Renal cell carcinoma (RCC) represents around 2% of cancer-related deaths worldwide per year. RCC is an immunogenic malignancy, and treatment of metastatic RCC (mRCC) has greatly improved since the advent of the new immunotherapy agents, including immune checkpoint inhibitors (ICIs). However, it should be stressed that a large proportion of patients does not respond to these therapies. There is thus an urgent need to identify predictive biomarkers of efficacy or resistance associated with ICIs or ICI/Tyrosine kinase inhibitor (TKI) combinations; this is a major challenge to achieve precision medicine for mRCC in routine practice. To identify potential biomarkers, it is necessary to improve our knowledge on the biology of immune checkpoints. A lot of efforts have been made over the last decade in the field of immuno-oncology. We summarize here the main data obtained in this field when considering mRCC. As for clinical biomarkers, clinician and scientific experts of the domain are facing difficulties in identifying such molecular entities, probably due to the complexity of immuno-oncology and the constant adaptation of tumor cells to their changing environment.

Renal-cell carcinoma (RCC) accounts for 2% of cancer diagnoses and deaths worldwide. Clear-cell RCCs represent the vast majority (85%) of kidney cancers and are considered morphologically and genetically as immunogenic tumors. Indeed, the RCC tumoral microenvironment comprises T cells and myeloid cells in an immunosuppressive state, providing an opportunity to restore their activity through immunotherapy. Standard first-line systemic treatment for metastatic patients includes immune-checkpoint inhibitors (ICIs) targeting PD1, in combination with either another ICI or with antiangiogenic targeted therapy. During the past few years, several combinations have been approved with an overall survival benefit and overall response rate that depend on the combination. Interestingly, some patients achieve prolonged complete responses, raising the question of whether these metastatic RCC patients can be cured. This review will focus on recent therapeutic advances in RCC and the clinical and biological aspects underpinning the potential for healing.

601 Background: Immunotherapy (IO) has revolutionized the management of metastatic renal cell carcinoma (mRCC) by improving survival, overall response and complete response (CR) rates. CR is achieved in 11 to 17% with the different PD-1-based IO combinations in first-line setting of mRCC. However, local treatment of residual disease after systemic treatment exposure may improve CR rates. We performed a retrospective study to characterize patients (pts) in CR with systemic therapy alone or combined to an ablative approach of residual disease. Methods: We included all consecutive mRCC pts treated with mRCC in first-line treatment with IO combination with IO or TKI, either alone or with local treatment at the Institut de Cancérologie Strasbourg Europe. Pts were characterized according to IMDC risk group. Radiologic response was defined according to RECIST v1.1. Results: We enrolled 80 pts with mRCC between 5/2015 and 5/2022; median age was 68 (41-89) years; 75% male; 36 pts (45%) had prior nephrectomy; IMDC risk group: 12 favorable (15%), 50 intermediate (63%), 18 poor risk pts (22%), respectively; 47 pts (59%) received IO + IO, 24 (30%) received IO + TKI and 9 pts (11%) received another IO-based therapy; 35 pts (44%) achieved partial response, 23 pts (29%) stable disease, 13 pts progressive disease and 9 pts achieved CR (11%) as best response with systemic therapy alone; 10 pts out of 35 PR pts achieved CR by adding local treatment on residual disease. Among CR pts: 5 out of 19 pts had a component of sarcomatoid histology; median age was 60 years. Characteristics of pts with CR are reported in the table. Median duration of IO exposure before local therapy was 13 months. Residual disease resected sites included kidney (N = 6), lymph node (N = 4), lung metastasis (N = 2) and liver metastasis (N = 1). Local treatment was surgery for 9 pts and liver thermoablation for 1 patient. Conclusions: The resection of residual disease after first line IO-based therapy in mRCC improves CR rates (from 11% up to 24%). This approach should be considered as an option for a selected population. Prospective trials assessing this strategy should be performed in the future. Characteristics of patients in CR. [Table: see text]

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