ESMO Congress 2026

177Lu-PSMA-617 is a PSMA-targeted radioligand therapy that delivers beta-particle radiation to PSMA-positive tumor cells and the surrounding microenvironment, and its position in mCRPC was established by the international phase 3 VISION trial: patients previously treated with at least one androgen-receptor-pathway inhibitor and one or two taxane regimens, with PSMA-positive disease on 68Ga-PSMA-11 PET, were randomized 2:1 to 177Lu-PSMA-617 (7.4 GBq every 6 weeks for four to six cycles) plus protocol-permitted standard care or standard care alone, with imaging-based progression-free survival and overall survival as primary end points ^[1]. Earlier evidence came from the single-centre single-arm phase 2 LuPSMA trial ^[2], the randomized phase 2 TheraP trial versus cabazitaxel ^[3], and the German multicenter retrospective analysis ^[5]; on toxicity, CTCAE assessment based on serial blood tests was established practice ^[5], and xerostomia was recorded as the only mentionable clinical side effect in the 225Ac-PSMA-617 case series ^[4].

At ESMO26, two pieces of information relate to this asset. The main one is Re-LuPSMA, the interim safety analysis of a prospective phase II trial of 177Lu-PSMA-617 retreatment in mCRPC, presented by Johanna Enke, MD: n=20/40 enrolled so far, median retreatment cycles of 3 (IQR 2–5); 165 AEs reported, of which 88 were possibly treatment-related — Gr1 (n=53), Gr2 (n=14), Gr3 (n=13), Gr4 (n=8); the most common TRAEs were anemia (n=15), leukopenia (n=12), thrombocytopenia (n=10) and xerostomia (n=10). The other is an analysis from Dana-Farber (@aloktewar) using ctDNA as correlates of intrinsic and acquired resistance to 177Lu-PSMA-617 in mCRPC.

In terms of the step forward, Re-LuPSMA extends the evidence to the retreatment setting after initial radioligand therapy — in VISION ^[1] and TheraP ^[3], 177Lu-PSMA-617 was given as initial treatment, with the VISION regimen being four to six cycles ^[1], and retreatment safety was not part of these pivotal trials; the interim data show that retreatment toxicity remains concentrated in hematologic parameters and xerostomia, echoing the toxicity pattern documented in earlier series ^[4][5]. The ctDNA analysis extends the discussion from efficacy to resistance-mechanism stratification (intrinsic versus acquired resistance), a dimension not covered by the phase 3 ^[1] or the phase 2 randomized ^[3] trials.

As for limitations, Re-LuPSMA is only an interim safety analysis with enrolment incomplete (20/40), and the post does not mention efficacy results; specific figures from the ctDNA analysis are likewise not disclosed in the post, and both await confirmation from full data.