The early detection of BCR in prostate cancer is essential to provide timely and effective treatment. A wide range of radiotracers could be used to detect prostate cancer. However, there is still no consensus on the optimal radiotracer to detect BCR in prostate cancer patients (53, 54). As a result, a high-quality summary of the available evidence is necessary to identify the optimal diagnostic strategy. 18F-DCFPyL and 18F-PSMA-1007 are the two most advanced radiotracers available to clinically screen prostate cancer. However, it is still debatable which radiotracer has the highest overall detection rate according to the PSA level and recurrence location.
PSMA, a transmembrane protein, is highly overexpressed in nearly all prostate tumors (100–1,000 fold) (55). Currently, the most widely used PSMA-targeted radiopharmaceuticals are 68Ga-PSMA agents (56). However, compared to 68Ga radiolabeling for PET imaging, 18F-labelled PSMA agents may provide a few advantages, including a longer half-life (110 minutes versus. 68 minutes), a shorter positron range, and higher positron yield, and therefore provide a higher resolution on PET images. In addition, the production of the 18F cyclotron has been widely implemented, and its affordability and convenience make it more available worldwide (57, 58). However, 18F-PSMA-1007 provides better tumor-to-background ratios, thus facilitating the detection of small prostate cancer lesions (42, 50). On the other hand, 18F-DCFPyL, a novel second-generation agent, has a higher affinity to the PSMA surface antigen located on prostate cancer cells. Therefore, it can detect early prostate cancer recurrence even at very low PSA levels (18, 59).
In the previous studies, direct comparisons were conducted between 68Ga-PSMA-11 and 18F-DCFPyL(16), as well as 68Ga-PSMA-11 and 18F-PSMA-1007(48). In addition, two meta-analyses that focused on 18F-DCFPyL and 18F-PSMA-1007 were performed before we conducted our study (60, 61). However, few studies compared the efficacy of 18F-DCFPyL and 18F-PSMA-1007 in detecting BCR in prostate cancer. Therefore, we performed the first meta-analysis that summarized all the available publications to compare the detection rates between the 2 radiotracers according to the PSA levels and recurrence location.
In 2021, a network meta-analysis study showed that 18F-PSMA-1007 had higher surface under the cumulative ranking curve (SUCRA) values and overall detection rates in BCR prostate cancer than 68Ga-PSMA-11 and 18F-DCFPyL (62). However, as the authors stated, the results were based on the premise that only one study was available for 18F-PSMA-1007 (involving 40 patients), so the results must be interpreted cautiously. By extracting the data from 30 studies with 3,156 patients, a more robust result from our meta-analysis was obtained. Our findings indicate no significant difference in the detection rate for BCR prostate cancer between 18F-PSMA-1007 and 18F-DCFPyL (P = 0.35) except for PSA levels of 0.5-2.0 ng/ml, whereby 18F-PSMA-1007 had a significantly higher detection rate. The recurrent location had no impact on the detection rate. This result may provide more specific evidence for doctors to choose the most appropriate radiotracer to detect BCR in prostate cancer. Although the results of this study suggest a higher detection rate of 18F-PSMA-1007 at the PSA level of 0.5-2.0 ng/ml, this imaging agent still has some limitations, such as its non-specific bone uptake, which requires experience how to deal with. Furthermore, this study's results should be interpreted with attention to other available evidence: 18F-DCFPyL is currently FDA approved with a successful outcome of its pivotal trial. And that the registration trial of 18F-PSMA-1007 is still recruiting its final patients (NCT04742361), more evidence is still needed to obtain the efficacy of 18F-PSMA-1007.
Our study has some limitations that have to be acknowledged. The heterogeneity of the pooled overall detection rate was very high (I2 was 90% for 18F-DCFPyL PET and 83% for 18F-PSMA-1007 PET). To overcome this limitation, we performed additional statistical tests, including subgroup analysis, meta-regression analysis, and sensitivity analysis. The subgroup analysis and meta-regression analysis revealed the data analysis method (patient-based versus lesion-based) as a possible cause of heterogeneity for 18F-DCFPyL PET, while the study design (retrospective versus. prospective) was identified as a potential cause of heterogeneity for 18F-PSMA-1007 PET. However, the sensitivity analysis did not reveal any studies contributing to heterogeneity, confirming the stability of the results. Furthermore, in clinical practice, it is assumed that all BCR prostate cancer patients with a positive PSMA PET are always true positive. Therefore, histopathological confirmation is generally not required to select the systemic therapy, and hence most studies did not perform any further histopathological testing (63, 64). Nevertheless, it is important to note that patients with solitary lesions with high PSMA uptake not specific to the prostate may produce a false-positive test result, making the diagnosis questionable (65, 66). In view of this, we could not pool the sensitivity and specificity of each radiotracer, but instead, we pooled the detection rate. More prospective studies with histopathology as the gold standard are therefore recommended.