Study Title
Surveillance AFter Extremity Tumor surgerY (SAFETY) International Randomized Controlled Trial
Rationale
Post-treatment soft-tissue sarcoma surveillance is an integral element of patient care. Although earlier detection of metastatic disease may improve long-term survival, no study has yet provided definitive evidence to support this assumption. A thorough systematic review of the literature has identified only a single limited RCT evaluating this clinical question, and surveys of sarcoma surgeons have determined that surgeons typically follow their patients based on the way in which they were trained. The orthopaedic oncology field has identified sarcoma surveillance strategy as the top research priority in the field. In order to fill the evidence gap in sarcoma surveillance, a large international RCT is required. We, therefore, propose the SAFETY trial. In preparation for the SAFETY trial, we have completed the following preparatory work: A) establishment of a worldwide research collaborative group that spans 6 continents; B) collection of data from international sarcoma patients to determine their perceptions of sarcoma surveillance and their willingness to participate in a study in which randomization will determine their follow-up protocols; and C) the organization of a large Protocol Development Meeting with international and multidisciplinary participation, including sarcoma patient involvement, where critical aspects of the protocol were discussed and finalized.
Primary Objective
The overall objective is to determine the effect of surveillance strategy on patient survival after surgery for a soft-tissue sarcoma of the extremity by comparing the effectiveness of: A) a surveillance frequency of every three months vs. every six months; and B) CT scans vs. chest radiographs.
Secondary Objective
We will also explore: A) the effects of the post-operative surveillance strategies on patient-important outcomes (patient anxiety, overall satisfaction and quality of life), oncologic outcomes (local recurrence- and metastasis-free survival) and treatment-related complications (chemotherapy- and thoracotomy-related complications); and B) the net costs of post-operative surveillance strategies and of metastasis treatment and treatment-related complications.
Hypothesis
Because interventions for metastatic disease are not curative in the vast majority of STS patients, we hypothesize that less intensive surveillance will not be inferior to more intensive surveillance with respect to OS at 5 years.
Study Design
The SAFETY trial is a multi-center 2X2 factorial RCT of participants with extremity STS who present without metastases and who require surgical management and post-operative surveillance for local and systemic disease recurrence. Study personnel at participating clinical sites will screen patients for eligibility and, if eligible, will invite the patients to participate in the trial. Study participants will be randomized to one of four possible treatment arm:
▪ Clinical assessment and chest CT scan every 3 months for 2 years;
▪ Clinical assessment and chest CT scan every 6 months for 2 years;
▪ Clinical assessment and chest radiograph every 3 months for 2 years; or
▪ Clinical assessment and chest radiograph every 6 months for 2 years.
Randomization will occur at the end of active treatment (surgery ± systemic treatment ± local radiation) and the intervention phase will continue for a maximum of two years from the time of randomization. During this time, study participants will be assessed at intervals according to their treatment allocation. Upon completion of the 2-year ‘intervention phase’, study participants will continue to be followed in the study every 6 months for another 3 years. See the Study Flow Diagram Here
Potential Impact
Following treatment for a primary extremity sarcoma, patients remain at risk for the development of local and systemic disease recurrence. Metastasis (distant recurrence) to the lung is the most frequent single location of disease recurrence in sarcoma patients. Therefore, careful post-operative surveillance is an integral element of patient care. However, the detection of metastases does not necessarily affect long-term survival and may negatively impact quality of life. Surveillance strategies have not been well researched and have been identified as the top research priority in the sarcoma field. The SAFETY trial will provide the necessary evidence to develop evidence-based surveillance guidelines, and is poised to have a significant impact on the post-operative care and outcomes of extremity soft-tissue sarcoma patients.