IKCS 2022: Using Proper Risk Stratification and How to do it Accurately

(UroToday.com) The tenth session of the 2022 International Kidney Cancer Symposium (IKCS): North America meeting focused on risk stratification in renal cell carcinoma (RCC). In this context, Dr. Daniel Heng presented on prognostic factors in metastatic kidney cancer.

Beyond integrative risk factors such as the IMDC risk model or the MSKCC risk model, he noted numerous other prognostic factors including characteristics of the tumor microenvironment (typically associated with worse prognosis), immune-related adverse events (typically associated with improved prognosis), tumor burden, inflammation markers, nutrition, and body composition.

He noted that there are many models in mRCC including the MSKCC, CCF, French, IKCWG, and IMDC prognostic models. The MSKCC risk criteria developed in interleukin and interferon era. He emphasized that, despite significant overlap, there are marked differences between the prognostic models.

While the IMDC risk groups have been extensively validated, there is an ongoing interest to assess whether the addition of additional characteristics may improve its performance. He noted that bone metastases, liver metastases, elevated NLR, elevated CRP, non-clear cell RCC, and papillary RCC histology is independently associated with survival. However, Dr. Heng noted that adding these characteristics to the IMDC model increases complexity without significantly improving the model’s performance (as determined with c-index or other criteria).

Currently, he noted that the International mRCC Database Consortium includes more than 13,000 patients at more than 40 international institutions. As has been well characterised, the IMDC prognostic factors include six characteristics, Karnofsky performance status, time from diagnosis, hemoglobin, neutrophil count, platelet count, and corrected serum calcium. These factors are used to categorize patients into three risk groups: favourable (0 points), intermediate (1-2 points), and poor (3 or more points). Dr. Heng highlighted the importance of the time from diagnosis to treatment interval of less than a year. He noted that the use of adjuvant therapy doesn’t count as systemic therapy. This information is clearly informed by an estimation of the urgency for systemic therapy which can in turn be useful in deciding on the role of upfront cytoreductive nephrectomy.

He noted that the IMDC risk groups were derived in the context of the VEGF-targeted therapy era. In this context, median overall survival differed dramatically between risk groups: 43 months in patients with favourable risk disease, 23 months in those with intermediate risk disease, and 8 months in those with poor risk disease.

He noted that the IMDC group has developed an online risk calculator that may be used to inform patient counseling and care. Importantly, given changes in the standard of care for first-line therapy over the past few years, recent works have demonstrated that the IMDC risk groups still provide prognostic value with updated treatment approaches including combination therapy with immune checkpoint inhibition and VEGF-targeted therapy or dual immune checkpoint inhibition.

In terms of putting these prognostic factors into practice, Dr. Heng emphasized their value in patient counseling, clinical trial design and stratification, adjustment in observational research, and in patient treatment selection.

While the IMDC risk groups are premised on clinical and laboratory characteristics, Dr. Heng then turned his attention to a genomic approach to prognostication. He emphasized data from IMmotion151 from Drs. Motzer and Rini. In Dr. Heng’s view, this approach is “not ready for primetime yet” and there are numerous other genomic classification approaches, of which the dominant one has yet to be determined.

While developed in the context of a predictive approach for treatment selection, Dr. Hen suggested that these models may also provide prognostic information. In part, this is due to a correlation with existing prognostic factors. Thus, for clinical utility, there needs to be work in terms of optimizing accuracy and performing external validation.

In conclusion, Dr. Heng noted that IMDC models continue to provide clinically significant risk stratification in mRCC. It remains to be seen whether the addition of genomics can improve model performance, in terms of improving the c-index. However, its clear that overall survival benchmarks for each IMDC risk group have improved as we transition from the targeted therapy era to current combination immune checkpoint inhibition.