Surgical treatments for oral cavity (mouth) and oropharyngeal (throat) cancers

Review question

We evaluated clinical trials of surgical treatments for oral and oropharyngeal cancers to find out which were most likely to result in people with these cancers living longer (overall survival). living longer without symptoms (disease-free survival), and not experiencing a recurrence of the cancer at the same site or spread to other sites. We also wanted to find out how different treatments affect disease symptoms, quality of life, time in hospital, complications, side effects and cost.

Background

Oral cancer is among the most common cancers worldwide, with more than 400,000 new cases diagnosed in 2012. The treatment of these cancers can involve surgery, chemotherapy, radiotherapy, or a combination of two or all three therapies. This topic area was identified as a priority by an expert working group for oral and maxillofacial surgery in 2014. Authors working with Cochrane Oral Health conducted this review, which is an update of a review originally published in 2007 and first updated in 2011. The evidence is current to 20 December 2017.

Study characteristics

We included 12 trials (five new for this update) that investigated the success of surgical treatment for oral cancers. The studies involved 2300 participants, 2148 of whom had mouth cancers. The trials included seven comparisons of different treatment options. None of them compared different surgical approaches for cutting out the primary tumour.

Key results

The findings of the studies are mixed and it is not possible to draw firm conclusions about the optimal surgical approach for mouth and throat cancers.

Surgical removal of the lymph nodes in the neck that appear to be cancer-free, at the same time as the cancer is removed did not seem to be associated with longer survival in two studies whose results were combined. Another study, however, suggested there may be a benefit of early neck surgery in terms of overall survival and 'disease-free survival' (length of time after primary treatment without signs and symptoms of disease). One study found cancer recurrence at or around the same site was less likely with the early surgery, while three other studies did not favour either treatment.

There was no evidence that removal of all the lymph nodes in the neck resulted in longer survival compared to selective surgical removal of affected lymph nodes.

One study evaluated use of a special scan (positron-emission tomography-computed tomography (PET-CT)), after a combination of chemotherapy and radiotherapy, to guide decisions about neck dissection, and found no difference in mortality (death) compared with undertaking a planned neck dissection before or after chemoradiotherapy.

There were a number of other surgical approaches compared in the studies, but we were unable to use the results in this review.

Although removal of lymph nodes from the neck is known to be associated with significant negative effects related to appearance and functions such as eating, drinking and speaking, the studies reported poorly on these side effects and did not measure quality of life accurately enough or in large enough numbers to be included in any of our analyses.

Certainty of the evidence

The certainty of the evidence was very low as there were few studies for each comparison and they were at risk of bias because of the way they were designed. Some comparisons and outcomes had no useable results.

Authors' conclusions: 

Twelve randomised controlled trials evaluated ND surgery in people with oral cavity cancers; however, the evidence available for all comparisons and outcomes is very low certainty, therefore we cannot rely on the findings. The evidence is insufficient to draw conclusions about elective ND of clinically negative neck nodes at the time of removal of the primary tumour compared to therapeutic (delayed) ND. Two trials combined in meta-analysis suggested there is no difference between these interventions, while one trial (which evaluated elective supraomohyoid ND) found that it may be associated with increased overall and disease-free survival. One trial found elective ND reduced locoregional recurrence, while three were inconclusive. There is no evidence that radical ND increases overall or disease-free survival compared to more conservative ND surgery, or that there is a difference in mortality between PET-CT surveillance following chemoradiotherapy versus planned ND (before or after chemoradiotherapy). Reporting of adverse events in all trials was poor and it was not possible to compare the quality of life of people undergoing different surgical treatments.

Read the full abstract...
Background: 

Surgery is an important part of the management of oral cavity cancer with regard to both the removal of the primary tumour and removal of lymph nodes in the neck. Surgery is less frequently used in oropharyngeal cancer. Surgery alone may be treatment for early-stage disease or surgery may be used in combination with radiotherapy, chemotherapy and immunotherapy/biotherapy. There is variation in the recommended timing and extent of surgery in the overall treatment regimens of people with these cancers. This is an update of a review originally published in 2007 and first updated in 2011.

Objectives: 

To determine which surgical treatment modalities for oral and oropharyngeal cancers result in increased overall survival, disease-free survival and locoregional control and reduced recurrence. To determine the implication of treatment modalities in terms of morbidity, quality of life, costs, hospital days of treatment, complications and harms.

Search strategy: 

Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 20 December 2017), the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 11), MEDLINE Ovid (1946 to 20 December 2017) and Embase Ovid (1980 to 20 December 2017). We searched the US National Institutes of Health Trials Registry (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform for ongoing trials. There were no restrictions on the language or date of publication.

Selection criteria: 

Randomised controlled trials where more than 50% of participants had primary tumours of the oral cavity or oropharynx, or where separate data could be extracted for these participants, and that compared two or more surgical treatment modalities, or surgery versus other treatment modalities.

Data collection and analysis: 

Two or more review authors independently extracted data and assessed risk of bias. We contacted study authors for additional information as required. We collected adverse events data from included studies.

Main results: 

We identified five new trials in this update, bringing the total number of included trials to 12 (2300 participants; 2148 with cancers of the oral cavity). We assessed four trials at high risk of bias, and eight at unclear. None of the included trials compared different surgical approaches for the excision of the primary tumour. We grouped the trials into seven main comparisons.

Future research may change the findings as there is only very low-certainty evidence available for all results.

Five trials compared elective neck dissection (ND) with therapeutic (delayed) ND in participants with oral cavity cancer and clinically negative neck nodes, but differences in type of surgery and duration of follow-up made meta-analysis inappropriate in most cases. Four of these trials reported overall and disease-free survival. The meta-analyses of two trials found no evidence of either intervention leading to greater overall survival (hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.41 to 1.72; 571 participants), or disease-free survival (HR 0.73, 95% CI 0.25 to 2.11; 571 participants), but one trial found a benefit for elective supraomohyoid ND compared to therapeutic ND in overall survival (RR 0.40, 95% CI 0.19 to 0.84; 67 participants) and disease-free survival (HR 0.32, 95% CI 0.12 to 0.84; 67 participants). Four individual trials assessed locoregional recurrence, but could not be meta-analysed; one trial favoured elective ND over therapeutic delayed ND, while the others were inconclusive.

Two trials compared elective radical ND with elective selective ND, but we were unable to pool the data for two outcomes. Neither study found evidence of a difference in overall survival or disease-free survival. A single trial found no evidence of a difference in recurrence.

One trial compared surgery plus radiotherapy with radiotherapy alone, but data were unreliable because the trial stopped early and there were multiple protocol violations.

One trial comparing positron-emission tomography-computed tomography (PET-CT) following chemoradiotherapy (with ND only if no or incomplete response) versus planned ND (either before or after chemoradiotherapy), showed no evidence of a difference in mortality (HR 0.92, 95% CI 0.65 to 1.31; 564 participants). The trial did not provide usable data for the other outcomes.

Three single trials compared: surgery plus adjunctive radiotherapy versus chemoradiotherapy; supraomohyoid ND versus modified radical ND; and super selective ND versus selective ND. There were no useable data from these trials.

The reporting of adverse events was poor. Four trials measured adverse events. Only one of the trials reported quality of life as an outcome.

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