Assessing the impact of organ-specific lesion dynamics on survival in patients with recurrent urothelial carcinoma treated with atezolizumab or chemotherapy

BACKGROUND: Tumor dynamics typically rely on the sum of the longest diameters (SLD) of target lesions, and ignore heterogeneity in individual lesion dynamics located in different organs. PATIENTS AND METHODS: Here we evaluated the benefit of analyzing lesion dynamics in different organs to predict survival in 900 patients with metastatic urothelial carcinoma treated with atezolizumab or chemotherapy (IMvigor211 trial). RESULTS: Lesion dynamics varied largely across organs, with lymph nodes and lung lesions showing on average a better response to both treatments than those located in the liver and locoregionally. A benefit of atezolizumab was observed on lung and liver lesion dynamics that was attributed to a longer duration of treatment effect as compared to chemotherapy (P value = 0.043 and 0.001, respectively). The impact of lesion dynamics on survival, assessed by a joint model, varied greatly across organs, irrespective of treatment. Liver and locoregional lesion dynamics had a large impact on survival, with an increase of 10 mm of the lesion size increasing the instantaneous risk of death by 12% and 10%, respectively. In comparison, lymph nodes and lung lesions had a lower impact, with a 10-mm increase in the lesion size increasing the instantaneous risk of death by 7% and 5%, respectively. Using our model, we could anticipate the benefit of atezolizumab over chemotherapy as early as 6 months before the end of the study, which is 3 months earlier than a similar model only relying on SLD. CONCLUSION: We showed the interest of organ-level tumor follow-up to better understand and anticipate the treatment effect on survival.