Oncological outcomes of deferred systemic therapy for patients with metastatic renal cell carcinoma: A systematic review and quantitative analysis

Background and Objective While some patients with metastatic renal cell carcinoma (mRCC) may experience an indolent disease progression and could benefit from deferred systemic therapy (ST), including active surveillance (AS) or metastasis-directed therapy (MDT), the evidence on its oncological efficacy and safety are still not well-established. We aimed to provide an overview of the available evidence on oncological outcomes of patients with mRCC undergoing deferred ST. Methods A systematic review of the literature was conducted in August 2024 using the PubMed, Scopus, and Embase databases to identify prospective and retrospective studies evaluating AS or deferred ST for patients with mRCC (PROSPERO ID: CRD42024579021). The co-primary outcomes were ST-free survival (ST-FS) and overall survival (OS). A random-effects model was used for quantitative analysis. Key Findings and Limitations We identified 15 eligible studies including 2,912 patients. Of these, 4 were prospective (n = 589 patients) and 11 were retrospective (n = 2,323 patients). The estimated 1-, 2-, 3-, 4-, and 5-year ST-FS rates (n = 1,070) were 74%, 54%, 49%, 43%, and 37%, respectively. The estimated 1-, 2-, 3-, 4-, and 5-year OS rates (n = 2,872) were 96%, 89%, 80%, 71%, and 69%, respectively. Key limitations at a study-level included selection bias, unmeasured confounding, and variability across deferred ST/AS protocols, including the indications for metastasis-directed therapy. Moreover, most studies used tyrosine kinase inhibitors as ST. The proportion of patients receiving MDT, including metastasectomy or stereotactic body radiation therapy, ranged from 14 to 100%. Conclusions and Clinical Implications Deferring ST by AS or MDT was associated with favorable oncological outcomes in carefully-selected patients with mRCC, highlighting the potential value of this approach in the contemporary multidisciplinary management of mRCC. Considering the limitations of available evidence and the lack of data on the oncological efficacy and safety of deferred ST for mRCC in the immune-oncology era, our review calls for further research in this field.