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. 2023 Aug 31;8(8):CD006205.
doi: 10.1002/14651858.CD006205.pub5.

Interventions for the treatment of oral cavity and oropharyngeal cancers: surgical treatment

Helen V Worthington  1 , Vishal M Bulsara  2   3 , Anne-Marie Glenny  4 , Janet E Clarkson  1 , David I Conway  5 , Michaelina Macluskey  6
Affiliations

Interventions for the treatment of oral cavity and oropharyngeal cancers: surgical treatment

Helen V Worthington et al. Cochrane Database Syst Rev. .

Abstract

Background: Surgery is a common treatment option in oral cavity cancer (and less frequently in oropharyngeal cancer) to remove the primary tumour and sometimes neck lymph nodes. People with early-stage disease may undergo surgery alone or surgery plus radiotherapy, chemotherapy, immunotherapy/biotherapy, or a combination of these. Timing and extent of surgery varies. This is the third update of a review originally published in 2007.

Objectives: To evaluate the relative benefits and harms of different surgical treatment modalities for oral cavity and oropharyngeal cancers.

Search methods: We used standard, extensive Cochrane search methods. The latest search date was 9 February 2022.

Selection criteria: Randomised controlled trials (RCTs) that compared two or more surgical treatment modalities, or surgery versus other treatment modalities, for primary tumours of the oral cavity or oropharynx.

Data collection and analysis: Our 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. We used standard Cochrane methods. We reported survival data as hazard ratios (HRs). For overall survival, we reported the HR of mortality, and for disease-free survival, we reported the combined HR of new disease, progression, and mortality; therefore, HRs below 1 indicated improvement in these outcomes. We used GRADE to assess certainty of evidence for each outcome.

Main results: We identified four new trials, bringing the total number of included trials to 15 (2820 participants randomised, 2583 participants analysed). For objective outcomes, we assessed four trials at high risk of bias, three at low risk, and eight at unclear risk. The trials evaluated nine comparisons; none compared different surgical approaches for excision of the primary tumour. Five trials evaluated elective neck dissection (ND) versus therapeutic (delayed) ND in people with oral cavity cancer and clinically negative neck nodes. Elective ND compared with therapeutic ND probably improves overall survival (HR 0.64, 95% confidence interval (CI) 0.50 to 0.83; I2 = 0%; 4 trials, 883 participants; moderate certainty) and disease-free survival (HR 0.56, 95% CI 0.45 to 0.70; I2 = 12%; 5 trials, 954 participants; moderate certainty), and probably reduces locoregional recurrence (HR 0.58, 95% CI 0.43 to 0.78; I2 = 0%; 4 trials, 458 participants; moderate certainty) and recurrence (RR 0.58, 95% CI 0.48 to 0.70; I2 = 0%; 3 trials, 633 participants; moderate certainty). Elective ND is probably associated with more adverse events (risk ratio (RR) 1.31, 95% CI 1.11 to 1.54; I2 = 0%; 2 trials, 746 participants; moderate certainty). Two 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. Neither study found evidence of a difference in overall survival (pooled measure not estimable; very low certainty). We are unsure if there is a difference in effect on disease-free survival (HR 0.57, 95% CI 0.29 to 1.11; 1 trial, 104 participants; very low certainty) or recurrence (RR 1.21, 95% CI 0.63 to 2.33; 1 trial, 143 participants; very low certainty). There may be no difference between the interventions in terms of adverse events (1 trial, 148 participants; low certainty). Two trials evaluated superselective ND versus selective ND, but we were unable to use the data. One trial evaluated supraomohyoid ND versus modified radical ND in 332 participants. We were unable to use any of the primary outcome data. The evidence on adverse events was very uncertain, with more complications, pain, and poorer shoulder function in the modified radical ND group. One trial evaluated sentinel node biopsy versus elective ND in 279 participants. There may be little or no difference between the interventions in overall survival (HR 1.00, 95% CI 0.90 to 1.11; low certainty), disease-free survival (HR 0.98, 95% CI 0.90 to 1.07; low certainty), or locoregional recurrence (HR 1.04, 95% CI 0.91 to 1.19; low certainty). The trial provided no usable data for recurrence, and reported no adverse events (very low certainty). 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 participants. 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 participants). The data were unreliable because the trial stopped early and had multiple protocol violations. In terms of adverse events, subcutaneous fibrosis was more frequent in the surgery plus radiotherapy group, but there were no differences in other adverse events (very low certainty). One trial evaluated surgery versus radiotherapy alone for oropharyngeal cancer in 68 participants. 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).

Authors' conclusions: 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.

Trial registration: ClinicalTrials.gov NCT00193765 NCT00571883 NCT03691441 NCT01334320.

PubMed Disclaimer

Conflict of interest statement

HW: none known. I am Emeritus Co‐ordinating Editor of Cochrane Oral Health, and was not involved in the editorial process. VB: none known. AMG: none known. I am joint Co‐ordinating Editor of Cochrane Oral Health, and was not involved in the editorial process. JC: none known. I am joint Co‐ordinating Editor of Cochrane Oral Health, and was not involved in the editorial process. DC: none known. MM: none known.

Figures

1
1
PRISMA diagram showing study selection process.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
3
3
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
1.1
1.1. Analysis
Comparison 1: Elective neck dissection (ND) versus therapeutic (delayed) ND, Outcome 1: Total mortality
1.2
1.2. Analysis
Comparison 1: Elective neck dissection (ND) versus therapeutic (delayed) ND, Outcome 2: New disease, progression, and mortality
1.3
1.3. Analysis
Comparison 1: Elective neck dissection (ND) versus therapeutic (delayed) ND, Outcome 3: Locoregional recurrence
1.4
1.4. Analysis
Comparison 1: Elective neck dissection (ND) versus therapeutic (delayed) ND, Outcome 4: Recurrence
1.5
1.5. Analysis
Comparison 1: Elective neck dissection (ND) versus therapeutic (delayed) ND, Outcome 5: Total adverse events
2.1
2.1. Analysis
Comparison 2: Elective radical neck dissection (ND) versus elective selective ND, Outcome 1: Total mortality
2.2
2.2. Analysis
Comparison 2: Elective radical neck dissection (ND) versus elective selective ND, Outcome 2: New disease, progression, and mortality
2.3
2.3. Analysis
Comparison 2: Elective radical neck dissection (ND) versus elective selective ND, Outcome 3: Recurrence
3.1
3.1. Analysis
Comparison 3: Sentinel node biopsy versus elective neck dissection (ND), Outcome 1: Total mortality
3.2
3.2. Analysis
Comparison 3: Sentinel node biopsy versus elective neck dissection (ND), Outcome 2: New disease, progression, and mortality
3.3
3.3. Analysis
Comparison 3: Sentinel node biopsy versus elective neck dissection (ND), Outcome 3: Locoregional recurrence
4.1
4.1. Analysis
Comparison 4: PET‐CT following chemoradiotherapy versus planned neck dissection (ND) before or after chemoradiotherapy, Outcome 1: Total mortality
4.2
4.2. Analysis
Comparison 4: PET‐CT following chemoradiotherapy versus planned neck dissection (ND) before or after chemoradiotherapy, Outcome 2: Locoregional recurrence
5.1
5.1. Analysis
Comparison 5: Surgery plus radiotherapy (RT) versus RT alone, Outcome 1: Total mortality
6.1
6.1. Analysis
Comparison 6: Surgery versus radiotherapy (RT) alone, Outcome 1: Mortality
6.2
6.2. Analysis
Comparison 6: Surgery versus radiotherapy (RT) alone, Outcome 2: New disease, progression, and mortality
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