AUA 2023: Radioligand Therapy With 177Lu-PSMA-I&T in Patients With Metastatic Castration-resistant Prostate Cancer: Oncological Outcomes and Toxicity Profile

( The 2023 AUA annual meeting included an advanced prostate cancer session, featuring a presentation by Dr. Baris Esen discussing oncologic outcomes and toxicity associated with radioligand therapy with 177Lu-PSMA-I&T for patients with metastatic castration-resistant prostate cancer (mCRPC). PSMA-targeted radioligand therapy with 177Lu-PSMA-617 is associated with prolonged overall survival in patients with mCRPC. However, data regarding the oncological efficacy and toxicity profile of 177Lu-PSMA-I&T is limited. At the 2023 AUA annual meeting, Dr. Esen and colleagues aimed to investigate the oncological outcomes and toxicity profile of 177Lu-PSMA-I&T radioligand therapy in patients with mCRPC.

This study had 33 consecutive patients with mCRPC treated with a total of 88 cycles (median 2 cycles, range 1-7) of 177Lu-PSMA-I&T radioligand therapy. The 177Lu-PSMA-I&T was given a median activity of 7.5 GBq (IQR: 6.7 – 8.1) per cycle. Response to radioligand therapy was assessed according to PSA changes and imaging response. Oncological outcomes were reported using clinical progression-free survival and overall survival. The time interval from the first radioligand therapy cycle to any radiological or biochemical progression was considered clinical progression-free survival. Standard Toxicity Criteria for Adverse Events (CTCAE) criteria were utilized to assess toxicity.

 The mean patient age at the time of the first radioligand therapy cycle was 71.6 ± 10.7 years, and any PSA decline was detected in 22 (69%) cases after radioligand therapy. The number of patients achieving PSA declines of ≥30% and ≥50% were 18 (56%) and 11 (34%), respectively. As follows is the waterfall plot showing the best PSA response with 177Lu-PSMA-I&T radioligand therapy:

Best PSA Response graph.jpg
The clinical progression-free survival and overall survival after the first cycle of radioligand therapy were 6.3 and 21.4 months, respectively. During radioligand therapy, nephrotoxicity occurred in 4 cases (12.1%). CTCAE grade according to estimated glomerular filtration rate worsening from I to II (n=2), II to III (n=1), III to IV (n=1). Six patients (18.2%) experienced grade I/II myelotoxicity and 3 cases (9.1%) had grade III/IV myelotoxicity.

Dr. Esen concluded his presentation by discussing oncologic outcomes and toxicity associated with radioligand therapy with 177Lu-PSMA-I&T for patients with mCRPC with the following take-home messages:

  • 177Lu-PSMA-I&T radioligand therapy achieved a good PSA response (≥30%) in more than half of the patients with mCRPC with an acceptable toxicity profile
  • Further studies are required to assess the role of 177Lu-PSMA-I&T radioligand therapy in mCRPC 

Presented by: Baris Esen, MD, PhD, FEBU, MSc, Koc University Hospital, Istanbul, Turkey

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2023 American Urological Association (AUA) Annual Meeting, Chicago, IL, April 27 – May 1, 2023