This is the third of two previously published articles1,2 reporting utility of the cell cycle progression (CCP) score biomarker in predicting metastasis after local resection of RCC but the first to focus on its utility in pathologic T1 disease. In the prior publications, we confirmed the prognostic value of the CCP score for predicting metastatic progression after resection of organ-confined pathologic stage T2a-T3b RCC, while Morgan et al1 reported similar CCP score utility in predicting RCC aggressiveness in men of varying stage disease at the University of Michigan and at Massachusetts General Hospital. In this most recent article, we show the expression levels of the 31 cell cycle genes and 15 control genes (of the PROLARIS® test developed for prostate cancer) are also useful for determining the metastatic potential of stage T1 RCC. The median CCP score was 1.2 points greater in tumors which metastasized (0.95 versus -0.15). Furthermore, the CCP score was noted to offer a potential binary cut-point (-0.25) for identifying patients whose stage T1 tumors were aggressive enough to metastasize prior to resection. All patients (40.5% of cohort) with CCP score less than this cut-point did not demonstrate metastasis within five years. Similarly, in our first study (Askeland et al), of 17 resected pathologic T3 RCC tumors less than seven centimeters (eleven 4−7 cm and six <4 cm), metastasis only developed within five years in six (35.3%) who had a CCP score greater than -0.5.
While tumor size and growth kinetics have proven useful for identifying patients at increased risk for metastatic spread, neither is foolproof. We know some very small (<2cm) tumors can have aggressive histology, develop sarcomatoid differentiation (Current Urology article in press) or have metastasized at presentation while other small RCCs with no or negligible growth may develop metastatic disease while on active surveillance. Given we have no current curative therapy for metastatic RCC and 40.5% of our stage pT1 patients (and approximately half of pT1a patients) had CCP scores less than -0.25, this currently commercially available test has potential to improve patient selection for treatment in a significant number of patients with small RCCs. The CCP score in RCC additionally has the potential to inform how "active" active surveillance needs to be. Given the great current enthusiasm for genetic tests in the management of prostate cancer, we appear to now have a commercially available test for determining prostate cancer aggressiveness with the potential to do the same for urology's most lethal malignancy.
Written by: James A. Brown, MD, Andersen-Hebbeln Professor, Residency Program Director, Medical Director, Department of Urology, University of Iowa Healthcare
References:
- Askeland, Eric J., Vincent A. Chehval, Ryan W. Askeland, Placede G. Fosso, Zaina Sangale, Nafei Xu, Saradha Rajamani, Steven Stone, and James A. Brown. "Cell cycle progression score predicts metastatic progression of clear cell renal cell carcinoma after resection." Cancer Biomarkers 15, no. 6 (2015): 861-867.
- Morgan, Todd M., Rohit Mehra, Placede Tiemeny, J. Stuart Wolf, Shulin Wu, Zaina Sangale, Michael Brawer, Steven Stone, Chin-Lee Wu, and Adam S. Feldman. "A multigene signature based on cell cycle proliferation improves prediction of mortality within 5 yr of radical nephrectomy for renal cell carcinoma." European urology 73, no. 5 (2018): 763-769.