Abstract
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Objectives: The aim of this study was to determine the influence of timing of Lu-177 PSMA radioligand therapy (PRLT) in metastatic prostate cancer (mPC).
Methods: Out of 512 mPC patients restaged due to rising PSA by Ga-68 PSMA PET/CT since April 2013, 224 (mean age 71 years, mean Gleason score 8) received totally 649 Lu-177 PRLT cycles (1 - 9 cycles, 3.5 - 12 GBq Lu-177 PSMA ligand per cycle) and were included in the intention-to-treat analysis. The patients were grouped according to previous therapies for mPC - chemotherapy (n=110) including 2nd line with cabazitaxel (n=20), androgen deprivation (n=206), newer drugs abiraterone (n=91) and enzalutamide (n=79), Ra-223 chloride (n=19) and no previous therapy (n=18). The primary tumor had been previously treated by surgery in 154 and external beam radiation therapy in 151 patients. The median overall survival (OS) was computed. Median follow-up was 16 months (3 - 55). The most frequent sites of metastases were bone (184) followed by lymph node (168), liver (28) and lung (26). Serum prostate specific antigen (PSA) levels were monitored before and after therapy. Results: Reduction in PSA was observed in 157/224 (70 %) patients; 121/224 patients (54 %) demonstrated a PSA decline by >50 % and the best response was complete remission with undetectable PSA. The median overall survival (OS) in all patients was 27 months. First-line PRLT was associated with the longest OS (median not reached at 55 months, all 18 patients are alive). Chemotherapy-pretreated patients had a significantly shorter survival (median OS 19 months) as compared to chemotherapy-naive patients (38 months, p<0.05). OS was also shorter in patients with previous Ra-223 treatment (17 months). Addition of Abiraterone or Enzalutamide provided a significant prolongation of survival (40 months, p<0.05). On the other hand, prior surgical or radiation treatment of primary tumor had no significant effect on the OS (30 months, p>0.05). In patients demonstrating a PSA decline of > 50% after at least 2 PRLT cycles, the OS was significantly longer (38 months). Conclusions: Early initiation of Lu-177 PSMA radioligand therapy is effective in metastatic prostate cancer, offering a significant survival benefit. Additional treatment with newer antiandrogen agents Abiraterone or Enzalutamide probably has a synergistic effect in combination with Lu-177 PRLT. PSA response after PRLT predicts a longer OS. Previous chemotherapy (1st or 2nd line) and Ra-223 treatment were associated with a worse prognosis. Randomized controlled studies are required to best determine the place of this agent (for e.g. before chemotherapy) in the management of mPC.
