Recently, new magnetic resonance imaging (MRI)-transrectal ultrasound (TRUS) techniques and imaging features of Prostate Imaging and Report and Data System (PI-RADS) 4 or 5 have been reported. The aim of this study was to validate the outcomes of new TRUS-guided biopsy techniques for cancer detection in patients with PI-RADS 4 or 5.
Between June 2018 and November 2018, 94 men underwent TRUS-guided biopsy after PI-RADS 4 (n=59) or 5 (n=35) was categorized as an index lesion on MRI. For PI-RADS 4 group, target biopsy was performed in 5 and combination biopsy (target and systematic biopsies) was in 54. For PI-RADS 5 group, target biopsy was performed in 19 and combination biopsy was in 16. Target to combination biopsy ratios and significant cancer detection rates (CDRs) were compared between the groups. Significant cancer was defined as a Gleason score ≥ 7 tumor. Standard reference was biopsy examination. Fisher’s exact were used for statistical analysis.
Target to combination biopsy ratios was 5:54 in the PI-RADS 4 group and 19:16 in the PI-RADS 5 group (P<0.0001). The significant CDR of the target biopsy were 42.4% (25/59) in the PI-RADS 4 group and 82.6% (29/35) in the PI-RADS 5 group (P=0.0002). The significant CDR of combination biopsy was 44.1% (26/59) in the PI-RADS 4 group and 85.7% (30/35) in the PI-RADS 5 group (P<0.0001).
New TRUS biopsy techniques provides high significant CDR patients with PI-RADS 4 or 5. Therefore, TRUS should be performed prior to fusion or in-bore biopsy to determine if these categories are visible.
Prostate Imaging and Report and Data System version 2 (PI-RADSv2) has been introduced to use in the clinical practice since 2015 [
TRUS is not used for lesion targeting because it is generally accepted that prostate cancer is not clearly seen on TRUS. However, it is still unclear if significant cancer is really invisible on TRUS. Recently, new TRUS techniques and imaging features have been reported to detect significant cancer in patients with PI-RADS 4 or 5 [
Between June 2018 and November 2018, 166 men underwent TRUS-guided biopsy (
The remaining 94 men (median, 67.5 years; range, 40 to 87) met for the following inclusion criteria: high (≥ 2.5 ng/mL) PSA, pre-biopsy MRI, and PI-RADS 4 or 5. Their PSA, prostate volume, PSA density, MRI-biopsy interval, and tumor size ranged 2.8 to 2,783.6 ng/mL (median, 5.7), 12 to 304 mL (35), 0.04 to 108.73 ng/mL2 (0.17), 0 to 646 days (40), and 2.1– to 41.0 mm (12.0), respectively. These patients were divided into PI-RADS 4 group (n=59) and PI-RADS 5 group (n=35). Patient demographics in each group were summarized in the
Multi-parametric MRI was performed prior to prostate biopsy and the MRI sequences included T2-weighted, diffusion-weighted, and dynamic contrast-enhanced axial magnetic resonance (MR) images according to the guidelines of PI-RADSv2 [
First, target biopsy was performed in PI-RADS 4 and 5 if these categories were visible on TRUS. Then, systematic biopsy was added when tumor margin was not completely visible on TRUS. Determining whether or not the combination biopsy (target and systematic biopsies) was necessary simply depended on how TRUS operator subjectively assessed the lesion visibility on TRUS. He tried to add systematic biopsy as many as possible not to miss significant cancer in the prostate other than PI-RADS 4 or 5. Target cores were sampled within the PI-RADS 4 or 5 and then systematic cores were obtained from the other prostate tissue categorized as PI-RADS 1 or 2.
The biopsy operator was familiar with the following TRUS techniques and imaging features [
MRI images were not reviewed at Picture Archiving and Communication System (PACS) station to re-categorize prostate lesions with PI-RADSv2. The original PI-RADS scores which were made by a radiologist prior to biopsy, were used for analysis.
Overall cancer detection rate (CDR) was calculated by the number of all cancer cases divided by the number of all biopsy cases in each group or each biopsy. Significant cancer was defined as one with Gleason score (GS) ≥ 7. Significant CDR was calculated by the number of all GS ≥ 7 cases divided by the number of all biopsy cases in each group or each biopsy. Overall and significant CDRs were compared between the groups or between the biopsies.
Positive core rate (PCR) was calculated by the number of all cancer cores divided by the number of all biopsy cores. PCRs were compared between the groups or between the biopsies.
The size of peripheral tumor was measured at diffusion-weighted axial images and that of transition tumor was measured at T2-weighted axial MR images. When a tumor involved both zones, the tumor size was measured depending on the dominant location. Therefore, when a tumor involved peripheral zone more dominantly than transition zone, the tumor size was measured on diffusion-weighted MR images. The median numbers of all or cancer cores obtained by target biopsy were compared between the groups. The median GSs of the target biopsy were compared between the groups.
Mann-Whitney test was used to compare patient age, PSA, prostate volume, PSA density, MRI-biopsy interval, tumor size, biopsy core, and GS between the groups. Fisher’s exact test was used to compare CDRs and PCRs between the groups or the biopsies. Odds ratio was obtained to quantify the strength of the association between the groups. The approximation of Woolf was used to calculate 95% confidence interval.
Commercially available software (PASW Statistics version 20.0, IBM Co., Armonk, NY, USA) was used for statistical analysis. A two-side P-value of less than 0.05 was considered statistically significant.
This retrospective study was conducted on human and was approved by Institutional Review Board of Samsung Medical Center (IRB number: 2019-02-102-001). Informed consent was waived.
PI-RADS 4 group had younger age (P=0.0002), lower PSA (P=0.0002), lower PSA density (P=0.0037), longer MRI-Biopsy interval (P=0.0075), and smaller tumor size (P<0.0001) than PI-RADS 5 group (
The overall CDR was 57.6% (34/59) in the PI-RADS 4 group and 94.3% (33/35) in the PI-RADS 5 group (P=0.0001) (
The overall CDR of the target biopsy was 52.5% (31/59) in the PI-RADS 4 group and 91.4% (32/35) in the PI-RADS 5 group (P<0.0001) (
The overall CDR of the systematic biopsy was 31.5% (17/54) in the PI-RADS 4 group and 50.0% (8/16) in the PI-RADS 5 group (P=0.2363) (
The overall CDR of the combination biopsy was 53.7% (29/54) in the PI-RADS 4 group and 87.5% (14/16) in the PI-RADS 5 group (P=0.0189) (
Of 34 cancer-proven PI-RADS 4 cases, 14 were diagnosed by both, 17 by target biopsy (
PI-RADS 4 and 5 have a higher risk of significant cancer than PI-RADS 1–3. As a prostate cancer becomes GS 7 or higher, the tumor has stronger signal intensity on diffusion-weighted or T2-weighted MR images. Target biopsy is performed in PI-RADS 4 or 5 under MRI-TRUS fusion or in-bore MRI guidance because this category is clearly visible on MRI. In contrast, TRUS has not been concerned in targeting a prostate cancer because this modality cannot clearly depict it. Interestingly, it is not uncommon for an experienced operator to see a well-demarcated tumor on TRUS. This tumor frequently turns out to be a significant cancer. Besides, it is still unclear if PI-RADS 4 or 5 is visible on TRUS or if this category is targeted by TRUS. Our study showed that the significant CDRs of PI-RADS 4 and 5 using TRUS is not inferior to those using MRI-TRUS fusion or in-bore MRI in previously published investigations. They reported that the significant CDRs of PI-RADS 4 and 5 are 22.1% to 78.0% and 72.4% to 90.7%, respectively [
New TRUS techniques were applied in our study. One is that prostate was not compressed until a lesion was detected. If prostate is compressed, a cancer is likely to be compressed so that it cannot be seen on TRUS. A small peripheral cancer near Denonvilliers’ fascia becomes flat frequently due to prostate compression. It is difficult to differentiate the compressed hypoechoic tumor from the thick hypoechoic rectoprostatic fascia. The other is that tumor location on TRUS looked quite different from that on MRI. The axial TRUS images are obtained obliquely to urethra, whereas the axial MR images are done perpendicular to urethra. For the same reason, the tumor size or shape on TRUS also appears different from that on MRI. The difference of MRI-TRUS scan axis makes it difficult for TRUS operators to find a lesion that is categorized as PI-RADS 4 or 5 lesion on MRI.
New TRUS features of significant cancer were also applied in our study. It is generally accepted that prostate cancer is not clearly depicted on TRUS. However, peripheral cancer becomes more hypoechoic on TRUS if a GS becomes 7 or higher. Our study demonstrated that the CDR of peripheral PI-RADS 4 or 5 was 100% with target biopsy alone when the tumor was completely demarcated on TRUS. Unfortunately, the TRUS features of transition cancer are not well known. Our study assumed that transition cancer becomes hyperechoic if GS increases. Investigations reporting the TRUS features of transition cancer are extremely rare. Several studies [
Systematic biopsy was frequently performed in our study even if PI-RADS 4 or 5 was all visible on TRUS. The lesion visibility was different each other. Systematic biopsy was added to target biopsy when an operator was not convinced that tumor margin was completely visible on TRUS. The overall and significant CDR had been improved approximately 10% to 20% by means of increasing the number of systematic biopsies before. Systematic biopsy yielded 13% to 25% significant CDR in the prostate other than PI-RADS 4 or 5 in our study. These CDRs are much lower than those of target biopsy in PI-RADS 4 or 5. These findings indicate that prostate cancer is frequently multifocal [
Our study had some limitations. First, there were no objective criteria for adding systematic biopsy to target biopsy. The lesion visibility is a key finding to determine whether or not systematic biopsy is performed. However, it relies on operator’s skill and experience. Second, the optimal protocol of systematic biopsy was not established in PI-RADS 4 or 5. Increasing number of systematic cores increases not only significant CDR, but also complication rate such as pain, urinary retention, bleeding, and infection [
In conclusion, new TRUS biopsy techniques provide a good significant CDR in patients with PI-RADS 4 and 5 if an operator is familiar with the new TRUS techniques and imaging features. However, systematic biopsy is difficult to skip because it can detect additional cancers which are missed or underscored by target biopsy. When these categories are identified on pre-biopsy MRI, TRUS should be first performed to assess lesion visibility prior to MRI-TRUS fusion or in-bore MRI-guided biopsy.
No potential conflict of interest relevant to this article was reported.
Conception or design: TA, BKP.
Acquisition, analysis, or interpretation of data: TA, BKP.
Drafting the work or revising: TA, BKP.
Final approval of the manuscript: TA, BKP
Flow diagram for study population. TRUS, transrectal ultrasound; PI-RADS, Prostate Imaging Reporting and Data System; PSA, prostate specific antigen; MRI, magnetic resonance imaging.
A 64-year-old man with Prostate Imaging Reporting and Data System (PI-RADS) 4 peripheral cancer. (A) Diffusion-weighted axial magnetic resonance image shows a hyperintense mass (white arrow) in the left mid-gland peripheral zone. The lesion measures 5.3 mm. His prostate specific antigen was 4.28 ng/mL. (B) Transverse transrectal ultrasound (TRUS) image shows that the mass (white arrow) is hypoechoic and located in the left base peripheral zone. TRUS-guided target biopsy confirmed Gleason score 7 (3+4) adenocarcinoma in all target cores (n=4). TRUS-guided systematic biopsy did not detect prostate cancer.
A 69-year-old man with Prostate Imaging Reporting and Data System (PI-RADS) 5 transition cancer. (A) T2-weighted axial magnetic resonance image shows a hypointense mass (white arrowheads) in the left base transition zone. The lesion measures 15.4 mm. His prostate specific antigen was 6.98 ng/mL. (B) Transverse transrectal ultrasound (TRUS) image shows that the mass (white arrowheads) is hyperechoic and located in the left midglnad transition zone. TRUS-guided target biopsy confirmed Gleason score 7 (4+3) adenocarcinoma in all target cores (n=4). TRUS-guided systematic biopsy detected Gleason score 7 (3+4) adenocarcinoma in two cores from sextant cores.
Patient demographics
Demographic | TRUS-guided biopsy (n=94) |
P-value | |
---|---|---|---|
PI-RADS 4 (n=59) | PI-RADS 5 (n=35) | ||
Age (yr) | 64 (40–82) | 71 (57–87) | 0.0002 |
PSA (ng/mL) | 4.9 (2.8–30.3) | 7.8 (2.9–2,783.6) | 0.0002 |
Prostate volume (mL) | 34 (12–162) | 36 (16–304) | 0.9813 |
PSAD (ng/mL2) | 0.14 (0.04–0.76) | 0.20 (0.07–108.7) | 0.0037 |
MRI-biopsy interval (day) | 46 (8–646) | 30 (0–73) | 0.0075 |
Tumor size (mm) | 9.3 (2.1–14.6) | 20.0 (15.0–41.0) | <0.0001 |
Values are presented as median (range).
TRUS, transrectal ultrasound; PI-RADS, Prostate Imaging Reporting and Data System; PSA, prostate specific antigen; PSAD, prostate specific antigen density; MRI, magnetic resonance imaging.
Comparison of biopsy outcomes between PI-RADS 4 and 5
Biopsy outcome | TRUS-guided biopsy (n=94) |
OR (95% CI) | P-value | |
---|---|---|---|---|
PI-RADS 4 (n=59) | PI-RADS 5 (n=35) | |||
Overall CDR (%) | 57.6 (34/59) | 94.3 (33/35) | 12.132 (2.658–55.372) | 0.0001 |
Significant CDR (%) | 44.1 (26/59) | 85.7 (30/35) | 7.615 (2.593–22.370) | <0.0001 |
PCR (%) | 26.7 (188/703) | 58.5 (175/299) | 3.866 (2.909–5.138) | <0.0001 |
Target to combination biopsy ratio | 5:54 | 19:16 | 12.825 (4.133–39.797) | <0.0001 |
PI-RADS, Prostate Imaging Reporting and Data System; TRUS, transrectal ultrasound; OR, odds ratio; CI, confidence interval; CDR, cancer detection rate; PCR, positive core rate.
Comparison of target biopsy outcomes between the PI-RADS 4 and 5
Biopsy outcome | Target biopsy (n=94) |
OR (95% CI) | P-value | |
---|---|---|---|---|
PI-RADS 4 (n=59) | PI-RADS 5 (n=35) | |||
Overall CDR (%) | 52.5 (31/59) | 91.4 (32/35) | 9.634 (2.654–34.978) | <0.0001 |
Significant CDR (%) | 42.4 (25/59) | 82.6 (29/35) | 6.573 (2.371–18.224) | 0.0002 |
PCR (%) | 44.0 (159/361) | 77.7 (157/202) | 4.432 (2.997–6.555) | <0.0001 |
PI-RADS, Prostate Imaging Reporting and Data System; OR, odds ratio; CI, confidence interval; CDR, cancer detection rate; PCR, positive core rate.
Comparison of systematic biopsy outcomes between PI-RADS 4 and 5
Biopsy outcome | Systematic biopsy (n=70) |
OR (95% CI) | P-value | |
---|---|---|---|---|
PI-RADS 4 (n=54) | PI-RADS 5 (n=16) | |||
Overall CDR (%) | 31.5 (17/54) | 50.0 (8/16) | 2.176 (0.6988–6.779) | 0.2363 |
Significant CDR (%) | 13.0 (7/54) | 25.0 (4/16) | 2.238 (0.5615–8.921) | 0.2589 |
PCR (%) | 8.5 (29/342) | 18.6 (18/97) | 2.459 (1.299–4.654) | 0.0083 |
PI-RADS, Prostate Imaging Reporting and Data System; OR, odds ratio; CI, confidence interval; CDR, cancer detection rate; PCR, positive core rate.
Comparison of combination biopsy outcomes between PI-RADS 4 and 5
Biopsy outcome | Combination biopsy (n=70) |
OR (95% CI) | P-value | |
---|---|---|---|---|
PI-RADS 4 (n=54) | PI-RADS 5 (n=16) | |||
Overall CDR (%) | 53.7 (29/54) | 87.5 (14/16) | 6.034 (1.248–26.168) | 0.0189 |
Significant CDR (%) | 38.9 (21/54) | 81.3 (13/16) | 6.810 (1.731–26.791) | 0.0040 |
PCR (%) | 22.4 (149/664) | 43.5 (84/193) | 2.664 (1.900–3.735) | <0.0001 |
PI-RADS, Prostate Imaging Reporting and Data System; OR, odds ratio; CI, confidence interval; CDR, cancer detection rate; PCR, positive core rate.