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Small lung micronodules at diagnosis in patients with osteosarcoma might not be a predictor of worse overall survival (OS), according to findings from a single-center study.

At 5 years, no significant OS difference was seen between 44 patients with micronodules less than 10 mm and 53 with no lung nodule at presentation (P=0.36), reported Reid Davison, a medical student at Rush Medical College in Chicago.

Closer analysis revealed that while there was no difference in 5-year OS in those with nodules smaller than 5 mm (vs no nodules), patients with 5- to 9-mm nodules had significantly shorter OS than those with 1- to 2-mm lung nodules (P=0.049) or without any nodule (P=0.021) at diagnosis, Davison said during his presentation at the virtual Connective Tissue Oncology Society annual meeting.

Even multiple nodules appeared to yield no detriment in OS when they cumulatively added up to less than 5 mm.

In the last quarter century, high-resolution CT scans have been able to show previously undetectable pulmonary micronodules (<1 cm), but it has not been well established whether their presence truly represents metastatic disease at diagnosis and or affect long-term survival chances.

"The frequent identification of micronodules on presentation leaves clinicians in a difficult position regarding the need to biopsy, resect, or follow the lesions, and whether to consider the patient metastatic or non-metastatic," Davison explained.

Furthermore, Children's Oncology Group (COG) guidelines say to remove all visible nodules via surgery, though these recommendations predate high-resolution CT.

Development of nodules <10 mm within a year of diagnosis was also examined. Here, 5-year OS was worse among patients who developed nodules within 2 months of their initial diagnosis (P=0.017) or within a year (P=0.017). But when restricted to patients with a Huvos score of 3-4, which signifies at least 51% necrosis of the primary tumor following chemotherapy, no survival differences were found.

"Our data suggest surgery or biopsy may not be necessary for several small nodules identified on presentation," Davison concluded.

"It may be necessary to define an intermediate group, between localized and metastatic disease," he continued. "This group may benefit from maintenance treatment instead of surgical resection."

Discussant R. Lor Randall, MD, of the University of California Davis in Sacramento, noted a genuine discrepancy in the literature on the relevance of micronodules in osteosarcoma, with linking indeterminate findings on chest CTs to poorer survival.

"The data is contrarian to COG guidelines," said Randall. "[It] raises some very good questions, but it's obviously controversial."

For their study, Davison and colleagues collected data on 97 osteosarcoma patients diagnosed at Rush University Hospital from 1995 to 2020 and had a CT scan within 2 months of diagnosis. Only patients under age 50 were included (mean age 20), 53% were male, and about 45% had lung nodules on presentation. Data on nodule size was taken from original patient records.

Patients with nodules of 1 cm or greater were excluded, as were those with a history or prior cancer and those who underwent surgery for a pulmonary nodule. The researchers restricted their analysis to osteosarcoma as surgery or biopsy (no radiation or chemotherapy) is seen as the only curative approach, said Davison.

All patients underwent standard treatment for their primary tumor, consisting of surgical resection along with either neoadjuvant or adjuvant chemotherapy (methotrexate, cisplatin, and doxorubicin).

For limitations, Davison noted that there were small numbers of patients among the group with larger nodules (5 to 9 mm). Also, survival was based upon analysis of patients' hospital records.

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