⁶⁸Ga-PSMA-11 PET/CT in patients with biochemical recurrence of prostate cancer and low PSA levels: diagnostic accuracy and PET positivity predictors.

Introduction: ⁶⁸Ga-PSMA-11 PET/CT is nowadays the most promising PET tracer in the detection of prostate cancer recurrence. The principal aim of this study is to assess the detection rate of this technique in patients with prostate cancer biochemical recurrence (BCR) with low PSA levels, and then to evaluate which are the predictors of PET positivity in order to identify cost-effectiveness criteria to perform this exam in this subset of patients.

Methods: We prospectively enrolled patients referred to our Center between November 2016 and December 2017 for BCR, after primary surgical treatment either before or after subsequent adjuvant or salvage radiotherapy (SRT). All patients underwent ⁶⁸Ga-PSMA-11 PET/CT according to international procedure guidelines acquisition protocol; in case of PSA >1.5 ng/ml the exam was performed only if previous choline PET/CT or other imaging technique were negative. Clearly positive ⁶⁸Ga-PSMA-11 PET/CT findings were considered as true positive; dubious findings were explored by other imaging techniques or monitored and defined as true positive or true negative by a multidisciplinary consensus. The potential clinical, laboratory and histo-pathological determinants for PET postivity were evaluated by univariate and multivariate logistic regression models.

Results: A total of 107 ⁶⁸Ga-PSMA-11 PET/CT scans were performed in 57 (53.3%) patients after radical surgical treatment only and in 50 (46.7%) patients after radical surgery and adjuvant or SRT. Gleason Score (GS) was &#8804;3+4 (ISUP Grade 1-2) in 44 (41.1%), ≥4+3 (ISUP Grade 3-4-5) in 62 (58%) and not known in 1 (0.9%) patients, respectively. T stage was T1c-T2b-c in 53 (49.5%), T3a-b in 51 (47.7%) and not known in 3 (2.8%) patients, respectively. Surgical margins after surgery were positive in 53 (49.5%), negative in 47 (43.9%) and not reported in 7 (6.5%) patients, respectively. Median PSA value at the moment of PET/CT was 0.7 ng/ml (range 0.23-8.90); in particular, PSA was >0.2 and &#8804;0.5 ng/ml in 36 (33.6%), >0.5 e &#8804;1 ng/ml in 38 (35.5%), >1 and &#8804;1.5 ng/ml in 20 (18.7%) and >1.5 ng/ml in 13 (12.2%) patients, respectively. Median PSA doubling time and PSA velocity were 8.6 months (range 0.6-264.8) and 0.6 ng/ml/yr (range 0-30.2), respectively. ⁶⁸Ga-PSMA PET/CT was considered positive in 38 patients (35.5%); recurrence was located in prostate bed (n=3), lymph nodes (n=29) and distant sites (n=6). While a significant association was observed for PSA velocity (median 0.9 in PET+ vs 0.4 ng/ml/yr in PET-, p<0.001), the 2 main risk factors for PET positivity were the last absolute PSA value before ⁶⁸Ga-PSMA PET/CT (OR 1.59, 95% CI 1.03-2.48, p=0.038) and a T ≥3 stage (OR 3.37, 95% CI 1.40-8.11, p=0.007), both in univariate and multivariate logistic models.

Conclusions: Preliminary data suggest that ⁶⁸Ga-PSMA PET/CT results may be clinically useful to detect prostate cancer recurrence at low PSA values too, when dealing with the most aggressive disease patterns. In this setting, a proper selection of the patients that could really benefit of ⁶⁸Ga-PSMA PET/CT is mandatory, in order to reach a more cost-effective profile.