(UroToday.com) The 2023 European Association of Urology (EAU) annual congress held in Milan, Italy between March 10th and 13th, 2023 was host to a game changing session. Dr. Maria Carmen Mir led the discussant session following Professor Peter Mulders’ earlier presentation of the phase 3 ZIRCON trial results.
Dr. Mir highlighted that non-invasive diagnostic tests for the characterization of renal masses are sorely needed. Renal mass biopsy (RMB) is operator dependent, and 20-30% of RMBs are non-diagnostic, depending on tumor size. 20% of renal masses >4 cm are benign, with this figure as high as 40% in small renal masses. As such, ZIRCON is a much-needed phase III prospective single arm trial evaluating 89Zr-DFO-girentuximab in patients with cT1 renal masses detected on CT or MRI. Fortuitously, girentuximab is excreted via the liver.
What are the important test performance characteristics to consider for such a test in this setting?
- Test accuracy, specificity, and negative predictive value
- Radiation exposure
- Adverse events
- Inter-reader variability
- Cost-effectiveness thresholds
- Long-term surrogate endpoints
Putting these characteristics into perspective for 89Zr-DFO-girentuximab PET, the negative predictive value was 75% (i.e. a negative PET was false 25% of the time). There were 28 cases of false negative readings, whereby patients had a negative PET findings, yet were found to have a clear cell RCC on pathologic evaluation.
Can we draw parallels from the PRIMARY PSMA-PET trial in prostate cancer?1 PRIMARY was a prospective, multicenter phase II trial that included 291 patients with suspected PCa, no prior biopsy, and a recent mpMRI examination (6 mo) and for whom prostate biopsy was planned. In total, 291 men underwent a mpMRI, a pelvis-only 68Ga-PSMA PET/CT, and a systematic biopsy with or without targeted biopsy. With respect to the outcome of clinically significant prostate cancer, 68Ga-PSMA/PET/CT had the following performance characteristics:
- Sensitivity: 88%
- Specificity: 66%
- PPV: 76%
- NPV: 81%
As such, we can see that 89Zr-DFO-girentuximab PET actually outperforms 68Ga-PSMA/PET/CT in the corresponding primary diagnostic setting.
How do the results from 89Zr-DFO-girentuximab PET compare to those from contrast-enhanced CT? A UCLA retrospective analysis from UCLA evaluated the performance characteristics of multiphasic CT (4 phases) in 289 patients (170 with clear cell RCC) who subsequently underwent a nephrectomy. The objective was to determine if the enhancement patterns helped to discriminate clear cell from other subtypes. As demonstrated in the table below, the sensitivity, specificity, PPV, and PVs were 94%, 62%, 86%, and 81%, respectively.
When compared to the results from the ZIRCON trial, we see that 89Zr-DFO-girentuximab PET outperforms contrast-enhanced CT with respect to specificity (87% versus 62%) and subsequent PPV (93% versus 86%). However, it appears that CT has a higher sensitivity (94% versus 86%) and subsequent NPV (81% versus 75%).
We must also keep in mind the radiation exposure with 89Zr-DFO-girentuximab PET. The total radiation exposure is 21mSv, compared to 16mSV with a CT abdomen/pelvis.
Revisiting the critical test performance characteristics needed in this setting, how does 89Zr-DFO-girentuximab PET perform?
- Test accuracy, specificity, and negative predictive value: Equivocal
- Radiation exposure: Higher (21 mSv vs 16 mSv)
- Adverse events: Minimal
- Inter-reader variability: Acceptable (0.92)
- Cost-effectiveness thresholds: Unknown
- Long-term surrogate endpoints: Unknown
Dr. Mir concluded that these positive results suggest that 89Zr-DFO-girentuximab improves the identification of primary clear cell RCC compared to cross-sectional imaging. 89Zr-DFO-girentuximab has the potential to improve management by aiding risk stratification, selecting appropriate patients for treatment, or suggesting where further imaging/biopsy could be indicated. 89Zr-DFO-girentuximab holds promise to improve staging in clear cell RCC, therapeutic target (radiopharmaceutical), or image other solid tumors (true hypoxia) all of which are ongoing initiatives.
Presented by: Dr. Maria Carmen Mir, MD, PhD, FEBU, Department of Urology, Fundacion Instituto Valenciano Oncologia, Valencia, Spain
Written by: Rashid K. Sayyid, MD, MSc – Society of Urologic Oncology (SUO) Clinical Fellow at The University of Toronto, @rksayyid on Twitter during the 2023 European Association of Urology (EAU) Annual Meeting, Milan, IT, Fri, Mar 10 – Mon, Mar 13, 2023.
References: