Fred Saad, MD, highlights PSA end points from the phase 3 PSMAddition trial

In the following video, Fred Saad, MD, CQ, FRCS, FCAHS, discusses prostate-specific antigen (PSA)–related end points from the phase 3 PSMAddition trial (NCT04720157) evaluating ¹⁷⁷Lu-PSMA-617 in combination with androgen deprivation therapy (ADT) plus an androgen receptor pathway inhibitor (ARPI) in patients with PSMA-positive metastatic hormone-sensitive prostate cancer (mHSPC). These results were presented at the 2026 American Urological Association Annual Meeting in Washington, DC.

Saad is the director of prostate cancer research at Montreal Cancer Institute and a full professor in the department of surgery at Université de Montréal.

PSMAddition was designed to determine whether adding ¹⁷⁷Lu-PSMA-617 to contemporary standard-of-care treatment could further improve outcomes in patients with newly diagnosed or minimally treated PSMA-positive mHSPC. Eligible patients with at least 1 PSMA-positive metastatic lesion on [⁶⁸Ga]Ga-PSMA-11 PET/CT were randomly assigned to receive ¹⁷⁷Lu-PSMA-617 plus ADT and an investigator-selected ARPI or ADT plus ARPI alone. Previously reported findings from the study demonstrated a statistically significant improvement in radiographic progression-free survival with the addition of ¹⁷⁷Lu-PSMA-617, corresponding to a 28% reduction in the risk of radiographic progression or death (HR, 0.72; 95% CI, 0.58 to 0.90; P = .002).

Saad explained that the AUA analysis focused on PSA-related outcomes as early indicators of treatment benefit while overall survival data continue to mature. Among patients with baseline and at least 1 post-baseline PSA measurement, PSA levels decreased from baseline in 98.2% of patients receiving ¹⁷⁷Lu-PSMA-617 plus ADT and ARPI (n = 557) and 98.7% of patients receiving ADT plus ARPI alone (n = 553). PSA90 response rates were numerically higher with the triplet regimen. At week 48, 87.4% of patients in the ¹⁷⁷Lu-PSMA-617 arm achieved a PSA nadir below 0.2 ng/mL compared with 74.9% of patients in the control arm. Saad noted that achieving very low PSA levels has consistently been associated with improved long-term outcomes across prior studies.

The analysis also showed that the addition of ¹⁷⁷Lu-PSMA-617 prolonged time to PSA progression. The risk of PSA progression was reduced by 58% with the triplet regimen compared with ADT plus ARPI alone (HR, 0.42; 95% CI, 0.30 to 0.59), with median time to PSA progression not reached in either arm. According to the authors, these findings provide further evidence that adding ¹⁷⁷Lu-PSMA-617 to standard therapy increased the depth of PSA responses and delayed the time to PSA progression, complementing the previously reported improvements in radiographic progression-free survival.