Prognostic factors in spinal chordoma: An update of current systematic review and meta‐analysis

Dear Editor, We read with great interest the recent article entitled “Prognostic factors in surgical resection of sacral chordoma” by Angelini et al. The authors performed a retrospective cohort analysis of 71 patients in a single center. They found that tumor volume was an independent prognostic factor of local recurrence-free survival (LRFS), while resection level, tumor volume, and surgical margin were independent predictors of overall survival (OS) in the patients on multivariate analysis. We commend the authors for performing this interesting study as these helpful results would be useful to make a balanced treatment decision. However, we noted that the authors did not find extent of tumor invasion or worse preoperative Frankel score to be an independent predictor, which contradicts the results from previous studies. To date, an increasing number of clinical and histopathologic factors as well as molecular biomarkers have been investigated for their association with spinal chordoma prognosis, but the results are still inconclusive or controversial. We previously performed a systematic review on prognostic factors in spinal chordoma, but no definitive conclusions could be derived due to heterogeneity and the scarcity of included studies. Furthermore, several recent studies involving large sample sizes and long-term results published in 2015 or 2016were not included in this literature review. Therefore, we believe an updated systematic review is required. The aim of this study was to systematically review the prognostic factors in spinal chordoma and to establish pooled estimates of the effect of specific prognostic factors by performing a meta-analysis. A total of 18 papers (Supplementary material 1) met the initial methodological criteria and were thus included. Characteristics of the included studies are shown in Table I. All studies were retrospective cohort studies with a low chance of bias (level of evidence, 2+ or 2++). Patients ranged from 23 to 215. Most studies performed multivariate analysis on factors found significant in univariate analysis. Seven studies evaluated type of surgical resection as a factor of LRFS, but six studies provided data comparing Enneking inappropriate (EI) resection with Enneking appropriate (EA) resection and three studies provided data comparing marginal resection with wide resection.We performed a subgroup sensitive analysis and found no subgroup difference between the results from six studies comparing EI resection with EA resection and three studies comparing marginal resection with wide resection (I= 0%, P for subgroup heterogeneity = 0.38) (Fig. 1). Six studies comparing EI resection with EA resection yielded a pooled RR of 3.49 (95%CI: 2.48-4.92, P < 0.00001; I= 0%, P for heterogeneity = 0.49) (Fig. 1). Three studies comparing marginal resection with wide resection yielded a pooled RR of 2.78 (95%CI: 1.92-4.04, P < 0.00001; I= 0%, P for heterogeneity = 0.58) (Fig. 1). Five studies evaluated age as a factor of OS in multivariate analyses by regarding it as a continuous variable and pooled analysis showed that an increasing age was associatedwith an increased risk of death (HR = 1.03, 95%CI: 1.02-1.05, P < 0.0001) (Supplementary material 2). Four studies contributed to the pooled analysis of prognostic role of tumor invasion on OS and the results showed that increasing tumor invasion was associated with an increased risk of death (HR = 2.14, 95%CI: 1.40-3.26, P = 0.0005) (Supplementary material 3). Five studies evaluated type of surgical resection as a factor of OS, but four studies provided data comparing EI resection with EA resection and three studies provided data comparing marginal resection with wide resection. Similarly, a subgroup sensitive analysis was also performed and we observed no strong subgroup difference between the results from four studies comparing EI resection with EA resection and three studies comparing marginal resection with wide resection (I = 33.9%, P for subgroup heterogeneity = 0.22) (Supplementary material 4). Four studies comparing EI resection with EA resection yielded a pooled RR of 1.97 (95%CI: 1.29-2.99, P = 0.002; I = 0%, P for heterogeneity = 0.66) (Supplementary material 4). Three studies comparing marginal resection with wide resection yielded a pooled RR of 1.31 (95%CI: 0.81-2.14, P = 0.002; I = 0%, P for heterogeneity = 0.61) (Supplementary material 4). In conclusion, we provided a comprehensive overview of the current knowledge regarding prognostic factors in spinal chordoma. Although heterogeneity of the included studies, we have identified several clinical factors (especially EI resection and increasing tumor invasion) and molecular biomarkers are associated with survival up to tumor recurrence or mortality in spinal chordoma patients. These data may be helpful in guiding treatment planning to prolong survival and suggest targets for development of potential therapies. However, high-quality, prospective studies are still required to clarify and evaluate the effects of these factors. Ethical Review Committee Statement: The study protocol was approved by the Institutional Review Board of The Second Xiangya Hospital of Central South University, Hunan, China.