The Impact of Radiotherapy Timing on Postoperative Outcomes in Chordoma Patients—A TriNetX Study

Introduction: Chordomas are rare, locally aggressive tumors of the spine and skull base typically managed with maximal surgical resection followed by adjuvant radiotherapy. Although postoperative radiotherapy improves local control, the optimal interval for initiation remains uncertain, as early delivery may exacerbate wound-related complications while delayed initiation may allow tumor progression. Methods: We performed a retrospective cohort analysis using the multi-center, national TriNetX Research Network. Adults with histologically confirmed skull base and/or spinal chordoma who underwent surgical resection followed by radiotherapy were stratified into ultraearly (≤2 weeks), standard (4–6 weeks), or delayed (≥10 weeks) radiotherapy initiation groups. Propensity score matching was used to adjust for demographic and clinical covariates. The primary outcome was all-cause mortality at 1, 3, and 5-years. Secondary outcomes included wound dehiscence, surgical site infection, and neurologic complications. Results: A total of 378 patients met the inclusion criteria. Ultraearly radiotherapy was not associated with significant differences in mortality at 1 year (RR 1.338; 95% CI 0.833–2.15; p = 0.22), 3 years (RR 1.233; 95% CI 0.858–1.772; p = 0.25), or 5 years (RR 1.196; 95% CI 0.876–1.633; p = 0.25) compared with standard timing. Delayed radiotherapy, however, demonstrated significantly reduced mortality at 1 year (RR: 0.53; 95% CI: 0.331–0.851; p = 0.01), 3 years (RR 0.641; 95% CI 0.449–0.914; p = 0.01), and 5 years (RR 0.654; 95% CI 0.473–0.905; p = 0.01) compared with standard timing. Event counts for secondary outcomes were insufficient for robust statistical comparison. Conclusions: Radiotherapy timing following surgical resection of chordoma did not impact short-term survival, but delayed radiotherapy significantly decreased 1, 3 and 5-year mortality. Rare secondary complications were seen. These findings suggest that the delayed initiation of radiotherapy may be helpful for patients with chordoma, supporting the need for prospective, long-term studies to clarify the balance between oncologic efficacy and perioperative morbidity.