⁶⁸Ga-PSMA PET/CT in biochemically recurrent prostate cancer: association with genomic data

To assess the performance of ⁶⁸Ga-PSMA PET/CT in detecting biochemically recurrent prostate cancer and evaluate associations of PET imaging findings with alterations on genomic profiling.

⁶⁸Ga-PSMA PET/CT scans of 603 prostate cancer patients with biochemical recurrence or persistently elevated PSA and without known metastatic disease were retrospectively included (mean PSA 1.0 ng/mL; range, 0.08-5). All scans were analysed for presence of recurrence by two experienced nuclear medicine physicians independently; discrepancies were resolved by an additional expert reader. A subset of patients (n = 239) had undergone tumour genetic profiling using the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) sequencing assay. PET positivity and positive predictive value, inter-reader agreement, as well as associations between patient characteristics, location of recurrence, time to PET confirmed biochemical recurrence (PCBR), SUVmax, and most frequent gene alterations were investigated.

The overall recurrence detection rate of ⁶⁸Ga-PSMA PET/CT was 59.2% (357/603), with a positive predictive value of 0.98 (95% CI, 0.94-0.99), and a sensitivity of 0.60 (95% CI, 0.54-0.66). When analysed by PSA level, 43.8% of patients with PSA < 0.5 ng/mL, 64.1% with PSA 0.5-0.99 ng/mL, 73.6% with PSA 1.0-1.99 ng/mL, and 87% with PSA > 2.0 ng/mL were PET positive. Inter-reader agreement was excellent with κ-coefficient of 0.884. SUVmax was significantly higher in patients with higher PSA (P < 0.001), and extra-pelvic nodal metastases (P < 0.001). Patients with persistently elevated PSA, higher TNM stage, higher Gleason score, and without RT at baseline (all P < 0.001) had shorter time to PCBR. In patients with genetic alteration available, TP53 mutations were significantly associated with time to PCBR (alteration, n = 38; wildtype, n = 200; median time 4.3 versus 5.3 years, P = 0.04), and borderline significantly associated with SUVmax (median 11 versus 7, n = 33 and 121, P = 0.054).

⁶⁸Ga-PSMA PET/CT can detect prostate cancer recurrence potentially even among patients with a low PSA level. TP53 alterations on genetic analysis were associated with shorter time to PCBR and borderline associated with higher SUVmax, suggesting that an integrated diagnostic approach may identify more aggressive disease.