Risk factors for metastatic disease at presentation with chordoma and its prognostic value

Background: Chordoma is a rare bone cancer arising from the embryonic notochord with special predilection to the axial skeleton. The locally destructive nature and metastatic potential of chordomas can lead to devastating outcomes in terms of survival. The purpose of this study was to examine potential risk factors predictive of metastatic disease at presentation and prognostic factors in patients with metastasis.

Methods: SEER was used to classify each patient as having metastatic or localized disease at the time of diagnosis. Patient-specific and tumor characteristics were analyzed to determine which factors were predictive of an increased rate of metastatic disease at presentation. These factors were analyzed using univariate as well as a multivariate logistic regression model. Prognostic factors for survival were analyzed using the Kaplan-Meier estimates with log-rank tests, and Cox proportional hazards models.

Results: We identified 1,241 cases of chordoma affecting the axial skeleton, and 117 (9.4%) of the patients presented with metastatic disease. The most common locations for metastasis at presentation were lung (6.0%), followed by bone (5.1%) and liver (3.4%). Based on the unadjusted logistic regression analysis, patients had the highest odds of metastatic disease at presentation if they had a tumor located in the sacrococcygeal area (OR = 1.72; 95% CI, 1.11-2.68; p = .015), a tumor with a dedifferentiated histological subtype (OR = 7.42; 95% CI, 2.31-23.79; p = .001) and a tumor size greater than 10 cm (OR = 4.57; 95% CI, 2.52-8.28; p = .009). Only the histological subtype remained significant when combined in a multivariate model controlling for age, sex, race, tumor location, histology, and size. For patients with recorded tumor size information (n = 858), the odds of metastasis at presentation increased by 12.2% with each additional centimeter of tumor size (OR = 1.122; 95% CI, 1.072-1.175; p < .0001). However, this lost significance in the multivariate model. Advanced age (hazard ratio, 2.06; 95% confidence interval, (1.18-3.60); p = .011) and dedifferentiated subtype (hazard ratio, 4.7; 95% confidence interval, (1.33-16.8); p = .02) were significant prognostic factors for survival in patients with metastatic chordoma.

Conclusions: Chordoma patients with dedifferentiated histological subtype were more likely to have metastatic disease at presentation. Advanced age and dedifferentiated histological subtype were independent predictors of increased mortality in patients with metastatic chordoma. Identification of this high-risk group may help providers in counseling their patients regarding the likelihood of discovering metastatic disease at the time of diagnosis of chordoma and predicting long term prognosis.