Role of Systemic Therapy in Localized Renal Cell Carcinoma: Where Do We Stand and Where Are We Heading?

The effectiveness of immunotherapy and targeted therapy has been well established in metastatic renal cell cancer (mRCC). These therapies demonstrated higher overall response rates and led to prolonged survival. In contrast, in localized RCC, conventional treatment is either partial or complete nephrectomy. While surgery is a curative option in early stages, high recurrence rates remain a concern, with survival rates ranging from 53% to 85%, depending on the initial stage at the time of diagnosis. Given favorable outcomes with systemic therapies in the metastatic setting, there has also been an increased interest in utilizing these therapies for the localized stage with the rationale to eradicate the micro-metastatic clone, thereby reducing the recurrence rates. Despite these encouraging developments, challenges regarding the optimal timing, duration, and combination of systemic therapies are still under investigation. Adding to that, balancing the benefits of systemic therapies with potential toxicities is also crucial, especially in patients who might otherwise benefit from surgery alone. This review describes the current landscape, ongoing clinical trials, and future directions of systemic therapy in the management of localized RCC.