Plasma glycosaminoglycan (GAG) measurements can accurately distinguish metastatic clear-cell renal cell carcinoma (ccRCC) from healthy samples, and can provide accurate diagnostic and prognostic information that may be of value in managing the disease, according to new findings.
A new GAG score had 93.5% sensitivity and 94.7% specificity (discovery set) for differentiating RCC from healthy samples, and the sensitivity estimate was independently validated. The score remained independent and uncorrelated to tumor stage, grade, size, and histology, or confounders such as age or gender, according to investigators. The report is in European Oncology Urology.
The authors note that in both retrospective and prospective studies of metastatic ccRCC cases, the composition and levels of plasma and urine GAGs are significantly different when compared with healthy specimens, and GAG scores have correlated with patient outcomes including progression free and overall survival in some cohorts. But it remains unclear if the alterations in plasma and urine GAGs are limited to just metastatic cases of ccRCC or if they correlate with other histopathologic characteristics in RCC. It is also unclear if the correlation between GAG scores and prognosis is limited to patients who receive systemic therapy or if it is applicable to those who are surgically treated RCC as well.
“These results expand our knowledge on the diagnostic and prognostic potential of plasma GAGs in RCC, which was so far limited to metastatic ccRCC in our previous studies,” wrote Francesco Gatto, MD, of Chalmers University of Technology, Göteborg, Sweden, and his colleagues. “Plasma GAG alterations appear to originate as a response to the tumor and occur early if not concomitantly with tumor formation, and probably independent of its progression.”
To investigate the sensitivity and specificity of plasma GAGs for detection of early-stage RCC as well as its utility in predicting recurrence and death after RCC surgery, Dr. Gatto and his team conducted a retrospective case-control study that included 175 RCC patients who underwent surgery between May 2011 and February 2014 and 19 healthy controls.
Plasma GAGs were measured in both preoperative and postoperative RCC cases and the control group, and a discovery set was analyzed to update the historical GAG score. The sensitivity of the new GAG score that was developed for detecting RCC versus controls was then validated using the remaining samples.
In the first discovery set, which included 67 participants, the new GAG score distinguished RCC from controls with an area under the receiver operating characteristic curve (AUC) of 0.999. In their validation cohort (n = 108), the new GAG score achieved an AUC of 0.991 (95% CI 0.977-1) and at the prespecified cutoff, the validated sensitivity was 93.5%. Specificity could not be validated because the same control group was used in both sets.
Factors including tumor size, grade, and stage, radical nephrectomy, and positive surgical margins were significantly associated with overall survival as were three of five GAG properties in the new scoring system, although the new GAG score did not reach significance by itself (hazard ratio, 1.25; P = 0.08). When looking at whether the new GAG score changed after surgery, the authors found that it was quite variable across patients, and an increased score was observed for 53% of cases and a decrease for 47% after surgery. This change did not appear correlated with outcomes as shown by the recurrence rate within 2 years of surgery.
SOURCE: Gatto F et al. Eur Urol Oncol. 2018 Jun 13. doi: 10.1016/j.euo.2018.04.015.