Simple SummarySarcomas are rare cancers; they can arise anywhere in the body and most often spread to the lungs. When patients are diagnosed, they have a scan of the chest to look for this. The scan often finds small nodules whereby we cannot be certain whether they are cancer or not; these are called indeterminate pulmonary nodules or IPNs. We do not yet understand what the presence of IPNs means for patients with high-grade sarcomas in their soft tissues, although we know that some of these reveal themselves later on as being a spreading of the cancer. Currently, patients with IPNs normally have repeat scans a number of months down the line to see whether they have changed in size, suggesting that they may be cancer. This study has identified a number of different characteristics that make these IPNs more likely to be cancer.AbstractBackground: Sarcomas are rare, aggressive cancers which frequently metastasise to the lungs. Following diagnosis, patients typically undergo staging by means of a CT scan of their chest. This often identifies indeterminate pulmonary nodules (IPNs), but the significance of these in high-grade soft tissue sarcoma (STS) is unclear. Identifying whether these are benign or malignant is important for clinical decision making. This study analyses the clinical relevance of IPNs in high-grade STS. Methods: All patients treated at our centre for high-grade soft tissue sarcoma between 2010 and 2020 were identified from a prospective database. CT scans and their reports were reviewed, and survival data were collected from patient records. Results: 389 suitable patients were identified; 34.4% had IPNs on their CT staging scan and 20.1% progressed into lung metastases. Progression was more likely with IPNs ≥ 5 mm in diameter (p= 0.006), multiple IPNs (p= 0.013) or bilateral IPNs (p= 0.022), as well as in patients with primaries ≥ 5 cm (p= 0.014), grade 3 primaries (p= 0.009) or primaries arising deep to the fascia (p= 0.041). The median time to progression was 143 days. IPNs at diagnosis were associated with an increased risk of developing lung metastases and decreased OS in patients with grade 3 STS (p= 0.0019 andp= 0.0016, respectively); this was not observed in grade 2 patients. Conclusions: IPNs at diagnosis are associated with significantly worse OS in patients with grade 3 STS. It is crucial to consider the primary tumour as well as the IPNs when considering the risk of progression. Surveillance CT scans should be carried out within 6 months.