One size doesn't fit all: Personalizing PSMA-targeted therapy in prostate cancer

With lutetium Lu 177 vipivotide tetraxetan (Pluvicto) now approved across multiple prostate cancer settings — from metastatic castration-resistant disease to hormone-sensitive disease — oncologists are grappling with a critical question: how do you sequence and deliver this therapy for each unique patient? Dr. Jeremie Calais, a nuclear medicine and theranostics expert, says the answer lies in individualization, not uniformity.

Calais challenges the default of six consecutive treatment cycles, suggesting that patients who respond well early might benefit from a pause after just 2–4 cycles, with treatment adjusted based on response. He also cautions that earlier approval doesn't mean earlier use is always right — disease volume and PSMA expression on PET imaging should guide where radioligand therapy fits in the overall treatment plan. For patients with highly aggressive disease or actionable mutations, Calais favors leading with chemotherapy or targeted agents before turning to PSMA-directed therapy.

Key Takeaways:

• PSMA-targeted therapy is now FDA-approved across three distinct prostate cancer populations, each with different clinical profiles
• Disease volume, PSMA PET expression, circulating tumor DNA, and FDG PET findings should all inform sequencing decisions
• Patients with very aggressive disease or actionable mutations may benefit from chemotherapy or targeted therapy first

Why it matters: As Pluvicto's indications broaden, the risk of suboptimal sequencing grows. Tailoring treatment to individual disease biology — rather than applying a blanket protocol — could meaningfully improve outcomes and reduce unnecessary toxicity.