Hitting Hard and Early: Using Radioligand Therapy Earlier in mHSPC

Integrating novel radioligand therapies into earlier treatment lines represents a significant shift in the management of advanced prostate cancer. In an interview with CancerNetwork® at the 2026 American Society of Clinical Oncology Annual Meeting (ASCO), Fred Saad, MD, FRCS, CQ, FCAHS, discussed the clinical rationale behind moving lutetium-177-PSMA-617 (Pluvicto) into the metastatic hormone-sensitive prostate cancer (HSPC) setting, as evaluated in the phase 3 PSMAddition trial (NCT04720157). Building upon a standard-of-care backbone of androgen deprivation therapy (ADT) and an androgen receptor pathway inhibitor (ARPI), the addition of radioligand therapy aims to maximize early disease control when patients are in optimal physical condition.

Saad highlighted data regarding PSA declines, with nearly 90% of patients achieving undetectable levels below 0.2. He emphasized that safely introducing highly effective, targeted mechanisms earlier in the disease course could offer an opportunity to "hit hard," ultimately delaying disease progression to metastatic castration-resistant prostate cancer (CRPC) and postponing the need for subsequent, more intensive lines of therapy.

Saad is the director of Prostate Cancer Research at the Montreal Cancer Institute and a full professor in the Department of Surgery at the University of Montreal.

CancerNetwork: Moving radioligand therapy into the hormone-sensitive setting requires a tight, seamless collaboration between a number of subspecialists. What do these PSMAddition data tell us about the ideal timing of operational sequencing for these patients within a multidisciplinary clinic?

Saad: That’s a very important question. What is the ideal? I couldn’t tell you what the ideal is, but what we’re realizing more is that effective therapies given earlier seem to have a bigger impact overall. There is an opportunity to hit hard. We have already realized that with triplet therapy using docetaxel chemotherapy in addition to ADT and an ARPI. However, this study is building on ADT and an ARPI as a backbone, so this was a high bar.

I recently presented data on PSA declines by adding lutetium, and we see that we get to almost 90% undetectable PSAs below 0.2 by adding lutetium. Obviously, patients are in a better condition when they are still hormone sensitive. This is targeting the androgen receptor. It makes sense if we can introduce it earlier safely to try to delay as long as possible the progression to metastatic CRPC, the progression of the disease, and the eventual need for subsequent therapies.

Reference

Saad F, Tagawa ST, Sartor AO, et al. Subgroup analyses by disease volume and de novo/recurrent mHSPC in the PSMAddition study of [¹⁷⁷Lu]LU-PSMA-617. J Clin Oncol. 2026;44(suppl 16):5020. doi:10.1200/JCO.2026.44.16_suppl.5020