Outcome of patients with biochemical recurrence of prostate cancer after PSMA PET/CT-directed radiotherapy or surgery without systemic therapy

BACKGROUND: Radiotherapy (RT) and surgery are potential treatment options in patients with biochemical recurrence (BCR) following primary prostate cancer treatment. This study examines the value of prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT)-informed surgery and RT in patients with BCR treated without systemic therapy. METHODS: This is a post-hoc subgroup analysis of a prospective clinical trial. Inclusion criteria were: histologically proven prostate cancer at initial curative-intent treatment, BCR after primary treatment with curative intent, having five or fewer lesions identified on [(18)F]DCFPyL PET/CT, and treatment with either PET/CT-directed RT or surgery without systemic therapy. The biochemical progression-free survival after PSMA ligand PET/CT-directed RT and surgery was determined. Uni- and multivariate Cox regression analyses were performed for the association of patients’ characteristics, tumor-specific variables, and PSMA PET/CT imaging results with biochemical progression at the last follow-up. RESULTS: Fifty-eight patients (30 in surgery and 28 in radiotherapy groups) met the inclusion criteria. A total of 87 PSMA-positive lesions were detected: 16 local recurrences (18.4%), 54 regional lymph nodes (62.1%), 6 distant lymph nodes (6,8%), and 11 osseous lesions (12.7%). A total of 85.7% (24 of 28) and 70.0% (21 of 30) of patients showed a ≥ 50% decrease in prostate-specific antigen (PSA) levels after RT and surgery, respectively. At a median follow-up time of 21 months (range, 6–32 months), the median biochemical progression-free survival was 19 months (range, 4 to 23 months) in the radiotherapy group, as compared with 16.5 months (range, 4 to 28 months) in the surgery group. On multivariate Cox regression analysis, the number of PSMA positive lesions (2–5 lesions compared to one lesion), and the anatomic location of the detected lesions (distant metastasis vs. local relapse and pelvic nodal relapse) significantly correlated with biochemical progression at the last follow-up, whereas other clinical, tumor-specific, and imaging parameters did not. CONCLUSIONS: This study suggests that RT or surgery based on [(18)F]DCFPyL PET/CT are associated with high PSA response rates. The number and site of lesions detected on the PSMA PET/CT were predictive of biochemical progression on follow-up. Further studies are needed to assess the impact of targeting these sites on patient relevant outcomes. TRIAL REGISTRATION: Registered September 14, 2016; NCT02899312; https://clinicaltrials.gov/ct2/show/NCT02899312 SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40644-023-00543-0.