The PSMA-targeted fluorescent tracer OTL78 was shown to be safe and enabled real-time imaging during robot-assisted radical prostatectomy and provided valuable information on the localization and extent of prostate cancer.
Fluorescence-guided radical prostatectomy using the PSMA-targeted fluorescent tracer OTL78 enabled real-time identification of visually occult prostate cancer and has the potential to facilitate complete oncological resections, according to findings from a phase 2a feasibility trial published in the Lancet Oncology.1
To enroll in the adaptive design trial, which was conducted at The Netherlands Cancer Institute, patents had to be aged ≥18 years, have PSMA-PET avid prostate cancer with an International Society of Urological Pathology (ISUP) grade group of ≥2, and be scheduled to receive robot-assisted radical prostatectomy with or without extended pelvic lymph node dissection.
The study included 18 patients who were enrolled between June 29, 2020, and April 1, 2021. Patients had a median age of 69 years (interquartile range [IQR], 64-70) and a median PSA at baseline of 15 ng/mL (IQR, 9.3-22.0). Over two-thirds (67%) of patients had an ISUP grade group ≥3.
All patients underwent radical prostatectomy using OTL78, which was administered using a single intravenous infusion. Sixteen (89%) of the 18 patients had an extended pelvic lymph node dissection based on the estimated risk of nodal metastases.
Overall, there were 3 study cohorts, which were based on timing and dose: 0.06 mg/kg 1-2 hours before surgery (cohort 1), 0.03 mg/kg 1-2 hours before surgery (cohort 2), and 0.03 mg/kg 24 hours before surgery (cohort 3).
Pharmacokinetics and safety of OTL78 were the primary outcome measures.
The researchers found that the dose-normalized maximum serum concentration (Cmax/dose)was 84.1 ng/mL/mg for the 0.03 mg/kg dose and 79.6 ng/mL/mg for the 0.06 mg/kg dose. The half-life was 5.1 hours and 4.7 hours for the two doses, respectively. The volume distribution was 22.9 L vs 19.5 L and the clearance was 3.1 L/h vs 3.0 L/h for the 0.03 and 0.06 mg/kg doses, respectively.
“A single intravenous dose of 0.03 mg/kg OTL78 administered 24 h before surgery provided the highest signal-to-background ratio and the best tumor visualization in vivo and ex vivo,” according to the investigators, adding, “False-negative lesions on fluorescence microscopy were often characterized by either weak PSMA expression, low tumor volume, or low ISUP grade.”
Regarding safety, OTL78 was considered to be well tolerated overall. There were 3 serious adverse events (AEs) that all occurred in 1 patient and were determined to be unrelated to administration of OTL78 or intraoperative fluorescence imaging. The serious AEs were an infected lymphocele, a urosepsis, and an intraperitoneal hemorrhage. There were no dose reductions, discontinuations due to OTL78 toxicity, or patient deaths.
The investigators did note several limitations of their research, including, “The small sample size limited robust statistical analyses, and several challenges of PSMA-targeted fluorescence imaging.”
Summarizing the significance of their research, the authors wrote in their conclusion, “Our data show the safety and feasibility of OTL78 for PSMA-targeted fluorescence-guided surgery in patients with prostate cancer. OTL78 can intra-operatively enhance visualization of primary prostate tumors, surgical margins, residual prostate cancer in the resection bed, and nodal metastases. These promising results warrant validation in a larger cohort of patients with primary prostate cancer.”
1. Stibbe JA, de Barros HA, Linders DGJ, et al. First-in-patient study of OTL78 for intraoperative fluorescence imaging of prostate-specific membrane antigen-positive prostate cancer: a single-arm, phase 2a, feasibility trial [published online ahead of print April 13, 2023]. Lancet Oncol. doi: 10.1016/S1470-2045(23)00102-X