Oral Cavity Squamous Cell Carcinoma: Impact of Clear Margin Distance on Locoregional Control in Patients Undergoing Postoperative Radiotherapy

Abstract

We congratulate Lang and colleagues for their study investigating the impact of resection margin (RM) size on locoregional control (LC) outcomes, overall survival (OS), progression-free survival (PFS), and treatment-related toxicity in 162 patients with oral cavity squamous cell carcinoma (OCSCC) who received postoperative radiotherapy (PORT).1 In this study, 77 (47.5%), 22 (13.6%), and 63 (38.9%) patients had involved (5 mm) RM, respectively. A RM of ≤5 mm was found to be a significant predictor for worse LC (HR 2.6), but not for OS (HR 1.2) or PFS (HR 1.2). The findings of this study provide important insights into how the status of RM affects the local control and survival outcomes of OCSCC patients who undergo PORT. However, we have two concerns that we believe need to be addressed to interpret the results more comprehensively and guide future research on this critical topic.

Dear Editor,

We congratulate Lang and colleagues for their study investigating the impact of resection margin (RM) size on locoregional control (LC) outcomes, overall survival (OS), progression-free survival (PFS), and treatment-related toxicity in 162 patients with oral cavity squamous cell carcinoma (OCSCC) who received postoperative radiotherapy (PORT). ¹ In this study, 77 (47.5%), 22 (13.6%), and 63 (38.9%) patients had involved (<1 mm), close (1-5 mm), and clear (>5 mm) RM, respectively. A RM of ≤5 mm was found to be a significant predictor for worse LC (HR 2.6), but not for OS (HR 1.2) or PFS (HR 1.2). The findings of this study provide important insights into how the status of RM affects the local control and survival outcomes of OCSCC patients who undergo PORT. However, we have two concerns that we believe need to be addressed to interpret the results more comprehensively and guide future research on this critical topic.

First, the authors reported that the 5-year estimated OS and PFS were 69.2% and 70.8%, respectively. However, these results are statistically problematic based on the standard definitions of the survival endpoints. ² As per the established statistical definitions of survival endpoints, none of the other survival estimates can surpass the estimates provided by OS, except for cancer-specific survival. ³ Therefore, the estimated 5-year PFS rate must be <69.2% that is provided by the OS. This is because the OS definition encompasses only “any cause of death” as the event, while in contrast, PFS takes into account “any cause of death” as well as “local, regional, and distant relapses, and any combinations of these” as the event.^2,3 Therefore, we believe all survival data should undergo reanalysis per established survival endpoint definitions to ensure the provision of accurate survival outcomes and facilitate comparisons across similar studies.^2,3

And second, while the authors indicate that a RM of ≤5 mm is a significant predictor of poor LC, associated with over a twofold increase in local failure risk (p = 0.022, HR 2.6), the estimated difference in LC rates between these patients and those with >5 mm is merely 3.2% at 5-years (79.9% vs 76.7%). However, upon analysis of the LC rates graph (original Figure 1b), it becomes apparent that the 5-year LC rates are approximately 90% for patients with a RM of ≤5 mm and 81% for those with a RM of >5 mm. This signifies a 9% disparity in LC rates, surpassing the clinically marginal 3.2% reported by the authors. Hence, it is advisable to re-evaluate the analysis of LC rates to ascertain the prevailing rates at any given time point accurately. Failing to do so may result in the misinterpretation of Lang and colleagues’ findings, suggesting that PORT is warranted in both RM scenarios for patients with OCSCC, though it is only recommended for patients with a RM of ≤5 mm.^4,5 Moreover, adopting such a practice may result in an unjustified increase in the incidence of disabling severe late toxicities such as trismus and osteoradionecrosis, as documented by the authors. ¹