177Lutetium-PSMA-I&T Followed by Prostatectomy Safe in Locally Advanced High-risk Prostate Cancer

By Akhil Abraham Saji, MD - Last Updated: January 19, 2022

The benefit of radioligand therapy with lutetium-177 (177Lu)-prostate-specific membrane antigen (PSMA) in patients with metastatic prostate cancer has already been demonstrated, and many researchers are now focusing on investigating its impact in earlier stage disease. Several trials are underway with 177Lu-PSMA radioligands as neoadjuvant treatment in high-risk localized prostate cancer prior to prostatectomy, including the NALuPROST trial (NCT04297410).1 According to preliminary results of this feasibility trial, presented by Michael Frumer, MD, from the Department of Urology at the Rabin Medical Center, Petach Tikva, Israel, treatment with neoadjuvant 177Lu-PSMA-I&T followed by radical prostatectomy appears to be safe in patients with locally advanced, high-risk prostate cancer.2

Dr Frumer’s presentation updated another interim report from the trial with similar findings presented at the 2021 American Urological Association (AUA) annual meeting.3 177Lu-PSMA-I&T is a radiolabeled DOTAGA-chelated urea-based PSMA inhibitor being developed for SPECT/CT imaging and radionuclide therapy of prostate cancer.

NALuPROST is an ongoing prospective, single-arm, open-label clinical trial in which 177Lu-PSMA-I&T is administered to patients with high-risk localized prostate cancer (cT3/4 and/or Gleason Grade Group score ≥8 and/ or prostate biopsy or PSA ≥20 ng/dL) or loco-regional prostate cancer, i.e., pelvic lymphadenopathy of ≥2 cm on axial imaging. All patients have high PSMA expression confirmed on gallium-68 (68Ga) PSMA PET/CT. Dr Frumer and his colleagues anticipate completing the trial in 2022.

Patients entered into the trial receive two or three 7.4 Gbq doses of 177Lu-PSMA-I&T two weeks apart. After each treatment, a SPECT/CT scan is acquired to confirm 177Lu- PSMA-I&T retention in the prostate. Radical prostatectomy with lymph node dissection is performed 4 weeks after the last dose of 177Lu-PSMA-I&T. Data are collected on adverse events, intra- and post-operative parameters, and pathological and functional outcomes.

The 13 patients (median age 67 years) enrolled in the trial at the time of Dr Frumer’s presentation had Gleason Grade Group (GGG) 4 disease (7 patients) or GGG 5 disease (6 patients). Median PSA level decreased by 46% during treatment, from 11.4 ng/dL before treatment to 6.1 ng/dL after treatment. Adverse events reported during treatment consisted of fatigue in 2 patients and nausea and dry mouth in one patient each.

Twelve patients underwent surgery with no intraoperative complications. Mean surgical time was 220 min and median blood loss was 300 mL. Positive surgical margins were detected in 3 (25%) patients. Biochemical response was achieved in all 12 patients. Postoperative complications at 30 days included pneumonia in one patient and urinary tract infection and bacteremia in one patient. At 3 months, 11 (92%) patients had achieved continence recovery.

The results of this ongoing clinical trial support the continued exploration of the role of targeted radiotherapy in the neoadjuvant setting in patients with high risk, locally advanced prostate cancer, Dr Frumer and his colleagues have concluded.

Akhil Abraham Saji, MD is a urology resident at New York Medical College / Westchester Medical Center. His interests include urology education and machine learning applications in urologic care. He is a founding and current member of the EMPIRE Urology New York AUA section team.


  1. Shay G, Rabin Medical Center. 177Lu-PSMA-I&T prior to radical prostatectomy for locally advanced disease (NALuPROST). ClinicalTrials.gov Identifier: NCT04297410. https:// clinicaltrials.gov/ct2/show/NCT04297410
  2. Frumer M, Rosenbaum E, Kedar D, et al. Neoadjuvant 177Lu-PSMA-I&T radionuclide in high-risk prostate cancer before radical prostatectomy: a feasibility trial. Poster #140 presented at 22nd Annual Meeting of the Society of Urologic Oncology (SUO), December 1-3, 2021, Orlando, FL.
  3. Frumer M, Rosenbaum E, Kedar D, et al. Neo-adjuvant 177LU-PSMA-I&T radionuclide in high-risk prostate cancer before radical prostatectomy: a feasibility trial. J Urol. 2021;206(3S):e271. Abstract MP15-20. DOI: 10.1097/JU.0000000000001996.20