{"entity":{"id":"paper-zircon-lancet-oncol-2024","kind":"paper","name":"ZIRCON: [89Zr]Zr-girentuximab PET-CT for detecting clear-cell renal cell carcinoma","aka":[],"tldr":"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.","summary":"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.\n\nOf 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.\n\n[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.","asOf":"2026-09-22","links":[{"label":"PubMed: ZIRCON trial (Lancet Oncol 2024)","url":"https://pubmed.ncbi.nlm.nih.gov/39270701/"},{"label":"Telix Pharmaceuticals: ZIRCON results announcement","url":"https://telixpharma.com/news-views/highly-accurate-telixs-phase-iii-zircon-trial-for-kidney-cancer-imaging-published-in-the-lancet-oncology/"}],"tags":["renal cell carcinoma","PET imaging","CAIX"],"related":["girentuximab-zr89","caix-pet","rcc","immuno-pet","telix","zr-89"],"indications":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"journal":"Lancet Oncology","year":2024,"doi":"10.1016/S1470-2045(24)00402-9","pmid":"39270701","authors":"Shuch B, Pantuck AJ, Bernhard JC, Morris MA, Master V, et al.","paperType":"rct","findings":["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."],"whatItMeans":"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.","caveats":["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."],"changedPractice":false,"participants":300},"route":"/key-papers/paper-zircon-lancet-oncol-2024/","neighbours":{"drug":[{"id":"girentuximab-zr89","kind":"drug","name":"Zirconium-89 girentuximab","route":"/drugs/girentuximab-zr89/"}],"technology":[{"id":"caix-pet","kind":"technology","name":"CAIX PET (89Zr-girentuximab)","route":"/technologies/caix-pet/"},{"id":"immuno-pet","kind":"technology","name":"Immuno-PET","route":"/technologies/immuno-pet/"}],"indication":[{"id":"rcc","kind":"indication","name":"Renal cell carcinoma","route":"/indications/rcc/"}],"company":[{"id":"telix","kind":"company","name":"Telix Pharmaceuticals","route":"/companies/telix/"}],"isotope":[{"id":"zr-89","kind":"isotope","name":"Zirconium-89","route":"/isotopes/zr-89/"}]}}