The Evolving Role of Transoral Robotics Surgery in Oropharyngeal Cancer Treatment

Educational Objectives

The goal of this program is to improve management of oropharyngeal cancer with trans-oral robotic surgery. After hearing and assimilating this program, the clinician will be better able to:

1. Identify patients who may benefit from de-escalated adjuvant radiation therapy.
2. Use tonsillectomy to identify unknown primary tumors in the head and neck region.

Summary

Introduction: trans-oral surgery in human papilloma virus (HPV)-related oropharyngeal disease is used to produce excellent oncologic outcomes and minimize or deintensify functional disabilities; HPV-related oropharyngeal disease incidence continues to increase and has overtaken cervical cancer as the leading cancer caused by the HPV virus; stage 1 clinical disease affects 63% of patients, according to updated American Joint Committee staging; pathologic stage 1 disease occurs in 85% of patients

Toxicity: non-surgical treatment options are associated with acute and long term toxicity; the risk for long term toxicity is ≤43%; deintensification of treatment provides tumor control and minimizes organ dysfunction

Trans-oral surgery: may be used to de-escalate treatment with the goal of replacement of additional therapies (eg, definitive radiation); surgery may be used to obtain pathologic information for risk stratification and intensification of adjuvant treatment; trans-oral surgery may be performed with a robotic system (trans-oral robotic surgery [TORS]) or laser microsurgery; excellent oncologic outcomes are associated with proper patient selection and surgical expertise

Clinical data

ORATOR I (Nichols et al, 2019): the primary outcome was functional outcomes based on the MD Anderson Dysphagia Inventory (MDADI) score; a head-to-head comparison was made between standard of care (ie, radiation therapy (RT) with chemotherapy) and TORS followed by risk stratified adjuvant therapy; no difference between the groups was seen in survival at 2 to 3 yr; patients who underwent radiation had better swallowing outcomes, but the difference was not clinically significant; a subgroup analysis showed patients who had base of tongue cancer and received radiation had less dysphagia

ORATOR II (Nichols et al, 2021): the primary outcome was overall survival and the secondary outcome was quality of life; definitive treatment was deintensified to 60 Gy in the high risk group; patients in the trans-oral robotic surgery group had adjuvant treatment de-escalated to 50 Gy in patients at low risk and 60 Gy in patients at high risk; chemotherapy was omitted; the trial was stopped early because of 4 deaths in the trans-oral robotic surgery group; immature data on survival outcomes showed better outcomes in the RT arm; dysphagia was similar between trial arms; patient selection, surgeon expertise and the credentialing process affects outcomes; oncologic outcomes are similar between RT and TORS for low risk, early stage disease; quality of life functional outcomes were evaluated using the MDADI scale; symptom burden depends on treatment modality; patients undergoing robotic surgery may experience more pain, trauma, and numbness; patients undergoing radiation have dysgeusia

Pathologic information: TORS helps reduce use of adjuvant radiation; radiation of certain sites may be avoided, or the volume of radiation reduced; the ECOG-ACRIN 3311 trial (Ferris et al, 2022) showed that TORS was feasible and safe; grade 5 hemorrhagic bleeding with death occurred in 1 out of 495 patients undergoing trans-oral resection; Ma et al (2019) evaluated the effect of dose de-escalation in high risk patients; the study showed excellent 2 yr progression free survival (PFS) and overall survival; a phase III randomized trial by Ma et al (2021) compared de-escalated adjuvant radiation therapy (DART) with the standard of care and found similar overall survival and local and regional control at 2 yr between the 2 groups, with less toxicity in the DART arm; PFS was worse in the DART arm; a subgroup analysis found that worse PFS was because of extra-nodal extension (ENE); PFS was similar among patients with negative ENE; triple modality therapy should be avoided

Patient selection: unilateral tumors with small volumes are appropriate for TORS; nodal status determines the need for adjuvant therapy; patients with clinical 0 to 1 nodes may be treated with single modality therapy; clinicians should attempt to avoid chemotherapy and triple modality in patients with >1 lymph node

Outcomes: treatment related death in the ORATOR I trial was ≈10% and grade 5 toxicity in terms of bleeding was 3%; the rate of bleeding in the ECOG-ACRIN 3311 trial was 0.2%; a learning curve for surgeons exists with TORS; a surgeon must perform a minimum number of TORS to reduce operative time and minimize the rate of positive margin; 30 cases was the minimum in the ECOG-ACRIN 3311 trial; Hay et al (2017) found complication rates decreased from 33% to 10% over 5 yr; Nguyen et al (2020) found a correlation between the institutional volume and safety of TORS; Oliver et al (2022) evaluated 5,000 patients in the national cancer database and found data on positive surgical margin rate, rate of 30-day readmission and 30-day mortality among patients who underwent TORS; high volume was defined as a center which performed ≥10 cases a year; researchers found a two-fold increase in positive surgical margin rate and a three-fold increase in 30 day mortality in low volume centers

HPV-negative tumors: Jackson et al (2021) found an overall survival rate of 78% at 5 yr with use of TORS in 164 patients with HPV-negative oropharyngeal cancer; TORS was shown to be beneficial in select individuals

Patients with unknown primary: identification of the primary tumor improves survival rates and reduces adverse effects; retrospective evidence suggests that TORS may be useful in detection of primary in 90% of patients and may help obtain negative margin in ≤62% of patients; American Society of Clinical Oncology guidelines (2020) for the management of unknown primary recommend clinicians first perform an ipsilateral palatine tonsillectomy; lingual tonsillectomy should follow if initial tonsillectomy is negative; patients with bilateral nodal disease require lateral lingual resection; frozen sections should be sent to obtain negative margins once the primary is detected; using upper aero-digestive tract evaluation and endoscopy directed biopsy to find the primary has a success rate of 30%; the rate of detection with palatine tonsillectomy is 50%; the rate of detection with lingual tonsillectomy is 65%; the addition of contralateral lingual tonsillectomy increases the rate of identification of primary to 78%; clinicians should avoid performing bilateral palatine and lingual tonsillectomies because patients may experience significant stenosis

Salvage therapy: TORS improves survival in patients with recurrent tumors or second primary tumors irrespective of HPV status; a secondary analysis of the RTOG 1016 trial found that salvage neck dissection within 20 wk was associated with excellent outcome for patients with local regional failure; Brudasca et al (2023) found transoral laser microsurgery to be associated with shorter operative time, reduced blood loss, and lower complications compared with TORS; patients at 16 high volume international centers who underwent TORS or open surgery after radiation therapy because of residual disease, or recurrent disease or detection of new primaries, were included; a majority of patients selected for surgery had early stage disease

Precision oncology: circulating tumor DNA (ctDNA) is used to detect micro residual or minimal residual disease; ctDNA is useful for screening, early diagnosis, determination of prognosis, and treatment response, and the detection of recurrence; ctDNA for HPV is emerging as a powerful biomarker which may be used to study de-intensification of therapy, monitoring, and dose-response adaptive treatment

Readings

Brudasca I, Philouze P, Morinière S, et al. Transoral laser microsurgery versus robot-assisted surgery for squamous cell carcinoma of the tongue base (oncological and functional results)-A retrospective GETTEC multicenter study. J Clin Med. 2023 Jun 22;12(13):4210. doi: 10.3390/jcm12134210; Ferris RL, Flamand Y, Weinstein GS, et al. Phase II randomized trial of transoral surgery and low-dose intensity modulated radiation therapy in resectable p16+ locally advanced oropharynx cancer: An ECOG-ACRIN Cancer Research Group Trial (E3311). J Clin Oncol. 2022;40(2):138-149. doi:10.1200/JCO.21.01752; Fu TS, Foreman A, Goldstein DP, de Almeida JR. The role of transoral robotic surgery, transoral laser microsurgery, and lingual tonsillectomy in the identification of head and neck squamous cell carcinoma of unknown primary origin: a systematic review. J Otolaryngol Head Neck Surg. 2016;45(1):28. Published 2016 May 4. doi:10.1186/s40463-016-0142-6; Hay A, Migliacci J, Karassawa Zanoni D, et al. Complications following transoral robotic surgery (TORS): A detailed institutional review of complications. Oral Oncol. 2017 Apr;67:160-166. doi: 10.1016/j.oraloncology.2017.02.022. Epub 2017 Feb 28; Jackson RS, Stepan K, Bollig C, et al. Outcomes of HPV-negative oropharyngeal cancer treated with transoral robotic surgery. Otolaryngol Head Neck Surg. 2021;165(5):682-689. doi:10.1177/0194599821996647; Ma DJ, Price KA, Moore EJ, et al. Phase II evaluation of aggressive dose de-escalation for adjuvant chemoradiotherapy in human papillomavirus-associated oropharynx squamous cell carcinoma. J Clin Oncol. 2019;37(22):1909-1918. doi:10.1200/JCO.19.00463; Ma DJ, Van Abel KM. Treatment de-intensification for HPV-associated oropharyngeal cancer: a definitive surgery paradigm. Semin Radiat Oncol. 2021;31(4):332-338. doi:10.1016/j.semradonc.2021.07.001; Nichols AC, Theurer J, Prisman E, et al. Radiotherapy versus transoral robotic surgery and neck dissection for oropharyngeal squamous cell carcinoma (ORATOR): an open-label, phase 2, randomised trial. Lancet Oncol. 2019;20(10):1349-1359. doi:10.1016/S1470-2045(19)30410-3; Nichols AC, Theurer J, Prisman E, et al. Randomized trial of radiotherapy versus transoral robotic surgery for oropharyngeal squamous cell carcinoma: Long-term results of the ORATOR trial. J Clin Oncol. 2022;40(8):866-875. doi:10.1200/JCO.21.01961; Nguyen AT, Luu M, Mallen-St Clair J, et al. Comparison of survival after transoral robotic surgery vs nonrobotic surgery in patients with early-stage oropharyngeal squamous cell carcinoma. JAMA Oncol. 2020 Oct 1;6(10):1555-1562. doi: 10.1001/jamaoncol.2020.3172; Oliver JR, Persky MJ, Wang B, et al. Transoral robotic surgery adoption and safety in treatment of oropharyngeal cancers. Cancer. 2022 Feb 15;128(4):685-696. doi: 10.1002/cncr.33995.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Ku was recorded at the Cleveland Clinic 2023 Multidisciplinary Head and Neck Cancer Update, held virtually on March 17, 2023, in Fort Lauderdale, FL, and presented by Cleveland Clinic Taussig Cancer Center. For information about upcoming CME activities from this presenter, please visit clevelandclinicmeded.com. Audio Digest thanks the speakers and presenters for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0.75 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0.75 CE contact hours.

Lecture ID:

OT562303

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.

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