This retrospective study confirmed the value of PSMA PET/CT and PET/MR in prostate disease diagnosing and staging. In this study, whole-body PET/CT (PET/MR) and delayed pelvic PET/MR accurately diagnosed and staged all of the patients. When the SUVmax from a conventional scan was used as the only criterion, sensitivity and specificity reached 85.4% and 100%, respectively. Our optimal cutoff value is 5.25, which is close to literature reports of 5.94 23. However, PSMA uptake in the prostate is not significantly elevated in some patients; fortunately, nodal or bone metastases were observed on PET/CT or PET/MR imaging (Fig. 1), so combination of SUVmax with nodal or bone metastases further improved the sensitivity to 95.1%. There are still a few cases with neither bone, nodal metastasis nor positive prostatic PSMA uptake. In this situation, mpMRI may improve detection (Fig. 2B). Combination use of nodal metastases, bone metastases, SUVmax of primary lesions, and MR PIRAS score from whole-body PET/CT and PET/MR made the sensitivity and specificity reach 100% for prostate diseases diagnosis in this study.
Because it has been proven that the FDG SUV measured by PET/CT and PET/MR has clinically acceptable repeatability24, 25, we ignored the influence of SUV from different instrument in conventional scans for statistics. Our results showed that SUVmax values from delayed scans were significantly higher than those from conventional scans in patients with prostate cancer, indicating tracer accumulation increased overtime. Park, S. Y. reported similar results26. Our results revealed SUVmax values from conventional scanning at about 1 h post injection and those from delayed scan at about 3 h are linearly correlated, which is consistent with the results reported by Ringheim, et al27. However, they also found a mean 20% difference between PET/CT than on PET/MR (higher on PET/CT), which cannot be used interchangeably in followup27. Therefore, a more detailed study is needed to evaluate the quantitative accuracy of PET/MR and the factors governing it.
As for the optimal timing for prostate PSMA imaging, ROC analysis shows that SUVmax1 from conventional imaging has relatively good diagnostic performance compared with delayed imaging, so we believe that conventional imaging at about 1 h is sufficient for most patients. Delayed imaging takes up time, increases patient anxiety, and may make patients with urinary retention uncomfortable, so it is not necessary on a routine basis. However, for those patients who are difficult to diagnose and whose pelvic images were affected by urine in the bladder, it is necessary to perform delayed imaging after drinking plenty of water and urinating. Some studies have analyzed multiple time-point 68Ga-PSMA imaging, including early dynamic images, static scans after 60 min (conventional scan) and 180 min (delayed scan) post-injection. Kabasakal et al. 28 and Uprimny et al. 29 demonstrated that early PET/CT pelvic imaging has better lesion detectability of lesions in the pelvis than in late images because of the low incidence of halo artifact in the bladder. Another study showed that PET/MR early acquisition has high lesion contrast with very good agreement for lesion detectability with same-day whole-body PET/CT. However, 95% LOAs in SUVpeak and MTV are far beyond the clinically acceptable range. Therefore, they suggested whole-body PET/CT and early PET/MR should not be used interchangeably 19. Some studies compared conventional and delayed scans, and reported that detection rates were the same between 60 and 180 min, although improved contrast and an additional cancer focus was found, they concluded that delayed imaging has limited impact 26, 30. However, Afshar-Oromieh et al. 31 reported different results: compared with 1 h after injection, 3-h images revealed higher detection rates and more lesions, but these PET-positive lesions were not confirmed by histopathology.
PSA has a certain value for the identification of benign and malignant prostate lesions3. This study showed that the difference of fPSA/tPSA between benign and malignant groups is not statistically significant, while the differences of tPSA and fPSA between the two groups are statistically significant, but there are false positive and false negative results and the sensitivity and specificity are not as good as PSMA PET imaging. One study confirmed that SUVmax correlated significantly with PSA level26. However, our results detected no correlation between tPSA, fPSA and SUVmax, while fPSA/tPSA was negatively correlated with SUVmax. Incomplete data maybe one reason and further study is needed.
Gleason score is a commonly used grading method for prostate cancer. However, we could not find any correlation between SUVmax of primary tumor and Gleason scores. The same results were also reported in two studies, due to inherent bias of the limited range of Gleason scores 23, 32. Our results also showed lymph node and distant metastases presented in patients with low Gleason scores, so Gleason score cannot reflect clinical stage, the possible reason may due to underestimate of the actual Gleason score from biopsy in some patients. These results suggest that imaging techniques have better performance in the detection of prostate cancer than screening techniques such as PSA, DRE, and TRUS-guided biopsy.
Despite many studies reporting the advantages of PET/MR 26, 33–35, its limitations include expense, a relatively long whole-body scanning time, low visibility of lung lesions, and challenges in patients with claustrophobia and metal implants. For patients in advanced stages of disease, PET/CT is enough because these patients have nodal and/or distant metastases which can be easily diagnosed by PET/CT only, and PET/CT is better for lung lesion detection, and more time-saving and economic than PET/MR. However, to accurately stage those patients without obvious lymph node or bone involvement, to differentiate BPH or prostatitis from early stage or PSMA-negative prostate cancer, pelvic PET/MR is required mainly because of the high soft tissue resolution of MR20. PI-RADS 3 lesions are difficult to diagnose by MR only; PET/MR improves the detection of these patients through PET36. Therefore, whole-body PET/CT with or without pelvic PET/MR would be a sufficient, time-saving method for initial diagnosis and accurate staging of prostate cancer, rational use of pelvic PET/MR for proper patients is important. In centers with both PET/CT and PET/MR, we recommend that all patients undergo PET/CT scanning first, and if lymph node and/or bone metastases are found, the patient can be diagnosed as advanced prostate cancer and PET/MR is not necessary. Otherwise, according to whether the image quality and prostatic lesion detectability were affected by activity of 68Ga-PSMA from urine in bladder, pelvic PET/MR should be performed subsequently or at about 3 h post injection to further evaluate the prostate, surrounding tissue involvement, and small lymph nodes, if the patient has no contraindications. Undoubtedly, PET/MR provides superior diagnostic performance in local prostate cancer recurrence, especially biochemical failure, compared with 68 Ga-PSMA-617 PET/CT37–39.
There are some limitations to the present study. First, the number of cases is relatively limited. Second, due to it being a retrospective study, some patients did not have a histopathology confirmation and Gleason score, they were diagnosed through comprehensive clinical evaluation and followup after treatment. Third, some data are not suitable for statistical analysis, such as the results of tPSA > 100 ng/L, fPSA > 30 ng/L in some patients. Fourth, the high proportion of advanced prostate cancer in this study may have affected the final results. Therefore, more patients with early prostate cancer should be included for prospective studies to further verify our conclusions.