Active surveillance (AS) is an alternative to primary intervention (PI) in the management of small renal masses (SRMs; clinical stage T1a). However, AS remains underutilized due to a lack of strong, prospective data. We herein report mature outcomes results from the Delayed Intervention and Surveillance for Small Renal Masses (DISSRM) Registry, the world’s largest SRM clinical trial prospective registry.
Since January, 2009, the DISSRM Registry has prospectively enrolled patients with SRMs who are ≥18 years with a clinically localized, solid, enhancing renal mass ≤4.0 cm in diameter (cT1a) on axial imaging, and choose to undergo PI or AS. Patients can undergo delayed intervention (DI) or withdraw at any time. Progression-free survival (PFS) was defined as a priori at the inception of the registry based on previous retrospective data and is calculated by evidence of progression or crossover to intervention. Recurrence-free survival (RFS) was defined as freedom from any tumor recurrence or death. Protocol available at ClinicalTrials.gov (Identifier:NCT02346435).
A total of 958 were enrolled, 377(39.35%) PI and 581(60.65%) AS. The overall median follow-up time was 4.73 years (IQR: 2.13-7.18). Ultimately, 88 of 581 AS patients (15.15%) crossed over to DI after. CSS at 12-years was similar between PI and AS (99.3% vs 99.8%, respectively, log-rank P=0.43). OS was higher in patients undergoing PI compared to AS at 3-years (97.6% vs 92.9%), 6-years (92.8% vs 81.2%), 9-years (88.0% vs 63.7%), and 12-years (41.6% vs 57.9%) log-rank P<0.001. The median overall GR was 0.11 cm/year (IQR 0-0.33 cm/year), and 183 experienced a progression event. PFS was 84.3% at 3-years, 78.2% at 6-years, 77.3% at 9-years. Crossover rate is 15.16% (88/581) and was significantly different as the tumor size increases as fellow; size <2 cm;10.28% (11/107), 2 to <3 cm;16.25% (26/160); and ≥3 cm; 25.76% (51/198). RFS was not different between PI and DI (P=0.24).
With fourteen years of experience, the present analysis provides the world’s largest prospective comparison of PI to AS with or without DI. Given the absence of a randomized trial, DISSRM demonstrates the best available evidence of AS for SRM and confirms AS being non-inferior to PI as a management strategy. Additionally, the results provides an opportunity to refine the historical approach to AS, including criteria for crossover to intervention. A priori definitions of progression, including GR, do not foretell biological outcomes including adverse pathology, recurrence, or CSS, but prompt increased rates of DI with increasing GR. Tumor size at enrollment and throughout AS predicts DI and biological outcomes including adverse pathology, recurrence, and metastatic progression, and should be considered the primary trigger for DI in patients with a SRM.