Novel urine test shows promise for kidney cancer recurrence surveillance

The urine GAGome score appears to be a promising biomarker for detecting clear cell renal cell carcinoma (ccRCC) recurrence, findings from the AURORAX-0087A trial suggest.

“Recurrence rate in ccRCC is high (~20 percent 5 years after surgery) and there are no approved liquid biomarkers in ccRCC,” said Associate Professor Saeed Dabestani from Lund University in Sweden, at EAU25. Moreover, current follow-up protocols are suboptimal for early detection of potentially curable recurrences, as monitoring (via CT scan every 6–12 months) is typically stage- or risk-based.

“CT scans often pick up small lesions that are not large enough to biopsy, and we currently do not know whether they are a sign of the cancer returning or not,” Dabestani noted. “Our only option is to do more frequent scans to monitor more closely, which is unpleasant for patients and often brings little benefit.”

“If you have a urine test that can accurately show whether the cancer has returned, then you can better assess risk levels and reduce the frequency of scans required,” he continued.

GAGomes are specific profiles of different glycosaminoglycan (GAG) molecules found in biological fluids (eg, urine) through mass spectrometry, which are found to be deregulated in cancer patients. A GAGome score (ranging between 0 and 100 points) is a composite biomarker representing a numerical result of applying a mathematical model to measured GAGomes. [FEBS J 2012;279:1177-1197; Eur Urol Open Sci 2024:68:40-47]

The study included M0 ccRCC patients who had been curatively treated with partial or radical nephrectomy and had an intermediate-to-high recurrence risk (Leibovich Points [LP] ≥5). Of the 134 patients (median age 66 years, 69 percent men, median LP 6) in cohort 1, 21 (15.7 percent) had radiological recurrence* after a median follow-up of 15 months.

The GAGome score had 90-percent sensitivity, 51-percent specificity, 26-percent positive predictive value (PPV), and 97-percent negative predictive value (NPV).

These results imply that the GAGome score identified 90 percent of patients who had recurrence and over half who remained cancer-free, a 26-percent chance of an actual recurrence, and more importantly, a 97-percent chance of not having a recurrence.

“With regard to prognostic performance, for each 10-point increase in GAGome score, the likelihood of recurrence went up by 62 percent (hazard ratio, 1.62),” said Dabestani.

Lead time (time between first GAGome recurrence and confirmation of radiological recurrence) was 4.2 months earlier for GAGome recurrence. However, Dabestani noted that this may have been underestimated due to the short follow-up (18 months). The limited follow-up may have also underestimated recurrence-free survival and introduced bias specificity.

Takeaways

“[Nonetheless,] the negative test (NPV) strongly rules out recurrence, and the lead time reflects early recurrence detection. A negative test may halve CT scans (considering the lead time), while a positive test warrants guideline-based follow-up,” Dabestani said. “[The GAGome score] could reduce unnecessary imaging, lowering radiation exposure and healthcare costs.”

The GAGome score has yet to receive approval for clinical use in diagnostic procedures. Follow-up is ongoing, and results from cohort 2 shall validate its effectiveness in clinical practice.

A stepping stone for developing biomarkers

EAU Scientific Congress Office member Dr Carmen Mir Maresma from the University Hospitals La Ribera, Valencia, Spain, said, “Developing biomarkers for kidney cancer is a major challenge. This study provides a stepping stone towards that goal. The results are interesting [because] the test showed a high NPV. If the test comes back negative, you can be more or less sure there is no cancer recurrence, but if it is positive, then we need to look further.”

She added that the test provides a more robust basis for formulating treatment decisions because it is based on a suite of biomarkers rather than just one molecule.

Maresma noted that further investigation is needed to determine whether early recurrence detection will save patients’ lives. “Changes in postop treatment are also underway, with some countries licensing the immunotherapy pembrolizumab for kidney cancer. More research will also be needed to understand how this biomarker interacts with that therapy.”