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Molecular Testing Shows Promise for Predicting Outcomes of Patients with RCC

Key findings

  • Results from a 31-gene cell cycle proliferation (CCP) assay were strongly associated with mortality and recurrence after radical nephrectomy for renal cell carcinoma (RCC)
  • CCP score provided prognostic information that was additional to the Karakiewicz nomogram
  • A combination of the CCP score and Karakiewicz nomogram demonstrated excellent ability to predict cancer-specific mortality after nephrectomy
  • Using prespecified categories, the combined score identified a low-risk group of patients who had a 99% probability of five-year survival
  • These results suggest a potential role for molecular testing in RCC

Certain gene mutations are now known to have a substantial influence on survival in renal cell carcinoma (RCC). However, in localized tumors, individual mutations are not very accurate for predicting survival. An RNA expression assay that measures the activity of genes involved in cellular proliferation, currently utilized clinically as a prognostic marker in men with prostate cancer, may be helpful in identifying new prognostic markers and improving survival prediction.

A research team led by Adam S. Feldman, MD, MPH, director of Urology Research at Massachusetts General Hospital, determined that an existing cell cycle proliferation (CCP) assay provides additional RRC prognostic information in combination with the Karakiewicz nomogram, which considers clinical characteristics. Specifically, a weighted combination of the CCP score and the nomogram, called the R-CCP score, demonstrated excellent ability to identify patients at high-risk of cancer-specific mortality. The study was reported in European Urology.

The researchers reviewed archival tissue samples from patients who underwent radical nephrectomy for RCC at Mass General from 2000 to 2007 or at the University of Michigan from 2000 to 2009. Altogether, 565 patients with localized clear cell, papillary or chromophobe RCC were included who had at least 37 days of follow-up.

The researchers compared CCP scores, which they calculated based on expression of 31 cell cycle genes, with the Karakiewicz nomogram.

The CCP score correlated moderately with scores on the Karakiewicz nomogram, the researchers found, and the score was used to further stratify patients within a given nomogram risk score. A higher CCP score was associated with substantially increased risk of cancer-specific mortality (hazard ratio [HR] per interquartile range [IQR], 3.38; 95% confidence interval [CI], 2.21–5.16).

Multivariable analysis showed that the CCP score provided prognostic information that was added to the clinicopathologic factors included in the Karakiewicz nomogram. Specifically, when the analyses were adjusted only for nomogram score, CCP score was independently associated with both cancer-specific mortality (HR per IQR, 2.49; 95% CI, 1.53–4.04; P < .001) and the risk of cancer recurrence (HR per IQR, 1.50; 95% CI, 1.07–2.09; P = .016).

To create an even more robust prognostic model, the researchers created the R-CCP score, which calculates the weighted average of the CCP score and the nomogram score. The R-CCP scores ranged from –1.28 to 6.92. Using a prespecified method, the researchers classified patients with scores of –1.28 to 2.87 as being at low risk and those with scores over 2.87 as being at high risk.

Patients who were classified as high risk did demonstrate a greater likelihood of cancer-specific mortality within five years, compared with low-risk patients (P < .001). The R-CCP score outperformed the nomogram score at predicting mortality at five years.

The researchers comment that the R-CCP risk prediction model might be especially useful for the two extremes of the RCC patient population:

  • Patients with newly detected, low-risk disease who are considering what the initial management should be, and who need better characterization of the malignant potential of small renal masses than imaging and histology can provide
  • Patients with high-risk disease who might benefit from adjuvant therapy following nephrectomy

Before the R-CCP model can be used in clinical practice, it will need to be validated in an independent group of patients.

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