Atypical Response Patterns in Renal Cell Carcinoma Treated with Immune Checkpoint Inhibitors—Navigating the Radiologic Potpourri

SIMPLE SUMMARY: Immunotherapy is now standard treatment for renal cell carcinoma but the interpretation of its efficacy based on routine imaging can be tricky. This is because atypical response patterns are increasingly recognized, giving rise to new scenarios in the patient’s treatment course. We found that many of these atypical patterns can be observed with detailed analyses of the patients’ scans. These atypical patterns challenge the use of conventional and newer tumor response criteria, opening up a range of possibilities for optimizing the efficacy of immunotherapy in renal cell carcinoma. ABSTRACT: Background: Atypical response patterns have been a topic of increasing relevance since the advent of immune checkpoint inhibitors (ICIs), challenging the traditional RECIST (Response Evaluation Criteria in Solid Tumors) method of tumor response assessment. Newer immune-related response criteria can allow for the evolution of radiologic pseudoprogression, but still fail to capture the full range of atypical response patterns encountered in clinical reporting. Methods: We did a detailed lesion-by-lesion analysis of the serial imaging of 46 renal cell carcinoma (RCC) patients treated with ICIs with the aim of capturing the full range of radiologic behaviour. Results: Atypical response patterns observed included pseudoprogression (n = 15; 32.6%), serial pseudoprogression (n = 4; 8.7%), dissociated response (n = 22; 47.8%), abscopal response (n = 9; 19.6%), late response (n = 5; 10.9%), and durable response after cessation of immunotherapy (n = 2; 4.3%). Twenty-four of 46 patients (52.2%) had at least one atypical response pattern and 18 patients (39.1%) had multiple atypical response patterns. Conclusions: There is a high incidence of atypical response patterns in RCC patients receiving ICIs and the study contributes to the growing literature on the abscopal effect. The recognition of these interesting and overlapping radiologic patterns challenges the oncologist to tweak treatment options such that the clinical benefits of ICIs are potentially maximized.