ZIRCON: [89Zr]Zr-girentuximab PET-CT for detecting clear-cell renal cell carcinoma
A PET scan using a radioactively-labelled antibody could tell, without surgery, whether a suspicious kidney lump was the most common type of kidney cancer - correctly in about 9 out of 10 people.
Overview
ZIRCON was a prospective, open-label, multicentre phase 3 trial at 36 sites in nine countries. Adults with an indeterminate renal mass of 7 cm or less (cT1), suspicious for clear-cell renal cell carcinoma (ccRCC) and scheduled for nephrectomy, received a single dose of [89Zr]Zr-girentuximab (37 MBq, 10 mg antibody) intravenously, followed by PET-CT 5 (±2) days later. Blinded central histopathological review of the surgical specimen was the reference standard. Co-primary endpoints were sensitivity and specificity for ccRCC detection.
Of 332 enrolled patients, 300 received the tracer and 284 were evaluable in the primary analysis. Mean sensitivity was 85.5% (95% CI 81.5-89.6) and mean specificity was 87.0% (81.0-93.1) across three independent readers; positive predictive value was around 93%. The safety profile was favourable: most adverse events occurred peri-operatively and were unrelated to the tracer, with no treatment-related deaths.
[89Zr]Zr-girentuximab (TLX250-CDx, Telix Pharmaceuticals) targets carbonic anhydrase IX (CAIX), which is highly expressed in ccRCC but not in other renal-mass pathologies (oncocytoma, papillary or chromophobe RCC, angiomyolipoma). Non-invasive discrimination of ccRCC from these mimics could reduce unnecessary biopsies and nephrectomies and guide a choice between surveillance and surgery for small renal masses - though as of this record's date the agent had not yet received a marketing authorisation.
- Mean sensitivity for ccRCC detection: 85.5% (95% CI 81.5-89.6); mean specificity: 87.0% (95% CI 81.0-93.1) across three blinded central readers.
- Positive predictive value approximately 93%, including in small and difficult-to-detect lesions (per company summary of the same dataset).
- No treatment-related deaths; most adverse events (74%) occurred during or after surgery and were unrelated to the tracer.
- Most common grade 3+ adverse events were post-procedural haemorrhage (2%), urinary retention (1%) and hypertension (1%), attributable to the surgery rather than the tracer.
A single injection and a PET scan five days later can identify clear-cell kidney cancer accurately enough to help decide whether someone with a suspicious kidney lump needs surgery, avoiding some biopsies and unnecessary operations.
- All participants were already scheduled for nephrectomy, so the trial does not directly show the agent changes management in a broader population of patients under surveillance.
- As of the paper's publication the agent (TLX250-CDx / Zircaix) was investigational, not approved by FDA or EMA.
- Performance in masses larger than 7 cm, or in patients unfit for surgery, was not the focus of this trial.
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