Abstract
Purpose
This study aims to confirm the diagnostic accuracy of extra-prostatic extension (EPE) grading system and to explore the predictive capabilities of the prostate MRI while considering various MRI features such as lesion location, apparent diffusion coefficient (ADC) values and capsular enhancement sign (CES).
Methods
Our monocentric study is based on a retrospective analysis of 99 patients who underwent radical prostatectomy from January 2021 to January 2023. The observers reviewed for each lesion, including location (transitional or peripheral zone, anterior or posterior location), capsular contact length, irregular bulging of the capsule, asymmetry of the neurovascular bundle, obliteration of the recto-prostatic angle, macroscopic EPE, ADC value, and CES.
Results
Among 99 patients, 31 patients had EPE. Lesions with EPE have broadercapsule contact (24 mm vs 12 mm) with contact ≥14 mm being the optimal cut-off for EPE discrimination. Among the morphological MRI criteria used to determine the EPE, the one with major sensitivity was shown to be bulging (sen 81%), while macroscopic extension had highest specificity (100%). Univariate analysis showed as significative risk factors for EPE: capsular contact ≥14 mm (P < .001), International Society of Urological Pathology score ≥3 (P = .005), CES (P < .001), bulging (P = .001), neurovascular bundle asymmetry (P < .001) and EPE score ≥2 (P < .001), and in multivariate analysis CES (P = .001) and EPE score ≥2 (P = .004) were significant. The AUC of the EPE score was 0.76, raised to 0.83 when combining it with CES (P = .11).
Conclusion
CES in the setting of multiparametric MRI can increase diagnostic accuracy for the prediction of extracapsular disease.
Advances in knowledge
This study highlights the potential of contrast media in prostate cancer local staging.
Keywords: dynamic contrast enhanced imaging, magnetic resonance imaging, prostate cancer, staging
Introduction
Prostate cancer (PCa) represents the third commonest tumour in general population after breast and lung cancers, with a total of 1 414 259 new cases worldwide in 2020.1 The diagnostic workup of PCa starts with digital rectal examination (DRE) and the blood dosage of prostate-specific antigen (PSA). Second-level examinations involve radiologic assessments such as multiparametric magnetic resonance imaging (mpMRI) and biopsy of the suspected lesions that allow to indicate a precise histopathologic diagnosis. The latter is graded according to the Gleason score, which quantifies the architectural alterations of the prostate sample and defines a clinically significant prostate cancer (csPCa) when its value is ≥7 (3 + 4).2 The International Society of Urological Pathology (ISUP) also recommend to report both the Gleason score and the ISUP grade group, which classifies the PCa in five groups with a different prognostic value.3
Among all the clinical features assessable with MRI, one of the most crucial is represented by the extra-prostatic extension (EPE) of the tumour; EPE refers to the spread of prostate tumours beyond the prostate, carrying significant implications for disease progression and management; this modifies the T-staging (from T2 when the tumour is confined to the prostate to T3a4) of PCa and therefore the surgical approach, which may not spare neurovascular bundles (NVBs).5
The MRI allows also a precise local staging of the lesion.6 As supported by the Prostate Imaging-Reporting and Data System (PI-RADS) guidelines, the mpMRI provides detailed anatomical and functional information. mpMRI combines high-resolution morphologic T2-weighted (T2w) images, dynamic contrast enhanced (DCE) and diffusion-weighted imaging (DWI) sequences and the consequently obtained apparent diffusion coefficient (ADC); this multimodal approach enhances the sensitivity (Sens) and specificity of EPE detection. A recent meta-analysis has confirmed that this scoring system has high sensitivity and moderate specificity, with a good inter-reader agreement.7
Numerous radiological scores have been proposed to predict EPE, and the most widespread are the European Society of Urogenital Radiology (ESUR) score and the more recent “EPE grading system”.8,9 The EPE grading system consists of three grades of increasing risk of EPE (1: either length of capsular contact (LCC) ≥15 mm or capsular bulge and irregularity; 2: both LCC ≥15 mm and capsular irregularity or bulge; 3: frank capsular breach visible at MRI).9
Those scores evaluated only morphological T2 weighted features; however, different radiological characteristics such as the capsular enhancement sign (CES) suggest EPE.10 Furthermore, low ADC values of the tumour have been shown to be an independent predictor of EPE.11,12
The role of EPE is central for defining therapeutic strategies and long-term prognosis,13,14 and recent evidence suggest that EPE may be predicted by certain radiological features. In this light, the purpose of our study is to retrospectively confirm the diagnostic accuracy of EPE grading system and to evaluate whether mpMRI features such as CES and ADC may increase the predictivity of extracapsular extension in PCa.
Methods
Patient sample and study design
This is a monocentric, retrospective observational study approved by ethical regional committee with code “N. CET - Liguria: 100/2023 - DB id 12985”.
The population of the study is composed by a series of consecutive patients who underwent radical prostatectomy at IRCSS San Martino Hospital from January 2021 until January 2023 included. All patients underwent an MRI study and were diagnosed with PCa proven by systematic or MRI-ultrasound fusion biopsy.
The exclusion criteria used to select patients summarized in Figure 1 are:
Figure 1.
Cohort of the study.
MRI study not performed at our institution,
patients with MRI negative for suspected lesions (with tumour proven on systematic biopsy),
presence of magnetic susceptibility artefacts which degrade the quality of MRI images,
histopathological examination performed by different institutions.
MRI acquisition
The MRI protocol was in accordance with the recommendations by PI-RADS Guidelines version 2.1. The imaging was performed using a 1.5 T MRI machine (Magnetom AERA, Siemens).6
T2-weighted images were obtained in the sagittal plane and successively in the coronal and axial plane, where coronal and axial plane were parallel and perpendicular to the long axis of the prostate, respectively.
DWI images were acquired through single-shot echo-planar sequences: firstly, with a sequence with a high b-value (≥1500 s/mm2) and then with another one with three different b-values (0, 750 and 1000 s/mm2) which were used to calculate the ADC map.
Finally, during the intravenous administration of a gadolinium-based contrast agent with a 0,2 mL/kg dose at a flow rate of 3 mL/s and 15 mL of saline solution, DCE acquisition was accomplished with a temporal resolution of 9 s.
Both DWI and DCE were acquired with the same plane and thickness as the T2-weighted axial images, to better compare the different sequences.
No endo rectal coil was used; spasmolytics agents (Scopolamine butylbromide) were used only where motion artifacts were noted and compromised sequences were repeated. Sequences’ details can be found in Supplementary Table S1.
MRI analysis
Image analysis was performed independently by one of three radiology residents (F.M., M.M., and M.P.) respectively with 3, 3, and 4 years of experience in prostate MRI. The images with doubtful radiologic criteria for EPE were re-analysed by a fourth radiologist (J.P.Z.) with 7 years of experience in prostate imaging and 2000 MRI, and decisions were made by consensus to provide the highest possible standard in a retrospective setting.
Each radiologist reviewed the MRI scan with T2w images on the three planes, the DWI and the DCE sequences. The original report of the MRI was available (ensuring consensus in target lesion assessment), but readers were blinded to histopathologic results of prostatectomy.
For statistical analysis only the index lesion was considered for each patient and when a patient had two or more lesions, it was analysed the one with the greatest size.
For every lesion the location was differentiated between origin from the peripheral or transition zone (TZ) and also between anterior versus posterior half of the gland.
The T2w images were evaluated with the MRI criteria listed in the Grading System for the Assessment of the Risk of Extra-prostatic Extension of PCa at mpMRI which comprehend the LCC, the irregular bulging of the capsule, the asymmetry of the NVB in the setting of an unilateral PCa, the obliteration of the recto-prostatic angle (RPA) and the macroscopic EPE (tumour clearly visible outside the capsule or infiltrating rectum or bladder at MRI images).9
LCC was not prospectively reported on a consistent basis and, therefore, it was measured retrospectively in the axial plane as curvilinear LCC. In the DCE sequence, it was instead evaluated the presence of the CES, as an early enhancing capsule near the tumour, without capsular enhancement on the contralateral side.10 In the ADC map, the mean ADC-value was calculated positioning a region of interest (ROI) covering at least 50% of the target lesion.
Reference standard definition
Histopathological examination of the whole prostate after prostatectomy was considered the standard reference. Histopathological EPE as well as Gleason score and ISUP grade group were assigned among other parameters.15–17
Statistical analysis
Characteristics of the patients were described as mean value and standard deviation for continuous variables and as counts and percentage for categorical variables, overall and separately for patients with and without EPE. Characteristics were compared between the two groups using t-test or Mann-Whitney test for the continuous variables and chi square or Fisher exact test for the categorical variables.
The receiver operating characteristic (ROC) curve to assess the ability of LCC to discriminate between patients with and without EPE was plotted and the AUC was calculated. LCC best cut-off was calculated based on Liu, Youden and nearest to (0,1) criteria and patients with anteriorly and posteriorly positioned lesion were compared in terms of LCC, continuously (t-test) and as binary based on the best cut-off (Pearson chi square test).
Sensitivity, specificity, and percentage of correctly classified patients were derived for CES, bulging, RPA obliteration, asymmetry of NVB, macroscopic extension, and wide LCC (≥14 mm).
Univariate logistic regression models were performed to study the association between the previous MRI features and EPE.
Two separate multivariable models were fitted including variables with P < .10 in the univariable models, one including the final score and the other one including the variables that are part of the score. Since CES was found to be a relevant predictor of EPE in both the multivariable models, we created a new score that incorporated both EPE score and CES. The new “enhanced” score was defined based on internal validation: (1) we estimated the penalized coefficients from a bootstrapped lasso model with the EPE score and CES as independent variables (2) we built a model based on the coefficients estimated at (1) and we used that model to estimate the probability of EPE as exp (β0 + β1 × CES + β2 × EPE score)/(1 + exp β0 + β1 × CES + β2 × EPE score). The EPE probability was thus derived for each class of the new score which consists in all the combinations of EPE score values and CES. Finally, AUC for the new “enhanced” score was estimated for comparison with the original EPE score; the AUC from the two scores were compared using a nonparametric approach accordingly to DeLong test.
Results
A total of 251 consecutive patients were enrolled; of those 152 patients were excluded with 99 patients finally included in our study. The mean age of participants included in the study was 66.6 years, with a standard deviation of 5.6 years (Figure 1).
Among the patients included in the study, 31/99 (31.3%) patients had EPE while the other 68/99 (68.7%) patients had negative margins for EPE.
Lesion location and EPE
The peripheral zone (PZ) resulted the most involved area, with 86 out of 99 lesions (87%) exclusively located there, while 10 lesions (10%) were found in the TZ. Additionally, three lesions were large-volume tumours spanning both zones. Eighteen of 99 (18%) were located in the anterior zone, while 77/99 (78%) in the posterior zone. However, according to our results, the location of the tumour was not significantly correlated with extracapsular invasion (Table 1).
Table 1.
Clinicopathological characteristics of the study cohort and MRI features among patients with and without EPE.
| Total | EPE = 0 | EPE = 1 | P-value | |
|---|---|---|---|---|
| N = 99 | N = 68 (69%) | N = 31 (31%) | ||
| Age (years) | ||||
| 66.6 (5.6) | 65.9 (5.6) | 68.1 (5.5) | .074 | |
| ISUP category | .009 | |||
| 1 | 2 (2%) | 1 (1%) | 1 (3%) | |
| 2 | 60 (61%) | 48 (71%) | 12 (39%) | |
| 3 | 33 (33%) | 17 (25%) | 16 (52%) | |
| 4 | 1 (1%) | 1 (1%) | 0 (0%) | |
| 5 | 3 (3%) | 1 (1%) | 2 (6%) | |
| Position in the PZ or TZ (N = 96) | 1.000 | |||
| PZ | 86 (90%) | 59 (89%) | 27 (90%) | |
| TZ | 10 (10%) | 7 (11%) | 3 (10%) | |
| Anterior or posterior location (N = 95) | .086 | |||
| Posterior | 77 (81%) | 52 (76%) | 25 (93%) | |
| Anterior | 18 (19%) | 16 (24%) | 2 (7%) | |
| LCC (mm) | <.001 | |||
| 15.93 (13.46) | 12.18 (8.09) | 24.16 (18.54) | ||
| ROI ADC | .077 | |||
| 695.23 (161.18) | 714.56 (173.42) | 652.84 (122.47) | ||
| Wide capsular contact | .001 | |||
| Absent | 57 (58%) | 47 (69%) | 10 (32%) | |
| Present | 42 (42%) | 21 (31%) | 21 (68%) | |
| Bulging | .001 | |||
| Absent | 44 (44%) | 38 (56%) | 6 (19%) | |
| Present | 55 (56%) | 30 (44%) | 25 (81%) | |
| Obliteration of the RPA | .104 | |||
| Absent | 91 (92%) | 65 (96%) | 26 (84%) | |
| Present | 8 (8%) | 3 (4%) | 5 (16%) | |
| NVB asymmetry | <.001 | |||
| Absent | 86 (87%) | 66 (97%) | 20 (65%) | |
| Present | 13 (13%) | 2 (3%) | 11 (35%) | |
| Macroscopic extension | .002 | |||
| Absent | 94 (95%) | 68 (100%) | 26 (84%) | |
| Present | 5 (5%) | 0 (0%) | 5 (16%) |
Abbreviations: EPE = extra-prostatic extension; ISUP = International Society of Urological Pathology; LCC = length of capsular contact; NVB = neurovascular bundle; PZ = peripheral zone; ROI ADC = region of interest apparent diffusion coefficient; RPA = recto-prostatic angle; TZ = transition zone. Bold P-Values are significant.
ISUP category
We found that ISUP class and EPE were not independent (P = .009) and specifically, among patients with EPE, only 42% had ISUP < 3 compared to 72% of patients without EPE.
LCC discrimination
Patients with EPE had a mean capsular contact length of 24 mm versus 12 mm of those without EPE.
LCC demonstrates the capability to predict EPE; accordingly, to our data, the best cut-off for LCC calculated based on Liu, Youden and nearest to (0,1) was consistently ≥14 mm. At this cut point, sensitivity was 74.19%, specificity 67.65%, and proportion of correctly classified 69.70% (Figure 2).
Figure 2.
Receiver operating characteristic (ROC) curve for discrimination between patients with and without extra-prostatic extension (EPE) based on length of capsular contact (LCC; mm).
While considering the EPE-score threshold of 15 mm the sensitivity reduced slightly to 68%.
No significant differences in LCC were noted between anteriorly and posteriorly located lesion (P = .685) (Table 2).
Table 2.
LCC performance and distribution of LCC based on the position of the lesion.
| Total | EPE = 0 | EPE = 1 | P-value | |
|---|---|---|---|---|
| N = 99 | N = 68 (69%) | N = 31 (31%) | ||
| LCC (mm) mean (SD) | 15.93 (13.46) | 12.18 (8.09) | 24.16 (18.54) | <.001 |
| Total | Anterior lesion | Posterior lesion | P-value | |
|---|---|---|---|---|
| N = 95a | N = 18 (19%) | N = 77(81%) | ||
| LCC (mm) mean (SD) | 14.31 (10.73) | 13.72 (11.39) | 14.44 (10.65) | .800 |
| LCC ≥ 14 mm | 41 (43%) | 7 (39%) | 34 (44%) | .685 |
Abbreviations: EPE = extra-prostatic extension; LCC = length of capsular contact; PZ = peripheral zone; TZ = transition zone.
Four patients were removed as large lesion invading both PZ and TZ. Bold P-Values are significant.
MRI detection performance of EPE
Among the morphological MRI criteria that can predict EPE, the two with major sensitivity were shown to be bulging (sen 81%) and a large capsular contact (sen 68%). The most specific ones instead were macroscopic extension (spe 100%), asymmetry of the NVB (spe 97%) and obliteration of RPA (spe 96%). The most correctly classified was asymmetry of the NVB (78%) (Table 3).
Table 3.
MRI features performance in discriminating between patients with and without EPE.
| EPE absent | EPE present | Sensitivity (%) | Specificity (%) | Correctly classified (%) | |
|---|---|---|---|---|---|
| N = 68 | N = 31 | ||||
| CES | |||||
| Absent | 59 (87%) | 14 (45%) | 55 | 87 | 77 |
| Present | 9 (13%) | 17 (55%) | |||
| Bulging | |||||
| Absent | 38 (56%) | 6 (19%) | 81 | 56 | 64 |
| Present | 30 (44%) | 25 (81%) | |||
| RPA obliteration | |||||
| Absent | 65 (96%) | 26 (84%) | 16 | 96 | 71 |
| Present | 3 (4%) | 5 (16%) | |||
| Asymmetry NVB | |||||
| Absent | 66 (97%) | 20 (65%) | 35 | 97 | 78 |
| Present | 2 (3%) | 11 (35%) | |||
| Macroscopic extension | |||||
| Absent | 68 (100%) | 26 (84%) | 16 | 100 | 74 |
| Present | 0 (0%) | 5 (16%) | |||
| LCC ≥14 mm | |||||
| Absent | 46 (68%) | 8 (26%) | 74 | 68 | 70 |
| Present | 22 (32%) | 23 (74%) | |||
Abbreviations: CES = capsular enhancement sign; EPE = extra-prostatic extension; LCC = length of capsular contact; NVB = neurovascular bundle; RPA = recto-prostatic angle.
CES was observed in 26 cases, out of which 17 exhibited EPE. Consequently, CES emerged as a highly specific sign, with a specificity of 87%.
Patients with EPE exhibited a mean ADC value of 652, compared to 714 in those without EPE. ADC values overlapped within our population, and a reliable cut-off value was not identified.
Univariate and multivariate analysis
With univariate analysis our study showed a significant increase in the odd of EPE for LCC ≥14 mm (OR = 6.01, P < .001), ISUP score ≥3 (OR = 3.57, P = .005), CES (OR = 7.96, P < .001), bulging (OR = 5.28, P = .001), asymmetry of the NVB (OR = 18.15, P < .001) and EPE score ≥2 (OR = 13.77, P < .001). ADC value independently did not significantly correlate with an increasing odd of EPE.
In the multivariate analysis, associations remained significant for CES and asymmetry of the NVB and EPE score ≥2 was significant in the second model (Table 4).
Table 4.
Univariable and multivariable logistic regression model for pathologic EPE risk prediction by using different predictors.
| Univariable |
Multivariable without SCOREa |
Multivariable with SCOREa |
||||
|---|---|---|---|---|---|---|
| OR[95% CI] | P-value | OR(95% CI) | P-value | OR (95% CI) | P-value | |
| ROI ADC (100-unit increase) | 0.77 (0.58-1.03) | .080 | 0.98 (0.64-1.51) | .927 | 1.05 (0.67-1.64) | .835 |
| Capsular contact | ||||||
| ≤13 mm | 1.00 (ref) | – | 1.00 (ref) | – | – | – |
| ≥14 mm | 6.01 (2.32-15.57) | <.001 | 2.42 (0.64-9.14) | .193 | – | – |
| ISUP | ||||||
| 1 + 2 | 1.00 (ref) | – | 1.00 (ref) | – | 1.00 (ref) | – |
| 3 + 4 + 5 | 3.57 (1.47-8.68) | .005 | 1.83 (0.49-6.75) | .367 | 1.62 (0.44-5.93) | .466 |
| Position PZ vs TZ | ||||||
| 0 (PZ) | 1.00 (ref) | – | – | – | – | – |
| 1 (PZ) | 0.94 (0.22-3.90) | .928 | – | – | – | – |
| Position anterior vs posterior | ||||||
| Anterior | 1.00 (ref) | – | 1.00 (ref) | – | 1.00 (ref) | – |
| Posterior | 3.85 (0.82-18.04) | .088 | 4.31 (0.67-27.50) | .123 | 3.01 (0.49-18.46) | .233 |
| CES | ||||||
| Absent | 1.00 (ref) | – | 1.00 (ref) | – | 1.00 (ref) | – |
| Present | 7.96 (2.94-21.56) | <.001 | 8.11 (2.32-28.41) | .001 | 8.93 (2.39-33.38) | .001 |
| Bulging | ||||||
| Absent | 1.00 (ref) | – | 1.00 (ref) | – | – | – |
| Present | 5.28 (1.92-14.51) | .001 | 2.70 (0.68-10.69) | .157 | – | – |
| RPA obliteration | ||||||
| Absent | 1.00 (ref) | – | 1.00 (ref) | – | 1.00 (ref) | – |
| Present | 4.17 (0.93-18.71) | .063 | 0.23 (0.02-2.72) | .243 | 0.15 (0.01-2.11) | .160 |
| Asymmetry NVB | ||||||
| Absent | 1.00 (ref) | – | 1.00 (ref) | – | 1.00 (ref) | – |
| Present | 18.15 (3.71-88.78) | <.001 | 7.18 (1.15-44.93) | .035 | 7.25 (1.09-48.06) | .040 |
| EPE score | ||||||
| 0 + 1 | 1.00 (ref) | – | – | – | 1.00 (ref) | – |
| 2 + 3 | 13.77 (4.92-38.53) | <.001 | – | – | 8.77 (1.98-38.86) | .004 |
Abbreviations: CES = capsular enhancement sign; EPE = extra-prostatic extension; ISUP = International Society of Urological Pathology; NVB = neurovascular bundle; PZ = peripheral zone; ROI ADC = region of interest apparent diffusion coefficient; RPA = recto-prostatic angle; TZ = transition zone.
Multivariable models include variables showing P < .10 in the univariable models. Two separate models were performed: (1) including the EPE score and not its components; (2) including components of the EPE score instead of the score. Bold P-Values are significant.
Even if NVB asymmetry was associated with EPE, this MRI criterion was found to be rare thus, for this reason this criterion was not included in our final score.
Definition of the new score
We estimated the penalized coefficients from a bootstrapped lasso model with the original EPE score and CES as independent variables. Successively, we developed a new “enhanced” score considering EPE score together with CES and we subdivided the score in eight groups based on EPE original score and presence of CES. The highest probabilities (P) of EPE were referred to patients with EPE score = 3 and CES (P = .91), to those with EPE score = 2 and with CES (P = .77) and to those with EPE score = 3 and with no CES (P = .68) (Table 5).
Table 5.
Probability of EPE in the eight classes of the new SCORE based on the EPE original score and the CES presence.
| CES absence | CES presence | |
|---|---|---|
| Group 0 | P = .07 | P = .26 |
| Group 1 | P = .18 | P = .52 |
| Group 2 | P = .40 | P = .77 |
| Group 3 | P = .68 | P = .91 |
Abbreviations: CES = capsular enhancement sign; EPE = extra-prostatic extension.
No color: Score 0, P value: ≤ 0.07; Green: Score 1, P value: 0.18 - 0.26; Yellow: Score 2, P value: 0.40 - 0.52; Red: Score 3, P value: 0.68 - 0.91.
Examples of lesion classified with the new score can be found in Figure 3A and B.
Figure 3.
MRI feature of the new “enhanced” extra-prostatic extension (EPE) score. (A, B) T2-weighted and dynamic contrast enhanced (DCE) of a patient presenting a small lesion (white arrow) in the peripheral zone (PZ) demonstrating EPE score = 0 and absent capsular enhancement sign (CES); (C) histologic sample of the same patient showing prostate cancer (PCa) (asterisk) without EPE; (D, E) T2-weighted and DCE of a male presenting a large lesion (white arrows) in the transition zone (TZ) demonstrating EPE score = 1 (CCL = 19 mm) and absent CES; (F) histologic sample of the same patient showing PCa and an inflammatory infiltrated area (asterisk) without capsule involvement; (G, H) T2-weighted and DCE of a patient presenting a small lesion (dotted line) in the PZ demonstrating EPE score = 0 and present CES (white arrow); (I) histologic sample of the same patient showing PCa (asterisk) that grows in the periprostatic fat; (J, K) T2-weighted and DCE of a patient presenting a lesion in the PZ demonstrating EPE score = 2 and absent CES; (L) histologic sample of the same patient showing PCa (asterisk). The lesion causes a bulge (white arrow) in the capsule as seen in T2 images without capsule infiltration. (M, N) T2-weighted and DCE of a patient presenting a large lesion (white arrows) in the TZ demonstrating EPE score = 1 and present CES; (O) histologic sample of the same patient showing PCa (asterisk) with evident EPE; (P, Q) T2-weighted and DCE of a patient showing a lesion (white arrows) in the PZ demonstrating macroscopic EPE without CES; (R) histologic sample of the same patient showing PCa (asterisk) with growth outside the capsule (white arrow); (S, T) T2-weighted and DCE of a patient presenting a small lesion (white arrow) in the PZ demonstrating EPE score = 2 (CCL ≥14 mm and bulging) and present CES; (U) histologic sample of the same patient showing PCa (asterisk) growing in the periprostatic fat; (V, W, ) T2-weighted and DCE showing a giant lesion (white arrows) involving both PZ and TZ with macroscopic EPE and evident CES; (X) histologic sample of the same patient showing PCa (asterisk) with EPE surrounding a vessel (with arrow).
Although the area under the ROC curve was larger for the new score (EPE score: AUC = 0.76; 95%CI = (0.65-0.88); New “enhanced” score: AUC = 0.83; 95%CI = (0.74-0.92)), the Chi-square test yielded a P-value of .111 (Figure 4).
Figure 4.
AUC of the original SCORE and of the new SCORE.
Discussion
The preoperative evaluation of the presence of EPE in patients affected by PCa is decisive in the surgical management of this condition. Several different MRI characteristics have been correlated to EPE as independent predictor such as LCC, bulging of the capsule, breach of the capsule with macroscopic extracapsular extension, and obliteration of the RPA.9,18,19
We found that LCC has a good accuracy for predicting EPE independently from anterior or posterior location of the lesion, with a sen of 74% (considering the threshold obtained from our cohort of 14 mm). A recent meta-analysis of 23 studies with 3931 participants, concordant with our results, reports a sen of 79% for LCC, while cut-off values range from 6 to 20 mm, demonstrating that a shared and clear consensus on the correct threshold for LCC is still lacking.19
Matsumoto et al, reported that anterior tumours were less likely to invade extraprostatic tissues.20 This was also reported by Villers et al, which suggests the cause is due to the morphology of the prostate gland itself and for the presence of vessels penetrating the prostate starting from the NVB, precisely located posterolateral respect to the prostatic PZ.21 In a similar way, our study confirms a higher prevalence of tumours in the peripheral area (90%) however this ratio appears completely alike to that of tumours confined to the gland. Considering LCC, our study does not demonstrate a difference in the best dimensional cut-off in the different areas of the prostate, and appears consistent with the data of An et al.22
Another meta-analysis of 17 studies and 3062 participants reports LCC and macroscopic EPE as the most accurate predictors for EPE, while bulging and irregular margins of the capsule yield the lowest diagnostic odd ratio.18 These findings are understandable since these latter signs are qualitative features, therefore more prone to operator-dependent evaluations. In our study, macroscopic EPE showed the highest spe (100%) but the lowest sen (16%) and it has a low prevalence.
In our study, we showed that the asymmetry of the NVB is a highly specific sign for detecting pathologic EPE (spe 97%) but it has a low sensitivity (sen 35%). These results are concordant with Yu et al, who described that the asymmetry of NVB yields a specificity of 81%-95% and a sensitivity of 21%-38%.23 More recently, also Mehralivand et al found similar outcomes, reporting a specificity of 99% and a sensitivity of 15% respectively.9 This feature, however, has appeared to be rare and unreliable (wide confidence interval) so we did not incorporate it in our final score.
Furthermore, our study revealed that the CES demonstrated a high level of specificity (87%), although sensitivity was at 55%, mirroring findings by Caglic et al who reported a spe of 100% and sen of 16.5%. Their investigation also linked CES to lesions with higher Gleason grades and a higher prevalence of lymphovascular invasion, both of which were identified as predictors of biochemical recurrence following surgery.10
The utilization of the DCE sequence in prostate MRI remains a topic of debate in the field, particularly regarding its efficacy in tumour detection.24 However, it is noteworthy that several studies have highlighted benefits extending beyond mere detection, including increased reader confidence, as well as improved the inter-reader agreement, and improved local staging for seminal vesicles invaion.25,26 Consistent with this notion, our study underscores the advantages of mpMRI in locoregional staging of PCa, emphasizing an additional benefit beyond mere tumour detection.
In our population, we found that ADC value independently did not significantly correspond with an increasing risk of EPE, thus in contrast with other precedent studies.11,27 It is important to noticed that Woo et al, reported an additional value of the ADC only when the T2 signal was equivocal and Bengtsson et al, did not find any correlation between ADC value and ISUP-gg and tumour aggressiveness.12,28 In this light, further evaluations on ADC are suggested.
Macroscopic tumour extension was the most specific MRI feature. This is consistent with the findings of Mehralivand et al and Gatti et al who reported respectively 96% and 100% of specificity, on the other hand this feature has low prevalence.9,29
Nevertheless, different studies highlighted that the combination of all these features can improve the diagnostic accuracy of predicting EPE,9,29 thus our final score, combining EPE score with CES, performed better than the single variables and EPE score alone.
Our results confirm the validity of the EPE scoring system, and the probabilities of EPE for the different classes overlap (class I of 26% vs 24.3%; class II 40% vs 38.2% and class III 68% vs 66.1%), we have further divided the classification into eight subgroups which are then merged based on the probability of EPE into four classes. The authors acknowledge the complexity to use it in the clinical practice; on the other hand, its comprehensive nature helps to consider the importance to look for all the reported features when investigating the presence or absence of EPE.
Limits
Our study has some limitations and the results cannot be interpreted as conclusive. Firstly, the retrospective nature of this single-centre study with a per-patient analysis, however, readers were blinded to the histopathologic data mimicking a prospective reading.
The single centre study led to a little cohort of patients, therefore, the added value of CES is based on a small sample size, results show some overlap in CI intervals. Although close, Delong test did not reveal a statistically superiority of the “new enhanced score”.
Similarly, the limited size of the cohort and lesions arising from the transitional zone with EPE are specifically underrepresented. A broader validation study encompassing a bigger and more representative sample would enhance the robustness and applicability of the results.
Another limit is that all patients included underwent a total prostatectomy, therefore we cannot evaluate the false positives and we just obtain data from aggressive cancers.
In particular, our study includes only patients who underwent prostatectomy for histologically proven disease, it does not consider the presence of inflammatory alterations that could mimic CES in the absence of a target lesion, therefore the reported specificity of CES may be theorically overestimated.
Also, every MR images was evaluated by a single reader and only the doubtful cases we re-analysed. Therefore, an inter-observer agreement was not considered in our study.
Conclusion
The findings of our study underscore the complexity of the EPE detection through preoperative MRI.
Our classification system, which incorporates DCE alongside morphological features, enhances clinical accuracy in reporting locoregional staging. These results emphasize the importance of a comprehensive approach to mpMRI assessment for improved preoperative planning and patient outcomes.
Supplementary Material
Contributor Information
Federica Martini, Department of Health Sciences (DISSAL), Radiology section, University of Genoa, Genova 16132, Italy.
Maria Pigati, Department of Health Sciences (DISSAL), Radiology section, University of Genoa, Genova 16132, Italy.
Matilde Mattiauda, Department of Health Sciences (DISSAL), Radiology section, University of Genoa, Genova 16132, Italy.
Marta Ponzano, Department of Health Sciences, Section of Biostatistics, University of Genoa, Genova 16132, Italy.
Nataniele Piol, Anatomia Patologica Universitaria Unit, IRCCS Ospedale Policlinico San Martino, Genova 16132, Italy.
Simona Pigozzi, Anatomia Patologica Universitaria Unit, IRCCS Ospedale Policlinico San Martino, Genova 16132, Italy; Department of Surgical and Diagnostic Sciences (DISC), Urology Section, University of Genova, Genova 16132, Italy.
Bruno Spina, Pathology Unit, IRCCS Ospedale Policlinico San Martino, Genova 16132, Italy.
Giuseppe Cittadini, Department of Radiology, IRCCS Ospedale Policlinico San Martino, Genova 16132, Italy.
Veronica Giasotto, Department of Radiology, IRCCS Ospedale Policlinico San Martino, Genova 16132, Italy.
Jeries P Zawaideh, Department of Radiology, IRCCS Ospedale Policlinico San Martino, Genova 16132, Italy.
Supplementary material
Supplementary material is available at BJR online.
Funding
The study was supported by the Italian Ministry of Health (Ricerca Corrente Funds 2023 project code N746A).
Conflicts of interest
None declared.
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