MP51-14: 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

Elio Mazzone*, Daniele Robesti, Giorgio Gandaglia, Armando Stabile, Simone Scuderi, Alberto Martini, Carlo Andrea Bravi, Milano, Italy, Gabriele Sorce, Francesco Pellegrino, Luigi Nocera, Milan, Italy, Giuseppe Rosiello, Lucia D’Ambrosio, Milano, Italy, Giuseppe Cirulli, Milan, Italy, Laura Marandino, Daniele Raggi, Andrea Necchi, Milano, Italy, Vincenzo Mirone, Napoli, Italy, Francesco Montorsi, Alberto Briganti, Milano, Italy

Introduction: Use of 68Ga-PSMA PET/CT is recommended for prostate cancer (PCa) re-staging in patients with either PSA persistence or biochemical recurrence (BCR) after radical prostatectomy (RP). There is little evidence regarding the role of metastasis directed therapy (MDT) on hard clinical endpoints such as progression-free survival. We aimed at addressing the impact of a positive PSMA PET on outcomes and the impact of MDT on the risk of progression in patients with positive PSMA PET.

Methods: We retrospectively identified 207 patients who were evaluated with 68Ga-PSMA PET/CT for BCR after RP between 2016 and 2021. Patients were stratified according to PSMA PET into two groups: positive (n=129) vs negative (n=78). In patients with positive PSMA PET, MDT consisted of stereotactic ablative radiation therapy (SABR) on positive spots, either nodal, bony or visceral. Clinical recurrence (CR) was defined as any new metastases detected at imaging after a first PSMA PET/CT. Adverse pathological features (i.e. Grade Group 4-5 with =pT3a stage and/or lymph node invasion) and salvage treatments were compared. Cox regression analyses assessed the impact 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 hotmonal therapy (HT). Multivariable Cox-derived Kaplan- Meier (KM) analyses depicted the time from the first PSMA PET to CR.

Results: Median PSA at PSMA PET scan and time from surgery to BCR were 0.6 ng/ml and 51 months. Among men with a positive scan (n=129), 62 (48%) received MDT. Overall, 18 vs 20 vs 21 patients experienced disease progression in negative vs positive PSMA PET scan with or without MDT. No differences were observed in terms of adverse pathology, salvage RT and HT use between the two groups (all p=0.07). Median follow-up was 26 months after PSMA PET. The 3-year CR-free survival rates were 67 vs 36% for negative vs positive PSMA PET scan. 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). When testing interaction with use of MDT in patients with positive PSMA PET, 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. At the Cox-derived KM, 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.

Conclusions: A negative PSMA PET/CT scan at the time of BCR represents a protective factor for further metastases during follow-up. Notably, in patients with positive spots, MDT significantly improved progression-free survival.

Source of Funding: none