From August 2018 to July 2020, 100 participants were enrolled across nine sites (Figure 1). Two patients were excluded as their pre-scan PSA level was outside the eligibility criteria (PSA≥2.0) leaving 98 patients suitable for final analysis. A further one patient was excluded from comparison between diagnostic CTCAP and 18F-DCFPyL PET/CT as he could not undergo CT, leaving 97 patients eligible for analysis in this context.
Baseline characteristics (Table 1a) included a median age of 68.0 years, median pre-scan PSA of 0.32ng/ml, and median time between RP and imaging of 951.5 days. Over half our cohort, 58.9%, had ISUP grade group ≥3 disease. Pelvic nodal sampling/dissection was performed in 32.7% of patients with median nodal count 5.0 (95% CI 4.1-7.9) and 5.1% overall had N1 disease. Histopathological characteristics revealed extraprostatic extension in 68.4%, seminal vesicle invasion in 24.5%, positive surgical margin in 37%, presence of intraductal carcinoma in 31.3% and perineural invasion in 82.6%.
Patterns of 18F-DCFPyL avid disease
Overall, 46.9% (n=46) of our cohort had positive 18F-DCFPyL PET/CT scans and a further 5.1% (n=5) were equivocal. Taking these together, 52% (n=51) demonstrated positive or equivocal disease with 18F-DCFPyL uptake, the patterns of which are described in Table 2 and illustrated in Figure 2.
Local disease recurrence was identified in 28 patients (29.2%), 16 designated as prostate bed and 12 at seminal vesicle bed. Nodal disease was identified in 29 patients (29.6%), and distant bony metastases were seen in 7 (7.1%).
Overall, 71 nodal lesions were identified, with 3 designated as equivocal. Mean SUVmax of nodal lesions was 17.8 and mean size was 5.3mm. The majority of 18F-DCFPyL avid nodes were located along the internal, external and common iliac vessels which accounted for 57.7% (n=41). Presacral and mesorectal nodes accounted for 20.6% and 11% respectively, and no patients had detected para-aortic nodes. Of 29 patients with node positive or equivocal disease, 12 (41%) had a solitary node, 14 (48%) had 2-3 nodes, and 3 had ≥4 nodes detected.
Overall, 11 bony metastases were reported on 18F-DCFPyL PET/CT, with one being equivocal, in a total of 7 patients (7.1%). Location of bony sites of disease included pelvis, femur, ribs, scapula and thoracic spine. No distant metastases were identified in visceral sites.
Regarding exclusive sites of disease, 16 patients (16.3%) had local recurrence only, 17 patients demonstrated nodal disease only (17.3%), and 2 patients (2.0%) had bone oligometastases only. A combination of local recurrence and nodal disease was identified in 8 patients (8.2%), and local recurrence with bony metastases in 1 patient.
Diagnostic CTCAP vs 18F-DCFPyL PET/CT positivity
97 patients were eligible for comparison between diagnostic CTCAP and 18F-DCFPyL PET/CT after one patient was unable to complete the CT component. 18F-DCFPyL PET/CT scans were positive in 46.4% (n=45), compared to 15.5% (n=15) for diagnostic CTCAP (Table 3). This increased to 51.6% (n=50) and 19.6% (n=19) respectively, when including overall equivocal results of each modality.
Of the 80.4% (n=78) with a negative diagnostic CTCAP, 38 of these had a positive or equivocal 18F-DCFPyL PET/CT. Of the 19.6% (n=19) with a positive or equivocal CTCAP, 12 of these had a positive or equivocal 18F-DCFPyL PET/CT. In 4.1% (n=4), diagnostic CTCAP was positive whilst 18F-DCFPyL PET/CT was negative. Disease was identified on CT at the prostate bed in three of these patients, and an external iliac node in the other patient.
When comparing diagnostic CTCAP and 18F-DCFPyL PET/CT for detection of local recurrence only, the latter had higher rates of detection with 26 patients having 18F-DCFPyL avid local disease compared to 9 patients with positive or equivocal disease on CT. In 88 patients with no evidence of local disease on CT, 23 (26%) of these demonstrated positive or equivocal 18F-DCFPyL uptake at either the prostate bed or SV bed on PET/CT.
Comparison of the imaging modalities for detection of nodal disease demonstrated higher rates with 18F-DCFPyL avid nodes in 29 patients compared to 11 patients on CTCAP. In 86 patients with no evidence of nodal disease on CT, 24 (28%) of these demonstrated positive or equivocal 18F-DCFPyL uptake within pelvic nodes. This comparison was similar in distant bony disease, with higher rates of detection on 18F-DCFPyL PET/CT. In 96 patients with no evidence of bony metastases on CT, 7 demonstrated positive or equivocal 18F-DCFPyL uptake in distant sites.
Predictors of 18F-DCFPyL PET/CT positivity
The majority of patients with a positive or equivocal 18F-DCFPyL PET/CT had a pre-scan PSA between 0.2-0.49ng/ml, with a positive detection rate of 48% (37/77) in this PSA band (Table 4). Further analysis of this PSA band showed a positive 18F-DCFPyL PET/CT detection rate of 39.5% (19/48) for PSA 0.2-0.29ng/mL, 62% (15/24) for 0.3-0.39ng/mL, and 60% (3/5) for 0.4-0.49ng/mL.
The majority of our patients had ISUP grade group 2-3 disease, with a positive or equivocal detection rate on 18F-DCFPyL PET/CT of 27.7% and 58.9% respectively (Table 5).
Table 6 demonstrates results of tests of association between potential predictors of 18F-DCFPyL positivity. The significant factors were then used as predictors of 18F-DCFPyL positivity in logistic regression analysis, which demonstrated that ISUP grade group is a highly significant predictor (p=0.003) and pre-scan PSA is a moderately significant predictor (p=0.061).
ROC analysis was performed using the classifier 18F-DCFPyL PET/CT positivity and the markers ISUP grade group, log(PSA) and the probability predictions from the logistic regression denoted as the composite marker. The composite marker was calculated using the equation in Figure 3 to determine the probability of 18F-DCFPyL PET/CT based on these variables. For example, if PSA is 0.3ng/mL and ISUP grade group is 2, the predicted probability of a positive scan is 31.6%, whereas if the PSA is 1.0ng/mL and ISUP grade group 4, the probability is 81.0%. Figure 4 demonstrates the ROC curves showing improved prediction rate using combined ISUP and PSA rather than individually.
Safety of 18F-DCFPyL PET/CT
Within 30 days of 18F-DCFPyL administration, there were 5 adverse events in the original 100 patients (5%). This included chest pain, extravasation of tracer, headache, rash and vomiting. Only the extravasation was considered related to administration of 18F-DCFPyL, and the only Grade ≥3 event was chest pain. All 5 cases resolved without further intervention.