## 4 Discussion  
Systematic ultrasound-guided biopsy leads to sampling errors that delay the diagnosis of clinically significant PCa, overdiagnosis of clinically insignificant PCa, and misclassification of the disease. Based on literature data, it is known that the detection rate of clinically significant PCa in primary patients undergoing random systematic biopsy is only 23% [17]. It is known that repeated biopsies give even worse results: secondary systematic biopsy--14% and third repeated biopsy--6% for clinically significant PCa detection [18]. In this study, the clinically significant disease was detected in 34.28% of cases by targeted biopsy only; meanwhile, the detection rate of clinically significant disease after systematic biopsy only was just 8.48%. These results have essentially the same trend compared to the data reported in the literature. According to the PRECISION trial, men who underwent MRI-targeted biopsy had a significantly higher rate of ISUP \(\geq\) 2 cancer detection than those who underwent systemic biopsy (38% vs. 26%, \(p\) = 0.005, detection ratio 1.46) [12]. In the mpMRI era, saturating prostate biopsy also has rare indications and is used only in exceptional cases, i.e., secondary patients with negative mpMRI (PI-RADS 1-2 scores) and elevated PSA. According to the literature, the frequency of detection of clinically significant prostate cancer after saturation biopsy (24 biopsy cores) is only 16% [19]. It has been reported that 8-24% of clinically significant PCa may go unnoticed on mpMRI when a tumor has been diagnosed following radical prostatectomy [20]. However, according to our data, the overall detection rate of PCa improved only from 74.56% to 80.21% when an adapted systematic prostate biopsy was performed. A combination of systematic and targeted biopsy schemes has previously been suggested to provide the highest PCa detection rate, and our results are consistent with this fact [21]. However, based on our results, adapted systematic prostate biopsy improved the overall detection rate of PCa but did not provide additional benefit for the detection of clinically significant disease. The European Association of Urology recommends for primary patients to perform targeted plus systematic biopsy and targeted-only biopsy for secondary patients if their PIRADS score is \(\geq\)3, but our data suggest that only targeted biopsy could be performed safely in biopsy-naive patients with a PIRADS score \(\geq\) 3 by avoiding systematic biopsy and maintaining a high clinically significant PCa detection rate. We substantiate this on the fact that in patients for whom no clinically significant PCa was detected by targeted prostate biopsy, also, no clinically significant cancer was detected by adapted systemic prostate biopsy. Other randomized Controlled Trials focusing on primary patients with a positive MRI found that targeted biopsy detected significantly more ISUP \(>\) grade 2 cancers than a systemic biopsy (risk difference, \(-\)0.11 (95% CI: \(-\)0.2-0.0); \(p\) = 0.05) [22]. Another extremely important fact is that targeted biopsy without systematic biopsy reduces the detection of ISUP grade 1 PCa compared to systematic biopsy. In the PRECISION and 4M trials, the detection rate of clinically insignificant PCa was significantly lower in the targeted biopsy group as compared to the systematic-only biopsy group (9% vs. 22%, \(p\) < 0.001, detection ratio of 0.41 for PRECISION; 14% vs. 25%, \(p\) < 0.001, detection ratio of 0.56 for 4M) [12; 22]. According to the PROMIS study, a negative MRI could avoid unnecessary TRUS biopsies in 28% of patients, while 21% would be confirmed based on true negative results, but 7% would not be justified based on false negative results [23]. However, according to the presented results, it is not possible to assess whether these clinically significant PCa detected by targeted-only biopsy would have been detected by additional systematic biopsy.