Introduction
The European Association of Urology (EAU) guidelines in 2022 recommended performing combined multiparametric magnetic resonance imaging (mpMRI) targeted biopsy (TB) and ultrasound-guided systematic biopsy (SB) in biopsy-naïve patients with positive MRI findings [
1]. However, the combined biopsy (TB + SB) approach requires more biopsy cores than either TB alone or SB alone, potentially leading to increased complications and intraoperative discomfort. Furthermore, most patients benefit diagnostically from TB cores rather than SB, as SB detects higher rates of clinically insignificant cancer (cisPCa) [
2‐
7]. Therefore, it is necessary to explore the sampling schemes to minimize biopsy cores while maximize cancer detection.
Given the higher efficacy of TB in the diagnosis of clinically significant prostate cancer (csPCa), the research on optimizing the prostate sampling schemes was mainly focused on retaining TB cores and reducing the number of SB cores. Several studies have explored sampling schemes reducing the ipsilateral or contralateral SB cores [
8,
9]. However, these studies ignored the categorization of Prostate Imaging Reporting and Data System (PI-RADS) or histologic zones of MRI lesion.
TB combined with regional systematic biopsies (RSB) rather than standard SB have been explored as an alternative strategy to minimize biopsy cores. Some articles and meta-analysis have reported similar csPCa detection rates for TB + SB and TB + RSB [
10,
11]. Nevertheless, these approaches did not significantly reduce the number of biopsy cores.
As PI-RADS v2.1 recommended, lesions in the peripheral zone (PZ) and transitional zone (TZ) are assessed by different scoring principles [
12]. Therefore, it is necessary to stratify the MRI suspicious lesions based on different PI-RADS and histologic zones and individualize the sampling schemes reducing the biopsy cores for patients.
Currently, there is no consensus on the specific definition for RSB. Several RSB templates can be found in literatures, including four perilesional systematic cores, cores from adjacent sectors, two adjacent sector cores within a 2-cm of MRI lesions cores, and so on [
11,
13‐
15]. Large prospective multicenter research has found that the addition of four perilesional cores improved the detection of csPCa [
14]. This demonstrates that TB + RSB (four perilesional systematic cores) that adequately sampling the tissue adjacent to MRI lesion tissue could achieve a comparable detection rate with fewer cores.
The primary endpoint of our study was the cancer detection rate and diagnostic performances of TB + SB, TB + RSB, TB, or SB in MRI-positive patients. More importantly, we analyzed and individualized the sampling schemes of patients for different PI-RADS and histologic zones as subgroups within this cohort.
Discussion
The traditional TB + SB performed excess biopsy cores resulting in more complications and intraoperative discomfort. TB + RSB were explored as an alternative strategy to minimize biopsy cores. In the present study, we focused on the diagnostic performance of TB + RSB. Consistent with previous research, we found that TB + RSB detected significantly more csPCa than SB or TB and was nearly equivalent to TB + SB (70.9% vs. 71.0%, p = 0.50, Kappa = 0.996). TB + RSB could achieve a comparable detection rate, while requiring fewer biopsy cores and exhibiting higher diagnostic efficacy.
Several patients included in the study had more than one lesion. Multicenter research, however, has shown that the main lesion played a major role in patients with multiple lesions, and TB of secondary lesions could be safely omitted [
19]. The patients enrolled in our research showed the analogous results. None of the patients with multiple lesions had positive secondary lesions and negative primary lesions. Thus, the RSB (four perilesional systematic cores) were taken around the main MRI-positive lesions in the study.
Using combined biopsy as the reference standard, TB, SB, and TB + RSB detected 92.5% (933/1009), 94.4% (952/1009), 99.2% (1001/1009) PCa and 94.9% (877/924), 95.0% (878/924), 99.8% (922/924) csPCa, respectively. Only two cases of csPCa were missed by TB + RSB, which was superior to TB or SB (0.2% vs. 5.1%,
p < 0.001; 0.2% vs. 5.0%,
p < 0.001). This result tied well with previous studies [
10,
13,
14]. The TB + 4 perilesional SB approach in our cohort almost detected all cases of csPCa and reduced 6.1 biopsy cores on average.
PI-RADS and histologic zones were specifically discussed in a relatively large number of patients, which was a major advantage of our research. PI-RADS standardized the reports of prostate mpMRI and had distinguished value of clinical application [
20]. Several studies have suggested that PI-RADS was an independent predictor for csPCa diagnosis [
21]. Our research also demonstrated that PI-RADS was a well-performing predictor for csPCa (AUC: 0.830, 95%CI: 0.805–0.855,
p < 0.001). As PI-RADS v2.1 recommended, lesions in the PZ were mainly scored by diffusion-weighted imaging and adjusted by dynamic contrast-enhanced. Lesions in the TZ were assessed by T2-weighted imaging and adjusted by diffusion-weighted imaging [
12]. Due to the distinct scoring principles for PZ and TZ, it was essential to classify the PI-RADS and histologic zones when thoroughly analyzing detection rates.
For patients with lesions in PZ, TB + SB and TB + RSB had comparable detection rates for all PI-RADS. However, the remarkable finding was that TB also had a surprising detection rate for PI-RADS 5 in PZ lesion whatever PCa or csPCa (95.4% vs. 96.2%,
p = 0.125; 94.9% vs. 95.6%,
p = 0.125, respectively). Only four (0.8%) csPCa cases were missed by TB in these patients. Indeed, in most cases, TB + RSB offered a significant advantage over TB alone. However, this advantage is not apparent in PI-RADS 5 in the PZ (Supplementary Tables
S2,
3). SB also showed the same results for PI-RADS 5 PZ lesion, but it required a significantly higher number of cores, resulting in lower efficiency. For TZ PI-RADS 5 lesion, however, TB alone was insufficient to diagnosis due to its inferior detection rates than TB + SB. Above all, for lesions in TZ or PI-RADS 3-4 lesions in PZ, TB + RSB could be the practicable substitute for TB + SB. For PI-RADS 5 lesions in PZ, just TB alone might be sufficient to diagnosis. Of course, further prospective multicenter studies were required to validate this approach.
Compared with traditional SB, TB guided by mpMRI has shown a decrease in biopsy cores and detection rates of cisPCa, while increasing the csPCa. Despite the favorable results of TB only, there were also disadvantages such as targeting error and influence by operator experience. SB could make up for the inaccuracy of targeted puncture. Our study showed that the added value of SB for PCa and csPCa detection was 76/1009 (7.5%) and 47/924 (5.1%), respectively. It could be seen that TB and SB had complementary effects. We also found that TB detected fewer cisPCa (4.3% vs. 5.7%,
p = 0.006), which was in accordance with the previous study [
4,
14,
22]. It had been certified that TB + SB could improve csPCa detection and reduce grade misclassification, which was suggested and standardized by EAU guidelines [
1].
However, the combined biopsy should not be a simple “combination” of TB and SB, but should be effectively integrating them to optimize the core sampling site and improve the diagnostic efficiency of biopsy for csPCa. TB + RSB had a higher proportion of positive cores and higher diagnostic efficacy with fewer biopsy core numbers, which was expected to reduce complications and patient discomfort during the biopsy.
There were several limitations in our research. First, compared with the literature previous, our proportion of csPCa cases in MRI-positive lesion was significantly higher [
4,
6,
23]. This was probably due to the fact that many patients enrolled may have been diagnosed at local hospitals, and our hospital usually treated cases with more complex conditions as a referral center. However, this actually resulted in increasing statistical bias. Second, it was unclear whether these patients underwent prostatectomy in the future. The pathology of combined biopsy may not be surely accurate due to the lack of final surgical pathological results. Finally, our study was a retrospective, single-center study, further prospective multicenter studies were required to validate our novel sampling scheme.
In conclusion, our study demonstrated that TB + RSB detected significantly more csPCa than SB or TB and similar to TB + SB. Furthermore, TB + RSB could achieve a comparable detection rate with fewer cores and higher efficacy. TB and SB had similar csPCa detection rates, but TB detected fewer cisPCa substantially. For lesions in TZ or PI-RADS, 3–4 lesions in PZ, TB + RSB could serve as an alternative diagnostic approach to the TB + SB. For PI-RADS 5 lesions in PZ, employing TB alone may be a compelling diagnostic strategy.
Material availability
The data that support the findings of this study are available on request from the corresponding author upon reasonable request.
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