AUA 2018: Validation of the Preoperative Nomogram Predicting 12-Year Probability of Metastatic Renal Cancer

San Francisco, CA ( Nomograms can help guide patient management and counsel patients. In 2008, Raj et al.1 (working in conjunction with Dr. Kattan, well-known for his prostate cancer nomograms) generated a nomogram to predict 12-year probably of developing metastases in patients with cM0 clear cell renal cell carcinoma using pooled institutional data. In that original study, their nomogram, which was based on pre-operative clinical factors such as size of the primary renal mass, patient gender, evidence of lymphadenopathy or necrosis on preoperative imaging and the mode of presentation (incidental, symptomatic, etc), had a concordance index of 0.80; this exceeded TNM staging, which had a concordance index of 0.71. 

In this study, the authors aimed to assess the ability of newly identified somatic mutations in RCC to strengthen the previously published nomogram. They aimed to validate the prior nomogram and assess the added benefit of somatic mutations identified in the course of the MSK IMPACT analysis. 

MSK IMPACT is an initiative at Memorial Sloan Kettering Cancer Center to complete genetic evaluation of multiple malignancies simultaneously. They utilized capture-based next generation sequencing (NGS) assays to identify these common somatic mutations. 

Specifically retrospectively assessing 1015 patients treated at MSK between 2005-2011 with cM0 renal cell carcinoma who underwent surgery and had genetic analysis in the MSK IMPACT cohort, they first validated the original nomogram. Only 123 had complete genomics for subset analysis.  Seventy five patients experienced metastases. 12-year metastasis-free survival was 92% (95%CI:90-93%). Median follow up for survivors was 7.1 years (range:0.3-12.5). 

When assessing the original nomogram, it was associated with MFS (HR:2.89, 95%CI: 2.34-3.57, p<0.001). Discrimination was high with a CPE of 0.76, similar to the original study.  In the 123 patient with genomic analysis, the focus was on mutations in VHL, PBRM1, SETD2, BAP1, KDM5C – which had previously been identified in MSK IMPACT analysis. After accounting for the the pre-operative clinical nomogram, only the KDM5C mutation was associated with MFS (HR: 4.23, 95%CI: 1.16-15.41, p=0.028).

Based on this, the original nomogram still carries significant clinical weight. However, the genomic mutations have not been able to add much to the nomogram as of yet.

Limitations / Discussion Points:

1. Raj GV, Thompson RH, Leibovich BC, Blute ML, Russo P, Kattan MW. Preoperative nomogram predicting 12-year probability of metastatic renal cancer. J Urol. 2008 Jun;179(6):2146-51; discussion 2151. doi: 10.1016/j.juro.2008.01.101. Epub 2008 Apr 18.

Presented by: Mazyar Ghanaat, Memorial Sloan Kettering, NYC
Co-Author: Alejandro Sanchez, Cihan Duzgol, Debra A. Goldman, Kyle A. Blum, Mahyar Kashan, Maria F. Becerra, Alejandro Sanchez, Renzo DiNatale, Daniel Nassau, Jozefina Casuscelli, Nicole Benfante, Jonathan Coleman, Michael W. Kattan, Paul Russo, Oguz Akin, Irina Ostrovnaya, A. Ari Hakimi

Written by: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto, @tchandra_uromd at the 2018 AUA Annual Meeting - May 18 - 21, 2018 – San Francisco, CA USA