EEG studies of early readers. To address this challenge, we applied recent advances in analyzing high-density EEG using Steady-State Visual Evoked Potentials (SSVEPs) via data-driven Reliable Components Analysis (RCA) in a group of early readers spanning from kindergarten to second grade. Three controlled stimulus contrasts---familiar words versus unfamiliar pseudofonts, familiar words versus orthographically legal pseudowords, and orthographically legal pseudowords versus orthographically illegal nonwords---were used to isolate visual print/letter selectivity, sublexical processing, and lexical processing, respectively. We found robust responses specific to each of these processing levels, even in kindergarteners who have limited knowledge of print. Moreover, comparing amplitudes of these three stimulus contrasts across three reading fluency-based groups and three grade-based groups revealed fluency group and grade group main effects only for lexical contrast (i.e., words versus orthographically legal pseudowords). Furthermore, we found that sublexical orthography-related responses shifted their topographic distribution from the right to left hemisphere from kindergarten to first and second grades. Results suggest that, with more sensitive measures, the sublexical and lexical fine tuning for words---as a bio-marker of reading ability---can be detected at a much earlier stage than previously assumed.