Oral cavity and oropharyngeal cancer were grouped under the term oral cancer but are now considered two distinct cancers because of differences in risk factors, diagnosis, and clinical management. They form part of a broader head and neck cancer (HNC) grouping which represents the 7^th commonest cancer in the world with more than 660,000 new cases per year. Tobacco use, alcohol consumption and betel quid chewing are common risk factor for HNC while nasopharyngeal cancer is associated with Epstein Barr virus (EBV), and oropharyngeal cancer is increasingly associated with human papillomavirus (HPV). Diagnosis of HNC is mainly at an advanced stage, with implications for treatment and prognosis. Surgery plays an important part in management of oral cavity and oropharyngeal cancer and may be combined with radiotherapy, chemotherapy, or immunotherapy/ biotherapy.

The aim of this Cochrane review update was to evaluate the relative benefits and harms of different surgical treatment modalities for oral cavity and oropharyngeal cancers.

Methods

Searches were conducted in the Cochrane Oral Health’s Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) Medline, Embase, the US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform with no restrictions on the language or date of publication. Randomised controlled trials (RCTs) comparing two or more surgical approaches or surgery versus other treatments in patients with primary tumours of the mouth or throat were considered. Primary outcomes were overall survival, disease-free survival, locoregional recurrence, and recurrence; and our secondary outcomes were adverse effects of treatment, quality of life, direct and indirect costs to patients and health services, and participant satisfaction.  Standard Cochrane data collection and analysis procedures were followed.  Survival data was reported as hazard ratios (HRs), with HR of mortality for overall survival the combined HR of new disease, progression, and mortality for disease-free survival. GRADE was used to assess certainty of evidence for each outcome.

Results

• 15 RCTS were included involving 2820 randomised patients with 2583 analysed.
• 4 trials were considered to be at high risk of bias, 3 at low risk, and 8 at unclear risk.
• 9 comparisons were compared in the trials, none comparing different surgical approaches for excision of the primary tumour.
• 5 trials evaluated elective neck dissection (ND) versus therapeutic (delayed) ND in people with oral cavity cancer and clinically negative neck nodes. Compared with therapeutic ND Elective ND probably improves: –
  • overall survival HR = 0.64 (95%CI: 0.50 to 0.8) [ 4 trials, 883 patients, moderate certainty].
  • disease-free survival HR = 0.56 (95% CI: 0.45 to 0.70); [5 trials, 954 patients, moderate certainty].
• probably reduces: –
  • locoregional recurrence HR = 0.58 (95%CI: 0.43 to 0.78); [4 trials, 458 p patients; moderate certainty] and
  • recurrence RR = 0.58 (95%CI: 0.48 to 0.70) [3 trials, 633 patients; moderate certainty].
• Elective ND is probably associated with more adverse events (risk ratio (RR) =1.31 (95%CI: 1.11 to 1.54) [2 trials, 746 patients; moderate certainty].
• 2 trials evaluated elective radical ND versus elective selective ND in people with oral cavity cancer, but we were unable to pool the data as the trials used different surgical procedures.
• 2 trials evaluated super selective ND versus selective ND, but we were unable to use the data.
• One trial evaluated positron emission tomography-computed tomography (PET-CT) following chemoradiotherapy (with ND only if no or incomplete response) versus planned ND (before or after chemoradiotherapy) in 564 patients. There is probably no difference between the interventions in
  • overall survival, HR = 0.92 (95%CI: 0.65 to 1.31; moderate certainty) or
  • locoregional recurrence, HR = 1.00 (95%CI: 0.94 to 1.06; moderate certainty).
• One trial evaluated surgery plus radiotherapy versus radiotherapy alone and provided very low-certainty evidence of better overall survival in the surgery plus radiotherapy group (HR = 0.24, 95% CI 0.10 to 0.59; 35 patients). The data were unreliable because the trial stopped early and had multiple protocol violations.
• One trial evaluated surgery versus radiotherapy alone for oropharyngeal cancer in 68 patients. There may be little or no difference between the interventions for overall survival (HR = 0.83, 95% CI 0.09 to 7.46; low certainty) or disease-free survival (HR =1.07, 95% CI 0.27 to 4.22; low certainty). For adverse events, there were too many outcomes to draw reliable conclusions.
• One trial evaluated surgery plus adjuvant radiotherapy versus chemotherapy. We were unable to use the data for any of the outcomes reported (very low certainty).

Conclusions

The authors concluded: –

We found moderate-certainty evidence based on five trials that elective neck dissection of clinically negative neck nodes at the time of removal of the primary oral cavity tumour is superior to therapeutic neck dissection, with increased survival and disease-free survival, and reduced locoregional recurrence. There was moderate-certainty evidence from one trial of no difference between positron emission tomography (PET-CT) following chemoradiotherapy versus planned neck dissection in terms of overall survival or locoregional recurrence. The evidence for each of the other seven comparisons came from only one or two studies and was assessed as low or very low-certainty.

Comments

This Cochrane review updates an earlier version (Dental Elf – 14^th Jan 2019) and includes 4 new studies one of which we have covered in an earlier blog (Dental Elf – 29^th Jan 2019). The findings of this updated review and other reviews (Dental Elf – 29^th Jun 2020) favour elective neck dissection. While more RCTs are now being conducted the reviewers highlight the need to improve the quality of their reporting by following the CONSORT guidelines, using hazard ratios with 95% confidence intervals for survival data, or present data that allow it to be calculated. They also suggest that reporting of adverse events should be consistent and standardised and integral to trials of oral cavity and oropharyngeal cancers along with other outcome measures such as health-related quality of life, health economics, and resource use.

Links

Primary Paper  

Worthington HV, Bulsara VM, Glenny AM, Clarkson JE, Conway DI, Macluskey M. Interventions for the treatment of oral cavity and oropharyngeal cancers: surgical treatment. Cochrane Database Syst Rev. 2023 Aug 31;8:CD006205. doi: 10.1002/14651858.CD006205.pub5. PMID: 37650478.

Other references

Dental Elf – 14^th Jan 2019

Mouth and throat cancer: evidence for best surgical approaches uncertain

Dental Elf – 29^th Jan 2019

Elective neck dissection for early stage oral cancer?

Dental Elf – 29^th Jun 2020

Elective neck dissection versus observation for T1-2 oral squamous cell carcinoma