Background
Prostate cancer (PCa) is the most common cancer in men and has the second highest mortality in the USA [
1]. In 2018, approximately 164,690 PCa cases were identified, accounting for almost one in five new cancer diagnoses [
1]. Although PCa is common worldwide, the detection method and diagnostic technology has remained controversial. Generally, the following two significant problems about PCa diagnosis must be settled urgently: (a) prostate-specific antigen (PSA) has been widely adopted for screening PCa; however, the conventional threshold for biopsy (4.0 ng/ml) has been associated with a positive predictive value of approximately 20–30% [
2,
3]. Thus, a great number of patients underwent an unnecessary prostate biopsy. Are there better biomarkers to help physicians make biopsy decisions? (b) In 1989, Hodge et al. first reported the systematic sextant prostate biopsy to detect PCa by transrectal ultrasonography (TRUS) guidance [
4]. Since then, TR systematic prostate biopsy has been the most valuable technology for diagnosing PCa [
5]. Conventional prostate biopsy does have some limitations including severe complications and high rate of false negatives. Therefore, prostate biopsy strategies including guidance technology, biopsy approaches, and number of cores have emerged to improve the diagnosis rate of PCa [
6‐
11]. An urgent need to identify the most effective and safe way to diagnose PCa still remains.
There are the two principle approaches for the diagnosis of PCa: the transperineal (TP) biopsy and the transrectal (TR) biopsy. The systematic TR prostate biopsy, which is the gold standard for the detection of PCa, has been conducted for decades worldwide. This method, however, reportedly underestimates PCa incidence with a false negative rate up to 49% [
12]. Additionally, TR prostate biopsy has been reported to cause severe complications such as rectal bleeding, fever, sepsis, hematuria, and acute urinary retention [
13‐
15]. Due to the high false negative and complication rates of the systematic TR prostate biopsy, the TP approach was introduced to improve the detection rate and safety of prostate biopsy. Though a number of studies were carried out to compare the detection rate and complications of the TP and TR prostate biopsy approaches, the results were controversial regarding the detection rate of the two approaches [
16‐
19]. This controversy was mainly on account of the shortage of sample size and insufficient study design. For instance, the study by Tewes et al. reported cancer detection rates of 39% for TR and 75% for TP [
10]; however, the study included only 154 patients and the retrospective study design led to a relatively low comparability of the two cohorts. Therefore, the conclusion of the study was not convincing. Without the limitations of observational studies, randomized controlled trials (RCTs) represent the gold standard methodology for clinical studies but the results of several RCTs were also inconsistent [
20‐
23].
Meta-analysis could merge the evidence provided by observational studies and RCTs. To this end, we could not only attain the most extensive study population but also minimize the impact of methodological heterogeneity of each study and eliminate low-quality studies [
24]. A meta-analysis that offers a higher level of evidence is needed to draw a reliable conclusion about the two biopsy approaches. Previous meta-analyses simply merged observational studies and RCTs together, which brought methodological heterogeneity to the analyses because the study designs and quality assessment methods differed [
8]. Aiming to achieve a more precise and convincing conclusion about the detection rates and complications of TP and TR approaches, we separately synthesized observation studies and RCTs after a strict study quality assessment. Additionally, we systematically reviewed all eligible studies to compare the complications of the two biopsy methods.
Discussion
This meta-analysis of seven observational studies and four RCTs indicated that the transperineal prostate biopsy and the transrectal prostate biopsy were similar in diagnosis efficiency. A quantified
Q test and
I2 test were performed to appraise the intensity of heterogeneity between the studies and showed no significant heterogeneity. We calculated the synthesized RR again using the fixed effect model and the results remained the same (RR = 1.02, 95% CI 0.92–1.14 for observational studies and RR = 0.95, 95% CI 0.81–1.10 for RCTs). The heterogeneity of our study was not significant. Our results remained consistent upon sensitivity analysis, indicating that our results are stable and reliable. Additionally, no evidence of significant publication bias was detected with either Begg’s test or Egger’s test. These results vastly improved the reliability and certainty of our work. Our results were consistent with previous studies [
13,
16‐
23,
31,
32].
Apart from the detection efficiency of prostate biopsy, complications also play an important role in evaluating the safety and value of the biopsy method. Our study revealed that the TP approach significantly decreased the risk of complications including rectal bleeding and fever, while the TR approach significantly protected patients from pain. The two approaches had no significant difference in acute retention of urine and hematuria. Generally, rectal bleeding and hematuria are self-limited complications and patients would obtain relief within several days; however, bleeding can be severe, especially in patients taking anticoagulation drugs such as aspirin. For these patients, anticoagulation drugs should be withdrawn for at least 1 week prior to undergoing prostate biopsy to avoid severe bleeding events. Infections or fever are also common after prostate biopsy. Though enemas are conducted before the transrectal prostate biopsy, the TR approach still had a significantly higher risk of infection than the TP approach. For patients who are prone to infection including those with diabetes, prostatitis, and urinary catheterization, the transperineal prostate biopsy was recommended to avoid sepsis and severe fever after the procedure. Additionally, transperineal prostate biopsy was more comfortable prior to the biopsy because the enema was unnecessary. Most patients would undertake pain after prostate biopsy. Though our study showed that patients that underwent transperineal prostate biopsy were more likely have pain, it is often diminished within several days [
31]. Analgesia drugs could be used in moderation for relieving patients’ pain. On the other hand, the TP approach was confirmed to be superior in detecting tumors in the transitional zone and apex of the prostate [
16,
22,
23].
Our study evaluating the diagnosis accuracy of the two approaches was more credible because (a) a clear and powerful approach was taken to search the online database to obtain all potentially relevant publications and obedience to PRISMA guidelines and (b) the most comprehensive studies up to date were included in this study. We utilized a strict inclusion criteria constraint in which only RCTs with a low risk of bias and high-quality cohort studies (defined as NOS score > 6) were included. The RCT by Udeh et al. was excluded because 25% of patients were lost follow-up, indicating a high risk of bias [
27]. (c) Unlike previous meta-analyses, we separately synthesized observational studies and RCTs because they have different quality assessment methods and simply pooling these results may reduce the reliability of the meta-analysis [
8].
At the same time, some limitations should be mentioned. First, only four RCTs, which represented the gold standard methodology of clinical trials, were included in our study. For cohort studies, the selection and comparability problems could not be avoided. We could not solve the potential confounding factors such as free PSA, benign prostate hyperplasia, or other unreported factors in the included cohort studies. Second, though no significant publication bias could be detected, we could not rule out the possibility that our conclusions may be affected by potential publication bias mainly because of the language limitation and the screening approach that only published studies could be included in our study.
MRI/US fusion biopsy as a novelty for prostate biopsy could significantly reduce the biopsy cores. In light of the RCT by Baco et al., the detection efficiency of 2-core MRI/US fusion biopsy was similar with systematic transrectal biopsy [
33]; however, the MRI group in Baco’s trial included patients with negative MRI results that underwent only systematic transrectal biopsy. These patients could reduce the detection rate of MRI/US fusion biopsy. In the other RCT by Kasivisvanathan et al. [
34], the authors excluded patients with negative MRI results and detected a significantly higher detection rate upon MRI/US fusion biopsy compared to traditional transrectal biopsy. With these findings, we may conclude that along with improving the biopsy accuracy, MRI might also free patients from an unnecessary prostate biopsy [
33‐
36]. This result was in accordance with our previous review for observational studies in this field [
37].
Conclusion
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. Despite the increased risk of pain after TP biopsy, we recommend that doctors should perform transperineal prostate biopsy if possible. An MRI should be conducted before a biopsy to avoid an unnecessary prostate biopsy. To the best of our knowledge, a 2–4-core MRI/US fusion-targeted transperineal biopsy may be the best method for prostate biopsy. More studies should be conducted to confirm findings and discover a more effective diagnosis method for prostate cancer.
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