Minimally invasive (keyhole) surgery versus radiotherapy alone or radiotherapy and chemotherapy for early-stage throat cancer

Review question

We reviewed the evidence to compare two treatments for throat cancer. The treatments were keyhole surgery and radiotherapy alone or combined with chemotherapy.

Background

More than 400,000 cases of cancer of the middle part of the throat (oropharynx) are diagnosed each year worldwide and this number is rising, with human papillomavirus (HPV) being a significant contributing factor. Throat cancer caused by this virus affects younger patients and they often present with more advanced disease. However, it is associated with a better prognosis.

Until recently the first-line management of this type of throat cancer involved radiotherapy combined with chemotherapy, as research had demonstrated similar survival rates when compared with surgery but with significantly fewer side effects. However, treatments have now evolved with computerised planning and improvements in radiotherapy, and the advent of keyhole head and neck surgery, which have the potential for fewer side effects from treatment.

The oropharynx plays an essential role in swallowing, speech and protecting the airway as it is situated at the junction of the respiratory and digestive tracts. The choice of which treatment to use is based on which is associated with the best survival. As younger patients are being affected, establishing the safety of treatments with potentially fewer side effects and less disability is becoming increasingly important.

Search date

The evidence is current to November 2016.

Study characteristics

We found no completed studies that compared keyhole surgery and radiotherapy alone or combined with chemotherapy. Two ongoing trials did fulfil our selection criteria, however neither are yet complete. One has an estimated completion date of June 2021 and the other planned to start recruiting patients mid-2016.

Key results

There are not yet any completed studies to include in the review so there are no results.

Quality of the evidence and conclusions

The role of keyhole surgery in the management of throat cancer is expanding as is demonstrated by its incorporation into the current national guidelines in the USA. Evidence is mounting regarding its outcomes both in terms of survival and fewer side effects.

Based on this review, there is currently no high-quality evidence from randomised controlled trials that compare keyhole surgery with radiotherapy and chemotherapy for patients with throat cancer.

Authors' conclusions: 

The role of endoscopic head and neck surgery in the management of OPSCC is clearly expanding as evidenced by its more overt incorporation into the current National Comprehensive Cancer Network guidelines. Data are mounting regarding its outcomes both in terms of survival and lower morbidity. As confidence increases, it is being used in the management of more advanced OPSCC.

Based on this review, there is currently no high-quality evidence from randomised controlled trials regarding clinical outcomes for patients with oropharyngeal cancer receiving endoscopic head and neck surgery compared with primary chemoradiotherapy.

Read the full abstract...
Background: 

More than 400,000 cases of oropharyngeal squamous cell carcinoma (OPSCC) are diagnosed each year worldwide and the incidence is rising, partly as a result of human papillomavirus. Human papillomavirus-associated OPSCC affects younger patients and often presents at a higher stage; however, it is associated with a better prognosis.

Until recently, first-line management of OPSCC involved chemoradiotherapy, as research had demonstrated comparable survival outcomes when compared with open surgery, with significantly decreased morbidity. However, interventions have now evolved with computerised planning and intensity-modulated radiotherapy, and the advent of endoscopic head and neck surgery, which provide the potential for decreased treatment-associated morbidity.

The oropharynx plays an essential role in swallowing, speech and protecting the airway as it is situated at the bifurcation of the respiratory and digestive tracts. Treatment modality recommendations are based on survival outcomes. Given the younger patient demographic, establishing the safety of modalities that potentially have better functional outcome is becoming increasingly important.

Objectives: 

To assess the efficacy of endoscopic head and neck surgery (transoral robotic surgery or transoral laser microsurgery) for small-volume, primary (T1-2, N0-2) oropharyngeal squamous cell carcinoma (OPSCC) in comparison to radiotherapy/chemoradiotherapy.

Search strategy: 

The Cochrane ENT Information Specialist searched the ENT Trials Register; Central Register of Controlled Trials (CENTRAL 2016, Issue 10); PubMed; EMBASE; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 8 November 2016.

Selection criteria: 

Randomised controlled trials in patients with carcinoma in the oropharynx subsite (as defined by the World Health Organization classification C09, C10). Cancers included were primary squamous cell carcinomas arising from the oropharyngeal mucosa. The tumours were classified as T1-T2 with or without nodal disease and with no evidence of distant metastatic spread. The intervention was transoral, minimally invasive surgery with or without adjuvant radiotherapy or adjuvant chemoradiotherapy. The comparator was primary radiotherapy with or without induction or concurrent chemotherapy for the tumour. The treatments received and compared were of curative intent and patients had not undergone prior intervention, other than diagnostic biopsy.

Data collection and analysis: 

We used the standard methodological procedures expected by Cochrane. Our primary outcomes were overall survival (disease-related mortality was to be studied where possible), locoregional control, disease-free survival and progression-free survival or time to recurrence. All outcomes were to be measured at two, three and five years after diagnosis. Our secondary outcomes included quality of life, harms associated with treatment, patient satisfaction and xerostomia score.

Main results: 

No completed studies met the inclusion criteria for the review. Two ongoing trials fulfilled the selection criteria, however neither are complete.

'Early-stage squamous cell carcinoma of the oropharynx: radiotherapy versus trans-oral robotic surgery (ORATOR)' is a phase II randomised controlled trial comparing primary radiation therapy with primary transoral robotic surgery for small-volume primary (T1-2, N0-2) OPSCC. It is currently in progress with an estimated completion date of June 2021.

'European Organisation for Research and Treatment of Cancer 1420 (EORTC 1420-HNCG-ROG)' is a phase III, randomised study assessing the "best of" radiotherapy compared to transoral robotic surgery/transoral laser microsurgery in patients with T1-T2, N0 squamous cell carcinoma of the oropharynx and base of tongue. It was due to start accrual mid-2016.