A total of 194 patients were included in the final analysis (Table 1). The median age at the time of PET/CT was 70 years (IQR 63-75). The median PSA level prior to the PET/CT was 10 ng/mL (IQR 6.5 – 18). Using the EAU risk stratification system, 71 (36.6%) patients were classified as intermediate-risk (25.8% of patients with PSA 10-20 ng/mL or 48.2% of patients with ISUP grades 2 and 3) and 118 (60.8%) patients were classified as high-risk (22.2% of patients with PSA > 20 ng/mL or 47.6% of patients with ISUP grades 4 and 5). Further, 7.2% of patients had exposure to ADT prior to the PET/CT with a median of 2 months (IQR 2-5) duration of ADT exposure. Table 2 demonstrates the distribution of PSA levels within each ISUP grade in our imaged population.
ISUP grade & PSA level and metastasis risk
Overall, metastatic disease (regional and distant) was detected in 34% (66/194) of the population. ISUP grade data was unavailable for five patients resulting in 189 patients used for ISUP grade analysis. Metastases were detected in 13% (1/8) with ISUP grade 1 (low-risk), 25% (23/91) with ISUP grades 2 and 3 (intermediate-risk) and 43% (39/90) with ISUP grades 4 and 5 (high-risk). The ISUP grades 4 and 5 have an increased likelihood of metastasis compared to ISUP grades 2 and 3 (OR 2.26; 95% CI 1.20-4.25) and ISUP grade 1 (OR 5.35; 95% CI 0.63-45.3) (Table 3).
Metastases were detected in 28.7% (29/101) with PSA 10 ng/mL, 26% (13/50) with PSA 10-20 ng/mL and 55.8% (24/43) with PSA >20 ng/mL. Patients with PSA levels >20 ng/mL were more likely to have metastasis, compared to those with PSA levels 10-20 ng/mL (OR 3.60; 95%CI 1.50-8.60) and PSA levels ≤10 ng/mL (OR 3.14; 95% CI 1.50-6.58; Table 3). Multivariable modelling including ISUP grade, PSA level and ADT exposure demonstrated association of ISUP grade and PSA level with the presence of metastatic disease (p=0.008 and p=0.001, respectively) such that patients with higher ISUP grade and PSA level were more likely to have metastatic disease (Table 3). Although a higher proportion of metastatic disease was detected in patients with previous or current use of ADT prior to the PET/CT scan (50% vs. 33%; aOR 2.16, 95%CI 0.67-6.96), this was not statistically significant. Figures 2 and 3 show examples of [18F]PSMA-1007 PET/CT with localised prostate disease and extensive metastases, respectively.
ISUP grade & PSA level and distribution of metastasis
Overall, lymph node/nodal (regional and non-regional) metastases were detected in 22.2% (43/194), bone metastases were detected in 20.6% (40/194) and visceral metastases were detected in 3.6% (7/194) of patients. There were 12.5% (1/8) regional nodal metastases in ISUP grade 1, 11% (10/91) in ISUP grades 2 and 3 and 31% (28/90) in ISUP grades 4 and 5. ISUP grade 1 had no non-regional nodal, bone or visceral metastasis. ISUP grades 2 and 3 had 4.4% (4/91) non-regional nodal, 12.1% (11/91) bone and 3.3% (3/91) visceral metastases whereas ISUP grades 4 and 5 had 14.4% (13/90) non-regional nodal, 28.9% (26/90) bone and 4.4% (4/90) visceral metastases. There was significant positive association between ISUP grade and the presence of regional nodal (p = 0.003), non-regional nodal (p = 0.041) and bone (p = 0.006) metastases. There were too few visceral metastases for meaningful analysis (p = 0.780) (Table 4).
Similarly, there was an increase in the number of regional and non-regional nodal metastases with increasing PSA levels. There were 14.9% (15/101) regional nodal metastases in PSA ≤ 10 ng/mL, 18% (9/50) in PSA 10-20 ng/mL and 41.9% (18/43) in PSA > 20 ng/mL group. The non-regional nodal metastases were 5% (5/101) in PSA ≤ 10 ng/mL, 6% (3/50) in PSA 10-20 ng/mL and 23.3% (10/43) in PSA > 20 ng/mL group. The PSA level was positively correlated with the presence of regional (p = 0.001) and non-regional nodal metastasis (p = 0.004), but not bone (p = 0.087) metastases. There were too few visceral metastases for meaningful analysis (p = 0.51) (Table 5). Overall, the number of involved metastatic regions increases with increasing PSA level and ISUP grade, as depicted in Table 4 and 5.
ISUP grade, PSA level and AJCC stage with SUVmax of primary prostate tumour
There were seven negative [18F]PSMA-1007 PET/CT scans in the staging group that were excluded from the primary tumour SUVmax analysis. The median SUVmax of the primary prostate lesion was 17.2 (IQR 9.5-26.7). The SUVmax of the primary prostate tumour was higher in the ISUP grades 4 and 5 compared to ISUP grades 2 and 3 (median SUVmax 19.6 vs 14.9). Similarly, the primary tumour SUVmax was higher in the PSA > 20 ng/mL group than PSA 10-20 ng/mL group (median SUVmax 21.5 vs 17.4). The primary tumour SUVmax also increased with increasing AJCC stage with stage IIIB and below (median SUVmax 14.2), stage IIIC (median SUVmax 17.5), stage IVA (median SUVmax 19.8) and stage IVB (median SUVmax 20). A statistically significant association between ISUP grade (p=0.004), PSA level (p< 0.001) and AJCC stage (p=0.034) with SUVmax of the primary prostatic tumour (Table 4 - 6) was observed. Additionally, a higher primary tumour SUVmax was detected in the high-risk group compared to the intermediate-risk group (median SUVmax 20.2 vs 11.9; p<0.001).
Metastatic disease by EAU risk group
Overall, the high-risk group (PSA >20 ng/mL or ISUP 4 and 5) had significantly higher proportion of patients with nodal (regional and non-regional) (34.7% vs 1.4%; p<0.001) and bone (28% vs 8.5%; p=0.001) metastases compared to the intermediate-risk group (PSA 10-20 ng/mL or ISUP 2 and 3). Although the high-risk group had a higher proportion of patients with visceral metastases compared to the intermediate-risk group (4.2% vs 2.8%), there were too few patients for meaningful analysis (p=0.71) (Table 7).
Evaluation of EAU criteria for detection of metastatic disease
The EAU criteria for classifying high-risk prostate cancer patients includes PSA >20 ng/mL or ISUP grade > 3. PSA > 20 ng/mL had a specificity of 85% (95%CI 78-91%) and a sensitivity of 36% (95% CI 25-49%); whereas ISUP grade > 3 has a sensitivity of 62% (95% CI 49-74%) and specificity of 60% (95% CI 50-68%) for detection of metastatic disease using [18F]PSMA-1007 PET/CT in our population. Our referral criteria of ISUP grade ≥ 3 has a sensitivity of 94% (95% CI 85-98%) and specificity of 36% (95% CI 27-45%) for detection of metastatic disease.
Twenty-three patients had three PSA values within 12 months before the PET/CT for calculating PSA doubling time and velocity. Out of these 23 patients, the group with metastases (n=7) had higher median PSA velocity (12.5 vs 4.8 ng/mL/year; p = 0.32) and lower median PSA doubling time (7.3 vs 31 months; p = 0.23) compared to the patients without metastasis (n = 16).
PSMA scan referral criteria
Out of the 194 patients included in the study, 31 patients did not meet our referral criteria but underwent [18F]PSMA-1007 PET/CT scan due to one of five reasons: investigation of high-risk radiological features or indeterminate lesion demonstrated on either CT, bone scan or MRI (15 patients), pretreatment scan after a period of active surveillance (5 patients), perineural invasion identified on biopsy (2 patients), high PSA level (PSA >20 ng/mL) before the commencement of ADT (2 patients) and other/unknown reasons (7 patients). None of these scans were positive for metastatic disease.