Randomized Trial of Radiotherapy Versus Transoral Robotic Surgery for Oropharyngeal Squamous Cell Carcinoma: Long-Term Results of the ORATOR Trial

PURPOSE The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has risen rapidly, because of an epidemic of human papillomavirus infection. The optimal management of early-stage OPSCC with surgery or radiation continues to be a clinical controversy. Long-term randomized data comparing these paradigms are lacking. METHODS We randomly assigned patients with T1-T2, N0-2 (≤ 4 cm) OPSCC to radiotherapy (RT) (with chemotherapy if N1-2) versus transoral robotic surgery plus neck dissection (TORS + ND) (with or without adjuvant therapy). The primary end point was swallowing quality of life (QOL) at 1-year using the MD Anderson Dysphagia Inventory. Secondary end points included adverse events, other QOL outcomes, overall survival, and progression-free survival. All analyses were intention-to-treat. Herein, we present long-term outcomes from the trial. RESULTS Sixty-eight patients were randomly assigned (n = 34 per arm) between August 10, 2012, and June 9, 2017. Median follow-up was 45 months. Longitudinal MD Anderson Dysphagia Inventory analyses demonstrated statistical superiority of RT arm over time ( P = .049), although the differences beyond 1 year were of smaller magnitude than at the 1-year timepoint (year 2: 86.0 ± 13.5 in the RT arm v 84.8 ± 12.5 in the TORS + ND arm, P = .74; year 3: 88.9 ± 11.3 v 83.3 ± 13.9, P = .12). These differences did not meet the threshold to qualify as a clinically meaningful change at any timepoint. Certain differences in QOL concerns including more pain and dental concerns in the TORS + ND arm seen at 1 year resolved at 2 and 3 years; however, TORS patients started to use more nutritional supplements at 3 years ( P = .015). Dry mouth scores were higher in RT patients over time ( P = .041). CONCLUSION On longitudinal analysis, the swallowing QOL difference between primary RT and TORS + ND approaches persists but decreases over time. Patients with OPSCC should be informed about the pros and cons of both treatment options (ClinicalTrials.gov identifier: NCT01590355 ).

Perioperative Mortality Risk in Patients Undergoing Transoral Robotic Surgery for T1-T2 Oropharyngeal Squamous Cell Carcinoma: A National Cancer Database Study

The National Cancer Database is a joint project of the Commission on Cancer of the American College of Surgeons and the American Cancer Society. The American College of Surgeons and the Commission on Cancer have not verified and are not responsible for the analytic or statistical methods used or for the conclusions drawn from these data by the investigators.IntroductionTransoral robotic surgery (TORS) is well established as initial definitive treatment for early-stage oropharyngeal squamous cell carcinoma (OPSCC) as an alternative to radiation therapy with similar survival rates. While proponents of TORS focus on the reduced morbidity of treatment compared to open procedures, shortened hospital admissions and equivalent survival outcomes to non-surgical treatment, there remain concerns over the risk of mortality within the acute perioperative period. Therefore, we sought to determine the 30-day and 90-day perioperative mortality risk using the National Cancer Database.MethodsA retrospective cohort analysis was performed for patients diagnosed with pathologic T1/2 OPSCC between January 1, 2010, and December 31, 2016 that underwent primary surgical treatment with TORS and was not restricted by HPV status. The primary outcome was 30-day perioperative mortality. The secondary outcome was 90-day perioperative mortality. Univariable analysis was used to identify variables associated with 30-day perioperative mortality.ResultsIn total, 4,127 patients (mean [SD; range] age, 59 [9.5; 22-90] years; 3,476 [84%] men and 651 [16%] women) met inclusion criteria. The number of patients with pT1-2 OPSCC undergoing TORS increased three-fold between 2010 (279/4,127; 7%) to 2016 (852/4,127; 21%). The overall 30-day and 90-day perioperative mortality rate for TORS during the study period was 0.6% (23/4,127) and 0.9% (38/4,127), respectively. On univariable analysis (UVA), age≥65 was the only predictor of 30-day perioperative mortality (OR 3.41; 95% CI 1.49-7.81).ConclusionThe overall risk of all cause mortality following TORS for early-stage OPSCC remains low. The risk of mortality is higher in elderly patients and should be considered, in addition to previously established risk factors, during patient selection and counselling.

Contralateral nodal failures in oropharyngeal cancers after TORS and unilateral neck management: a retrospective study

Background Report the incidence of contralateral nodal failure rates in well-lateralized oropharyngeal carcinoma treated with upfront surgery and unilateral neck management. Methods Lateralized oropharyngeal carcinomas treated with upfront surgery using transoral robotic surgery (TORS) and unilateral neck management (unilateral neck dissection ± unilateral radiation treatment) were identified. Primary endpoint was contralateral regional control (CRC). Secondary endpoints were local control (LC), and overall survival (OS). Results Thirty-two patients were included. Pathologic T categories included 66% pT1, 31% pT2 and 3% pT3. Nodal diseases comprised 41% N0 and 47% N1 (AJCC 8th). Twenty-three (72%) patients had HPV related tumors. 3-years CRC, LC and OS were 100%, 96% (89–100) and 96% (CI 89–100). One patient developed a second primary with contralateral nodal disease. Only one patient died from another primary cancer. Conclusion In selected patients with lateralized oropharyngeal cancer, treatment with TORS and ipsilateral management of the neck may be oncologically safe without significant risk of contralateral failure. Level of evidence: Level 2. Graphical abstract

Swallowing Function Following Neoadjuvant Chemotherapy and Transoral Robotic Surgery for Oropharyngeal Carcinoma: A 2-Year Follow-up

Objective To evaluate 2-year follow-up swallowing function in patients with human papillomavirus–related oropharyngeal squamous cell carcinoma (HPV+ OPSCC) who completed neoadjuvant chemotherapy and transoral robotic surgery (NAC+S) Study Design Retrospective analysis of patients with OPSCC treated with NAC+S between 2010 and 2021. Setting A single academic institution. Methods This is a cross-sectional study of patient-reported swallowing function, assessed with the MD Anderson Dysphagia Inventory (MDADI) at least 2 years after completion of treatment. The inclusion criteria are patients with HPV+ OPSCC who underwent NAC+S at least 2 years ago. Those requiring adjuvant radiation or chemoradiation or experiencing relapse were excluded from the study. Results Completed MDADIs were received from 37 patients at a median 3.8 years posttreatment (interquartile range, 2.0-8.6 years). Of those, 94.6% (n = 35) were male and 81.1% (n = 30) were White. The median age at OPSCC diagnosis was 59.0 years (interquartile range, 41-80 years). The most frequent primary subsite of OPSCC was the base of the tongue (n = 20, 54.1%), followed by the tonsils (n = 16, 43.2%). In addition, 75.7% (n = 28) had stage IVa disease (TNM seventh edition), and 29 (78.4%) had scores ≥80, classified as optimal function. When compared with patients who received bilateral neck dissection, patients who received unilateral neck dissection were associated with an age <65 years old ( P = .036) and lower clinical TNM stage ( P = .04), as well as higher composite, emotional, functional, and physical MDADI scores ( P = .017, .046, .013, and .05, respectively). Conclusion Patients with OPSCC who were treated with NAC+S achieved satisfactory long-term swallowing outcomes. Unilateral neck dissection was significantly associated with higher MDADI scores in this patient cohort.