Introduction:

Current standard-of-care (SOC) for detection of clear cell renal cell carcinoma (ccRCC) in patients with indeterminate renal masses (IRMs) is based on conventional imaging (CI) with contrast-enhanced computed tomography (CT)/magnetic resonance imaging (MRI) and renal mass biopsy. However, CT/MRI is limited by challenges in accurately distinguishing benign from malignant lesions, and biopsy is invasive and often nondiagnostic. There remains an unmet need for a noninvasive diagnostic technique for ccRCC that can improve risk stratification, guide clinical decision-making, and minimize overtreatment and undertreatment. The Phase 3 ZIRCON study (NCT03849118) demonstrated high accuracy for detection, localization, and characterization of ccRCC with ⁸⁹Zr-girentuximab positron emission tomography (PET)/CT. We present results from ZIRCON-X, a post-hoc analysis using data collected from ZIRCON, to evaluate the impact of ⁸⁹Zr-girentuximab PET/CT on clinical management of patients presenting with IRMs. 

Methods:

ZIRCON-X was a non-interventional, post-hoc study assessing imaging data collected during ZIRCON. Eligibility criteria of ZIRCON were previously published (Shuch et al. Lancet Oncol. 2024;25(10):1277-1287).

Four multidisciplinary teams (MDT) at independent institutions reviewed cases and made clinical management decisions using clinical/laboratory data in 2 steps; first with CI (CT/MRI) images (Step-1), and, after ≥4 weeks (to minimize bias and ensure comparison integrity), with ⁸⁹Zr-girentuximab PET/CT images (Step-2). Step-1 outcomes were not available during Step-2, but teams were able to review CT/MRI during Step-2. Each patient case was reviewed once by a single MDT. Each MDT included ≥1 nuclear medicine physician and ≥2 urologists with >5 years of experience in RCC and genitourinary PET/CT interpretation. Clinical and laboratory data were available during case reviews, but MDTs were blinded to patient histology and management decisions from ZIRCON.

Primary endpoints were proportion of patients with change in clinical management driven by ⁸⁹Zr-girentuximab PET/CT versus CI and hypothetical changes (major/minor) in clinical management based on ⁸⁹Zr-girentuximab PET/CT versus CI (Table 1).

Results:

Of 294 patients included in analysis, 143 (48.6%) would have undergone change in clinical management due to ⁸⁹Zr-girentuximab PET/CT imaging versus CI; 28/143 (19.6%) escalated treatment, 14/143 (9.8%) de-escalated treatment, 31/143 (21.7%) avoided biopsy, 25/143 (17.5%) avoided additional imaging, and 45/143 (31.5%) had other changes. Major changes in clinical management would have occurred in 110/294 (37.4%) patients due to ⁸⁹Zr-girentuximab PET/CT imaging versus CI; 24/110 (21.8%) switched from biopsy to surgery, 19/110 (17.3%) from surgery to biopsy, 18/110 (16.4%) from additional diagnostic testing to surgery, 8/110 (7.3%) from partial to total nephrectomy, 7/110 (6.4%) from surgery to additional diagnostic testing, and 6/110 (5.5%) from total to partial nephrectomy. Minor changes in clinical management would have occurred in 33/294 (11.2%) patients. ⁸⁹Zr-girentuximab PET/CT imaging increased MDT confidence in clinical management plans versus CI for 93/294 (31.6%) patients.

Conclusion:

Nearly half of patients would have had a change in their clinical management plan based on ⁸⁹Zr-girentuximab PET/CT imaging results. This study demonstrates that ⁸⁹Zr-girentuximab PET/CT has significant potential to impact clinical decision making in the diagnostic workup of patients presenting with small IRMs. Furthermore, it may offer clinical utility in guiding the escalation or de-escalation of treatment strategies.

Disclosures: This trial is sponsored by Telix Pharmaceuticals.

Funding: Telix Pharmaceuticals