A matched pair analysis of oncological outcomes in human papillomavirus‐negative oropharyngeal squamous cell carcinoma: Transoral surgery versus radiotherapy or concurrent chemoradiation

Abstract

Background With the termination of RTOG 1221, there remains a lacuna regarding the optimal treatment for human papillomavirus (HPV)‐negative oropharyngeal squamous cell carcinoma (OPSCC). Methods Matched pair analysis with propensity score matching (PSM) between Arm I (transoral surgery [TOS] + risk‐stratified adjuvant treatment) and Arm II (nonsurgical treatment − radiation/chemoradiation) in HPV(−) OPSCC. Results Unmatched comparison of Arm I (n = 57) and Arm II (n = 89) indicated significantly better overall survival (OS) and disease‐free survival (DFS) for Arm I. PSM by matched pairs (n = 48, 24 each arm) indicated 5‐year OS at 80% and 72.1%, respectively, for Arm I and II (p > 0.05) and corresponding DFS at 65.3% and 33.4% (p > 0.05). Subgroup analysis did not demonstrate statistical difference in outcomes in stage II and III, but stage IV tumors had significantly better outcomes in Arm I than Arm II (4‐year OS: 100% vs. 21%, p = 0.04; DFS: 75% vs. 14.3%, p = 0.04). Conclusions TOS +/− adjuvant was found to have oncological outcomes at par with nonsurgical modalities in stage I–III OPSCC, whereas a distinct survival advantage was noted in case of stage IV tumors.

Analysis of T1‐T2 stage oropharyngeal squamous cell carcinoma treated with transoral robotic surgery

“…48 For oncologic results of stage III-IV patients treated with TORS, it can be found that compared with CRT, the survival results obtained by primary treatment with TORS and the adjuvant therapy under the condition of detailed pathological staging are more encoraging. [48][49][50] In our cohort, the survival rates of 58 patients with HPV-negative OPSCC were not statistically different from those of the HPV-positive group. The results presented in our study and previous findings suggested that HPV-negative patients might benefit from TORS.…”

“…Recently, an analysis based on the National Cancer Data Base (NCDB) and Surveillance, Epidemiology, and End Results (SEER) database from 2010 to 2016 support the frontline surgery in patients with T1‐2N1‐2bM0 HPV‐negative oropharyngeal cancer, which had improved OS as compared with the group who received CRT (5‐year OS: 74.0% vs 62.9%, P = .012) 48 . For oncologic results of stage III‐IV patients treated with TORS, it can be found that compared with CRT, the survival results obtained by primary treatment with TORS and the adjuvant therapy under the condition of detailed pathological staging are more encoraging 48–50 . In our cohort, the survival rates of 58 patients with HPV‐negative OPSCC were not statistically different from those of the HPV‐positive group.…”

Outcomes for Potentially Resectable Patients Undergoing Primary Chemoradiation Treatment for T1 – T2 HPV Negative Oropharyngeal Squamous Cell Carcinoma

“…Upon closer inspection, for the majority of these studies the TOS and primary RT group are unbalanced, with the TOS group having patients with earlier T and N classi cation disease on average (7,8).This surgical bias is rarely acknowledged in these manuscripts as a potential confounder. Some groups have carried out a case-control matching, such as an analysis of the National Cancer Database by Thakar and colleagues, which demonstrated superior survival outcomes for patients undergoing TORS over RT (n = 1698) (22), but this study still did not control for surgical resectability. Our work herein has highlighted that even if TOS and RT groups were matched for T and N classi cation, there is still an inherent bias of the patients that are selected for surgery.…”

“…RTOG 1221 was a prospective, randomized, control trial that aimed to compare TOS vs. primary (chemo)radiation for T1 -T2, N0 -N2b, HPV-negative OPSCC (24), and ORATOR 3 (NCT04220749) was a randomized trial with a very similar study schema, and both closed due to poor patients recruitment. Given the declining rates of HPVnegative OPSCC (22), and the failed accrual of these two studies, it is unlikely such a trial is possible. If a randomized controlled trial was attempted again, broad international participation would be critical.…”