INTRODUCTION
Prostate cancer (PCa) is among the most prevalent cancers worldwide [1,2]. Despite ongoing debates over the superiority of radical prostatectomy (RP) compared to combined androgen deprivation therapy and radiation therapy (RT) [3], RP continues to be a viable option for PCa treatment according to current guidelines [4].
The introduction of multiparametric magnetic resonance imaging (mpMRI) and the Prostate Imaging-Reporting and Data System (PI-RADS) has led to their widespread use in detecting clinically significant PCa with high sensitivity [5]. Specifically, for patients with PI-RADS 5 lesions, the cancer detection rate is approximately 85% [6]. However, despite these technological advancements, current guidelines still recommend combined systematic biopsy due to the risk of missing significant PCa [4]. Our prior data suggest that using frozen section target biopsy allows for the safe omission of systematic biopsy in 97% of patients showing indications of a PI-RADS 5 lesion along with either extracapsular extension (ECE) on MRI or a prostate-specific antigen (PSA) level > 20 ng/mL [7].
Recent reports describe performing RP without prior biopsy, guided by prostate-specific membrane antigen (PSMA) positron emission tomography (PET) and mpMRI [8,9]. However, one study reported a case where no tumor was found post-RP [9]. While RP without prior PCa confirmation via biopsy might offer some benefits, it also carries a significant risk of unnecessary RP. On the other hand, conventional combined systematic and targeted biopsies might lead to unnecessary systematic biopsies in selected high-risk patients, as our findings indicate [7]. This study assesses the feasibility of conducting targeted biopsies with frozen section analysis followed by immediate RP.
MATERIALS AND METHODS
We retrospectively analyzed and identified patients who underwent targeted biopsy with frozen sections and concurrent robot-assisted RP (RARP) between 2018 and 2022. The inclusion criteria were men with at least one PI-RADS 5 region of interest (ROI) on mpMRI, who also met one of the following: (1) MRI findings suggestive of ECE with a PSA level greater than 10 ng/mL, or (2) a PSA level higher than 20 ng/mL.
For each patient, the surgeon discussed the possibility of a negative result from the frozen section prostate biopsy specimen and the potential subsequent need for a routine systematic biopsy instead of proceeding directly to RP. After this explanation, patients provided informed consent for the possible switch to systematic biopsy instead of RP.
Each patient underwent between 1 to 4 cores of MRI-ultrasound (US) fusion-targeted transperineal prostate biopsy under general anesthesia in the operating room, positioned in the lithotomy position. The biopsies were conducted by 3 urologists with varying years of experience, all proficient in performing targeted biopsies. A BioJet MRI-US fusion device (Geoscan, Lakewood Ranch, FL, USA) facilitated the transperineal prostate biopsies. The MRI images stored at our institute were uploaded to the fusion system, where the operator delineated the contour of the mpMRI, creating a 3-dimensional model. Real-time transrectal ultrasonography (TRUS) allowed the operator to visualize the ROI via sonography. After the prostate contour was established and ROI lesions were marked with TRUS, the fusion system integrated both MRI and sonography data. An 18-G automatic biopsy gun, capable of extracting 22-mm specimens, was used to collect prostate biopsy samples. These specimens were promptly sent to a pathologist for frozen section analysis. Patients diagnosed with PCa were scheduled for immediate RP, while those with negative results were scheduled for an additional systematic biopsy. All RARPs were performed using the da Vinci Surgical System (Intuitive Surgical, Inc., Sunnyvale, CA, USA) by a single experienced surgeon who had completed over 500 cases. The patients were positioned in the Trendelenburg position, and the surgeries were conducted using the transperitoneal approach.
RP specimens were evaluated in accordance with the recommendations of the International Society of Urological Pathology (ISUP).
RESULTS
Twelve patients were enrolled in this study. The median age (interquartile range [IQR]) was 73.5 (69.5-75.3) years, body mass index (BMI) was 25.5 (22.7-26.5) kg/m2, PSA was 22.9 (17.0-29.9) ng/mL, Prostate volume (PV) was 35.6 (27.9-55.5) mL. Nine out of the 12 patients displayed MRI findings suggestive of ECE. The median operation, console, and biopsy times were 205 (183.8-220) minutes, 120 (106-133.3) minutes, and 18.5 (15-24.8) minutes, respectively.
All final pathology reports confirmed PCa. According to these reports, 2 patients had ISUP grade 2 disease, 7 had grade 3, 1 had grade 4, and 2 had grade 5 disease. Regarding staging, 4 patients were classified as stage pT2, 3 as stage pT3a, and 5 as stage pT3b. The median number of targeted biopsy cores taken was 2 (2-3). Four cores were obtained from 2 patients, 3 cores from 3 patients, 2 cores from 4 patients, and 1 core from 2 patients. Adenocarcinoma was identified in 2 out of 3 cores in 2 patients, and 1 out of 3 cores in another patient. Additionally, adenocarcinoma was found in every core from 9 patients. The patient characteristics and pathological outcomes are summarized in Table 1. The median time for immediate reporting of the target biopsy frozen section was 20 (19.3-24.5) minutes. PCa was diagnosed using frozen sections in all patients, who then underwent RP without any perioperative complications, conversion to open surgery, blood transfusions. Complications related to transperineal biopsy were not observed. These include perineal site infections or bleeding.
DISCUSSION
Since the advent of mpMRI and the PI-RADS, the use of MRI for PCa evaluation has increased [10]. MRI-US fusion biopsy has been shown to enhance the detection of clinically significant PCa [11].
In a previous study, we found that 97% of patients with a PI-RADS 5 lesion, either showing ECE on MRI or having PSA levels greater than 20 ng/mL, could forego systematic biopsy and immediately diagnose PCa via targeted biopsy with frozen section analysis [7].
This finding does not advocate for omitting systematic biopsies in all cases but suggests that targeted biopsy-only approaches may be adequate for specific patient groups without risking undetected PCa. Traditional systematic biopsy separates the diagnosis and treatment of PCa, leading to additional medical costs and patient discomfort due to treatment delays. Moreover, standalone prostate biopsy presents risks, including urinary retention, hematuria, and even septic shock [12,13], with an increased number of biopsy cores potentially contributing to these complications [13]. Furthermore, a study from another institution indicated some patients were reluctant to undergo a biopsy before prostatectomy [8]. Given these concerns, there have been efforts to perform RP without prior biopsy, following PSMA-PET imaging. However, as noted, this method risks performing RP in patients without cancer [9]. Therefore, we advocate for the use of frozen section analysis before immediate RP in selected patients, based on our inclusion criteria: (1) patients with at least one PI-RADS 5 ROI on mpMRI, and (2) either MRI evidence of ECE with a PSA level greater than 10 ng/mL, or a PSA level exceeding 20 ng/mL. In our study, all 12 patients were confirmed to have adenocarcinoma following frozen section analysis, supporting the suitability of immediate RP after targeted biopsy alone for this patient group. With a median immediate reporting time of 20 minutes for frozen biopsy sections, we minimized the time between diagnosis and treatment, thereby reducing patient anxiety related to this interval. Additionally, patients experienced no complications from the standalone prostate biopsy. The potential savings in healthcare costs from this approach remain a topic for further discussion.
Nevertheless, the simultaneous frozen target biopsy and RP approach outlined in this study has limitations. First, it is important to note that this method is not a standard protocol at our institution and should not be viewed as a routine procedure. We do not claim that every patient meeting the criteria should undergo frozen targeted biopsy and immediate RP; instead, a decision should be made after providing patients with adequate information.
Second, despite our previous study showing a 97% positivity rate for frozen sections [7], there is a concern about false-negative results due to the poorer quality of frozen specimens compared to permanent formalin-fixed specimens. Furthermore, since frozen analysis only confirms the presence or absence of PCa, there is a risk that RP might be performed on patients with clinically insignificant PCa. There are also disagreements regarding the optimal number of cores for targeted biopsy, with many studies recommending approximately 2 to 4 cores [14,15]. However, some suggest that even a single core may be sufficient [16,17]. Additionally, as this method heavily depends on MRI findings, the expertise of experienced radiologists is crucial. It is also important to recognize that this study is limited by its small sample size and retrospective design. Prospective studies with larger cohorts are needed to validate these findings.
CONCLUSIONS
For the patients with a strong suspicion of prostate cancer by MRI finding and high PSA level, the strategy of intraoperative targeted biopsy with frozen section analysis followed by immediate RARP demonstrates the potential for safely omitting systematic biopsy before RP in carefully selected patients without raising ethical concerns. However, our study is limited by its retrospective design and small sample size. Further prospective validation studies with larger cohorts are necessary to confirm the efficacy of this approach.
PDF Links
PubReader
ePub Link
XML Download
Full text via DOI
Download Citation
Print
