Based on the currently published research, our meta-analysis fills the gap of 68Ga-PSMA PET/CT in the diagnosis of middle/high-risk prostate cancer lymph node staging to a certain extent. We found that the indicators and results of 68Ga-PSMA PET/CT show a satisfactory diagnostic efficacy.
In previous treatments, LN staging of prostate cancer patients can only be determined by performing PLND according to the situation during the operation. However, this method is not always feasible . Clinically, the use of PLND is not always feasible, being restricted for the following reasons: not every patient will receive PLND, limited anatomical locations performed, and consideration regarding complications[28-30], resulting in suboptimal lymph node staging. 68Ga-PSMA PET/CT is a more accurate method to determine the LN stage of PCa patients before surgery, which can be incorporated into clinical practice. The common lymph node metastasis sites for prostate cancer are obturator lymph node, internal iliac lymph node, external iliac lymph node, common iliac lymph node, presacral lymph node, abdominal aortic lymph node and mediastinum, supraclavicular lymph node. Studies have shown that the most common lymph node metastasis sites for prostate cancer are external iliac lymph nodes and obturator lymph nodes, with the median percentages being 12.2% and 11.6%, respectively. Based on the current evidence, the diagnostic performance of auxiliary imaging and nomograms tool for prostate cancer lymph node metastasis still has limitations, especially for lymph nodes <5mm. Preoperative assessment of the degree of lymph node metastasis can guide the selection of surgical procedures, which can further assist the management of patients after radical prostatectomy[33-35]. Therefore, it is particularly important to find a non-invasive and better diagnostic method.
Our meta-analysis included 10 studies from different countries and regions, involving a total of 701 patients. The pooled specificity of 0.95 (95% CI: 0.87-0.98) for 68Ga-PSMA PET/CT. But pooled sensitivity was recorded as 0.84 (95% CI: 0.55-0.95), which is not enough to convince us to give up the remaining 20% of the patient. The Youden index was 0.79. AUC was 0.97 (95% CI: 0.95-0.98), which was in line with our initial predictions. Through these comprehensive indicators, we can think that 68Ga-PSMA PET/CT has better diagnostic efficacy in preoperative LN staging in patients with prostate cancer. In the past few decades, CT and MRI have been used to determine the LN staging before radical prostatectomy, but their accuracy rate is still low compared to the gold standard. Hovels et al. Performed a meta-analysis of 24 studies to assess CT/MRI for preoperative evaluation of LN staging. In his research, for CT, pooled sensitivity and specificity was 0.42 (95% CI: 0.26-0.56) and 0.82 (95% CI: 0.8-0.83) respectively. For MRI, pooled sensitivity and specificity was 0.39 (95% CI: 0.22-0.56) and 0.82 (95% CI: 0.79-0.83). From this point of view, the performance of CT and MRI in judging LN staging is not satisfactory. If clinicians rely on CT or MRI, they will easily make the wrong decision on the patient’s condition. In our analysis, we could see that two studies have lower sensitivity, 0.38(95%: 0.28-0.48) and 0.33 (95% CI: 0.24-0.43) respectively[13, 25]. The reason for this analysis was that, due to the technical level of the test, the sample size, and bias between the samples, it might have lead to different final results. The specificity value provided in one study is significantly lower. We thought that the main reason is that the patients included in Herlemann’s study received different PLNDs. Among them, 20 received primary PLND and 14 received secondary PLND, which may be the main reason for the lower specificity. Multi-parameter magnetic resonance (mpMR) also plays a large role in the preoperative evaluation of prostate cancer, especially in judging extraprostatic extension (EPE) of the tumor, invasion of the seminal vesicle (SVI). In a retrospective study by Van Leeuwen at al. They also compared the diagnostic accuracy of mpMR and 68Ga-PSMA PET/CT for LN metastasis in a patient with intermediate high-risk PCa. The sensitivity was 14% and 53%, respectively, and the specificity was 99% and 88%, respectively. All of these indicated that 68Ga-PSMA PET / CT has better diagnostic efficacy and was expected to be popularized and used in clinical.
The higher the value of DOR, the better the diagnostic value of this diagnostic method. In our study, The DOR value was 100 (95% CI: 18-545), indicating that the overall accuracy was high. Pooled PLR and NLR value was 17.19 (95% CI: 6.27-47.17) and 0.17 (95% CI: 0.05-0.56), respectively. This can be understood as the probability of 68Ga-PSMA PET/CT correctly judging LN metastasis is 17 times that of misjudging, and the probability of correctly judging LN non-metastasis is 0.17 times that of misjudging. At the same time, we also noticed that the publication bias shown by Deek’s funnel plot (Fig.5) has a P-value of 0.02. It is understandable that most of the articles we included were retrospective trials, which led to the results. In addition, meta regression and subgroup analysis showed that there is no statistical difference between the above-mentioned influencing factors for the obtained sensitivity and specificity values, excluding the influence of other factors on the results. From the data results, it is worth trying to use 68Ga-PSMA PET / CT to diagnose LN staging in patients with PCa.
We perform this meta-analysis strictly according to PRISMA checklist. However, there are still some limitations in our meta-analysis. First, most of the studies we included were single-center retrospective studies, and the existence of selection bias may affect our judgment. Second, the sample populations included in these articles are only Asia, Europe, and Australia, so population bias is unavoidable. Third, the sample size is too small. The current research is not registered, and there may be small deviations, but we still strictly follow the steps of systematic reviews. Due to the clinical application of 68Ga-PSMA PET/CT in the future, there is not a sufficiently large sample size to be included in our meta-analysis. Compared with PLND, although 68Ga-PSMA PET/CT has only moderate sensitivity and better specificity, it can perform relatively accurate LN staging of detected PCa patients. At this point, 68Ga-PSMA PET/CT is due to any other imaging examinations, but due to many limitations, our conclusions still require a larger sample size, multi-center prospective randomized controlled trial to verify.