68Ga-PSMA PET/CT and Metastasis-Directed Therapy in Prostate Cancer

The use of ⁶⁸Ga-PSMA positron emission tomography (PET) for prostate cancer (PCa) restaging is recommended for patients who still experience prostate-specific antigen (PSA) persistence or biochemical recurrence (BCR) after receiving radical prostatectomy (RP). However, the effect that metastasis-directed therapy (MDT) has on progression-free survival (PFS) is not yet fully understood. A study presented at the American Urological Association 2023 Annual Meeting sought to determine if MDT may affect PFS in patients with positive prostate-specific membrane antigen (PSMA) PET.

A group of 361 patients who were evaluated with ⁶⁸Ga-PSMA PET/computed tomography (CT) for BCR after RP between 2016 and 2022 were retrospectively identified. Each patient was placed in a negative (n=135) or positive (n=226) group based on PSMA PET results. In the positive group, MDT consisted of stereotactic ablative radiation therapy on positive spots. Adverse pathological responses (eg, Gleason Grade Group 4-5 with ≥pT3a stage and/or lymph node invasion) and salvage treatments were also compared between the 2 groups.

Clinical recurrence (CR) was defined as any new metastases detected at imaging after first PSMA PET. Cox regression analyses were used to measure the impact of a positive PSMA PET and its interaction with MDT on CR after adjusting for PSA level at PSMA PET. Multivariable Cox-derived Kaplan-Meier (KM) analyses depicted the time from the first PSMA PET to CR.

Among the total number of patients with a positive scan, 113 (31%) patients received MDT. The median follow-up was 30 months after PSMA PET. The 3-year CR-free survival rates for negative and positive PSMA PET scans since BCR were 72% and 42%, respectively. At Cox analyses, a positive PSMA PET scan was associated with a 2-fold higher risk of PFS during follow-up compared with a negative PSMA PET (hazard ratio [HR], 2.09; P=.003) after adjusting for confounders.

When testing interaction with the use of MDT in patients with positive PSMA PET, patients with positive PSMA PET not receiving MDT had a higher risk of CR (HR, 2.66; P<.001). This risk was higher but with lesser magnitude in patients with positive PSMA PET (HR, 1.74; P=.04) receiving MDT compared with patients with negative PSMA PET. At the time of Cox-derived KM analyses, the 3-year CR-free survival rate was 73% in patients with negative PSMA PET, 51% in patients with positive PSMA PET with MDT, and 29% in patients with positive PSMA PET without MDT.

A negative PSMA PET scan is seen as a protective factor for further metastases during follow-up. In patients with positive spots, MDT significantly improved PFS, but it is not comparable to the protective effect of a negative PSMA PET.