Prostate Cancer Risk Stratification by Simple Scoring of the Current pT3 Lesions: A Proposal for a New Pathologic T-Staging System.

Cancer spread beyond the prostate, including extraprostatic extension (other than seminal vesicle or bladder invasion; EPE)/microscopic bladder neck invasion and seminal vesicle invasion (SVI) currently classified as pT3a and pT3b lesions, respectively, does not uniformly indicate poor oncologic outcomes. Accurate risk stratification of current pT3 disease is therefore required. We herein further determined the prognostic impact of these histopathologic lesions routinely assessed and reported by pathologists, particularly their combinations. We assessed consecutive 2892 patients undergoing radical prostatectomy for current pT2 (n = 1692), pT3a (n = 956), or pT3b (n = 244) disease at our institution between 2009 and 2018. Based on our preliminary findings, point(s) were given (1 point to focal EPE, microscopic bladder neck invasion, or unilateral SVI; 2 points to nonfocal/established EPE or bilateral SVI) and summed up in each case. Our cohort had 0 point (n = 1692, 58.5%; P0), 1 point (n = 243, 8.4%; P1), 2 points (n = 657, 22.7%; P2), 3 points (n = 192, 6.6%; P3), 4 points (n = 76, 2.6%; P4), and 5 points (n = 32, 1.1%; P5). Univariate analysis revealed associations of higher points with significantly worse biochemical progression-free survival, particularly when P4 and P5 were combined. In multivariable analysis (P0 as a reference), P1 (hazard ratio [HR], 1.57; P = .033), P2 (HR, 3.25; P < .001), P3 (HR, 4.01; P < .001), and P4 + P5 (HR, 5.99; P < .001) showed significance for the risk of postoperative progression. Meanwhile, Harrell C-indexes for the current pT staging, newly developed point system, and the Cancer of the Prostate Risk Assessment post-Surgical (CAPRA-S) score were 0.727 (95% CI, 0.706-0.748), 0.751 (95% CI, 0.729-0.773), and 0.774 (95% CI, 0.755-0.794), respectively, for predicting progression. We believe our data provide a logical rationale for a novel pathologic T-staging system based on the summed points, pT1a (0 point), pT1b (1 point), pT2 (2 points), pT3a (3 points), and pT3b (4 or 5 points), which more accurately stratifies the prognosis of prostate cancer.

Risk of Biochemical Recurrence in Patients With Grade Group 1 Prostate Cancer With Extraprostatic Extension Treated With Radical Prostatectomy.

PURPOSE: We sought to examine the association of extraprostatic extension (EPE) with biochemical recurrence (BCR) separately in men with Grade Group (GG) 1 and GG2 prostate cancer (PCa) treated with radical prostatectomy. MATERIALS AND METHODS: We reviewed our institutional database of patients who underwent radical prostatectomy for PCa between 2005 and 2022 and identified patients with GG1 and GG2 disease on final pathology. Fine-Gray competing risk models with an interaction between EPE (yes vs no) and GG (GG1 vs GG2) were used to examine the relationship between disease group and BCR-free survival. RESULTS: The cohort consisted of 6309 men, of whom 169/2740 (6.2%) with GG1 disease had EPE while 1013/3569 (28.4%) with GG2 disease had EPE. Median follow-up was 4 years. BCR occurred in 400/6309 (6.3%) patients. For men with GG1, there was no statistically significant difference in BCR-free survival for men with vs without EPE (subdistribution HR = 0.88; 95% CI: 0.37-2.09). However, for GG2 patients BCR-free survival was significantly worse for those with vs without EPE (subdistribution HR = 1.97, 95% CI: 1.54-2.52). CONCLUSIONS: Although there is a subset of GG1 PCas capable of invading through the prostatic capsule, patients with GG1 PCa and EPE at prostatectomy experience similar biochemical recurrence and survival outcomes compared to GG1 patients without EPE. However, among men with GG2, EPE connotes a worse prognosis.

Does the extent of extraprostatic extension at radical prostatectomy predict outcome?-a systematic review and meta-analysis.

Extraprostatic extension (EPE) of prostate cancer is usually reported as either focal (F-EPE) or established (E-EPE), but data on the implication for outcomes of this subdivision are conflicting and no systematic review (SR) evaluating this exists. This SR aims to address this gap in the literature, focusing on the impact of F-EPE and E-EPE on outcome in radical prostatectomy (RP) patients. Searches on Embase, Medline(R), and Pubmed databases were conducted. Studies were included if they investigated the extent of EPE in RP patients and correlated this with defined outcomes (biochemical recurrence [BCR], death, metastasis). Quality was assessed using the Newcastle-Ottawa Scale. A random effects model was used for studies reporting hazard ratios (EPE extent and biochemical recurrence). 24 studies, including 49,187 men, were included. Six studies were of high quality. 20 studies reported how they measured EPE. 13 studies reported that the extent of EPE was associated significantly with BCR. Meta-analysis showed there was a significant correlation between BCR and both F-EPE and E-EPE when compared to organ-confined disease; no significant difference was found between F-EPE and E-EPE. This is the only SR to investigate the extent of EPE on outcomes after RP. EPE alone predicts outcome, but the value of subdivision by extent could not be demonstrated. Comparisons are limited due to variability in EPE assessment and in the methods used to report outcomes in the literature. Further work to standardize EPE reporting methods, in larger cohorts, may be helpful to resolve remaining questions.

Bicenter validation of a risk model for the preoperative prediction of extraprostatic extension of localized prostate cancer combining clinical and multiparametric MRI parameters.

BACKGROUND: This study aimed to validate a previously published risk model (RM) which combines clinical and multiparametric MRI (mpMRI) parameters to predict extraprostatic extension (EPE) of prostate cancer (PC) prior to radical prostatectomy (RP). MATERIALS AND METHODS: A previously published RM combining clinical with mpMRI parameters including European Society of Urogenital Radiology (ESUR) classification for EPE was retrospectively evaluated in a cohort of two urological university hospitals in Germany. Consecutive patients (n = 205, January 2015 -June 2021) with available preoperative MRI images, clinical information including PSA, prostate volume, ESUR classification for EPE, histopathological results of MRI-fusion biopsy and RP specimen were included. Validation was performed by receiver operating characteristic analysis and calibration plots. The RM's performance was compared to ESUR criteria. RESULTS: Histopathological T3 stage was detected in 43% of the patients (n = 89); 45% at Essen and 42% at Düsseldorf. Discrimination performance between pT2 and pT3 of the RM in the entire cohort was AUC = 0.86 (AUC = 0.88 at site 1 and AUC = 0.85 at site 2). Calibration was good over the entire probability range. The discrimination performance of ESUR classification alone was comparable (AUC = 0.87). CONCLUSIONS: The RM showed good discriminative performance to predict EPE for decision-making for RP as a patient-tailored risk stratification. However, when experienced MRI reading is available, standardized MRI reading with ESUR scoring is comparable regarding information outcome. A main limitation is the potentially limited transferability to other populations because of the high prevalence of EPE in our subgroups.

Predicting contralateral extraprostatic extension in unilateral high-risk prostate cancer: a multicentric external validation study.

PURPOSE: Accurate prediction of extraprostatic extension (EPE) is crucial for decision-making in radical prostatectomy (RP), especially in nerve-sparing strategies. Martini et al. introduced a three-tier algorithm for predicting contralateral EPE in unilateral high-risk prostate cancer (PCa). The aim of the study is to externally validate this model in a multicentric European cohort of patients. METHODS: The data from 208 unilateral high-risk PCa patients diagnosed through magnetic resonance imaging (MRI)-targeted and systematic biopsies, treated with RP between January 2016 and November 2021 at eight referral centers were collected. The evaluation of model performance involved measures such as discrimination (AUC), calibration, and decision-curve analysis (DCA) following TRIPOD guidelines. In addition, a comparison was made with two established multivariable logistic regression models predicting the risk of side specific EPE for assessment purposes. RESULTS: Overall, 38%, 48%, and 14% of patients were categorized as low, intermediate, and high-risk groups according to Martini et al.'s model, respectively. At final pathology, EPE on the contralateral prostatic lobe occurred in 6.3%, 12%, and 34% of patients in the respective risk groups. The algorithm demonstrated acceptable discrimination (AUC 0.68), comparable to other multivariable logistic regression models (p = 0.3), adequate calibration and the highest net benefit in DCA. The limitations include the modest sample size, retrospective design, and lack of central revision. CONCLUSION: Our findings endorse the algorithm's commendable performance, supporting its utility in guiding treatment decisions for unilateral high-risk PCa patients.

Significance of extraprostatic extension by Grade Groups 1-3 prostatic carcinoma on needle biopsy.

BACKGROUND: It is rare for extraprostatic extension (EPE) on biopsy to be seen with Grade Groups (GG) 1-3 (Gleason scores 3 + 3 = 6; 3 + 4 = 7; 4 + 3 = 7) prostatic adenocarcinoma, and there is no data whether this finding should be a contraindication for performing radical prostatectomy (RP). METHODS: Thirty eight cases with GG 1-3 prostatic adenocarcinoma as the highest grade in the case with EPE on biopsy were identified from our consultation files. Highly unfavorable findings at RP were those that if they could have been predicted preoperatively, might have factored into the decision of whether to proceed with surgery. For these purposes, highly unfavorable pathology at RP was defined as either the presence of seminal vesicle invasion or lymph node metastases or GG5 (Gleason score 9-10). RESULTS: Among 37 patients with clinical follow-up data, 18 (49%) received radiation and/or hormonal therapy (RT/HT), 13 patients (35%) either underwent (n = 11) or are planning (n = 2) RP, and 6 patients (16%) received either ablation therapy or active surveillance. Based on the 11 RP pathology reports, 8 were GG2, one GG3 with tertiary pattern 5, and two GG3. Ten cases were reported to have EPE and six cases had positive margins. Only one had highly unfavorable pathology with pT3bN1 disease. The only difference between the RP and the RT/HT groups in their pretreatment parameters was the mean age of the RP patients was 61 compared with 69 for the RT/HT men (p = 0.02); the lack of many cases with highly unfavorable pathology at RP cannot be attributable to a selection bias of men with lower volume cancer on biopsy or lower serum prostate-specific antigen levels choosing RP over RT/HT. CONCLUSIONS: Despite EPE on biopsy, most men do not have highly unfavorable pathology at RP, and this treatment should remain an option in this setting.

3D-Reconstructed Contact Surface Area and Tumour Volume on Magnetic Resonance Imaging Improve the Prediction of Extraprostatic Extension of Prostate Cancer.

This study is to determine whether the volume and contact surface area (CSA) of a tumour with an adjacent prostate capsule on MRI in a three-dimensional (3D) model that can predict side-specific extraprostatic extension (EPE) at radical prostatectomy (RP). Patients with localised prostate cancer (PCa) who underwent robot-assisted RP between July 2015 and March 2021 were included in this retrospective study. MRI-based 3D prostate models incorporating the PCa volume and location were reconstructed. The tumour volume and surface variables were extracted. For the prostate-to-tumour and tumour-to-prostate CSAs, the areas in which the distances were ≤ 1, ≤ 2, ≤ 3, ≤ 4, and ≤ 5 mm were defined, and their surface (cm2) were determined. Differences in prostate sides with and without pathological EPE were analysed. Multivariable logistic regression analysis to find independent predictors of EPE. Overall, 75/302 (25%) prostate sides showed pathological EPE. Prostate sides with EPE had higher cT-stage, higher PSA density, higher percentage of positive biopsy cores, higher biopsy Gleason scores, higher radiological tumour stage, larger tumour volumes, larger prostate CSA, and larger tumour CSA (all p < 0.001). Multivariable logistic regression analysis showed that the radiological tumour stage (p = 0.001), tumour volume (p < 0.001), prostate CSA (p < 0.001), and tumour CSA (p ≤ 0.001) were independent predictors of pathological EPE. A 3D reconstruction of tumour locations in the prostate improves prediction of extraprostatic extension. Tumours with a higher 3D-reconstructed volume, a higher surface area of tumour in contact with the prostate capsule, and higher surface area of prostate capsule in contact with the tumour are at increased risk of side-specific extraprostatic extension.

[Comparison of the efficiency of surgical excision methods for detecting extraprostatic extension and positive resection margin in prostate cancer]. / Sravnenie effektivnosti metodov vyrezki operatsionnogo materiala dlya vyyavleniya ekstraprostaticheskogo rasprostraneniya i polozhitel'nogo kraya rezektsii pri rake prostaty.

On the samples of 26 prostatectomies, the method of excision of the prostate gland according to Kim was tested. This method increased the number of blocks by 30.2% and increased the detectability of extraprostatic extension by 41.7% and positive surgical margin by 40.0% compared to the method of alternate prostate sections. Also, the method according to Kim reduced the number of blocks of prostate tissue by 34.3% compared to the method of complete prostate excision.

International Society of Urological Pathology (ISUP)-Grade Grouping in Prostatic Adenocarcinoma and its Prognostic Implications.

In this study, we evaluated the association of ISUP/WHO-grade groups with various pathological prognostic parameters and cancer-specific survival in patients with prostatic adenocarcinoma. We found 27 (15.7%) cases of grade group 1, 22 (12.8%) grade group 2, 30 (17.4%) grade group 3, 40 (23.3%) grade group 4 and 53 (30.8%) grade group 5 prostatic adenocarcinoma. We found that high-grade tumors (grade 3-5) had a higher frequency of perineural invasion and higher tumor volumes (>50%). Moreover, a significant association of tumor grade was noted with cancer-specific survival of patients, signifying prognostic significance of grade grouping in prostatic adenocarcinoma.

The relationship between amount of extra-prostatic extension and length of capsular contact: performances from MR images and radical prostatectomy specimens

Backround/aim: In prostate cancer, extraprostatic extension (EPE) is an unfavorable prognostic factor, and the grade of EPE is correlated with the prognosis. This study aims to evaluate the utility of length of capsular contact (LCC ) in predicting the grade of EPE by correlating the measurements from MRI images and the measurements performed from radical prostatectomy specimens. Materials and methods: MR images and specimens of 110 tumors are analyzed retrospectively. The specimens are used as reference to validate the presence of EPE and to measure the ground truth LCC. MR images are evaluated by two radiologists to identify the presence of EPE and to predict the LCC indirectly. Reliability, accuracy, sensitivity, and specificity of the evaluations are analyzed in comparison with the findings obtained from the specimens. Results: In detection of EPE existence, the radiologists achieve almost the same performance (all AUCs = 0.73) with optimal cut-off values lead to moderate sensitivity and specificity pairs (For cut-off = 15.8 mm; Se = 0.69, Sp = 0.68 and for cut-off of 14.5 mm: Se = 0.77, Sp = 0.62). In distinguishing high-grade EPE from low-grade EPE, the radiologists accomplish very similar performances (AUCs = 0.73 and 0.72) Optimal thresholds of 20.0 mm and 18.5 mm for the readers retrospectively reveal medium sensitivity and specificity pairs (Se = 0.64, Sp = 0.67; Se = 0.64, Sp = 0.67). Conclusion: Consistent LCC estimates can be obtained from MR images providing a beneficial metric for detecting the existence of EPE and for discriminating the grades of EPE.

Can Extraprostatic Extension Be Predicted by Tumor-Capsule Contact Length in Prostate Cancer? Relationship With International Society of Urological Pathology Grade Groups.

OBJECTIVE. The objective of our study was to evaluate the relationship between the tumor-capsule contact length, defined as tumor contact length (TCL), and extraprostatic extension (EPE) using the MRI-based TCL measurements and the real TCL measurements from pathology and to determine whether the International Society of Urological Pathology (ISUP) grade group of the tumors influenced this relationship. MATERIALS AND METHODS. In this retrospective study, we reviewed prostate multiparametric MRI (mpMRI) studies performed between 2012 and 2018 of 1576 patients and found that 134 patients also underwent radical prostatectomy (RP) after mpMRI. Finally, 86 patients with index lesions in contact with the prostate capsule in RP specimens were enrolled in the study. ROC analysis was used to evaluate the cutoff values of TCLs measured at pathology and TCLs measured on MRI in terms of EPE according to ISUP grade groups. RESULTS. There was no statistically significant cutoff value for pathology-based TCL measurements in individual ISUP grade groups and subgroups. Although not statistically significant, pathology-based TCL cutoff values decreased (from 21.0 to 11.0 mm) as ISUP grade group increased in terms of EPE positivity. When the relationship between MRI-based TCL measurements and EPE was considered, statistically significant cutoff values (range, 14.5-16.6 mm) could be determined in many groups and subgroups with low ISUP grades (sensitivity, 66.7-100%; specificity, 52.8-93.0%; p = 0.006-0.042). However, no statistically significant cutoff value was found for high ISUP grades. CONCLUSION. ISUP grade groups may have an effect on the TCL-EPE relationship. When the MRI-based TCL and EPE relationship is evaluated independent of ISUP grade group, a cutoff value around 15-16 mm may be usable to predict EPE.

Determining the cut-off values of tumor diameter, degree of extraprostatic extension, and extent of surgical margin positivity with regard to biochemical recurrence of prostate cancer after radical prostatectomy.

BACKGROUND: The pre-biopsy (bx) prostate-specific antigen (PSA) level, tumor volume/diameter, degree of extraprostatic extension (EPE), and extent of surgical margin positivity have been shown to be significant prognostic parameters of biochemical recurrence (BCR) after radical prostatectomy. The present study assessed the cut-off values of the pre-bx PSA level, maximum tumor diameter, radial and circumferential distances of EPE, and circumferential length of surgical margin (SM) positivity with regard to BCR. MATERIAL AND METHODS: The study included 445 radical prostatectomy specimens, and the cut-off values of all parameters were determined using receiver operating characteristic curve analysis. RESULTS: An ISUP grade group ≥ 3, radial distance of EPE >1 mm, and circumferential length of SM positivity ≥2 mm were identified as independent predictors of BCR after radical prostatectomy. The parameters that showed statistical significance in univariate analysis, such as pre-bx PSA level ≥ 7.20 ng/mL, tumor diameter ≥ 19.5 mm, presence of seminal vesicle invasion, and circumferential distance of EPE >3 mm, did not have independent prognostic values for BCR. CONCLUSIONS: An ISUP grade group ≥ 3, radial distance of EPE >1 mm, and circumferential length of SM positivity ≥2 mm are predictors of BCR. Our findings might have significance in risk classification and adjuvant therapy consideration among patients with localized prostate cancer.

Comparison of preoperative locoregional Ga-68 PSMA-11 PET-CT and mp-MRI results with postoperative histopathology of prostate cancer.

BACKGROUND: Conventional imaging modalities are inadequate to evaluate locoregional extension of prostate cancer (PCa). The aim of the current retrospective study was to investigate the diagnostic efficacy of Gallium-68 prostate-specific membrane antigen-11 (Ga-68 PSMA-11) positron emission tomography/computed tomography (PET/CT) and multiparametric magnetic resonance imaging (mp-MRI) for staging preoperative PCa patients with correlating histopathology. MATERIALS AND METHODS: Twenty-four patients with histologically proven PCa underwent both Ga-68 PSMA-11 PET/CT and mp-MRI before robot-assisted laparoscopic radical prostatectomy. For each tumor area, correlations with histopathological results were defined for tumor localization, extraprostatic extension (EPE) of the tumor, invasion of seminal vesicle (SVI) and bladder neck invasion (BNI). In patients with regional lymph node (LN) dissection, histopathological results were also correlated with imaging modalities. RESULTS: Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for detection of EPE and SVI were higher for mp-MRI than Ga-68 PSMA-11 PET/CT. On the other hand Ga-68 PSMA-11 PET/CT had significant successful results for detection of LN metastases when compared with mp-MRI. But for BNI detection both modalities had same insufficient results. Ga-68 PSMA-11 PET/CT had strong results for appropriate tumor localization in the gland. CONCLUSION: Ga-68 PSMA PET/CT has superior results for assessing local LN metastases and for intraprostatic tumor localization. Whereas, mp-MRI must be the preferred modality for determining SVI and EPE. But both imaging modalities failed for determining BNI accurately. Both modalities should be used in conjunction with each other for better treatment planning.

Evaluation of MRI for diagnosis of extraprostatic extension in prostate cancer.

PURPOSE: To assess the ability of magnetic resonance imaging (MRI) to diagnose extraprostatic extension (EPE) in prostate cancer. MATERIALS AND METHODS: With Institutional Review Board (IRB) approval, 149 men with 170 ≥0.5 mL tumors underwent preoperative 3T MRI followed by radical prostatectomy (RP) between 2012-2015. Two blinded radiologists (R1/R2) assessed tumors using Prostate Imaging Reporting and Data System (PI-RADS) v2, subjectively evaluated for the presence of EPE, measured tumor size, and length of capsular contact (LCC). A third blinded radiologist, using MRI-RP-maps, measured whole-lesion: apparent diffusion coefficient (ADC) mean/centile and histogram features. Comparisons were performed using chi-square, logistic regression, and receiver operator characteristic (ROC) analysis. RESULTS: The subjective EPE assessment showed high specificity (SPEC = 75.4/91.3% [R1/R2]), low sensitivity (SENS = 43.3/43.6% [R1/R2]), and area-under (AU) ROC curve = 0.67 (confidence interval [CI] 0.61-0.73) R1 and 0.61 (CI 0.53-0.70) R2; (k = 0.33). PI-RADS v2 scores were strongly associated with EPE (P < 0.001 / P = 0.008; R1/R2) with AU-ROC curve = 0.72 (0.64-0.79) R1 and 0.61 (0.53-0.70) R2; (k = 0.44). Tumors with EPE were larger (18.8 ± 7.8 [median 17, range 6-51] vs. 18.8 ± 4.9 [12, 6-28] mm) and had greater LCC (21.1 ± 14.9 [16, 1-85] vs. 13.6 ± 6.1 [11.5, 4-30] mm); P < 0.001 and 0.002, respectively. AU-ROC for size was 0.73 (0.64-0.80) and LCC was 0.69 (0.60-0.76), respectively. Optimal SENS/SPEC for diagnosis of EPE were: size ≥15 mm = 67.7/66.7% and LCC ≥11 mm = 84.9/44.8%. 10th -centile ADC and ADC entropy were both associated with EPE (P = 0.02 and < 0.001), with AU-ROC = 0.56 (0.47-0.65) and 0.76 (0.69-0.83), respectively. Optimal SENS/SPEC for diagnosis of EPE with entropy ≥6.99 was 63.3/75.0%. 25th -centile ADC trended towards being significantly lower with EPE (P = 0.06) with no difference in other ADC metrics (P = 0.25-0.88). Size, LCC, and ADC entropy improved sensitivity but reduced specificity compared with subjective analysis with no difference in overall accuracy (P = 0.38). CONCLUSION: Measurements of tumor size, capsular contact, and ADC entropy improve sensitivity but reduce specificity for diagnosis of EPE compared to subjective assessment. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;47:176-185.

Multiparametric Magnetic-Resonance to Confirm Eligibility to an Active Surveillance Program for Low-Risk Prostate Cancer: Intermediate Time Results of a Third Referral High Volume Centre Active Surveillance Protocol.

BACKGROUND: To evaluate the role of confirmatory multiparametric magnetic resonance imaging (mpMRI) of the prostate at the time of Active Surveillance (AS) enrollment to reduce disease misclassification. MATERIALS: From 2012 to 2016, 383 patients with low-risk disease respecting Prostate Cancer Research International AS criteria underwent confirmatory 1.5-T mpMRI. AS was proposed to patients with Prostate Imaging and Report and Data System (PI-RADS) score ≤3 and no extraprostatic extension (EPE), whereas patients with PI-RADS score ≥4 and/or EPE were treated actively. Kaplan-Meier analyses quantified progression-free survival (PFS) in patients enrolled in the AS program. Logistic regression analyses tested the association between confirmatory mpMRI and clinically significant prostate cancer (csPCa) at radical prostatectomy (RP). Diagnostic performance of mpMRI was calculated in patients submitted to immediate RP. RESULTS: PFS rate was 99, 90 and 86% at 1, 2 and 3 years respectively. At multivariable analysis, PI-RADS 3, PI-RADS 4, PI-RADS 5 and EPE increased the probability of having csPCa at immediate RP (PI-RADS 3 [OR] 1.2, p = 0.26; PI-RADS 4 [OR] 5.1, p = 0.02; PI-RADS 5 [OR] 6.7; p = 0.009; EPE [OR] 11.8, p < 0.001). Confirmatory mpMRI showed sensibility, specificity, positive predictive value and negative predictive value of 85, 55, 68 and 76% respectively. CONCLUSIONS: MpMRI at the time of AS enrollment reduces the misclassification rate of csPCa. We suggest to perform target biopsies in patients with PI-RADS score 3 and 4 lesions.

MRI assessment of pathological stage and surgical margins in anterior prostate cancer (APC) using subjective and quantitative analysis.

PURPOSE: To evaluate magnetic resonance imaging (MRI) for assessment of extraprostatic extension (EPE) and positive surgical margins (PSM) in anterior prostate cancer (APC). MATERIALS AND METHODS: With Institutional Review Board approval, 25 APC (>2/3 of tumor anterior to urethra) were assessed using 3T MRI by two blinded radiologists for: size and maximal leading edge of tumor (relative to anterior fibromuscular stroma [AFMS]) on b ≥1000 sec/mm2 echo-planar-MRI fused onto T2 -weighted-MRI, invasion of AFMS and EPE. Comparisons were performed between APCs by EPE/PSM using chi-square, multivariable analysis, and receiver operator characteristic (ROC) analysis. RESULTS: The prevalence of EPE and PSM were 52% (13/25) and 36% (9/25). Tumor sizes were larger with EPE (22.5 ± 8.4 vs. 14.7 ± 6.3, P = 0.02) and PSM (23.0 ± 9.3 vs. 16.4 ± 7.0, P = 0.06). Area under ROC curve (AUC-ROC) for the diagnosis of EPE by tumor size was 0.77 (95% confidence interval [CI] 0.58-0.95); ≥16 mm size = sensitivity/specificity 69.2/66.7%. Maximal leading edge of tumor was greater with EPE (2.4 ± 2.2 vs. -0.2 ± 3.0) and PSM (2.8 ± 2.3 vs. -0.3 ± 2.5), (P = 0.023, 0.031). AUC-ROC for diagnosis of EPE/PSM by leading edge was 0.78 (CI 0.57-0.97) and 0.75 (CI 0.56-0.94). A ≥1 mm leading edge yielded sensitivity/specificity of 76.9/75.0% and 77.8/62.5% for diagnosis of EPE/PSM. 60-72% (15-18/25) tumors invaded AFMS (k = 0.74), which was not associated with EPE/PSM (P = 0.12-0.14). Radiologists' assessment of EPE had sensitivity/specificity of 61.5-69.2/50.0-75.0% (k = 0.53). CONCLUSION: Tumor size and leading edge of tumor relative to AFMS may enable diagnosis of EPE and positive surgical margins in APC. LEVEL OF EVIDENCE: 2 J. MAGN. RESON. IMAGING 2017;45:1296-1303.

Prognostic value of Prostate Imaging and Data Reporting System (PI-RADS) v. 2 assessment categories 4 and 5 compared to histopathological outcomes after radical prostatectomy.

PURPOSE: To assess Prostate Imaging and Data Reporting System (PI-RADS) v. 2 score 4/5 lesions compared to Gleason score (GS) and stage after radical prostatectomy (RP) and to validate the proposed 15-mm size threshold that differentiates category 4 versus 5 lesions. MATERIALS AND METHODS: With Institutional Review Board (IRB) approval, 140 men underwent 3T magnetic resonance imaging (MRI) and RP between 2012-2015. Two blinded radiologists: 1) assigned PI-RADS v. 2 scores, 2) measured tumor size on axial T2 -weighted-MRI, and 3) assessed for extraprostatic extension (EPE). Interobserver agreement was calculated and consensus diagnoses achieved through reference standard (MRI-RP maps). PI-RADS v. 2 scores and tumor size were compared to GS and stage using chi-square, analysis of variance (ANOVA), and receiver operating characteristic (ROC) curve analysis. RESULTS: In all, 80.7% (113/140) of tumors were category 4 (n = 45) or 5 (n = 68) lesions (κ = 0.45). Overall tumor size was 18.2 ± 7.7 mm and category 5 lesions were larger (22.6 ± 6.8 versus 11.5 ± 1.9 mm, P < 0.001). High-risk (GS ≥8) tumors were larger than low- and intermediate-risk tumors (P = 0.016) and were more frequently, but not significantly so, category 5 lesions (78.9% [15/19] vs. 22.1% [4/10], P = 0.18). 67.3% (76/113) of patients had EPE. Category 5 lesions were strongly associated with EPE (P < 0.0001). Area under the ROC curve for diagnosis of EPE by size was 0.74 (confidence interval 0.64-0.83), with size ≥15 mm yielding a sensitivity/specificity of 72.4/64.9%. Size improved sensitivity for diagnosis of EPE compared to subjective assessment (sensitivity/specificity ranging from 46.1-48.7%/70.3-86.5%, κ = 0.29) (P = 0.028). CONCLUSION: PI-RADS v. 2 category 5 lesions are associated with higher Gleason scores and EPE. A 15-mm size threshold is reasonably accurate for diagnosis of EPE with increased sensitivity compared to subjective assessment. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:257-266.

Extraprostatic extension (EPE) of prostatic carcinoma: is its proximity to the surgical margin or Gleason score important?

OBJECTIVE: To examine the association between histopathological factors of extraprostatic prostate cancer and outcome. PATIENTS AND METHODS: Patients with extraprostatic extension (EPE) without positive margins, seminal vesicle or lymph node involvement were analysed from a consecutive radical prostatectomy cohort of 1136 (2002-2006) for: (i) distance of EPE from the margin; (ii) Gleason score of the EPE; and (iii) extent of EPE. Log-rank, Kaplan-Meier, and Cox regression analyses were performed. RESULTS: The study included 194 pT3a, pN0, R0 patients with a median follow-up of 5.4 years, with 37 (19%) patients experiencing biochemical relapse (BCR). On univariable analysis, patients with a Gleason score of ≥8 in the extraprostatic portion showed increased incidence of BCR compared with those with Gleason scores of ≤7 (P = 0.03). The proximity of the EPE to the margin (0.01-7.5 mm) did not correlate with BCR. On multivariable analysis, the extent of EPE, the Gleason score of the dominant nodule or of the EPE portion did not correlate with BCR. CONCLUSION: Data from this study using current International Society of Urological Pathology Gleason scoring and EPE criteria indicate that close proximity of EPE to the margin is not associated with recurrence. Gleason score ≥8 within EPE is associated with an increased BCR risk on univariable analysis, but larger studies are required to confirm whether extensive Gleason pattern 4 in an EPE indicates increased risk in an otherwise overall Gleason score 7 cancer.

Automated Detection and Grading of Extraprostatic Extension of Prostate Cancer at MRI via Cascaded Deep Learning and Random Forest Classification.

RATIONALE AND OBJECTIVES: Extraprostatic extension (EPE) is well established as a significant predictor of prostate cancer aggression and recurrence. Accurate EPE assessment prior to radical prostatectomy can impact surgical approach. We aimed to utilize a deep learning-based AI workflow for automated EPE grading from prostate T2W MRI, ADC map, and High B DWI. MATERIAL AND METHODS: An expert genitourinary radiologist conducted prospective clinical assessments of MRI scans for 634 patients and assigned risk for EPE using a grading technique. The training set and held-out independent test set consisted of 507 patients and 127 patients, respectively. Existing deep-learning AI models for prostate organ and lesion segmentation were leveraged to extract area and distance features for random forest classification models. Model performance was evaluated using balanced accuracy, ROC AUCs for each EPE grade, as well as sensitivity, specificity, and accuracy compared to EPE on histopathology. RESULTS: A balanced accuracy score of .390 ± 0.078 was achieved using a lesion detection probability threshold of 0.45 and distance features. Using the test set, ROC AUCs for AI-assigned EPE grades 0-3 were 0.70, 0.65, 0.68, and 0.55 respectively. When using EPE≥ 1 as the threshold for positive EPE, the model achieved a sensitivity of 0.67, specificity of 0.73, and accuracy of 0.72 compared to radiologist sensitivity of 0.81, specificity of 0.62, and accuracy of 0.66 using histopathology as the ground truth. CONCLUSION: Our AI workflow for assigning imaging-based EPE grades achieves an accuracy for predicting histologic EPE approaching that of physicians. This automated workflow has the potential to enhance physician decision-making for assessing the risk of EPE in patients undergoing treatment for prostate cancer due to its consistency and automation.

Incidence and Pitfalls of Adipose Tissue Encountered in Prostatic Transurethral Resections and Related Specimens.

While the presence of adipose tissue and its involvement by prostatic cancer (extraprostatic extension) is well-recognized in prostate biopsies, adipose tissue in transurethral resections of the prostate (TURP) is largely unexplored. Herein, 200 consecutive TURPs and related specimens were reviewed, including a separate 3-year analysis of specimens containing prostatic cancer, with the following data collected: presence of fat, presence of cancer within fat, and quantity of fat. For specimens with both fat and prostatic cancer, specimen weight and tumor volume were recorded. Within the 200 consecutive TURPs and related specimens, adipose tissue was identified in 20%; 55% had 2.5 mm of adipose tissue; the number of fragments with adipose tissue ranged from 1 to 14. No correlation between specimen weight and measured extent of adipose tissue or number of fragments with adipose tissue was identified. Of all the specimens with prostatic cancer, 15/56 (27%) involved adipose tissue, with two specimens with large cancer volume (>90%) demonstrating extensive involvement of adipose tissue. Adipose tissue is frequently present within TURP and related specimens with variability in extent. The etiology behind encountering adipose tissue is uncertain, and it could represent resection into peri-prostatic fat, intraprostatic fat, or bladder neck fat sampling. Although encountering adipose tissue involved by cancer in TURP and related specimens may imply extraprostatic extension (pT3a), further studies are needed to corroborate these findings as well as to determine if these should be included in reported synoptics.