Intermediate-term oncological and functional outcomes of neoadjuvant 177-Lu-PSMA-I&T radionuclide treatment followed by radical prostatectomy

Purpose: To describe the intermediate-term oncological and functional outcomes in patients with high-risk prostate cancer (HRPCa) who were treated with neoadjuvant lutetium-177-prostate-specific membrane antigen (LuPSMA) followed by robotic-assisted laparoscopic radical prostatectomy (RARP). Methods: An open-label, single-arm clinical trial enrolled patients with HRPCa and increased uptake on PSMA-PET/CT. Two or three LuPSMA doses (7.4 GBq) were given followed by RARP with lymph node dissection. Oncological outcomes (histological and radiological findings, biochemical recurrence-free survival [bRFS]), changes in urinary and sexual functions and quality of life were analyzed. Results: Thirteen patients (median age 67) were included. Over a median follow-up of 58 months (IQR 52, 63), bRFS rate was 42% with a median of 12 months (IQR 12, 30) from surgery to biochemical recurrence (BCR). BCR occurred in all three patients with significant positive surgical margins (sPSM) compared to 4/9 patients (44%) without sPSM. Log-rank analysis revealed a statistically significant difference in bRFS between these two groups (p = 0.009). In the subgroup of patients with BCR, the adverse effects of salvage radiation and androgen deprivation therapy after LuPSMA and subsequent RARP did not appear to be exacerbated by prior administration of LuPSMA. The preliminary nature of this trial, combined with the small cohort, requires that the oncological findings be interpreted with caution. Conclusions: Follow-up for more than four years showed that treatment with neoadjuvant LuPSMA followed by RARP appears to be safe for patients with HRPCa. However, more than half of these patients experienced BCR and required salvage therapy.