Introduction
Prostate cancer is one of the most prevalent malignancies in men [1, 2]. Prostate cancer is mostly hormone-sensitive [3]. Magnetic resonance imagining is the most effective non-invasive method for prostate cancer detection. It should be always performed with the Prostate Imaging and Reporting and Data System (PI-RADS). PI-RADS v. 2.1 has been used since 2019 [4, 5]. Definitive diagnosis of prostate cancer is established based on histological findings from biopsy samples [4].
At present, transrectal ultrasound (TRUS)-guided core biopsy is the most frequently performed procedure [6]. However, the tumour location can be detected only in a small number of cases (≤ 30%) when TRUS is applied [7]. Tissue samples are collected from specific prostate areas with systemic TRUS-guided biopsy. It is often difficult to obtain cancer tissue. This leads to a large percentage of false-negative results, which is related to consecutive biopsies and treatment [6, 8].
The introduction of multiparametric MRI (mpMRI) has been a breakthrough in the diagnosis of noninvasive clinically significant prostate cancer [9–11]. MpMRI with a 3 T scanner enables the most precise prostate assessment. It shows the location of a clinically significant cancer, which allows a targeted biopsy [9].
Biopsies performed with MRI [also known as MR-directed biopsies or magnetic resonance imaging-guided biopsies (MRI-GB)] include cognitive transrectal biopsy (COGTB), MRI-transrectal ultrasound fusion biopsy (FUS-TB), and in-bore MRI transrectal biopsy (MRI-TB) [12]. Of these, COGTB is the most commonly applied after initial MR evaluation [12]. Biopsy is performed under TRUS in correlation with MR images, which allows for the identification of suspected lesions. However, it requires considerable experience of the operator both in the assessment of MRI and ultrasound (US). It is insufficient but useful mainly for the detection of large lesions. On the other hand, it is possible to combine COGTB with systematic biopsy [12].
FUS-TB biopsy is a more effective approach. It is used under TRUS guidance after the fusion of US and MRI images. The specialist who performs the biopsy sees both images, which increases the likelihood of collecting cancer samples. The most significant limitation is related to difficulties with the fusion of images obtained from two different modalities [13].
In-bore MRI-TB is considered the most precise in-real time biopsy (preferably using a 3T scanner). A specialized system compatible with the MRI electromagnetic field is required [14]. In-bore biopsy is mostly performed using the transrectal approach with an MRI needle guide connected to a computer-operated robot.
MR sequences allow for the detection of the most suspicious lesions, and the use of the robot allows for the optimal needle position. T2-weighted images and diffusion weighted imaging/apparent diffusion coefficient (DWI/ADC) are performed during MRI-guided biopsy. The prostate cancer is usually characterized by diffusion restriction. The areas suspected of the highest malignancy can be visualized when MRI examination is applied [15].
After correct positioning of the guide, the needle is inserted and the radiologist collects samples from the suspected region(s). Proper positioning of the needle or the biopsy route must be always confirmed and documented on MRI. The procedure, including patient preparation and positioning in the MRI scanner, usually takes approximately 30–60 min, depending on the number of lesions [12, 15]. During an MRI-guided biopsy, usually 2–4 samples are collected from each lesion, which is less than the standard systematic TRUS biopsy. A lower number of obtained samples is associated with a lower risk of biopsy-related complications such as haemorrhage or infection and is connected with better comfort of patients [7].
Currently, in-bore prostate biopsy is one of the methods of MRI-GB in patients suspected of primary prostate cancer. There are several algorithms of procedures and diagnostic strategies in which MRI examination and biopsies are used [7, 9, 14–18].
The aim of the study was a retrospective analysis of the correlation between MRI results and histological findings of prostate samples suspected of malignancy, which were taken during in-bore biopsy.
Material and methods
Thirty-nine patients with 57 lesion biopsies were enrolled in the study. Patients were aged 48-84 years (mean age 67.2 ± 9.4 years). Prostate-specific antigen (PSA) levels in patients with the suspicion of primary cancer ranged from 6.4 to 13.16 ng/mL. PSA levels in patients suspected of local recurrence ranged from 0.86 to 4.45 ng/mL. Single lesions were assessed in 25/39 (64%) patients, 2 lesions in 10/39 (26%) patients, and 3 lesions in 4/39 (10%) patients. The material was collected in the Radiology and Diagnostic Imaging Department, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice from November 2019 to December 2020.
Patients were divided into 2 subgroups:
Diagnostic mpMRI prostate examinations performed outside of the Maria Sklodowska-Curie National Research Institute of Oncology were accepted; however, most patients (n = 26) underwent examination using a 3T scanner in the Maria Sklodowska-Curie National Research Institute. The examinations that were performed outside of the Research Centre were sent to the PACS system. Large lesions that were visible on TRUS examination were not referred for MRI biopsy. They were referred to cognitive transrectal ultrasound (TRUS TB – COGTB) after the evaluation made by the radiologists experienced in assessment of MR and TRUS biopsies. Characteristics of the patients and lesions are given in Figures 1 and 2.
Biopsy procedure
In-bore biopsies were performed on a 3T scanner (Magnetom Vida, Siemens Healthineers, Erlangen, Germany). A remote-controlled manipulator RCM (Soteria Medical B, Arnhem, Netherlands) was used for the biopsies.
The remote-controlled manipulator (robot) was positioned between the lower limbs of patients and connected with the controller unit (including a compressor and a computer), which was located in the steering room. The robot and the compressor were connected using plastic tubes. The movement of the robot was controlled by the computer using the pressure difference in the plastic tubes.
The guide, dedicated to the MRI electromagnetic field, was inserted into the rectum and was later connected to the robot.
MRI examination protocol
The protocol includes the following procedures:
A dedicated guide and a needle were used for the biopsies:
Patient position
Patients were in a prone position. A special pillow was located under the pelvis (2 different sizes of pillows depending on patient anatomy, prostate size, and lesion location). The rectum was anaesthetised topically using a lidocaine gel (Lidocaini hydrochloridum; 20 mg/g; PharmaSwiss, Czech Republic).
Course of the procedure
After the patients were positioned prone and anaesthetised, the guide was inserted into the rectum and connected to the robot. The localizer and very rapid T2-weighted TRUFI sequences were performed (parallel to the guide; sagittal and transverse planes). Next, diagnostic T2-weighted and diffusion-weighted images (DWI) were also done. The position of the guide was calibrated, and the target lesion suspected of cancer was determined. Next, the robot was activated and re-located towards the lesion. The correct positions of the guide and the trajectory were confirmed using TRUFI sequences. Next, the biopsy sample was collected by a radiologist. The same protocol was repeated to obtain biopsy samples from different lesion locations.
Patient preparation
Patients were prepared for the procedure (transrectal enema, implementation of oral antibiotic therapy one day prior to the procedure; blood tests, including complete blood count and blood clotting tests).
Whenever possible, patients were asked to discontinue anticoagulants prior to biopsy. Low-molecular-weight heparin was not contraindicated. However, heparin was not administered on the day of the biopsy. The final decision related to the discontinuation or change in therapy was taken by a general practitioner or a cardiologist prior to biopsy.
After the procedure, patients were monitored in the Department of Radiology for 3 hours. Biopsy-related adverse effects included malaise at the time of biopsy (n = 2), which required termination of the procedure (but not hospitalization). Following the consultation, asymptomatic patients were discharged home. No early- or late-onset complications were reported.
Histological assessment
Two to five samples were taken from each lesion. They were embedded in formalin and sent to the Department of Cancer Pathology, National Research Institute of Oncology, Gliwice, Poland. Tissue samples were fixed for 12-24 hours, and histological evaluation was performed. The samples were embedded in paraffin and cut on the microtome into 3-µm sections. Histological samples were stained with haematoxylin and eosin (H + E).
Statistical analysis
Mean values for variables with normal distribution and median values for variables with non-normal distribution with the data on the prevalence in subgroups are given in Tables 1 and 4. Kruskal-Wallis One-Way ANOVA rank test was used for the differential analysis for independent samples, and the post-hoc test was applied for multiple comparisons. The c2 test was used to verify the size of the subgroups, depending on the selected variables. The level of statistical significance was established at a = 0.05. Statistica v. 12 was used for the analysis.
Results
Group analysis
Histological evaluation was performed, and cancer was detected in 18/39 (46%) patients, whereas malignancy was not confirmed in 21/39 (54%) patients.
11/39 (28%) patients underwent biopsy due to the suspicion of local recurrence (cancer was confirmed in 8 patients, while malignancy was not histologically detected in 3/11 patients).
Biopsy was collected from 28/39 patients due to the suspicion of primary cancer, which was confirmed in 10/39 (26%) subjects, and 18/39 patients did not present with primary cancer. Benign prostate hyperplasia and prostatitis were histologically confirmed.
Fifty-seven lesions were assessed. Histological findings were as follows: primary cancer was found in 14 lesions, local recurrence in 10 lesions, and cancer was not detected in the remaining lesions (n = 33).
Histological characteristics are given in Figure 3.
Analysis of histological findings
Cancer was histologically confirmed in 24 lesions. Malignancy was confirmed in 90% of lesions previously reported as PI-RADS 5. Cancer cells were not found in any of the 23 lesions defined as PI-RADS 3. Cancer was detected in 50% of the lesions defined as PI-RADS 4.
Cancer was confirmed in 10/14 patients in most lesions suspected of recurrence (71.4%) following radiation therapy. Table 1 shows the number of malignant lesions confirmed by in-bore biopsy.
|
MRI results |
Non-malignant lesions (n = 33; 58%) |
Malignant lesions (n = 24; 42%) |
|
PI-RADS 3 |
23 |
0 |
|
PI-RADS 4 |
5 |
5 |
|
PI-RADS 5 |
1 |
9 |
|
Suspicion of local recurrence on MRI |
4 |
10 |
Analysis of PSA results
PSA levels of patients ranged from 0.86 to 13.16 ng/mL (median 6.83 ng/mL). These levels were significantly lower in the group suspected of recurrence (2.91 ng/mL) compared to the group with confirmed primary tumour (10.30 ng/mL) and the group with no primary cancer (8.99 ng/mL) (p < 0.001). No significant PSA differences were found between the group with primary cancer and the group with no cancer (Tab. 2). Detailed patient characteristics are given in Table 2.
|
|
Patients with confirmed local recurrence (n = 8) |
Patients in whom local recurrence was not confirmed (n = 3) |
Patients with confirmed primary cancer (n = 10) |
Patients in whom primary cancer was not confirmed (n = 18) |
|
Mean age [years] ± SD |
70 ± 10 |
67 ± 8 |
68.2 ± 9.2 |
64.4 ± 9.5 |
|
Median PSA [ng/mL] Quartile range |
2.91 2.31–4.17 |
2.50 0.86–4.45 |
10.30 6.40–13.16 |
8.99 6.79–12.00 |
|
Time between MRI examination and biopsy [months] Interquartile range |
1.40 1.10–2.23 |
0.85 0.68–1.24 |
2.03 1.16–5.35 |
1.4 0.9–2.4 |
Analysis of lesion size
The mean size of lesions was 12.7 mm (SD ± 5.2 mm). The recurrence lesions were significantly smaller (9.8 mm) compared to primary cancer (15.6 mm) (p = 0.016). The results are given in Table 3.
|
|
Lesions with no primary cancer (n = 29) |
Lesions with primary cancer (n = 14) |
Lesions with local recurrence (n = 10) |
Lesions with no local recurrence (n = 4) |
|
Mean largest lesion dimension [mm] ± SD |
12.5 ± 5.7 |
15.6 ± 4.6 |
9.8 ± 3.0 |
11.3 ± 3.4 |
Analysis of lesion location
Most primary lesions (23/43) were localized in the transitional zone, and malignant lesions were confirmed only in 7% of the lesions. However, most malignancies were detected in the peripheral zone (Fig. 4–6).
Assessment of MRI findings
T2-weighted images
T2-weighted images for lesions suspected of primary cancer are given in Table 4.
|
T2-weighted images score |
Lesions with no primary cancer (n = 29) |
Primary cancer (n = 14) |
|
2 |
3 |
0 |
|
3 |
19 |
0 |
|
4 |
5 |
4 |
|
5 |
2 |
10 |
PI-RADS = 3 on T2-weighted images was predominant (65%) in the group in whom cancer was not detected whereas PI-RADS = 5 was found for malignant lesions in 72% (p < 0.001).
DWI images
Primary cancer scored as PI-RADS 4 or PI-RADS 5 on DWI was found in 13/14 lesions. Only one primary cancer had PI-RADS 3. PI-RADS 3 was mostly found in non-malignant lesions (55%; Tab. 5).
|
DWI score |
Non-malignant lesions (n = 29) |
Malignant lesions (n = 14) |
|
2 |
6 |
0 |
|
3 |
16 |
1 |
|
4 |
6 |
5 |
|
5 |
1 |
8 |
Diffusion restriction is characteristic of malignancy, i.e. high signal intensity (SI) on DWI bmax ≥ 1400 s/mm2 and low SI on the ADC map. All malignant lesions were characterized by diffusion restriction. No diffusion restriction was found in 16/29 (55%) benign lesions, whereas diffusion restriction was reported in 13/29 (45%) non-malignant lesions (Tab. 6).
|
DWI/ADC |
Non-malignant lesions (n = 29) |
Malignant lesions (n = 14) |
|
Non-restricted diffusion |
16 |
0 |
|
Diffusion restriction |
13 |
14 |
Discussion
In-bore prostate biopsy a method of magnetic resonance imaging-guided biopsies (MRI-GB) that allows precise collection of tissue samples suspected of cancer for histological assessment [9, 14, 15]. However, many studies showed a large discrepancy in detecting primary cancer using in-bore biopsy. Detection rates range from 37% to 73% for PI-RADS ≥ 3. These results were significantly better for PI-RADS 4 and 5, and reached as much as 88% [15, 19]. In our study, the rate was 46% for PI-RADS ≥3 and 70% for PI-RADS 4 and 5 (Fig. 7AB).
Twenty-three lesions assessed as PI-RADS 3 were suspected of primary cancer (53.5%). Most of them were located in the transitional zone (n = 19).
Only 4 PI-RADS 3 lesions were found in the peripheral zone. According to the American Congress of Radiology, PI-RADS 3 is inconclusive and hence difficult for clear assessment, especially if localized in the transitional zone [4, 5].
Nodules in the transitional zone are often characterized by diffusion restriction. However, it does not have to be related to malignancy. In some benign nodules, diffusion restriction can mimic cancer, considering the structure and an increase in the number of cells in the nodule [20–22].
Therefore, PI-RADS 2.1 is the revised version used for the assessment of lesions in the transitional zone. However, there are still problems related to the interpretation of the lesions in the transitional zone [4].
In our study, histological evaluation of all PI-RADS 3 lesions showed no malignancy. Vilanova et al. found 20% of cancers for PI-RADS 3 lesions using robot-assisted transrectal MRI-guided biopsy [15]. In other studies, including PRECISION, the detection rates ranged from 6 to 20% and were related to the quality of MRI, the experience of the investigator, the biopsy type, and the disease prevalence in the population. Therefore, detection rates were higher and reached as much as 33% in non-naïve men [23, 24].
In our group, large lesions or lesions feasible for cognitive TRUS biopsy were not referred for MRI biopsy, which resulted in a higher proportion of lesions assessed as PI-RADS 3.
Studies have shown that cognitive biopsy can be useful, mainly when lesions are localized in the posterior peripheral zone (for lesions assessed as PI-RADS 4 and 5, 80–88% of them were visible on second-look TRUS) [25, 26].
Histological reports should be correlated with MRI PI-RADS score. However, MRI evaluation must be performed again if histological assessment does not correspond to PI-RADS. In specific cases, second MRI with second biopsy should be performed if clinically indicated.
In our study, only one PI-RADS 5 lesion was histologically negative (prostatitis). The lesion resolved and was not found on follow-up MRI 3 months later. Additionally, PSA level was not elevated in 4 negative PI-RADS 4 lesions in the follow-up, the progression of lesions was not reported, and some lesions were even more difficult to detect on follow-up MRI.
One of the largest studies on in-bore biopsy was conducted by Pokorny et al. [27], in which 607 targets in 554 men were biopsied. The findings showed that the overall cancer detection rate was 80% in patients and 76% in lesions. PI-RADS 3, 4, and 5 demonstrated cancer in 36%, 79%, and 97%, respectively.
Pokorny et al. [27] also reviewed the literature on in-bore biopsy from 2013 to 2018. Twenty-three studies were analysed, in which 4061 patients underwent MRGB. Cancer was detected in from 38 to 80% of patients. Only 9 studies assessed cancer detection depending on the PI-RADS results — PI-RADS 3 (6–49%), PI-RADS 4 (34–77%), and PI-RADS 5 (82–96.3%).
Vural et al. [28] assessed PI-RADS 4 and 5 in 246 patients who had undergone in-bore biopsy. The overall prostate cancer detection rates were 80.5% per patient and 78% per target. The detection rate was 68% and 92% in PI-RADS 4 and 5, respectively.
Additionally, those authors compared the literature on in-bore biopsy from 2018 to 2021 in 10 papers, in which the overall detection cancer ranged from 45.6 to 84%, for PI-RADS 4 from 48.6% to 78%, while 87.5 to 97% for PI-RADS 5.
D’Agostino et al. [29] showed a comparable value of in-bore bore and FUS-TB biopsy. After analysing the target biopsy in 297 patients, those authors did not observe the clear superiority of one technique over another. The lesion site and localization were equally comparable among 2 groups. The overall detection rate was similar (45.5% of the FUS-TB group vs. 52.8% of the “in-bore” group). Histological ISUP grade was also comparable among 2 groups. Furthermore, it should be noted that in-bore biopsy is characterized by real-time feedback in needle placement, fewer sampled cores, and a low likelihood of missed target. Additionally, it has the potential to reduce the sampling error related to unselective standard biopsy scheme by providing better disease localization.
In 2017, in their meta-analysis, Wegelin et al. [30] analysed 43 studies and found that MRI-GB allowed the detection of more clinically significant cancers compared to TRUS biopsy. Statistically significant higher sensitivity was detected when in-bore biopsy was used as compared to COGTB. However, no statistically significant difference was found between FUS-TB and COGTB or between FUS-TB and MRI-TB.
In the case of clinically significant cancer, sensitivity of in-bore biopsy was 0.92, 0.89 in the case of FUS-TB, and 0.86 for COGTB. A large limitation of this meta-analysis was the lack of PI-RADS assessment. Additionally, the size and location of lesion were not assessed, which is of crucial importance when biopsy methods are compared.
Prince et al. [31] assessed 286 men (191 in-bore biopsy, 95 FUS-TB). In-bore MRI-targeted prostate biopsy was connected with significantly greater likelihood of target-specific detection of prostate cancer and with non-significantly higher likelihood of target-specific detection of ISUP GG2 or more advanced prostate cancer than is FUS-TB.
There are still too few reports related to the verification of prostate lesions that are suspected of local recurrence after radiation therapy.
Currently, biochemical recurrence is reported in as much as 50% of patients within 10 years after undergoing external-beam radiotherapy (EBRT) for prostate cancer [32].
Microscopic confirmation of local recurrence may provide crucial information before salvage treatment [33]. Such therapy may be beneficial for relapsing patients, but it is related to a higher probability of adverse events. Therefore, patients should be selected for salvage brachytherapy, salvage prostatectomy, and other invasive procedures very carefully [32–37].
Prostate assessment using TRUS following radiation therapy is very difficult. From our experience, the post-radiation prostate is very often a small, non-homogeneous hypoechogenic structure. From the practical point of view, it is not possible to indicate active cancer. The recurrence is best seen on MRI, particularly on diffusion imaging as the diffusion restriction. Next to T2-weighted images, DWI/ADC sequences are also performed during biopsy. Therefore, it is possible to precisely localize the suspected area and collect samples (Fig. 8AB, 9AB).
Fourteen lesions suspected of local recurrence were assessed in our study. Cancer was found in approximately 72% of the lesions (Fig. 10AB). The smallest lesion was of 5 mm. PET PSMA was performed in negative biopsy patients suspected of local relapse in whom malignancy was not confirmed histologically. PET PSMA results were negative. Additionally, PSA level was not elevated in patients during the follow-up. Patients were under oncological surveillance.
Conclusions
Multiparametric MRI shapes modern oncology. There is a need for good quality images assessed by experienced specialists. Moreover, a wide range of different biopsy techniques may allow for the most reliable histological results. It is our first study to demonstrate the experience related to in-bore prostate biopsy whose results are promising. Further studies are warranted to confirm the usefulness of this method.
Conflicts of interest
The authors declare no conflict of interest.
Funding
This research received no external funding.
