Timing of occurrence of the pulmonary metastases has been reported to be a significant prognostic factor [11]. According to their results, the entire patients with the pulmonary metastases were divided into four groups: patients with the pulmonary metastases identified at the initial presentation, during pre- or postoperative chemotherapy, and after the completion of the treatment. They concluded that the patients with the pulmonary metastases identified after the completion of the treatment display a markedly better prognosis than any of the other patients (P < .0001). On the other hand, OS is known as a one of tumor subtype that the patients with pulmonary metastases at initial presentation (so-called M1 tumor) can be cured by an aggressive treatment. Bacci et al. described that 91 M1 patients underwent the complete surgical resection of all metastatic nodules and received systemic chemotherapy achieved a 5-year event-free survival rate of 27.4 % [16]. Yonemoto et al. also reported that the 5-year overall survival of nine M1 patients was 64.8 % with the complete removal of average 12.7 pulmonary nodules [17]. These data encourage us to make more effort to improve the survival of this patient group.

Laterality of the metastatic nodules is also considered to be an important prognostic factor [3, 4, 6, 8, 9]. Kempf-Bielack et al. found that 52.1 % of patients with the pulmonary metastases are unilateral and that is a favorable prognostic factor for survival as examined by uni- and multivariate analyses (P < 0.001) [3]. Interestingly, Bielack et al. described that the patients with unilateral metastases are associated with the development of the ipsilateral recurrences and postulated that some of those recurrences might be derived from the local recurrences of the incompletely removed pulmonary metastasis rather than new metastasis [8].

It has been described that the patients with an involvement of more than one lobe show a poorer outcome comparing to those with single lobe [14, 18]. Wu et al. demonstrated that 85.7 % of the patients with the pulmonary metastases have more than one lobe involved and their outcome is poorer among patients with more than one lobe (5-year survival; 27.0 % vs 56.5 %, P = 0.006) [14].

Metastatic location inside the lung (central or peripheral) is also one of the predictor for survival of those patients. Letourneau et al. strongly suggested an impact of the location of the pulmonary metastases in pediatric OS patients [19]. According to their results, the median overall survival after first pulmonary metastases was 1.06 years among the patients with the peripheral location as compared with 0.38 years in those with the central location (P = 0.008).

Time interval from the initial treatment to the metastatic relapse is a representative strong predictor for the outcome (Table 19.2). Bacci et al. examined the outcome of 235 patients with relapsed OS (80 % of those are pulmonary metastases) and demonstrated that the median interval from the initial treatment to the first relapse is 25.4 months (range, 3–135 months). Interestingly, the interval was longer in the patients showing a good response to chemotherapy compared to those of a poor responder (26.2 months and 24.2 months, P < 0.04) [4]. Based on the report from St. Jude children’s research hospital, among the patients who achieved complete remission (CR) after relapse, the median interval from CR to the next relapse was shorter with the subsequent relapse [9]. Additionally, the interval from the initial diagnosis to the first relapse less than 18 months was correlated with poorer event-free and overall survivals after relapse (P < 0.0001). Similar observations showed that a longer interval to the relapse is associated with a better survival with a threshold of 12 months [10, 20], 18 months [8], and 24 months [5, 6, 13, 21].

Another striking clinical feature, pleural disruption by the pleural metastases, has been reported by COSS [3]. They defined a pleural disruption as pulmonary metastases caused by a contiguous growth into the pleural cavity, chest wall, diaphragm, or mediastinum or resulting in a malignant pleural effusion. The 5-year overall survival was 7 % or 25 % for the patients with or without pleural disruption by pulmonary metastases (P < 0.0001), respectively.