Oligometastases in prostate cancer: Metabolic response in follow-up PSMA-PET-CTs after hypofractionated IGRT

Background: Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMAPET/CT) is a new and evolving diagnostic method in prostate cancer with special impact on treatment planning in image-guided radiotherapy (IGRT). Initial results of metabolic response in repeated PSMA PET/CTs after hypofractionated IGRT for metastatic lesions are reported here. Materials and methods: Of 280 patients investigated with ⁶⁸Ga-PSMA PET/CT in the period from 01/2014 through 12/2016 in the authors’ department, patients were selected according to the following criteria: oligometastatic disease at initial PSMA PET/CT defined as not more than five metastatic lesions, hypofractionated IGRT to all lesions, no systemic therapy in the last 6 months and during follow-up, and at least one follow-up PSMA PET after radiotherapy. Radiotherapy was administered to all PSMA PET-detected lesions (CTV = PET-GTV + 1 to 2 mm), mostly with 35 Gy in five fractions (one lesion with four fractions of 7 Gy due to dose constraints, two lymph nodes with 50 Gy in 25 fractions to an extended volume plus a boost of 7 Gy × 2 to the PET-positive volume). Metabolic response of irradiated lesions was evaluated on repeated PSMA PET/CTs according to PERCIST criteria. Five patients with a total number of 12 PSMA PETs matched the criteria. Patients received radiotherapy to all PET-positive lesions and had at least one (in one case three) follow-up PSMA PET examinations after radiotherapy with an interval to the first PET of 2–15 months; the median follow-up for all patients was 11 months. Results: The mean prostate-specific antigen (PSA) values at the time of examination were 8.9 ± 8.5 ng/ml (median 3.3 ng/ml, range 0.17–21.8 ng/ml). A total number of 18 metastatic deposits were detected. The PET-positive tumor volume was 5.9 ± 13.3 cm³ (median 1.25 cm³). The mean standardized uptake value (mean SUV_max) of the 18 metastatic lesions decreased from 19.9 ± 23.3 (mean ± SD) prior to RT to 5.4 ± 4.6 at post-radiotherapy PSMA PET/CT. Using PERCIST criteria, 14 lesions (78%) showed a metabolic response in PSMA PET with a reduction of SUV of at least 30%, as well as a significant decrease in lesion size; in seven of these lesions, no uptake of ⁶⁸Ga-PSMA was detectable. In follow-up PET scans, only two lesions showed metabolic progression with an increase in SUV_max yielding a local progression-free survival of 88% after 1 year. There was a correlation between the time interval after radiotherapy (median 3 months, range 1–9 months) and response (p = 0.04) with better metabolic response after longer follow-up. Conclusions: Preliminary results of this study show high metabolic response rates of PSMA PET-positive metastatic lesions after hypofractionated radiotherapy in follow-up PSMA PET with promising local control rates. An interval of several months may be required to fully estimate the efficacy of radiotherapy in control PSMA PET.