Cancers or the oral cavity, pharynx and larynx are collectively referred to as Head and Neck cancers and together make up about 5% of all malignant tumours and are the 6^th most common cancer in the world. Tobacco use, alcohol consumption and betel quid chewing are the main risk factors in the aetiology of oral cancer while there is a strong link between oncogenic HPV and oropharyngeal cancer . Surgery is an important aspect of treatment and may be combined with one or more other treatments, radiotherapy, chemotherapy and immunotherapy/biotherapy.

The aim of this Cochrane review update was to determine which surgical approaches for oral (mouth) and oropharyngeal (throat) cancers result in increased overall survival, disease- free survival, locoregional control and reduced recurrence.

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. Cancers were primarily oral squamous-cell cancer (SCC) although histological variants of SCCs (e.g. adenosquamous, verrucous, basaloid, papillary) were included epithelial malignancies of the salivary glands, odontogenic tumours, all sarcomas and lymphomas were excluded.    The primary outcomes considered were, overall survival, disease-free survival, locoregional recurrence and recurrence.  Standard Cochrane approaches to data collection and analysis were followed.

Results

• 12 trials involving 2300 patients 2148 with cancers of the oral cavity are included in this update adding 5 new trials.
• 4 trials are considered to be at high risk of bias, 8 at unclear risk.
• None of the included trials compared different surgical approaches for the excision of the primary tumour.
• Seven main comparisons are presented but future research may change the findings as there is only very low‐certainty evidence available for all results.
• 5 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.
• 4 of these trials reported overall and disease‐free survival.
• Meta‐analyses (2 trials) found no evidence of either intervention leading to
  • greater overall survival (hazard ratio (HR) = 0.84 (95% CI; 0.41 to 1.72) [571 patients],or
  • disease‐free survival HR = 0.73 (95%CI; 0.25 to 2.11) [ 571 patients].
  • 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 patients] and
    • disease‐free survival HR = 0.32 (95%CI; (0.12 to 0.84) [67 patients].
• 4 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.
• 2 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.
• 1 trial compared surgery plus radiotherapy with radiotherapy alone, but data were unreliable because the trial stopped early and there were multiple protocol violations.
• 1trial 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 patients]. The trial did not provide usable data for the other outcomes.
• 3 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.

Conclusions

The authors concluded: –

Twelve randomised controlled trials evaluated neck dissection (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.

Comments

This Cochrane review is one of a series of reviews that looks at treatments for oral cancer including surgery, radiotherapy, chemotherapy and immunotherapy. This review updates an earlier review but now only includes studies that compare different surgical treatment approaches against one another or compare surgery to different treatments.  While 12 trials were included the overall certainty of the evidence was very low as all trials were considered to be at high or unclear risk of bias so the findings should be considered cautiously.

It is interesting to note that a new review by Ding et al comparing elective ND and therapeutic ND has very recently been published.  This includes 6 studies, 5 of which were included in the Cochrane review. Ding et al  have been  more generous in their assessment of the quality of the included studies and  in their interpretation of the findings than the Cochrane reviews   concluding

‘that elective ND considerably decreases regional recurrences and the death related to it in early-stage oral SCC with clinically N0 neck, especially SCC of the oral tongue and floor of the mouth, confirming the necessity of elective ND for these patients’.

Links

Primary Paper

Bulsara  VM, Worthington  HV, Glenny  AM, Clarkson  JE, Conway  DI, Macluskey  M. Interventions for the treatment of oral and oropharyngeal cancers: surgical treatment. Cochrane Database of Systematic Reviews 2018, Issue 12. Art. No.: CD006205. DOI: 10.1002/14651858.CD006205.pub4.

Other references

Cochrane Oral Health Group Blog – Surgical treatments for mouth and throat cancer: uncertainty in the evidence

Ding Z, Xiao T, Huang J, Yuan Y, Ye Q, Xuan M, Xie H, Wang X. Elective Neck Dissection Versus Observation in Squamous Cell Carcinoma of Oral Cavity With Clinically N0 Neck: A Systematic Review and Meta-Analysis of Prospective Studies. J Oral Maxillofac Surg. 2019 Jan;77(1):184-194. doi: 10.1016/j.joms.2018.08.007.  Epub 2018 Aug 22. Review. PubMed PMID: 30218654.

Dental Elf – Oral Cancer Blogs