Response Evaluation Criteria in Metastatic Renal Cell Carcinoma: Improved Assessment of Response and Progression by Spectral-CT

Response evaluation criteria in metastatic renal cell carcinoma: Improved assessment of response and progression by Spectral CT?

Clinical Background

Renal cancer accounts for 2-3% of all cancers. The incidence of renal cancer in Denmark is approximately 900 new cases per year. Renal cell carcinoma (RCC) arises from the renal parenchyma and is by far the most common type. In 20-30% of all new cases, metastases exist at the time of diagnosis. Up to 25-50 % of patients treated with nephrectomy for localized RCC will eventually develop metastases. Untreated, the 5-year survival rate for metastatic RCC (mRCC) is 2%, and the median survival is 3 months. Within the last 10 years, an increased understanding of kidney cancer biology, and the immune system, has resulted in the development and approval of more than 12 new biological drugs. These are characterized by inhibiting the formation of new blood vessels (angiogenesis inhibitors) or by activating the patient's own immune system to attack the cancer disease (check-point inhibitors). Survival has significantly improved for the patient group with these drugs. The treatment results in control of tumor growth in the majority of patients, for a certain length of time, but should be given continuously, has side effects, and is expensive. In case of disease progression, treatment is changed to another drug. Thus, treatment for mRCC comprises sequential alternating drugs for as long as possible. However, progression is difficult to characterize at the right time and approximately 50 % of the patients are 'lost' to further treatment at the time of progression and die. The investigators therefore need improved diagnostic tools for early or more accurate detection of treatment failure, resulting in appropriate change of therapy at the right time. Routinely, treatment efficacy is evaluated by CT scans at baseline and every 3 months, using the criteria laid out in RECIST 1.1 (Response Evaluation Criteria In Solid Tumors). When interpreting the CT scan, the sizes of target lesions are measured, and an increase in the sum of target lesions by 30%, or the appearance of a new lesion, are interpreted as disease progression. However, the size of the tumor does not necessarily represent biological and physiological changes within the tumor; Tumors treated with angiogenesis inhibitors may show little or no change in tumor size, or may enlarge slowly during therapy, in spite of clinical benefit to the patient and extended time-to-progression. New lesions or tumor enlargement may be seen as part of pseudo-progression in patients treated with check-point inhibitors.

Therefore, the criteria from RECIST 1.1, despite being the best available at the moment, are far from an optimal tool for evaluating response and progression in patients with mRCC treated with biological therapy.

Recent studies from the research group behind the current pH.D. project have shown that functional imaging with Dynamic Contrast Enhanced Computer Tomography (DCE-CT) was able to measure changes in blood flow over time in a single metastasis. Using DCE-CT, the best clinical effect of angiogenesis inhibitor therapy was seen in patients with the greatest decline in blood volume and blood flow, measured after 1 month of treatment compared with baseline. In contrast, patients with low blood volume and low blood flow at baseline had the worst survival, with almost no benefit from treatment, regardless of whether they were treated with angiogenesis inhibitors or immunotherapy.