The clinical significance of indeterminate pulmonary nodules in patients with primary bone sarcoma: a systematic review.

OBJECTIVE: To report the incidence of Indeterminate Pulmonary Nodules (IPN) and the rate of progression of IPN to metastasis in patients with primary bone cancers. We also aimed to evaluate clinical or radiological parameters that may identify IPNs more likely to progress to metastatic disease and their effect on overall or event-free survival in patients with primary bone sarcoma.

MATERIALS AND METHODS: A systematic search of the electronic databases Medline, Embase and Cochrane Library was undertaken for eligible articles on IPNs in patients with primary bone sarcomas, published in the English language from inception of the databases to 2023. The Newcastle-Ottawa Quality Assessment Form for Cohort Studies was utilised to evaluate risk of bias in included studies.

RESULTS: Six studies, involving 1667 patients, were included in this systematic review. Pooled quantitative analysis found the rate of incidence of IPN to be 18.1% (302 out of 1667) and the rate of progression to metastasis to be 45.0% (136 out of 302). Nodule size (less than 5 mm diameter), number (more than or equal to 4), distribution (bilaterally distributed), incomplete calcification and lobulate margins were associated with an increased likelihood of IPNs progressing to metastasis, however, their impact on overall or event-free survival remains unclear.

CONCLUSION: The risk of IPN progressing to metastasis in patients with primary bone sarcoma is non-negligible. Large IPN have a high risk to be an actual metastasis. We suggest that IPNs in these patients be followed up for a minimum of 2 years with CT imaging at 3-, 6-, and 12- month intervals, particularly for nodules measuring >5 mm in average diameter.

ADVANCES IN KNOWLEDGE: This is the first systematic review on IPN in only patients with primary bone sarcomas and proposes viable management strategies for such patients.