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

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.

Immune-related dissociated response as a specific atypical response pattern in solid tumors with immune checkpoint blockade

“…DR2 and DR3 were observed in 44% and 10% of patients, respectively, and the rate of DR1 was 8%, which was consistent with previous evaluation criteria for DR. Similarly, Wong et al 13 reported a relatively high frequency of DR (47.8%), where DR was defined as a mixed response with new lesions, as well as mixed stable and progressing or regressing lesions. Thus, the rate of DR occurrence could be overestimated because of the incorporation of stable target lesions for DR evaluation.…”

“… 11 In an open, nonrandomized, current care study, 62 NSCLC patients were scheduled to initiate immunotherapy as their first or later systemic treatment and were prospectively evaluated, and five patients developed DR. 12 Different ICI monotherapies, including nivolumab, pembrolizumab, and atezolizumab, contribute to the occurrence of DR. DR has also been found in patients receiving combination immunotherapy, such as nivolumab in combination with ipilimumab and PD-1/PD-L1 inhibitors in combination with chemotherapy, targeted therapy, or radiotherapy. 13 , 14 In a retrospective study including 360 cancer patients who participated in clinical trials for combination immunotherapy, DR was observed in 12 (3.3%) patients and PsPD in 10 (2.8%) patients. 14 Several metastatic solid tumors, including NSCLC and RCC, can develop as DR after immunotherapy.…”

“… 14 Several metastatic solid tumors, including NSCLC and RCC, can develop as DR after immunotherapy. 12 – 19 Like general atypical response patterns such as PsPD and HPD, 20 , 21 different rates of DR have been described depending on the tumor type. A combination analysis of published documents showed that there seemed to be an association between the frequency of DR and type of solid cancer, with a DR rate of 30.3% in RCC, 14.3% in endometrial carcinoma, 13.2% in NSCLC, and 12.5% in mesothelioma ( Figure 3 ).…”

“…DR occurred between 4.7% and 22.1% in four retrospective and one prospective trial involving 672 NSCLC patients from 2018 to 2021. Recently, Wong et al 13 reported that DR occurred in nearly half of patients with advanced RCC via a detailed lesion-by-lesion analysis of serial imaging. Thus, the rate of DR reported in these studies encompasses a wide range of 3.3–47.8%.…”

Abscopal Effects in Metastatic Cancer: Is a Predictive Approach Possible to Improve Individual Outcomes?

“…In addition, the abscopal response patterns were very divergent between the patients. Most patients experienced isolated abscopal responses in one to two lesions, while two patients presented a more extensive response in lung and liver [100].…”