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177Lu-Prostate-Specific Membrane Antigen Neoadjuvant to Stereotactic Ablative Radiotherapy for Oligorecurrent

Amar U Kishan1,2, Luca F Valle1,3, Holly Wilhalme4

  • 1Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, CA.

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology
|November 12, 2025
PubMed
Summary
This summary is machine-generated.

Adding prostate-specific membrane antigen (PSMA)-targeting radioligand therapy to stereotactic body radiotherapy (SBRT) significantly improved progression-free survival for oligorecurrent hormone-sensitive prostate cancer. This combination therapy demonstrated enhanced efficacy without increased toxicity compared to SBRT alone.

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Area of Science:

  • Oncology
  • Radiotherapy
  • Nuclear Medicine

Background:

  • Oligorecurrent hormone-sensitive prostate cancer (orHSPC) frequently progresses after metastasis-directed therapy like SBRT.
  • There is a need for improved treatment strategies to prolong progression-free survival in orHSPC patients.

Purpose of the Study:

  • To evaluate the efficacy of combining neoadjuvant prostate-specific membrane antigen (PSMA)-targeting radioligand therapy with SBRT in patients with orHSPC.
  • To determine if this combination improves progression-free survival (PFS) compared to SBRT alone.

Main Methods:

  • A randomized, controlled phase II trial (LUNAR) involving 92 patients with orHSPC.
  • Patients received either SBRT alone or two cycles of 177Lu-PNT2002 followed by SBRT.
  • Primary endpoint was PFS, assessed by PSMA PET/CT, salvage hormonal therapy, or death.

Main Results:

  • The combination of 177Lu-PNT2002 and SBRT significantly improved PFS (17.6 months vs. 7.4 months).
  • The hazard ratio for progression was 0.37 (P < .0001) favoring the combination therapy.
  • No significant increase in grade 3 adverse events, such as lymphopenia, was observed.

Conclusions:

  • Adding 177Lu-PNT2002 to SBRT is an effective strategy for improving PFS in orHSPC.
  • The combination therapy offers a significant survival benefit without a substantial increase in toxicity.
  • This approach represents a promising advancement in the treatment of orHSPC.