Impact of ⁶⁸Ga-Prostate-Specific Membrane Antigen PET/CT on Prostate Cancer Management

DISCUSSION

⁶⁸Ga-PSMA PET/CT led to a change in management plans in 39% of patients with BCR. Changes occurred more often in patients with higher PSA levels and in patients originally treated with radiotherapy rather than radical prostatectomy.

The proportion of changes in management in the present study was lower than that in some other published studies in which management impact was assessed, but the proportion of studies with positive results in our cohort was also relatively lower.

In a retrospective study of 42 patients who had BCR and were scanned for radiotherapy planning, Sterzing et al. reported a change in target volume or dose in 60.5% of patients, with 73.5% of scans having positive results (6). Shakespeare found that an alteration in any aspect of management occurred in 53.7% of cases after ⁶⁸Ga-PSMA PET/CT, with a change to radiotherapy in 46.3% and a change to androgen deprivation therapy in 33.3% (7).

Dewes et al. observed that ⁶⁸Ga-PSMA PET/CT led to a change in staging classification in 53.3% of analyzed patients; revisions to the radiotherapy concept occurred in 33.3% of patients, with relevant changes in the planned target volume (8).

Albisinni et al. (9) evaluated 131 patients and found positive scan results in 75% and an impact on management in 76%. Although PSA levels were studied in relation to the positivity of scan results, the authors did not differentiate cases into the key groups of prostatectomy and radiotherapy, as was done in the present study. The fact that a larger proportion of patients was treated with radical prostatectomy in the present study may have accounted for the different results, as patients who had undergone prostatectomy had a lower rate of management changes. In addition, the smaller number of positive study results in our patient population would have influenced the proportion of management changes. However, in a prospective study with predominantly radical prostatectomy patients, Morigi et al. found an impact on management after ⁶⁸Ga-PSMA PET/CT in 24 (63%) of 38 patients, and 68% of the scans had positive results (10).

The proportion of PET/CT scans with positive results in the present study (47%) was significantly lower than the proportions described by Afshar-Oromieh et al. (82.8%) (11) and Ceci et al. (74.2%) (12) for recurrent prostate cancer. The large number of patients with very low PSA levels in our patient population (in view of the large proportion of patients treated with prostatectomy, after which PSA relapse occurs at significantly lower PSA levels) and the large number of patients with low PSA levels referred to our center may have accounted for the different results.

Positive study results were associated with higher PSA levels, higher PSA velocities, and higher T stages. No significant association was demonstrated with PSA doubling times. There was a trend toward higher Gleason scores in patients with positive scan results, but this finding did not reach significance.

It is possible that the smaller proportion of patients for whom data were available to calculate kinetics may have led to the masking of an association with PSA doubling times. In a recent metaanalysis, PSMA positivity was 64% for PSA doubling times of greater than 6 mo and 92% for PSA doubling times of less than 6 mo. High heterogeneity between subgroups was noted and, in the subgroup with long PSA doubling times, there was evidence of a small-study effect (13).

The relationship between PSA and positive scan results has also been investigated by others (11,14,15). The proportion of scans with positive results at each PSA threshold was lower in the present study than in previous reports. For example, 15.8% of studies had positive results at PSA levels of 0.2–<0.5 ng/mL, compared with 57.89% in the study by Eiber et al. (15) and 50% in the study by Afshar-Oromieh et al. (11), and 20% of studies had positive results at PSA levels of 1–<2 ng/mL, compared with 93.06% (15) and 71.8% (11). A possible explanation is that the exclusion of patients on androgen deprivation therapy from our study would have reduced PSA levels at the time when scans with positive results were obtained in other studies, from which such patients were not excluded. In addition, patients may have been referred at earlier time points within the biochemical recurrence pathway in the present study, as ⁶⁸Ga-PSMA for early investigation has become more routine practice since older studies were performed.

Limitations of the present study include a retrospective design, which prevented the collection of data on how ⁶⁸Ga-PSMA PET/CT may have affected confidence in management decisions. Only a small number of patients had pathology as validation, in common with other studies on BCR. However, good sensitivity and specificity of ⁶⁸Ga-PSMA PET/CT for disease detection have already been described in multiple reports (13), and this information is part of the rationale for its accelerated acceptance into clinical practice.