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

Introduction: Radiation therapy (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 improving biochemical progression-free survival in patients with BCR treated without systemic therapy.

Methods: This is an interim post hoc analysis of data from a prospective clinical trial. Inclusion criteria were: histologically proven prostate cancer, BCR after primary treatment with curative intent, having five or fewer lesions identified on [¹⁸F]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 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 70.0% (21 of 30) and 85.7% (24 of 28) of patients showed a ≥ 50% decrease in prostate-specific antigen (PSA) levels after surgery and RT, 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 [¹⁸F]DCFPyL PET/CT are associated with high PSA response rates, delaying the time to biochemical progression by a median value of 18 months. The number and site of lesions detected on the PSMA PET/CT were predictive of biochemical progression on follow-up.

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