Combination of fusion guided multiparametric MRI—transrectal US with systematic biopsy of the prostate for the detection of clinically significant prostate cancer: A prospective single‐center study

To investigate the diagnostic efficacy of fusion guided multiparametric MRI (mpMRI)—transrectal ultrasound (TRUS) biopsy versus systematic biopsy of the prostate in patients with suspicion of prostate cancer.

Many associations have considered and proposed multiparametric magnetic resonance imaging of the prostate (mpMRI) as the modality of choice prior to transrectal ultrasound-guided (TRUS) prostate biopsy in biopsy naive patients for the diagnosis and local staging of prostate cancer. 1,2 The need for imaging is strongly indicated by prostate-specific antigen (PSA) testing combined with clinical examination. 3 Various studies have shown that mpMRI is the gold standard of imaging in the noninvasive detection of prostate cancer, with high sensitivity and negative predictive value with percentages up to 96.1% based on recent meta-analyses. 4,5 However, there is still conflicting evidence regarding biopsy methods whether a systematic TRUS approach or a fusion mpMRI-TRUS guided technique is superior for prostate cancer detection. [6][7][8][9][10] The aims of this population-based study were (i) to evaluate the results of fusion mpMRI-TRUS guided biopsy and systematic TRUS biopsy and its correlation with routine mpMRI imaging grading in patients with suspected prostate cancer (ii) to assess the detection rate of clinical versus nonsignificant prostate cancer based on pathologic-radiologic correlations of biopsy samples (iii) to explore the benefit of PSA density as a surrogate marker for prostate cancer detection.

| Study design and participants
This is a prospective single-center study that lasted 2 years. Twohundred thirty-four consecutive male patients with abnormal PSA testing and suspected prostate cancer based on either digital rectal examination or family history were enrolled in the present prospective study. The age range of patients was between 43 and 89 years; PSA levels ranged from 0.4 to 50 ng/mL and prostate volumes from 23 cc to 255 cc. Patients with prior prostate biopsies or with previous treatment for prostate cancer were excluded from the study (Figure 1). Forty-seven patients with PIRADS scores 1 and 2 were excluded from the protocol. Also, low quality images of the examinations due to technical or patient problems were also excluded.
A total of 185 patients formed our final study group. Patients were referred by their urologists. They were found to have PI-RADS v2.1 category 3 or greater and high suspicion for prostate cancer. All men underwent fusion-guided mpMRI-TRUS and systematic biopsy of the prostate. Informed consent was taken by all participants that were included in the study. Subsequently, the systematic biopsy approach was performed with a 12-core standard template. All samples were further analyzed by Department of Pathology of our hospital. Positive results were defined as Gleason 6 (3 + 3) and higher. Clinically significant prostate cancer (CS-Pca) was defined as Gleason 7 (3 + 4) and higher.

| Fusion-guided mpMRI-TRUS biopsy
Cancer detection rate was calculated by the number of cancers detected independently from the biopsy method that was used from the total number of patients biopsied. Also, cancer detection rate was calculated by the number of cancers detected by each biopsy method (fusion guided mpMRI-TRUS targeted and systematic) from the total number of cancers detected.

| Statistical analysis
As of 2014, a revised system was proposed by the International Society of Urological Pathology with a simpler classification of prostate cancer with five grades (Table 1). In our institute, clinically significant prostate cancer was defined as ISUP grade group 2 and above.
Descriptive analysis was used to assess demographic, imaging, laboratory, and histopathologic data. Cancer detection rates of the two biopsy methods were compared pairwise utilizing the nonparametric two-sided McNemar's test. Statistical significance level was set at a = 0.05, while Bonferroni correction was applied to adjust the significance level in case of multiple comparisons. Cohen's Kappa coefficient was additionally calculated to assess the degree of agreement between the two methods. Kendall's tau rank correlation coefficient was used to assess the correlation between ISUP categories and PIR-ADS categories, as well as ISUP categories and PSA Density values.
The nonparametric Mann-Whitney U test (a = 0.05) was selected, according to the Shapiro-Wilk test for normality ( p < .001), to assess PSA Density differences of CS-PCa. Additionally, receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic capacity of PSA density. All statistical analyses were performed with IBM SPSS Statistics version 28.     Table 4).

| Ethics statements
Results are shown in Graph 1 and  Axis Title G R A P H 3 Prostate-specific antigen density receiver operating characteristic analysis.

| DISCUSSION
The main goal of fusion guided mpMRI-TRUS guided prostate biopsy is to increase the detection rate of CS-PCa and better stratify patients with severe prostate disease. The diagnosis of non-significant prostate cancer seems to have no benefit for the patient; reported data indicate that such cases on either active surveillance or invasive treatment had similar mortality rates after 20 years of monitoring. 1,3 Cochrane meta-analysis from Drost et al, 6 showed that mpMRI fusion guided biopsy allows for the most optimal result in diagnosing significant and insignificant prostate cancer compared with the systematic approach. Therefore, targeted method was statistically comparable to the systematic method in the detection of CS-PCa, result that is also confirmed in our study. Previous trials however, such as the PRECISION study 11 showed that there is a higher per- which emphasized the need for better selection of men to avoid overdiagnosing cases. Further limitations of our study include the learning curve of this method, as mentioned above, which showed improvement over time. Also, findings of radical prostatectomy were not available for comparison with histopathological result of the core biopsies.
There is a small consecutive bias on the lesions biopsied, due to the fact that the same urologist performed both methods.
In conclusion, it may be suggested that the combined implementation of fusion guided mpMRI-TRUS and systematic biopsy leads to optimum detection rates of prostate cancer, in everyday practice. Systematic results are considered comparable to targeted results for detecting CS-PCa. The implementation of systematic biopsy only seems to be related to the detection of increased number of indolent prostate cancers whereas omitting a method may lead to missed cases of CS-PCa.