Comparison of prostate cancer detection rates and complications between transrectal ultrasound-guided transperineal and transrectal biopsies: a systematic review and meta-analysis

Introduction

Prostate cancer (PCa) is the most frequently diagnosed solid malignancy among men and has the second highest mortality rate after lung cancer in the world (1), posing a serious threat to men’s health. A 2017 report indicated that approximately 10 million men worldwide were diagnosed with PCa, 700,000 of whom had distant metastases (2). In the early stage, most patients with PCa show no obvious clinical symptoms, while others exhibit clinical manifestations such as urinary tract obstruction (3). Remarkably, definitive treatments, such as radical prostatectomy and radiotherapy, often provide a cure in patients with localized disease. Therefore, the early detection of PCa is crucial.

Routine screening for PCa includes serum prostatic-specific antigen (PSA) measurement. If elevated, digital rectal examination (DRE) and imaging should be considered (4,5). PSA is the most commonly used tumor marker for PCa; however, other benign lesions can also cause PSA elevation (6). DRE has a limited value in the diagnosis of PCa due to its low sensitivity (7). Ultrasonography of the prostate may reveal hypoechoic nodules in the peripheral zone, but generally transrectal ultrasound (TRUS) has a low detection rate for PCa (8) and is mainly used to guide prostate biopsy. Multiparametric magnetic resonance imaging can guide biopsy decision-making by increasing the likelihood of detecting clinically significant PCa while lowering detection of insignificant disease (5). Due to the limitations of these tests, the definitive diagnosis of PCa relies on biopsies guided by TRUS (9-11). The cancer detection rate (CDR) increases with the increase in the number of biopsy specimens obtained.

Transrectal (TR) and transperineal (TP) biopsies are the two main approaches for obtaining prostate tissue samples in PCa detection (12,13). In TR biopsy, the needle is guided through the anterior rectal wall using ultrasound transducers with lateral, end-fire, or biplanar capability. Whereas, in TP biopsy, the needle passes through the perineal skin, which requires the guidance of a lateral or biplanar transducer (14). Several clinical trials have compared the effects of TRUS-guided TR and TP biopsies on CDRs and associated complications (14-18). However, the conclusions are inconsistent and even contradictory. Therefore, in this study, we performed a meta-analysis to investigate the impact of TRUS-guided TP and TR biopsies on the CDR and complications associated with the procedure in order to provide evidence-based clinical practice recommendations for the systematic biopsy of the prostate. We present this article in accordance with the MOOSE reporting checklist (available at https://tau.amegroups.com/article/view/10.21037/tau-2025-150/rc) (19).

Methods

Literature retrieval

In September 2024, we searched PubMed, Web of Science, Embase, Cochrane Library, China Wanfang data, and China National Knowledge Infrastructure (CNKI) and collected relevant literature on TP and TR biopsies of the prostate. The search keywords were “prostate cancer”, “prostatic neoplasms”,“prostatic adenocarcinoma”, “transrectal ultrasound”, “TRUS”, “transrectal”, and “transperineal”. The language was limited to English and Chinese. The search was conducted independently by two authors and finally cross-checked. When there was any inconsistency, agreement was reached through discussion.

Eligibility criteria

The inclusion criteria for the literature were as follows: (I) a randomized controlled trial (RCT), case-control study, or cohort study design; (II) a population of patients undergoing systematic biopsy of the prostate; (III) a test group that underwent TRUS-guided TP biopsy and a control group that underwent TRUS-guided TR biopsy; (IV) CDR as the outcome; and (V) complications of rectal bleeding, urinary retention, gross hematuria, fever, and post-biopsy pain evaluated.

The exclusion criteria for the literature were as follows: (I) abstracts, reviews, and preclinical studies; (II) insufficient data; and (III) biopsy not guided by TRUS.

Literature bias risk assessment and data extraction

Two authors independently assessed the risk of bias in the literature and extracted the data. The methodological quality of RCTs was assessed using the Cochrane Risk Assessment Scale (20) which consists of the following seven items: random sequence generation, allocation hiding, participant and investigator blinding method, blind outcome assessment, integrity of the resulting data, selective reporting of research findings, and other risks of bias. The trial quality was rated as low risk, high risk, or unclear. The Newcastle-Ottawa scale (NOS), consisting of eight questions, totaling nine points, with ≥6 points indicative of high-quality research, was applied to determine the quality of cohort or case-control studies (21).

Information extracted from the literature included first author, year, country, age and number of patients, study design, serum PSA level, CDR, and post-biopsy complications.

Statistical analysis

Statistical data were analyzed using Stata 15.0 software (StataCorp., San Diego, CA, USA). The relative risk (RR) and 95% confidence interval (CI) were used to assess differences in CDR and complications between the groups. The Chi-squared test and I² statistic were used to verify the heterogeneity hypothesis. The fixed-effects model (Mantel-Haenszel method) and random-effects model (DerSimonian-Laird method) were applied to combine the data. If high heterogeneity was detected (I²≥50% or P≤0.05), a random-effects model was used; otherwise, a fixed-effects model was used. A funnel plot of CDR was created, and the P value of the Egger test was calculated to evaluate whether publication bias was present. The stability of the results was evaluated via sensitivity tests. P<0.05 was considered statistically significant.

Results

Literature search results and quality assessment

Employing our screening criteria, a total of 20 articles (14-18,22-36) were finally included in this meta-analysis (Figure 1), comprised of seven RCTs, four prospective cohort studies (PCSs), and nine retrospective cohort studies (RCSs). There were 2,979 patients with PCa in the TP group and 2,610 patients in the TR group. The basic characteristics of the included studies are shown in Table 1. The results of RCT bias risk assessment are illustrated in Figure 2A,2B. None of the NOS scores of the PCSs and RCSs were lower than 6, indicating high quality.

Figure 1 Flowchart of article inclusion. CNKI, China National Knowledge Infrastructure; TRUS, transrectal ultrasound.

Figure 2 Assessment of bias risk of the included RCTs. (A) Graph of bias risk. (B) Summary risk of bias. RCT, randomized controlled trial.

Principal results of the meta-analysis

Heterogeneity analysis

The heterogeneity was not high in the combined analysis of CDR (I²=24.0%; P=0.16; Figure 3), rectal bleeding (I²=16.2%; P=0.30; Figure 4A), urinary retention (I²=0.0%; P=0.78; Figure 4B), fever (I²=0.0%; P=0.90; Figure 4C), pain (I²=22.9%; P=0.27; Figure 5A), and hematuria (I²=43.0%; P=0.06; Figure 5B), and the fixed-effects model was therefore used for further analysis.

Figure 3 Forest plot of the CDR in TRUS-guided TP and TR prostate biopsies. CDR, cancer detection rate; CI, confidence interval; MH, Mantel-Haenszel; RR, relative risk; TP, transperineal; TR, transrectal; TRUS, transrectal ultrasound.

Figure 4 Forest plots of rectal bleeding (A), urinary retention (B), and fever (C) in TRUS-guided TP and TR prostate biopsies. CI, confidence interval; MH, Mantel-Haenszel; RR, relative risk; TP, transperineal; TR, transrectal; TRUS, transrectal ultrasound.

Figure 5 Forest plots of pain (A) and hematuria (B) in TRUS-guided TP and TR prostate biopsies. CI, confidence interval; MH, Mantel-Haenszel; RR, relative risk; TP, transperineal; TR, transrectal; TRUS, transrectal ultrasound.

Comparison of CDR

The detection rate of PCa was reported in all 20 studies (Figure 3). There was no statistically significant difference in CDR between the TP and TR biopsy groups (RR =0.98; 95% CI: 0.92–1.04; P=0.46).

Comparison of complications

Rectal bleeding (Figure 4A), urinary retention (Figure 4B), and fever (Figure 4C) were analyzed in 9, 12, and 12 studies, respectively. The fixed-effects model indicated that compared with the TR biopsy approach, the TP approach involved a lower risk of rectal bleeding (RR =0.05; 95% CI: 0.02–0.13; P<0.001), urinary retention (RR =0.70; 95% CI: 0.49–0.99; P=0.046), and fever (RR =0.24; 95% CI: 0.15–0.39; P<0.001).

Pain (Figure 5A) and hematuria (Figure 5B) were analyzed in 4 and 11 studies, respectively. The risk of pain was higher in the TP approach group than in the TR approach group (RR =2.04; 95% CI: 1.47–2.82; P<0.001). No significant difference in hematuria was observed between the two groups (RR =1.05; 95% CI: 0.91–1.22; P=0.52).

Detection of publication bias

The funnel plot of CDR was symmetric (Figure 6), and the P value of the Egger test was greater than 0.05 (P=0.88), indicating no publication bias in the meta-analysis.

Figure 6 Funnel plot of the detection rate of PCa. PCa, prostate cancer; RR, relative risk.

Sensitivity analysis

Figure S1 shows the results of sensitivity analysis. A significant difference was observed in the analysis of urinary retention when seven studies (17,18,23,25,27,33,35) were excluded. However, no statistically significant difference occurred in CDR, rectal bleeding, hematuria, fever, or pain when any study was omitted (Figure S1A-S1F). Therefore, in general, the overall findings of this meta-analysis were considered to be robust.

Discussion

To clarify the effects of TRUS-guided TP and TR biopsies of the prostate on the detection rate of PCa and associated complications, we conducted this meta-analysis. At present, the commonly used puncture biopsy routes are TP and TR (37). TP biopsy was the first to appear, but the procedure is relatively complicated and is substantially associated with pain. In 1989, Hodge et al. (38) first adopted the standard six-core biopsy method via TR biopsy. Due to the advantages of a more simple procedure that is well-tolerated by patients, TR biopsy has gradually become a widely used method of prostate biopsy in clinical practice (39).

After the application of strict inclusion and exclusion criteria, a total of 20 articles were included in this meta-analysis. The results suggested that CDR was essentially comparable between the TP and TR methods, without significant difference. The meta-analysis of complications showed that the TP biopsy approach was associated with a lower risk of rectal bleeding, urinary retention, and fever compared to the TR biopsy approach, whereas TP biopsy was associated with a higher risk of post-procedure pain. No significant difference was observed in the risk of hematuria between the two groups. The main complications of prostate biopsy are infection, hematuria, bloody stool, and lower urinary tract symptoms, among others (40,41). Although most of the complications related to needle biopsy are minor, there is the possibility of sepsis, severe bleeding, and even death in rare cases (40). The main manifestations of infection are fever and bacteremia. Compared with the TP route, which does not pass through the rectum, the TR route has been suggested to cause a higher risk of infection (41), although not all investigations have supported this (42).

The funnel plot of CDR was symmetric, and the P value of the Egger test was greater than 0.05. These findings suggest no significant publication bias in this meta-analysis. Consistent with those of our study, a 2019 meta-analysis conducted by Xiang et al. that included 11 articles (43) found that TR and TP biopsies had similar diagnostic accuracy for PCa, with the TP method being associated with a lower risk of rectal bleeding and fever.

It is important to note that TR and TP biopsies had a similar CDR and that the TP method involved lower risks of rectal bleeding, urinary retention, and fever. Nevertheless, the TR approach remains more popular worldwide (44,45). This is because compared to the TP method, TR prostate biopsy is less time-consuming, relatively simple to perform, and does not typically require substantial anesthesia. The American Urological Association and Society of Urologic Oncologists recommend the use of either TR or TP biopsy (46). However, in terms of the CDR, it has been found in clinical practice that prostate apical tumors can escape through the TR route (47), resulting in the missed diagnosis of some apical tumors. TP biopsy thus involves a higher CDR in the prostatic apex than does TR biopsy (48,49). While adjusting the angle of TR biopsies for better apical sampling is possible, TP biopsy can be considered a useful alternative (46).

The meta-analysis involved several limitations that should be discussed. First, the included studies and sample sizes in some of the studies were relatively small, which might reduce the robustness of the conclusions. Second, the included studies were only from four countries, China, Japan, Italy, and Kuwait, which might reduce the generalizability of the findings to populations in other countries/regions. Third, only published studies in the English and Chinese languages were eligible in this meta-analysis, and those published in other languages, as well as unpublished studies, were omitted, which might have introduced a degree of publication bias.

Conclusions

Our meta-analysis indicates that TRUS-guided TP and TR biopsies have similar detection rates for PCa. Nonetheless, compared with the TR approach, TP biopsy was found to be associated with a lower risk of rectal bleeding, urinary retention, and fever but a higher risk of pain. Our findings of this meta-analysis should be verified by high-quality clinical trials and/or meta-analysis in the future.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the MOOSE reporting checklist. Available at https://tau.amegroups.com/article/view/10.21037/tau-2025-150/rc

Peer Review File: Available at https://tau.amegroups.com/article/view/10.21037/tau-2025-150/prf

Funding: This work was supported by the Medical Youth Innovation Research Project of Sichuan Province (No. Q22051), the Research Project of Sichuan Medical Hygiene and Health Promotion Association (No. KY2022QN0139), and the Liangshan Science and Technology Program (No. 22ZDYF0076).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-2025-150/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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(English Language Editor: J. Gray)