Biochemical failure after radical prostatectomy with PSA ≤ 1 ng/mL: prediction of PSMA-positive metastatic disease.

[OBJECTIVES] The identification of metastatic disease in patients with biochemical failure of prostate cancer (PCa) after radical prostatectomy (RP) determines subsequent treatment management. Our objectives were (i) to assess the prevalence of metastatic PCa in patients with biochemical failure following RP and PSA levels ≤ 1 ng/mL, as detected by F-PSMA-1007 PET/CT (PSMA-PET), and (ii) to identify predictors of metastatic disease.

[METHODS] Fifty-five patients with biochemical recurrence (BCR, n = 47) or persistent disease (n = 8) following RP as their primary and only prior treatment were retrospectively included if presenting with PSA levels ≤ 1 ng/mL. Patients who received any other anticancer treatment were excluded. PSMA-PET findings were categorized as either local recurrence (i.e., prostatic fossa and seminal vesicles) or metastases. Predictors of PSMA-PET positivity were assessed with univariate and multivariate regression analyses both in the whole sample and in two subgroups defined according to PSA levels (Group A = PSA < 0.5 ng/mL; Group B = PSA between 0.5 and 1 ng/mL).

[RESULTS] Median PSA at the time of PET/CT was 0.37 ng/mL (range: 0.13-1.0). PSMA-PET was positive in 22/55 (40%) patients, 14/55 (25%) patients had metastatic disease. Overall, 31 PSMA-positive lesions were identified: 12/31 (39%) and 19/31 (61%) were local recurrences and metastases, respectively. In the whole cohort, ISUP grade > 3 (p = 0.003), pN1 status after surgery (p = 0.011), time to BCR ≤ 26 months (p = 0.03), and persistent disease (p = 0.003) were significantly associated with a higher rate of PSMA-positive metastases. At multivariate analysis, ISUP grade > 3 (p = 0.016) was the only independent predictor of metastases. Metastatic disease was detected in 8/38 (21%) patients in Group A and in 6/17 (35%) patients in Group B, respectively. In Group A, pN1 (p = 0.043) and persistent disease (p = 0.040) were significant predictors of metastases. In Group B, ISUP grade > 3 was the only predictor (p = 0.028).

[CONCLUSIONS] ISUP grade > 3, time to BCR ≤ 26 months, pN1 status, and persistent disease after surgery indicated a higher likelihood of PSMA-positive metastatic disease in a homogeneous cohort of patients with biochemical failure and low PSA values. pN1 status and persistent disease were significant predictors of metastatic disease also in patients with PSA levels < 0.5 ng/mL.