AUA 2022: Impact of 68Ga-PSMA PET/CT and Metastasis-Directed Therapy on Clinical Recurrence in Patients with Biochemical Recurrence after Radical Prostatectomy. Results from a Single Center Series

( In a moderated poster presentation at the 2022 American Urologic Association Annual Meeting held in New Orleans and virtually, Dr. Elio Mazzone discussed the effect of 68Ga- prostate specific membrane antigen (PSMA) PET/CT guided metastasis directed therapy (MDT) on clinical recurrence rates in patients with either PSA persistence or biochemical recurrence (BCR) after radical prostatectomy (RP). Currently, PSMA-PET/CT is recommended in this clinical scenario. However, the clinical outcomes of the use of this approach and the image guided therapy that may follow is relatively sparse. Thus, the authors sought to assess the outcomes of patients with positive PSMA PET treatment with MDT in the context of BCR following RP.

To do so, they retrospectively identified 207 patients who underwent 68Ga-PSMA PET/CT for evaluation of BCR after RP between 2016 and 2021. Among these 207 patients, 129 had evidence of disease on PSMA-PET while the remainder 78 had negative scans. Among those patients with positive PSMA PET, MDT consisted of stereotactic ablative radiation therapy (SABR) to regions with radiographic evidence of disease, whether nodal, bony, or visceral. The authors assessed the outcome of clinical recurrence (CR), defined as any new metastases detected at imaging after a first PSMA PET/CT. The authors further considered the influence of adverse pathological features at the time of RP (i.e. Grade Group 4-5 with ≥pT3a stage and/or lymph node invasion) and any previously received salvage treatments. They used Cox regression analyses to assess the association of a positive PSMA PET and its interaction with MDT use on CR after adjusting for PSA level at PSMA PET, number of positive spots, and concomitant hormonal therapy (HT). Multivariable Cox-derived Kaplan- Meier (KM) analyses were used to depict the time from the first PSMA PET to CR.

Among the 207 included patients, the median time from surgery to BCR was 51 months. At the time of PSMA-PET, the median PSA was 0.6 ng/ml. Among those men with radiographic evidence of disease on PSMA-PET (n=129), 62 (48%) received MDT.

Disease progression was identified in 18 patients with negative PSMA-PET scans (of 78), 20 with positive PSMA-PET scans treated with MDT (of 62), and 21 of those with positive PSMA-PET scans not treated with MDT (of 67). Notable, the authors found no differences in terms of adverse pathology, salvage RT and HT use between the two groups (all p≥0.07).

Over a median follow-up of 26 months after PSMA PET, the 3-year CR-free survival rates were 67 vs 36% for those patients with a negative and a positive PSMA PET scan, respectively. A positive PSMA PET scan was associated with approximately 3-fold higher risk of CR as compared to negative PSMA PET (HR 2.7, p=0.001). However, this increased risk was modified by whether the patient received MDT: men with positive PSMA PET not receiving MDT had significantly higher risk of CR (HR 3.39; p<0.001), while such risk was higher but with lesser magnitude in men with positive PSMA PET receiving MDT (HR 2.14, p=0.02) compared to patients with negative PSMA PET. Using adjusted Cox-derived Kaplan Meier estimates, the 3-year CR-free survival rates were 71 vs 48 vs 19% in patients with negative PSMA PET vs positive PSMA PET receiving MDT vs positive PSMA PET not receiving MDT. 

Thus, the authors conclude that a negative PSMA PET/CT scan at the time of BCR represents a favourable prognostic factor. However, among those with positive PSMA-PET/CT, MDT significantly improved progression-free survival.

Presented by: Elio Mazzone, MD, San Raffaele Scientific Institute

Written by: Christopher J.D. Wallis, University of Toronto Twitter: @WallisCJD during the 2022 American Urological Association (AUA) Annual Meeting, New Orleans, LA, Fri, May 13 – Mon, May 16, 2022

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