Active surveillance in metastatic renal-cell carcinoma: a prospective, phase 2 trial

Abstract

Background: A subset of patients with metastatic renal-cell carcinoma show indolent growth of metastases. Because of the toxicity and non-curative nature of systemic therapy, some of these patients could benefit from initial active surveillance. We aimed to characterise the time to initiation of systemic therapy in patients with metastatic renal-cell carcinoma under active surveillance.

Methods: In this prospective phase 2 trial, we enrolled patients with treatment-naive, asymptomatic, metastatic renal-cell carcinoma from five hospitals in the USA, Spain, and the UK. Patients were radiographically assessed at baseline, every 3 months for year 1, every 4 months for year 2, then every 6 months thereafter. Patients continued on observation until initiation of systemic therapy for metastatic renal-cell carcinoma; a decision that was made at the discretion of the treating physician and patient. The primary endpoint of the study was time to initiation of systemic therapy in the per-protocol population. The follow-up of patients is ongoing.

Findings: Between Aug 21, 2008, and June 7, 2013, we enrolled 52 patients. Median follow-up of patients in the study was 38·1 months (IQR 29·4-48·9). In the 48 patients included in analysis, median time on surveillance from registration on study until initiation of systemic therapy was 14·9 months (95% CI 10·6-25·0). Multivariate analysis showed that higher numbers of International Metastatic Database Consortium (IMDC) adverse risk factors (p=0·0403) and higher numbers of metastatic disease sites (p=0·0414) were associated with a shorter surveillance period. 22 (46%) patients died during the study period, all from metastatic renal-cell carcinoma.

Interpretation: A subset of patients with metastatic renal-cell carcinoma can safely undergo surveillance before starting systemic therapy. Additional investigation is required to further define the benefits and risks of this approach.

Funding: None.

Figure 1:. Kaplan-Meier curves for time on active surveillance (A), progression-free survival (B), and overall survival (C)

Tick marks are censored patients. *22 patients died, two were lost to follow-up, and two withdrew consent.

Figure 2:. Swimmer’s plot of time on active surveillance

For patients who progressed by RECIST criteria but continued to be observed, the endpoint of their bar represents discontinuation of surveillance. RECIST=Response Evaluation Criteria in Solid Tumors.

Figure 3:. Active surveillance in patients with 0–1 IMDC risk factors and two or less organs involved with metastatic disease (favourable group) compared with all other patients (unfavourable group)

Tick marks are censored patients. IMDC=International Metastatic Database Consortium.