We found that the median survival of patients with BM from sarcomas surgically treated was comparable to that from carcinomas [63]. Additionally, postoperative KPS was improved in 50% (11/22) of the patients and postoperative mortality was 0%. Surgical resection remarkably improved KPS and the patients’ quality of life (QOL). Despite the large size of the BM, 95% of the patients underwent complete removal of the lesion, which is compatible with the data in previous reports [5, 12, 64]. These results suggest that BM from sarcomas may have features facilitating its safe and complete removal. When we select surgical removal as a treatment option for patients with BM, we ought to consider local control for not only the survival benefit but also for the immediate improvement of QOL.
Our cohort study revealed a few differences in clinical features between BM from sarcomas and that from carcinomas. Sarcomas occur in younger people than carcinomas do. The median age of the patients in this study was 45 years. Given the risk of surgery, resection may be more suitable for BM from sarcomas than for BM from carcinomas, since young people have fewer systemic complications or frailty. However, older age (30–76 years old) was a positive prognostic factor in both our cohorts and the validation group. This result contradicts that of the patients with BM from carcinomas [62]. We hypothesize on two possible reasons for this discrepancy. One is the selection bias for surgical removal in this retrospective study. Another is that adolescents and young adult patients had more aggressive sarcomas in this heterogeneous patient group.
We found that a histological diagnosis of ASPS is a significant positive prognostic factor for BM from sarcomas with surgical removal. Sarcomas include a variety of pathological diagnoses. ASPS is an extremely rare sarcoma, which accounts for about 0.5%–1% of soft-tissue sarcomas [65]. However, ASPS is characterized by a high incidence (30%) of BM [66]. In this study, patients with BM from ASPS showed significantly longer OS than those with BM from other tissue types, which is consistent with previous reports [5, 64].
We developed a new GPA system from the data of multiple institutions in Japan, and validated it with 100 cases from 48 published reports [3-5, 13-57]. This GPA comprised patients’ age and primary diagnosis because our study demonstrated only age (≥ 30 years old) and histological diagnosis of ASPS as significant preoperative prognostic factors. This GPA on surgical resection of BM from sarcomas enabled prediction of the postoperative survival. This result may help patients and clinicians to select resection as an option for treating BM from sarcomas.
Grossman et al. reported that the RTOG-RPA classification was applicable to patients who were operated on for BM from sarcomas [12]. However, we demonstrated that none of the constitutive factors of RTOG-RPA (age < 65 years old, preoperative KPS, control of primary lesion, and extracranial metastasis) presented significance as a positive prognostic factor in our cohort. Additionally, Grossman’s cohort did not contain patients with ASPS who have a high incidence of BM and significantly longer postoperative OS. Regarding age, 86% and 88% of the patients were under 65 years of age in our cohort and the validation group, respectively. Preoperative KPS > 60 was reportedly associated with a good prognosis [3, 5, 17]. However, in our cohort, KPS was dramatically improved by surgical resection, especially in patients with worse preoperative KPS, because impaired KPS often depends on neurological deficits before surgery. In addition, patients usually had extracranial metastasis when BM was detected, as our data and previous reports showed [64, 66]. On the other hand, control of the primary lesion was not significantly related to OS in our cohort. This discrepancy with previous reports may have resulted from the small size of the study, various degrees of malignancy, and heterogeneous postoperative treatments [11, 64]. Therefore, we concluded that the RTOG-RPA classification for cancerous BM is not appropriate for patients undergoing surgical removal of BM from sarcomas.
Our study has some limitations. The retrospective nature of this study is associated with potential bias of selection for surgical removal, and this study also has a small sample size because of the rarity of sarcomas with BM. Moreover, we analyzed the results in only sarcoma patients with BM surgically treated. Their pre- and postoperative treatments for BM and systemic sarcomas were heterogeneous and individualized. In addition, various subtypes of sarcomas were included in this study because of the rarity of this entity. These factors may have impacted on study outcomes and may limit the strength of the conclusions drawn here.