Randomized phase 2 trial of addition of neoadjuvant PSMA-targeting radioligand therapy to SBRT for oligorecurrent prostate cancer

After metastasis-directed stereotactic body radiotherapy (SBRT) for oligorecurrent hormone-sensitie prostate cancer (orHSPC; one to five lesions), progression is common. The randomized phase 2 LUNAR trial at the University of California Los Angeles evaluated addition of neoadjuvant ¹⁷⁷Lu-PSMA-targeting radioligand therapy to SBRT for orHSPC. The study included 92 patients, who were randomized to SBRT to all lesions (n=47) or SBRT + ¹⁷⁷Lu-PNT2002 (n=45), with 87 evaluable patients (SBRT n=42 and ¹⁷⁷Lu +SBRT n=45). At a median follow-up of 22 months, best PSA response, progression-free survival, and salvage hormonal therapy-free survival were significantly improved by addition of neoadjuvant ¹⁷⁷Lu to SBRT. The only grade 3 adverse events were lymphopenia (two patients in the SBRT group and three patients in the ¹⁷⁷Lu + SBRT group). The authors conclude that compared with SBRT alone, the addition of ¹⁷⁷Lu-PNT2002 to SBRT significantly improved outcomes of patients with orHSPC, without attendant increase in toxicity.