Impact of site of metastatic involvement on IMDC classification in metastatic renal cell carcinoma patients treated with immunotherapy.
Authors: Laia Fernandez-Mañas, Irene Ortiz, Javier Pozas, Chloe Beland, James Larkin, Alba Moll-Febrer, Laura González-Aguado, Judit Sanz Beltran, Georgia Anguera, Nil Navarro, Alejo Rodriguez-Vida, Silvia Rubio Novella, Marina Sierra, Alicia Carrasco, Nuria Sala González, Eleonor Paola Murata Yonamine, Iria González Maeso, Mariona Figols, Maria Marin Alcalá, Òscar Reig
Journal: Journal of Clinical Oncology (2025)

483 Background: The IMDC risk classification is indispensable for managing metastatic renal cell carcinoma (mRCC) patients (pts). However, it was not developed for pts treated with immunotherapy (ICI) and lacks certain clinically relevant prognostic factors. We aim to explore whether the site of metastatic (SM) involvement can improve prognostic accuracy, as organotropism may be dictated by the underlying tumor's biology. Methods: This multicenter retrospective study analyzed ICI-treated mRCC pts from 2015 to 2023. Overall survival (OS) and progression-free survival (PFS) were evaluated using Kaplan-Meier and multivariate Cox regression analyses. We developed a new score, IMDC-SM, by incorporating SM independently associated with OS into the IMDC classification. Model fitness was assessed using the AIC and BIC. Results: 525 pts were enrolled (73% male, 87% clear cell RCC, 10% with sarcomatoid dedifferentiation), including 191 (36.4%) pts treated in first line (1L). Among pts in 1L and ≥2L, 25% and 18%, 56% and 60%, and 25% and 22% were classified as favorable risk (FR), intermediate risk (IR), and poor risk (PR) by IMDC, respectively. In 1L cohort, most pts were treated with ICI + ICI (56%) and ICI + tirosine kinase inhibitors (38%). 70% of pts had lung involvement, 50% nodal, 29% bone, 20% adrenal, 17% liver, 16% tumoral thrombosis, 9% pleural, 9% peritoneal carcinomatosis, and 7% pancreatic involvement. Pleural, bone, and adrenal metastases were independently associated with worse OS in the multivariate analysis after adjusting for IMDC classification, age, sarcomatoid or rhabdoid dedifferentiation and histology. These SM were incorporated into the IMDC, adding 1 point for each SM present, to create the IMDC-SM score. Using the IMDC-SM, in 1L setting, 16 pts (8%) were reclassified from FR to IR and 28 pts (15%) from IR to PR Results of mOS and mPFS in 1L using both scores are shown in the table. IMDC-SM demonstrated better performance than the original IMDC classification for both in OS (Table). Within PR pts, those with ≥5 points had the worst mOS and mPFS (7 and 5.8m) than the remaining PR pts (24 and 14m). When applying the SM-IMDC in ≥2L pts 31 (9%) were reclassified from FR to IR, 66 pts (20%) from IR to PR and 1pt (0,2%) risk changed from FR to PR. The IMDC-SM classification also shows a superior prognostic value (Table). Conclusions: Combining site of metastasis information with the IMDC classification into a single scoring system significantly improves prognostic accuracy in ICI-treated mRCC pts, in both 1L and 2L. A validation cohort is necessary to determine a prediction model’s reproducibility. Group Risk Score 1L 2L N mOS (m) mPFS (m) N mOS (m) mPFS (m) FR IMDCIMDC-SM 4731 NANA NANA 5927 3748 1015 IR IMDCIMDC-SM 9684 4254 1318 198164 2026 88 PR IMDCIMDC-SM 4876 1521 1212 76142 58 33 OS-AIC IMDCIMDC-SM 691.5686.2 2404.72397.5 OS-BIC IMDCIMDC-SM 696.2690.9 2411.72404.5