The goal of this randomized controlled trial (RCT) is to evaluate the diagnostic efficacy of two novel prostate biopsy schemes, including targeted and perilesional biopsy (TB+PB) and combination of sextant-systematic biopsy and targeted biopsy (TB+6SB). The main questions it aims to answer are: Does TB+PB promote the accurate diagnosis of clinically significant prostate cancer (csPCa)? Could TB+6SB achieve the non-inferior diagnostic efficacy compared to TB+PB scheme? What's the value of TB+6SB in improving the detection of prostate cancer in the negative prostate lobe (contralateral to the index lesion)? In the era of MRI-targeted biopsy (TB), when TB and PB is effectively conducted and allows confident detection of the ROI, do we still need to perform SB? Researchers will compare the cancer detection rates of TB+PB and TB+SB to explore the efficacy of different prostate biopsy schemes. They will evaluate the diagnostic profile of different prostate biopsy schemes through the spatial analysis of the prostate. Participants will: Receive TB+PB or TB+6SB.
In recent years, the combined MRI-targeted biopsy (TB) and extended 12-core systematic biopsy (TB+12SB) has been recommended for prostate cancer (PCa) diagnosis in biopsy-naïve patients with MRI-suspected lesions. However, it's worthwhile to note that currently the systematic biopsy (SB) still applies the traditional 10 to 12 or even 24 cores while combined with MRI-TB. However, current evidence indicates a diagnostic plateau beyond a biopsy-core threshold, where increasing biopsy-cores fails to enhance csPCa detection. The enhanced diagnostic efficacy of MRI-TB challenges the imperative for routine extended 12-core SB in the contemporary TB+12SB scheme. Moreover, escalating the number of biopsy-cores would unavoidably increase the discomfort and distress level, heighten the incidence of biopsy-related complications, lead to overdiagnosis, and exacerbate biopsy-related procedural cost and time. In recent years, urological and radiologic thinking has changed after realizing that SB may be optimized or omitted when the chance of missing a clinically significant lesion is low. More and more radiologists and urologists focused on the issue of optimization of prostate biopsy schemes. Previous studies found that the majority of clinically significant PCa (csPCa) was found within a band of 10-mm radius outside MRI lesions (the penumbra). Based on the penumbra theory, targeted and perilesional biopsy (TB+PB) has gradually received urologists' attention. Deng et al. conducted a single-center RCT and demonstrated that TB+PB achieved non-inferior csPCa diagnostic efficacy compared to TB+12SB in men with unilateral MRI-visible lesions. Some other studies supported the application of TB+ipsilateral SB for unilateral positive MRI lesions. The latest EAU guideline has recommended TB+PB for the diagnosis of patients with visible suspicious lesions on MRI, supporting the application of this scheme in clinical practice. However, some urologists suggested that SB at the time of MRI-TB should not be omitted. Multifocality and intratumoral heterogeneity, the two important features of PCa, pose diagnostic challenges for PB-based schemes. Emerging basic researches highlighted the intratumoral heterogeneity of PCa and have suggested that the disease aggressiveness could not always be driven by the index lesion, and non-index tumor foci may harbor distinct genomic drivers of disease progression. Contemporary mpMRI demonstrated limited detection sensitivity for non-index lesions. With the negative predictive values ranging from 63% to 91% for PCa detection and the false-negative value ranging from 10% to 54%, the mpMRI is characterized by suboptimal sensitivity for low-grade and low-volume disease, and underestimations of tumor volume. Previous studies reported that among the 123 patients who received TB+SB and then underwent robotic assissted radical prostatectomy (RARP) treatments, 112 (91.1%) of them had bilateral PCa in the RP specimens. The proportion of bilateral invasion was significantly higher than the pre-biopsy mpMRI assessment. The presence of csPCa outside the index lesion demonstrates strong clinicopathological correlation with adverse surgical outcomes including nodal metastasis, extraprostatic extension, and seminal vesicle invasion. Omitting the csPCa outside the index lesion is related to increased biochemical recurrence, underscoring its prognostic implications. Therefore, SB mapping of the prostate outside the index lesion could provide information regarding the multifocal nature of the disease. Since exceeding the saturation threshold for systematic biopsy (SB) fails to significantly enhance the detection of csPCa while increasing procedural morbidity, including urinary dysfunction, infection, and hematuria, recent efforts have focused on optimizing biopsy protocols by reducing core counts and refining their spatial distribution. Deng et al. conducted a head-to-head RCT and demonstrated that compared with TB+12SB, TB+6SB (six-core sextant-SB bilaterally with each side two cores in the peripheral zone and one core in the transitional zone) exhibited non-inferior diagnostic efficacy, lower procedural morbidity, reduced pain level, and improved post-biopsy quality of life with decreased biopsy-cores and operative duration. The diagnostic efficacy of TB+6SB was non-inferior to that of TB+12SB in all subgroups, further confirming the effectiveness of the TB+6SB scheme. Performing TB+6SB significantly increased the proportion of positive cores, reflecting the improvement of diagnostic efficiency. Consistent with the previous studies, the csPCa detection rates of contralateral-SB in the TB+12SB and TB+6SB groups were 16.7% (42/252) and 15.0% (38/254). Furthermore, the concordance of pathological characteristics between RP and biopsy schemes could reflect the diagnostic accuracy. Comparable histopathological upgrading between RP and biopsy schemes validated the non-inferior diagnostic concordance of TB+6SB vs. TB+12SB in risk stratification accuracy. While recent studies have validated the diagnostic efficacy of TB+PB and TB+6SB using TB+12SB as the reference standard, direct head-to-head comparisons between these two novel strategies remain scarce. Despite sharing identical total core counts, the schemes differ significantly in spatial distribution: TB+PB concentrates cores around the index lesion, whereas TB+6SB distributes three cores ipsilaterally and three contralaterally to the index lesion. In alignment with the EAU guidelines recommending TB+PB for PCa diagnosis, this strategy was adopted as the reference standard in the present study. This RCT aims to determine whether TB+6SB achieves non-inferior diagnostic efficacy compared to TB+PB-specifically by omitting three ipsilateral cores-while evaluating its utility in detecting occult malignancy within the contralateral (radiographically negative) lobe. This study would provide high-quality evidence for the further optimization of prostate biopsy schemes. The main questions it aims to answer are: Does TB+PB promote the accurate diagnosis of clinically significant prostate cancer (csPCa)? Could TB+6SB achieve the non-inferior diagnostic efficacy compared to TB+PB scheme? What's the value of TB+6SB in improving the detection of prostate cancer in the negative prostate lobe (contralateral to the index lesion)? In the era of MRI-targeted biopsy (TB), when TB and PB is effectively conducted and allows confident detection of the ROI, do we still need to perform SB? This prospective RCT compared the csPCa detection rates of TB+6SB and TB+PB. Participants were prospectively enrolled at Peking University First Hospital (Beijing, China) from March 2026 to December 2026. Participants were randomly allocated to TB+6SB group and TB+PB group. Researchers will compare the cancer detection rates of TB+PB and TB+6SB to explore the efficacy of different prostate biopsy schemes. They will evaluate the diagnostic profile of different prostate biopsy schemes through the spatial analysis of the prostate. Participants will: Receive TB+PB or TB+6SB.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
DIAGNOSTIC
Masking
SINGLE
Enrollment
592
The biopsy procedure was conducted by a highly skilled and experienced urologist who specializes in performing prostate biopsies. Prophylactic antibiotics were routinely used both before and one day prior to scheduled surgery. Each patient was placed in the left lateral position or lithotomy position. The ultrasound equipment used included a color Doppler ultrasound diagnostic instrument (Hitachi HiVision, Philips Epiq 7), transrectal probes, and corresponding puncture needle guns. Color Doppler examination was performed from the base to the apex. For patients in the TB+PB group, three-core TB was obtained within the predefined MRI suspicious lesion (ROI), followed by ring-distributed 6-core PB within a 10 to 15 mm radius around the ROI. The location of these nine cores depended on the shape and location of the suspicious lesion. Each core was placed in an individual container and reported separately in accordance with the Ginsburg scheme.
The biopsy procedure was conducted by a highly skilled and experienced urologist who specializes in performing prostate biopsies. Prophylactic antibiotics were routinely used both before and one day prior to scheduled surgery. Each patient was placed in the left lateral position or lithotomy position. The ultrasound equipment used included a color Doppler ultrasound diagnostic instrument (Hitachi HiVision, Philips Epiq 7), transrectal probes, and corresponding puncture needle guns. Color Doppler examination was performed from the base to the apex. For patients in the TB+6SB group, three-core TB within the predefined mpMRI index lesion (ROI) was firstly performed. Then patients received six-core sextant-SB bilaterally with each side two cores in the peripheral zone and one core in the transitional zone. Each core was placed in an individual container and reported separately in accordance with the Ginsburg scheme.
Peking University First Hospital
Beijing, Beijing Municipality, China
RECRUITINGThe clinically significant prostate cancer (csPCa) detection rate for TB+PB and TB+6SB.
csPCa was defined as PCa with a grade group ≥ 2 or GS ≥ 7. The reference standard was the pathological result.
Time frame: One month after the biopsy procedure.
The PCa detection rate
The PCa detection rate for TB+PB and TB+6SB.
Time frame: One month after the biopsy procedure.
The clinically insignificant PCa (ciPCa) detection rate
The clinically insignificant PCa (ciPCa) was defined as PCa with a grade group \< 2 or GS \< 7. The reference standard was the pathological result.
Time frame: One month after the biopsy procedure.
The high-grade PCa detection rate
The high-grade PCa was defined as PCa with a grade group ≥ 3 or GS ≥ 4+3. The reference standard was the pathological result.
Time frame: One month after the biopsy procedure.
The Gleason score (GS) of the biopsy sample
The Gleason score was reported by senior uropathologists according to the Standards of Reporting for MRI Targeted Biopsy Studies (START) criteria and interpreted according to the recommendations of the International Society of Urological Pathology (ISUP) Grade Group.
Time frame: One month after the biopsy procedure.
The GS of radical prostatectomy (RP) specimens
The overall grade was assigned based on the part with the highest GS according to the recommendations of the ISUP. For the RP specimens, the overall grade was assigned based on the part with the highest Gleason score according to the recommendations of the ISUP.
Time frame: One month after the biopsy procedure.
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