In this study, we used mpMRI and 68Ga-PSMA PET/CT to retrospectively analyze and compare their diagnostic value for determining whether patients had low-, medium-, or high-risk PCa. In the high-risk PCa cohort, the diagnostic performance of 68Ga-PSMA PET/CT was superior to that of mpMRI, which was consistent with prior studies [11, 14, 20, 15]. However, by further comparing the 2 modalities in the low- and intermediate-risk PCa group, we found that the diagnostic performance of mpMRI was superior to that of 68Ga-PSMA PET/CT and that 68Ga-PSMA PET/CT may upregulate the staging of some low- and intermediate-risk PCa individuals. Furthermore, through an exploratory multivariate analysis, we found that some patients who had low- or intermediate-risk PCa ,whose age threshold exceeded 62.5 years, and/or whose serum PSA threshold exceeded 9.4 ng/ml may be more likely had a high uptake of PSMA. These results highlighted the value of mpMRI in the initial examination of low- and intermediate-risk PCa, and the possible conditions in which PCa patients might benefit from undergoing a combination of both 68Ga-PSMA PET/CT and mpMRI. This was particularly the case for patients who had a high suspicion of low- and intermediate-risk PCa, although a negative mpMRI result was determined.
In the last decade, mpMRI has become the leading imaging modality in the primary detection and localization of PCa. Level 1 evidence has recently shown mpMRI to improve clinically significant PCa diagnosis and to decrease unnecessary biopsies and nonsignificant PCa diagnoses [21, 8]. However, mpMRI is limited by both the specificity of its detection and the subjectivity of its diagnosis, with a meta-analysis having showed that the accuracy of mpMRI for detecting clinically significant PCa varied widely between studies (44-87%). PSMA-based imaging modalities such as 68Ga-PSMA PET/CT have developed rapidly and have significantly contributed to disease management. In our high-risk PCa cohort, the diagnostic performance of 68Ga-PSMA PET/CT was superior to that of mpMRI. Furthermore, the missed diagnosis rate of mpMRI for some LN metastases and bone metastases was relatively high, which can lead to an underestimation of clinically significant PCa. Of the PSMA-avid lymph and distant lesions found in this study’s high-risk PCa group, 34 patients (51.5%) had suspicion for pelvic LN metastases, 21 (31.8%) had suspicion for bone metastases on 68Ga-PSMA PET/CT, and 17 individuals had both bone and LN metastases. In addition, studies have shown that 68Ga-PSMA PET/CT can lead to management change in up to 52% of the patients depending on the extent of the disease [22, 11, 14, 23].
68Ga-PSMA PET/CT is being increasingly recognized as a powerful tool for the detection and assessment of metastatic disease in PCa. However, conventional abdominal imaging and bone scans are still recommended for staging those diagnosed with high-risk PCa. 68Ga-PSMA PET/CT remains expensive and is unavailable as a routine tool, especially for low- and intermediate-risk PCa patients. Currently, the available literature on 68Ga-PSMA PET/CT is concentrated on primary staging in high-risk PCa and for PCa patients who demonstrate biochemical recurrence after localized treatment. The results of the current study highlight that 68Ga-PSMA PET/CT is more accurate than is mpMRI for high-risk PCa. Our results also suggest that high-risk PCa patients who have both a high PSA level and GS score may be strong candidates for 68Ga-PSMA PET/CT. This finding is consistent with previous studies . Only 2 (3%) of the 66 high-risk PCa patients in our study returned a negative result through both 68Ga-PSMA PET/CT and mpMRI imaging, as the tumor did not show the PSMA tracer uptake and there were abnormal signals on the mpMRI. The reason for these 2 double-negative results, as well as the underlying biology of high-risk PCa, requires further investigation in the future.
Clinically, the proportion of low- and intermediate-risk PCa patients who were recommended to undergo 68Ga-PSMA PET/CT were relatively small. In our study, the low- and intermediate-risk PCa patients who underwent 68Ga-PSMA PET/CT accounted for only 34.7% (35/101) of the total cohort. Elaborating whole-body staging with 68Ga-PSMA PET/CT might be of limited use in low- and intermediate- risk disease, given the low prevalence of metastases and therefore have limited impact on imaging management. Some studies, which largely included unclassified instances of PCa with a high proportion of high-risk PCa, especially in patients who had 68Ga-PSMA PET/CT imaging, generally found that 68Ga-PSMA PET/CT had a higher detection rate of primary lesions than did mpMRI [24, 19, 23, 25, 13, 15]. There have been very few studies which provide a direct comparison between mpMRI and 68Ga-PSMA PET/CT for the detection and evaluation of low- and intermediate-risk PCa. According to our results, after an analysis of low- and intermediate-risk PCa as a separate subgroup, the final lesion detection rate of mpMRI was better than that of 68Ga-PSMA PET/CT. This is because, as PSA levels decreased, the lesion detection rate of 68Ga-PSMA PET/CT also gradually decreased. This relatively low detection rate could be due to the high occurrence of microlesions (even as small as 1 mm) [26, 27]. Another explanation of the lower diagnostic efficacy of 68Ga-PSMA PET/CT could be the weaker biochemical affinity of the ligand to the PSMA receptor in low- and intermediate-risk PCa [3, 28, 14]. In this case, a high anatomical MRI resolution is considered to be more advantageous.
In our study, mpMRI failed to detect low- and intermediate-risk PCa in 3 of 35 patients. In the low- and intermediate-risk group, 18 patients had both a positive mpMRI and 68Ga-PSMA PET/CT, while only 2 individuals had both a negative mpMRI and 68Ga-PSMA PET/CT. In addition, there were 3 patients who had a negative mpMRI and positive 68Ga-PSMA PET/CT (Table 5). From this we found that it would be helpful to identify the specific population who might benefit from 68Ga-PSMA PET/CT.
To this end, we found that low- and intermediate-risk PCa patients who returned a negative mpMRI would benefit from a combination of both modalities. In this study, 21/35 had a positive 68Ga-PSMA PET/CT result, which indicates that the improvement of combined MRI and PET occurred on lesions with low- and intermediate-risk PCa. Guidelines recommend that for low- and intermediate-risk PCa patients, a biopsy may be more appropriate than using mpMRI alone (this depends on other factors, such as high PSA, family history, and age) [29, 30]. Our study showed that an additional 68Ga-PSMA PET/CT could be helpful for deciding if these low- and intermediate-risk PCa patients should undergo a prostate biopsy or further management. Another key finding was that low- and intermediate-risk PCa patients with a PSA ≥ 9.4 ng/ml and age ≥ 62.5 years were more likely to have a positive 68Ga-PSMA PET/CT result. Based on our study of low- and intermediate-risk PCa, we found patients with both a positive mpMRI and 68Ga-PSMA PET/CT indicated the possible necessity for a prostate biopsy.
We should also note that our study has limitations, including the relatively small number of men who underwent RP and the retrospective nature of the data collection (which had an inherent bias among the reporters). Nonetheless, the final RP specimen remains the most accurate final arbiter to determine presence or absence of PCa on a per-lesion analysis. Moreover, the nuclear medicine physicians of our study were aware that patients had high-risk PCa, which could have increased the risk for confirmation bias. It would have been helpful to have had low- and intermediate-risk PCa patients in this study. However, it is not yet standard of care in our hospital to perform 68Ga-PSMA PET/CT imaging in low-risk patients. Lastly, the evaluation of 68Ga-PSMA PET/CT was subjective and did not include other objective features like semi-quantification, lesion shape, or location, which may alone account for the low specificity of 68Ga-PSMA PET/CT.