Dr Nawfal on the Rationale for Assessing Radiological Tumor Burden in mccRCC

Rashad Nawfal, MD, postdoctoral research fellow at Dana-Farber Cancer Institute, discusses the rationale for assessing the independent prognostic value of radiological tumor burden for survival outcomes with first-line immuno-oncology (IO)-based regimens in metastatic clear cell renal cell carcinoma (ccRCC), as well as the potential utility of radiological tumor burden for guiding first-line immunotherapy selection for patients with this disease.

RECIST 1.1 is a widely used method to calculate tumor burden in clinical trials by assessing up to 5 measurable lesions, with a maximum of 2 lesions per organ, Nawfal begins. However, this approach does not provide a comprehensive reflection of the total tumor burden in the body, he says. Limited data have indicated a potential link between radiological tumor burden and survival outcomes in patients treated with VEGF TKIs, Nawfal reports. However, there has been a lack of data on the relationship between radiologic tumor burden for outcomes with first-line immuno-oncology (IO) regimens, he notes. To address this gap, Nawfal and colleagues conducted a study evaluating the prognostic significance of radiological tumor burden, as calculated by RECIST 1.1 criteria, in patients with metastatic ccRCC treated with first-line IO-based therapies.

Results from this investigation were presented at 

. At a median follow-up period of 44.8 months, the study showed that baseline radiological tumor burden was an independent prognostic factor for overall survival (OS) in this patient population. Specifically, each 1 cm increase in baseline radiological tumor burden was associated with a 5% increase in OS events (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.03-1.08; P < .0001). This prognostic value persisted even after adjusting for multiple variables, including previous nephrectomy, IMDC risk group, and the presence of metastases in the brain, bone, or liver prior to initiating frontline therapy (HR, 1.04; 95% CI, 1.00-1.08; P = .03).

Given its simplicity and prognostic relevance, baseline radiological tumor burden could become an important factor in initial assessments before starting first-line therapy for metastatic ccRCC, Nawfal states. The next steps involve validating these findings across different clinical trial cohorts and assessing inter-radiologist variability in tumor burden calculations, he details. If these efforts confirm its prognostic utility and reproducibility, radiological tumor burden could be routinely included in the evaluation of patients before beginning IO-based regimens, potentially guiding treatment decisions and improving patient outcomes, Nawfal concludes.

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Rashad Nawfal, MD, discusses radiological tumor burden as an independent prognostic factor for survival in metastatic clear cell renal cell carcinoma.

Dr Nawfal on Radiological Tumor Burden as an Independent Prognostic Factor of Survival in mccRCC

Rashad Nawfal, MD, postdoctoral research fellow at Dana-Farber Cancer Institute, discusses the efficacy of radiological tumor burden as an independent prognostic factor for survival in patients with metastatic clear cell renal cell carcinoma (mccRCC) treated with first-line immuno-oncology (IO)-based regimens.

Data were reviewed from 183 patients with mccRCC treated at Dana-Farber Cancer Institute between August 2014 and October 2023. These patients received at least one dose of an IO-based regimen, including combinations of dual immunotherapy agents or an IO agent plus a VEGF inhibitor. Of the 150 patients included in the study, 9% had favorable risk, 51% had intermediate risk, and 20% had poor risk by International Metastatic RCC Database Consortium (IMDC) criteria. Additionally, 73% of patients had undergone nephrectomy prior to first-line therapy initiation, and 41% had metastases in the brain, bone, or liver.

Results from the abstract were presented at the 

 Summit with median follow-up of 44.8 months. The findings demonstrated that baseline radiological tumor burden is an independent prognostic factor for overall survival (OS) in this population, as every 1 cm increase in baseline radiological tumor burden was associated with a 5% increase in OS events (HR, 1.05; 95% CI, 1.03-1.08; 

 < .0001). This finding remained significant after multivariable analysis (HR, 1.04; 95% CI, 1.00-1.08; 

 = .03), which accounted for variables such as previous nephrectomy, IMDC risk group, and the presence of metastases in the brain, bone, or liver prior to frontline therapy.

The study also categorized baseline radiological tumor burden by tertiles: tertile 1 (0-7.5 cm), tertile 2 (7.6-15.3 cm), and tertile 3 (15.4-47.7 cm). The 4-year OS estimates were 84% (95% CI, 74%-97%) for the first tertile, 60% (95% CI, 45%-81%) for the second tertile, and 43% (95% CI, 29%-66%) for the third tertile (log-rank 

 < .0001). Nawfal also notes that although baseline radiological tumor burden was a significant predictor of OS, it did not show a significant association with time to treatment failure (TTF) or time to next treatment (TTNT) on both univariable and multivariable analyses.

Overall, the results underscore the utility of baseline radiological tumor burden as a prognostic marker for OS in patients with mccRCC treated with IO-based regimens, Nawfal says. These findings may support integrating radiological tumor burden assessments into routine clinical practice to improve prognostic accuracy and guide treatment decisions for better patient outcomes.

Rashad Nawfal, MD,

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Dr Nawfal on the Rationale for Assessing Radiological Tumor Burden in mccRCC

Dr Nawfal on Radiological Tumor Burden as an Independent Prognostic Factor of Survival in mccRCC