TOPLINE:

Deferring systemic therapy — via active surveillance or metastasis-directed therapy — was associated with favorable overall survival and systemic therapy-free survival outcomes in carefully selected patients with metastatic renal cell carcinoma (RCC), a recent systematic review and quantitative analysis suggested. However, the evidence largely comes from nonrandomized studies.

METHODOLOGY:

• Metastatic RCC can advance slowly in certain patients, and these patients may benefit from deferring systemic treatment. However, the efficacy and safety of this approach remains unclear.
• To assess the impact of deferred systemic therapy on survival outcomes, researchers conducted a systematic review of 15 studies — four prospective and 11 retrospective — which included 2912 patients with metastatic RCC. Of these studies, 12 were single-arm studies and only included patients who had deferred systemic therapy (n = 654), whereas three studies compared a deferred therapy cohort with a conventional care group (n = 2258).
• Overall, most studies enrolled patients with oligometastatic disease, and approximately 90% of these patients had two or fewer metastatic sites. Researchers classified patients undergoing deferred therapy into favorable (one or no risk factors and two or less metastatic organ sites) and unfavorable groups.
• The primary outcomes were systemic therapy-free survival and overall survival. The median follow-up duration ranged from 18.0 to 54.8 months.

TAKEAWAY:

• Pooled systemic therapy-free survival rates across 10 studies (n = 1070) were 74% at 1 year, 49% at 3 years, and 37% at 5 years. Pooled overall survival rates in patients undergoing deferred therapy across 14 studies (n = 2872) were 96% at 1 year, 80% at 3 years, and 69% at 5 years.
• In the three studies comparing deferred management with systemic therapy, deferred systemic therapy was associated with significantly longer overall survival (hazard ratio [HR], 0.27; P < .001). Estimated overall survival rates were higher among patients receiving deferred therapy: 96% vs 72% at 1 year, 79% vs 56% at 3 years, and 69% vs 31% at 5 years.
• In a subgroup analysis, systemic therapy-free survival rates were higher among patients in the favorable- vs unfavorable-risk group — 88% vs 42% at 1 year and 61% vs 29% at 2 years. A favorable risk profile was associated with significantly longer systemic therapy-free survival (HR, 0.44; P = .001).

IN PRACTICE:

Deferring systemic therapy “was associated with favorable oncological outcomes in carefully-selected patients with [metastatic] RCC,” the authors concluded. However, given the quality of the available studies, “our review calls for further research in this field.”

SOURCE:

The study, led by Ichiro Tsuboi, MD, Comprehensive Cancer Center, Medical University of Vienna in Vienna, Austria, was published online in Urologic Oncology: Seminars and Original Investigations.

LIMITATIONS:

Most studies were single-arm retrospective studies, potentially leading to considerable patient selection bias and residual unknown confounding. Many studies used TKI as systemic therapy, making it challenging to apply findings directly to the current immuno-oncology era. Additionally, the protocol of active surveillance or deferred systemic therapy, including assessment timing, imaging modality types, and delayed systemic therapy timing, differed significantly across studies.

DISCLOSURES:

The study did not receive any funding. The authors reported having no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.