What is the safest type of prostate biopsy?

In conclusion, our study indicated that transperineal prostate biopsy has the same diagnosis accuracy of transrectal prostate biopsy; however, transperineal prostate biopsy is safer and more valuable because it poses a significantly lower risk of infection and rectal bleeding.

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Literature search

Figure 1 details our retrieval and selection and collection process. Briefly, 544 publications were identified after duplicates were removed. Of these, a large portion of the publications was excluded after scanning the headings and abstracts because they were reviews, fundamental research, meeting abstracts, or extraneous to our study. Next, we identified and carefully reviewed 42 potentially relevant publications of which 31 studies were excluded for language restriction, not available for full passage or not meeting our selection criteria (details in Additional file 1: Table S1). No publications were obtained by trailing through the references of the included articles. Hence, a total of seven cohort studies and four RCTs meeting the inclusion criteria were included in this meta-analysis [13, 16,17,18,19,20,21,22,23, 31, 32].

Fig. 1 Flowchart of study assessment and selection Full size image

Study characteristics

We displayed the components of the seven observational studies in Table 1 and four RCTs in Table 2. The study population in the 11 studies was from Italy, China, and Japan. All the included studies were reported between 2002 and 2017. The sample volume fluctuated from 107 [16] to 402 [32]. The total population included in this meta-analysis reached 2569 with 1644 for the TP approach and 1634 for the TR approach (study by Emiliozzi et al., Pepe et al., and Watanabe et al. were performed with a self-control method). More than two potential confounding factors were adjusted in all observational studies. Table 1 Study characters of RCTs comparing TP and TR prostate biopsy Full size table Table 2 Study characters of observational studies comparing TP and TR prostate biopsy Full size table

Data obtained from RCTs

The general RR and its 95% CI showed no significant difference between the TP and TR approaches on diagnosis accuracy (Fig. 2, RR 0.94, 95% CI 0.81–1.10). No significant heterogeneity was detected among these studies with Q = 1.52, I2 = 0%, and P = 0.678. Generally, all RCTs were assessed to have a low risk of bias (Additional file 1: Figure S1). The performance bias was high in all studies because blinding patients with biopsy approach is not possible; however, in this study, performance bias may not affect the accuracy of the results. Fig. 2 Relative risks for RCTs assessing the diagnosis rate of the TP approach vs the TR approach. Notes: diamonds represent study-specific relative risks (RRs) or summary relative risks with 95% confidence intervals (CIs). Horizontal lines represent 95% CIs. Test for heterogeneity among studies: P = 0.678, I2 = 0.0% Full size image

Data obtained from observational studies

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The general RR and its 95% CI showed no significant difference between the TP and TR approaches on diagnosis accuracy (Fig. 3, RR 1.01, 95% CI 0.87–1.18), which is consistent with the results of the RCTs. No significant heterogeneity was detected among the observational studies (Q = 9.42, I2 = 36.3%, and P = 0.151). All included observational studies were assessed to be of high quality (NOS score > 6). Fig. 3 Relative risks for observational studies assessing the diagnosis rate of the TP approach vs the TR approach. Notes: diamonds represent study-specific relative risks (RRs) or summary relative risks with 95% confidence intervals (CIs). Horizontal lines represent 95% CIs. Test for heterogeneity among studies: P = 0.151, I2 = 36.3% Full size image

Comparison of complications of the two approaches

As every RR for each complication was not available, we systematically reviewed all studies comparing the complications of the two approaches. The detailed number of patients with complications is shown in Table 3. In addition, we calculated the RR of each complication using the synthesized data. The TP approach significantly protected the patients from rectal bleeding (RR = 0.02, 95% CI 0.01–0.06) and fever (RR = 0.26, 95% CI 0.14–0.28); however, the TP approach significantly increased patient pain (RR = 1.83, 95% CI 1.27–2.65). No significant difference was found in the acute retention of urine and hematuria between the two approaches. Table 3 Comparison of complications of TP and TR prostate biopsy Full size table

Sensitivity analysis

To confirm the stability of the merged results, a sensitivity analysis of the integrated RRs was conducted. Based on the random effects model, the general RRs were once again calculated through discarding every single study in the meta-analysis. As a result, the RRs (Additional file 1: Tables S2-S3) persist constantly.

Publication bias

For the RCTs, neither Begg’s test (P = 0.31) nor Egger’s test (Fig. 4, P = 0.74) demonstrated a significant publication bias. Similarly, for the observational studies, publication bias was not significant upon Begg’s test (P = 0.37) or Egger’s test (Fig. 5, P = 0.49). Fig. 4 Egger’s publication bias plot for RCTs. Notes: Egger’s regression asymmetry test (P = 0.74). Standardized effect was defined as the odds ratio divided by its standard error. Precision was defined as the inverse of the standard error Full size image Fig. 5 Egger’s publication bias plot for observational studies. Notes: Egger’s regression asymmetry test (P = 0.49). Standardized effect was defined as the odds ratio divided by its standard error. Precision was defined as the inverse of the standard error Full size image

Comparison of MRI/US fusion-guided biopsy with systematic transrectal biopsy

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Emerging evidence has shown that multiparametric magnetic resonance imaging (mpMRI) as an innovative guidance approach for prostate biopsy increases the detection rate of prostate cancer. Hence, we also reviewed RCT studies comparing MRI/US fusion-guided biopsy and traditional systematic transrectal biopsy. This review was not included in our meta-analysis as our aim was to assess the diagnosis accuracy of transperineal and transrectal biopsy. Observational studies have limitations in population selection, comparability, and recall bias; however, RCT studies as the gold standard in clinical trial design could significantly avoid known disadvantages. Here, we identified two RCT studies comparing MRI/US fusion-guided transperineal biopsy with systematic transrectal biopsy. Both the studies were assessed to have a low risk of bias. In the study by Baco et al. [33], a total of 175 biopsy-naive patients with suspicion for PCa were randomized into two groups: the MRI group (n = 86) and the control group (n = 89). In the MRI group, the patients underwent an MRI/US fusion-guided 2-core biopsy followed by a traditional 12-core transrectal biopsy. In the cases with negative MRI findings, only a 12-core RB was performed. For the patients in the control group, a 2-core targeted biopsy for abnormal DRE/TRUS and 12-core traditional transrectal biopsy were conducted. The authors revealed a comparable detection rate between the 2-core MRI/US fusion biopsy and traditional 12-core systematic transrectal biopsy, suggesting that the traditional systematic transrectal biopsy could be replaced by the transrectal 2-core MRI/US fusion biopsy. In the other RCT study by Kasivisvanathan et al. [34], the authors randomized 252 patients in an MRI-targeted group and 248 patients in a standard biopsy group. In the MRI-targeted group, 71 patients did not undergo prostate biopsy because of negative MRI results. The patients in the MRI-targeted group received a 4-core MRI/US fusion biopsy and the patients in the standard biopsy group received a systematic transrectal biopsy. Clinically significant prostate cancer was diagnosed in 38% patients in the MRI-targeted group and 26% patients in the standard biopsy group. The detection rate of the MRI-targeted biopsy is significantly higher than the traditional biopsy.

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