|Ahead of print publication
Evaluation of clinically significant prostate cancer using biparametric magnetic resonance imaging: An evolving concept
Manik Mahajan1, Vikrant Gupta1, Puneet Gupta2, Poonam Sharma3, Deepak Abrol4
1 Department of Radio-Diagnosis and Imaging, Government Medical College, Jammu, Jammu and Kashmir, India
2 Department of Radio-Diagnosis and Imaging, ASCOMS Hospital, Jammu, Jammu and Kashmir, India, India
3 Department of Pathology, Government Medical College, Jammu, Jammu and Kashmir, India
4 Department of Radiation Oncology, Government Medical College, Kathua, Jammu and Kashmir, India
|Date of Submission||06-Sep-2020|
|Date of Decision||16-Dec-2020|
|Date of Acceptance||03-Jan-2021|
|Date of Web Publication||05-Aug-2021|
House No 109, Sector-7, Channi Himmat, Jammu - 180 015, Jammu and Kashmir
Source of Support: None, Conflict of Interest: None
Background: Multiparametric magnetic resonance imaging (mp-MRI) of prostate involves a combination of T2-weighted imaging, diffusion-weighted imaging, and dynamic contrast-enhanced (DCE) scans. However, controversy exists in the literature regarding the true value of DCE in the detection of clinically significant (CS) prostate cancer (PCa).
Aim: The aim of this study is to compare the role of biparametric MRI (bp-MRI) and mp-MRI in the detection of CS PCa.
Materials and Methods: Thirty-six patients with raised serum prostate-specific antigen levels were included. Bp-MRI was performed in all patients, whereas mp-MRI was performed in 30 cases only. The findings were characterized on the basis of prostate imaging reporting and data system (PI-RADS) v2 grading. PI-RADS v2 score of 3 or more was considered CS PCa. All patients underwent transrectal ultrasound-guided biopsy. Gleason score >6 was considered CS. Statistical analysis was done using the SPSS software and results interpreted.
Results: CS PCa was observed in 31 cases on histopathology. On bp-MRI, CS PCa was seen in 31 patients. Five cases of PI-RADS v2 score 3 were seen on bp-MRI and 3 of them were upgraded to PI-RADS 4 on DCE images. One case of PI-RADS 3 had low Gleason score on biopsy, whereas 1 case of PI-RADS 2 had CS PCa on biopsy. No significant difference was observed between bp-MRI and mp-MRI in the detection of CS PCa.
Conclusions: Both bp-MRI and mp-MRI have high sensitivity, specificity, and diagnostic accuracy and were nearly identical in the detection of CS PCa with no significant advantage of DCE images.
Keywords: Bi-parametric, carcinoma, diffusion-weighted imaging, magnetic resonance imaging, prostate
|How to cite this URL:|
Mahajan M, Gupta V, Gupta P, Sharma P, Abrol D. Evaluation of clinically significant prostate cancer using biparametric magnetic resonance imaging: An evolving concept. J Can Res Ther [Epub ahead of print] [cited 2022 Jul 3]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=323170
| > Introduction|| |
Prostate cancer (PCa) is the second most common cancer among men, and its detection remains a diagnostic challenge. The World Health Organization has recommended the early detection of PCa using two strategic approaches: Screening and early diagnosis. Digital rectal examination (DRE) and serum prostate-specific antigen (PSA) levels are commonly used in the clinical practice in the evaluation of suspected patients with PCa. Primary obstacles in the early diagnosis of PCa include the inability of rectal examination and PSA to distinguish benign and subclinical conditions and CS PCa., Hence, there is a need of appropriate diagnostic modality and protocol to categorize patients with elevated PSA and/or altered DRE and to diagnose CS PCa with high sensitivity, specificity, and diagnostic accuracy to avoid further investigations and unnecessary biopsies of the patient.
Magnetic resonance imaging (MRI) is the diagnostic modality of choice in the early diagnosis, location, and staging of PCa.,, Multiparametric MRI (mp-MRI) has become standard technique in the evaluation of prostate. It involves the use of high-resolution T2-weighted (T2W) images (for zonal anatomy) and functional MRI sequences (diffusion, perfusion, and spectroscopy) that not only evaluate anatomy but also cellularity and tissue vascularity, thus improving diagnostic accuracy. The European Society of Urogenital Radiology in 2012 published a series of guidelines recommending the interpretation of mp-MRI images to obtain a report called prostate imaging reporting and data system (PI-RADS). Later, PI-RADS was improved and updated to PI-RADS v2 by American College of Radiologists, EUSR, and AdMe Tech Foundation. Updated PI-RADS v2 has discontinued the application of spectroscopy in the evaluation of prostate.
A major limitation of the mp-MRI is that it is a time-consuming procedure, requiring 30 min or more during a standard scan and is especially cumbersome in elderly patients as they cannot remain still in the MRI scanner for a long time. In addition, mp-MRI involves the administration of intravenous gadolinium which is not always possible in patients with deranged renal functions. Furthermore, long-term effects of gadolinium in the human body are still unknown, and it increases the cost of examination to the patient. Dynamic contrast-enhanced (DCE) sequence does not have any significant effect in transition zone lesions and have a high inter-reader variability, so it plays a secondary role to T2W and diffusion-weighted imaging (DWI). Recently, biparametric MRI (bp-MRI) using axial T2W and DWI has been proposed as a suitable alternative to mp-MRI in the detection and localization of CS PCa. Hence, the study was performed to compare the efficacy of bp-MRI and mp-MRI for the detection of CS PCa using histopathology as the gold standard.
| > Materials and Methods|| |
This retrospective, observational study was carried out in 36 clinically suspected patients of PCa (raised PSA levels and/or abnormal digital rectal examination). Patients with prior treatment for any prostatic disease or contraindication to MRI were excluded from the study. Detailed history was recorded and patient subjected to MRI using Siemens 1.5 T Essenza and Siemens 3.0 T Spectra MRI scanner using sense body coil. Turbo spin-echo (TSE) T2W sequence was obtained in axial, coronal, and sagittal planes. Field of view (FOV) of 12–20 cm and slice thickness/gap of 3 mm/0.3 mm was used. TSE T1-weighted sequence was performed in the axial plane using FOV of 12–20 cm and slice thickness/gap of 3 mm/0.3 mm. DWI was performed in axial planes using EPI sequence with FOV of 16–22 cm and slice thickness/gap of 3 mm/0.3 mm. B values of 0, 400, 800, and 1200 were used. Corresponding Apparent Diffusion Coefficient (ADC) images were also obtained. DCE scan was obtained using volumetric interpolated breath hold sequence (VIBE) after administering intravenous gadopentetate dimeglumine at a dose of 0.1 mmol/kg at a rate of 2.5 ml/s followed by 20 ml of saline flush. DCE was not performed in patients with altered renal functions and in case of refusal by the patient.
Both mp-MRI and bp-MRI images were reviewed by three radiologists and lesions evaluated. The size of the lesion was obtained in all planes, and the largest value was considered. PI-RADS v2 scoring was performed in all cases by the consensus, and in case of any discrepancy, the opinion of senior radiologist was considered. PI-RADS v2 score of 3 and above was considered to have CS PCa. PI-RADS v2 score 3 was upgraded to PI-RADS v2 score 4 on the basis of DCE scan, wherever applicable. All patients were subjected to trans-rectal ultrasound (TRUS)-guided biopsy using Bard Trucut Biopsy Needle. Histopathological examination was performed in all biopsy specimens and interpreted by a single pathologist. Gleason score of >6 on histopathology was considered CS. The results were tabulated, and statistical analysis was carried out using the Statistical Package for the Social Sciences (IBM Statistical Package for the Social Sciences Statistics for Windows, Version 24.0. Armonk, NY: IBM Corp.).
| > Results|| |
Thirty-six patients with the clinical suspicion of PCa were included in the study. Age of the patients ranged from 51 years to 85 years, with a mean age of 66.6 ± 9.4 years.
On bp-MRI evaluation, evidence of CS PCa (PI-RADS 3 and above) was seen in 31 out of 36 cases. Among these PI-RADS 5, PI-RADS 4 and 3 lesions were seen in 41.7%, 30.6%, and 13.9% cases, respectively [Table 1]. DCE scans were performed in 30 patients only as 4 patients had deranged renal functions and 2 patients refused DCE imaging due to cost involved. Hence, mp-MRI evaluation was possible in 30 patients only.
|Table 1: Distribution of patients according to prostate imaging reporting and data system v2 score (dynamic contrast-enhanced imaging was performed in 30 cases only|
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On mp-MRI examination (30 cases), evidence of CS PCa (PI-RADS v2 score 3 and above) was seen in 25 cases, and among these, PI-RADS 5, PI-RADS 4 and 3 lesions were seen in 36.7%, 40%, and 6.7% cases, respectively [Table 1]. All five cases with PI-RADS v2 score 3 on bp-MRI had undergone DCE scans, and three of these five cases showed early enhancement and were upgraded as PI-RADS 4 on mp-MRI. Six cases who were not subjected to DCE images in our study were reported as PI-RADS 4 (2 cases) and 5 (4 cases) on bp-MRI examination. On both bp-MRI and mp-MRI, three cases were given PI-RADS v2 score 2, whereas two cases were reported as PI-RADS 1.
On histopathological examination, evidence of malignancy was seen in 35 cases with a single negative case. Of these 35 cases, CS PCa (Gleason score >6) was seen in 31 cases, whereas four cases had Gleason score ≤6 and were considered clinically insignificant.
All cases with PI-RADS 4 and PI-RADS 5 on bp-MRI and mp-MRI had evidence of CS PCa on biopsy. Furthermore, no case with PI-RADS 1 on bp-MRI and mp-MRI had evidence of CS PCa on biopsy. One case of PI-RADS 3 (on both bp-MRI and mp-MRI) had Gleason score of 6 on histopathology, whereas 1 case of PI-RADS v2 score 2 was detected as CS PCa on histopathology (Gleason score 7). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy of bp-MRI and mp-MRI in the evaluation of CS PCa are described in [Table 2].
|Table 2: Sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy of bi-parametric magnetic resonance imaging and multiparametric magnetic resonance imaging|
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| > Discussion|| |
PCa is the second most common malignancy in males. Clinical applications of MRI have revolutionized the conventional approach (DRE and TRUS) in suspected patients of PCa., DRE and TRUS are suboptimal in the diagnosis of PCa. TRUS has low sensitivity in the detection of PCa, with PSA levels remaining the only significant indicator for the diagnosis of PCa. On clinical and/or biochemical suspicion, MRI can help in the detection and localization of CS PCa.
The use of complete protocol of mp-MRI, including DCE imaging, in the detection of CS PCa is already established by many studies.,, According to PI-RADS v2, T2W and DWI are the predominant sequences for PCa in the peripheral and transition zones, respectively, and DCE sequence plays a secondary role in PI-RADS assessment category. Many studies have even demonstrated a significantly better accuracy for the detection of PCa with DWI compared to T2W MRI.,, Being used as noninvasive diagnostic technique for PCa detection, MRI should be fast and as cost-effective as possible. Contrast-enhanced mp-MRI is expensive, time-consuming, has potential allergic reactions, may cause nephrogenic systemic fibrosis and gadolinium brain tissue deposition., Hence, in our study, we have compared the effectiveness of bp-MRI (using DWI and T2W only) and mp-MRI (including DCE scan) in the diagnosis of CS PCa using biopsy as the gold standard.
In our study, age of the patients ranged from 51 years to 85 years with a mean age of 66.6 ± 9.4 years. Among 36 cases, PCa was seen in 35 cases with negative biopsy in one patient. Clinically significant (CS) PCa (Gleason score >6) was seen in 31 cases on histopathology. On bp-MRI, evidence of CS PCa (PI-RADS v2 score 3 and above) was seen in 31 of 36 cases, whereas on mp-MRI, CS PCa (PI-RADS v2 score 3 and above) was observed in 25 out of 30 cases [Figure 1]. One case of PI-RADS v2 score 3 (on both bp-MRI and mp-MRI) was not CS on histopathology, whereas 1 case of PI-RADS v2 score 2 had evidence of CS PCa on histopathology (Gleason score 7) [Figure 5]. Both bp-MRI and mp-MRI had high and nearly similar sensitivity, specificity, PPV, NPV, and diagnostic accuracy in diagnosing CS PCa [Table 2]. No significant difference was obtained between bp-MRI and mp-MRI in the diagnosis of CS PCa in our study.
|Figure 1: Venn diagram showing relationship between the two study groups (biparametric magnetic resonance imaging and multi-parametric magnetic resonance imaging group)|
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|Figure 2: Axial T2-weighted image (a) sequence reveals a small ill-defined hypointensity in the peripheral zone of prostate on the right side (white arrow). The corresponding area shows mild hyperintensity (white arrow) on diffusion-weighted imaging (b) and mild hypointensity (white arrow) on ADC maps (c), representing prostate imaging reporting and data system three lesion on biparametric magnetic resonance imaging. On dynamic contrastenhanced images (d), early significant enhancement seen in the area (white arrow) with subsequent upgradation of prostate imaging reporting and data system v2 score to 4. Patient had serum prostate-specific antigen level of 29 ng/ml and biopsy of the lesion revealed intermediate grade adenocarcinoma (Gleason score 3 + 4=7)|
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|Figure 3: Axial T2-weighted image (a) sequence reveals small hypointense area (<1.5 cms) in the transition zone of prostate on the right side (white arrow) along the anterior aspect. Corresponding diffusion-weighted imaging (b) and ADC (c) images reveal marked hyperintensity and hypointensity in the involved area (white arrow), respectively. Prostate imaging reporting and data system v2 score of 4 was assigned to the lesion|
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|Figure 4: Axial T2-weighted image (a) sequence reveals a large (>1.5 cms) ill-defined hypointensity in the peripheral zone of prostate on the left side, extending into contralateral side across midline (white arrow). The corresponding area shows marked hyperintensity (white arrow) on diffusion-weighted imaging (b) and marked hypointensity (white arrow) on ADC maps (c), representing prostate imaging reporting and data system 5 lesion. On dynamic contrast-enhanced images (d), early enhancement seen in the area (white arrow). Patient had serum prostate-specific antigen level of 57 ng/ml and biopsy of the lesion revealed high-grade adenocarcinoma (Gleason score 4 + 5=9)|
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|Figure 5: (Adenocarcinoma Prostate, Gleason Score 3 + 4=7). (a) Tumor cells composed of single cells and gland-like structures in prostatic biopsy (H and E, ×40). (b) High-power view showing tumor predominantly composed of glands of variable size (Gleason Pattern 3) (H and E, ×400). (c) High-power view showing the second component composed of single cells infiltrating into stroma (Gleason Pattern 4) (H and E, ×400)|
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Mussi et al. also observed no statistical difference between accuracies, sensitivities, specificities, PPV, and NPV in bp-MRI and mp-MRI for CS PCa with an inter-reader agreement of 0.59. Junker et al. in their study observed that both bp-MRI and mp-MRI have comparable diagnostic performance in detecting PCa (area under the curve = 0.914 and 0.917, respectively). Kuhl et al. in their study investigated 542 patients with raised PSA (PSA ≥3 ng/mL) and negative TRUS-guided biopsy findings and observed that both bp-MRI and mp-MRI have similar accuracy in the diagnosis of CS PCa (89.1% vs. 87.2%) and inter-reader agreement for the bp-MRI protocol was substantial (k = 0.81), while for mp-MRI, it was moderate (k = 0.60). Similar results were also obtained in studies by Scialpi et al., Swarna et al., and Xu et al.
In our study, five cases with PI-RADS v2 score 3 on bp-MRI underwent DCE scans and 3 of these 5 cases showed early enhancement and were subsequently upgraded to PI-RADS 4 category [Figure 2]. However, all these cases had evidence of CS PCa on pathology, and no added advantage of DCE images could be perceived in our study. Six cases who were not subjected to DCE images in our study were reported as PI-RADS 4 (2 cases) [Figure 3] and 5 (4 cases) [Figure 4] on bp-MRI examination and so did not require DCE according to PI-RADS v2 recommendations. Many authors have stated that in evaluation of PCa on mp-MRI, DCE plays a supplementary role only and DCE positivity only upgrades DWI category 3 lesions in the peripheral zone to category 4,, which is of no prognostic importance as both category 3 and 4 lesions are CS cancers and need urgent management. As mp-MRI is associated with long acquisition time of DCE images, risks and additional cost of intravenous gadolinium, patient discomfort with contrast agent injection, and insignificant benefit of DCE images, many authors have suggested that it should be abandoned., Hence, through this study, we suggest that bp-MRI should be recommended as standard investigation in the evaluation of PCa instead of mp-MRI, particularly in nations with limited resources and low-income population.
In our study, on mp-MRI, DCE images were obtained using VIBE sequences every 5-10 s before, during and several minutes after intravenous administration of MRI contrast agent in a sequential fashion for up to 10 min. Hence, with the use of bp-MRI, this additional imaging time of approximately 10–15 min can be avoided, thus improving patient compliance and limiting patient movement, leading to better image quality due to less motion artefacts. Furthermore, by omitting the use of intravenous contrast agent and DCE, it was possible to reduce the monetary burden to patient, which is a significant amount for the patient in a low-income nation like India.
There were a few limitations in our study. First, the sample size was small and so more such studies should be carried out in future to further substantiate the results obtained in our study. Another limitation of the study was nonavailability of DCE images in six cases. Another limitation of the study was that we considered TRUS-guided biopsy as reference standard and not prostatectomy specimens. Few previous studies have suggested that histological analysis of TRUS-guided biopsy samples underestimate the Gleason score in 26%–41% of patients as compared to prostatectomy.,,,
Hence, it is concluded that no significant difference was observed in performances of mp-MRI (with DCE) and bp-MRI (without DCE) for detection of CS PCa. Only advantage of DCE was upgradation of PI-RADS v2 score 3 to PI-RADS v2 score 4 in 3 patients, which had no bearing on the diagnosis or treatment of CS PCa. In evaluation of PCa, bp-MRI is sufficient and should be preferred over mp-MRI as it avoids the use of intravenous contrast and reduces the scan time and cost for patients, especially in a low-resource country like India. Further studies should be performed to substantiate these results and optimize the bp-MRI protocol in the evaluation of PCa.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
[Table 1], [Table 2]