Background:Soft-tissue sarcomas (STSs) are rare malignancies predominantly found in the extremities, comprising less than 1% of all cancers. Surgery and radiation are standard treatments for localized STS, but post-operative surveillance is crucial due to a high recurrence rate, with lungs being the primary metastasis site. Post-treatment surveillance, involving clinical visits and thoracic imaging (chest x-ray – CXR, or computed tomography – CT scan), aims to detect recurrences early, but frequent imaging can cause anxiety and lead to false positives, while treatment options for systemic disease rarely result in cure. Current surveillance guidelines lack a robust evidence base, leading to variability in practice. Methods:The Surveillance AFter Extremity Tumor SurgerY (SAFETY) randomized controlled trial is a 2X2 factorial trial designed to determine the impact of surveillance frequency (every three versus six months) and imaging modality (CXR versus CT) on overall survival and other outcomes, including patient-reported outcomes. Eligible patients for the SAFETY trial are those 18 years or older who have undergone surgical excision of their localized grade II or III STS of the extremity and are without residual disease. Patients are randomized into four groups based on surveillance frequency and imaging modality. The SAFETY trial pilot phase, coordinated by McMaster University, involved 17 clinical sites across seven countries. The pilot phase assessed feasibility of patient enrolment, protocol adherence, and data quality, as well as aggregate outcomes at the two-year surveillance follow-up time point.Results:One-hundred patients were enrolled in the pilot phase of the SAFETY trial and completed the two-year surveillance protocol. The 100 patients were enrolled from a total of 300 patients screened across 17 international sites. Minor protocol deviations were common, mostly due to unscheduled clinic visits for wound complications. Follow-up, data completeness and data quality met the a priori feasibility metric of 85%. Of the 100 patients, 15 died, 21 had metastases, seven had local recurrence and 30 experienced at least one serious adverse event. The pilot phase informed necessary adjustments for the definitive trial, including increasing the number of participating sites to meet the definitive enrolment target.Conclusions:The SAFETY trial pilot phase established feasibility of enrolment and data quality, and confirmed the need to emphasize protocol adherence in the real world setting of sarcoma care. The ongoing SAFETY trial is projected to complete enrolment in 2024 and, once follow-up is complete, is expected to provide crucial evidence to standardize surveillance practices for STS patients, ultimately improving patient management and expectations.