Management of oesophageal cancer, like most upper gastrointestinal malignancies, is controversial. The disease is commonly locally advanced, cures are difficult to achieve and there is conflicting evidence from randomised controlled trials.

Localised Thoracic Oesophageal Cancer

Single Modalities

Surgery Alone

The standard approach is partial oesophagogastrectomy, and a variety of techniques exist. Regardless of technique, 5 year survival with surgery alone for resectable disease is about 20%. This has led to consideration of ways of improving surgical outcomes with neo-adjuvant or adjuvant therapies, or doing away with surgery altogether.

  • The exception is stage I disease (T1). These tumours have close to 50-60% 5 year survival and the addition of chemoradiotherapy has not been shown to improve outcomes in this group.

Radiotherapy Alone

Radiotherapy alone was used historically for patients unable to have surgery, and most frequently for upper and middle oesophageal tumours. Dose is limited by the oesophagus' inherent radiosensitivity to doses over 50 Gy and lung toxicity. 5-year survival is about 5% with this approach and it has been largely replaced by chemoradiotherapy.

Chemotherapy Alone

Chemotherapy has a limited role in localised thoracic oesophageal cancer. Most single agents have 20% response rates, and only for a few months.

Chemoradiotherapy Alone

Chemoradiotherapy has been evaluated for inoperable patients. The landmark study is the RTOG 85-01, which randomised patients to 50.4 Gy with concurrent 5-FU/cisplatin against 64 Gy in 32 fractions. 5 year survival was significantly better for the chemoradiotherapy arm (27% vs 0%).

  • Further studies into radiotherapy dose levels have not shown any superiority over 50.4 Gy, even when combined with similar chemotherapy (INT 0123 study)
  • Chemoradiotherapy alone is only established as curative treatment for squamous cell carcinoma as most randomised trials have had high numbers of SCC patients or excluded adenocarcinoma
  • Chemoradiotherapy is usually offered to patients with adenocarcinoma who are surgically unresectable despite the lack of evidence

Surgery + Neoadjuvant Therapy

The main controversy is the role of neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy.

Neoadjuvant Radiotherapy

Neoadjuvant radiotherapy has not been extensively studied but trials have demonstrated minimal impact of radiotherapy alone on surgical outcomes.

Neoadjuvant Chemoradiotherapy

Alone, chemoradiotherapy has good response rates (92% able to receive R0 in CROSS study), and 28% of patients have complete pathological response; despite this about 50% of patients will fail locally within one year. In combination with surgery, chemoradiotherapy improves 2 year survival by an absolute 8.7% (ie. about 30% versus 20% seen with surgery alone). This has been demonstrated in an Australian meta-analyais (Sjoquist et al).

Neoadjuvant Chemotherapy

There are variable results with randomised neoadjuvant chemotherapy studies.
Neoadjuvant chemotherapy was looked at separately in the Sjoquist trial. Although there was no absolute benefit of chemoradiotherapy over chemotherapy alone in the neoadjuvant setting, there was a trend towards improved outcomes in the chemoradiotherapy arm and much higher rates of complete pathological response in the trimodality arm.
Neoadjuvant chemotherapy is frequently used for adenocarcinomas of the gastro-oesophageal junction, as per the MAGIC trial from the UK. This trial compared epirubicin, cisplatin and 5-fluorourcail given for 3 cycles pre- and post-operatively.
Neoadjuvant chemotherapy versus chemoradiotherapy has been evaluated in two trials, an Australian trial by Burmeister et al and the German POET trial. Both trials had non-significant results but the POET trial showed a trend towards improved outcomes for chemoradiotherapy (3 year survival 47 vs 28%).

Novel Approaches

The DOCTOR trial administeres cisplatin/5-fluorouracil neoadjuvant chemotherapy for 2 cycles and then restages with PET scan. Non responders are then randomised to radiotherapy with docetaxal, cisplatin and 5-FU versus DCF chemotherapy alone prior to surgery. Responders proceed with standard therapy then oesophagectomy.

Current Recommendations

Patients should receive neoadjuvant chemoradiotherapy unless:

  • The tumour is very small (T1) with minimal risk of lymphatic spread
  • The tumour is inoperable for patient or tumour factors (chemoradiotherapy alone)
  • The patient is unable to receive chemotherapy (surgery alone)
  • The patient is unable to receive radiotherapy (chemotherapy alone) or is convinced to have chemotherapy alone.

Surgery + Adjuvant Therapy

Adjuvant radiotherapy in particular has not been extensively studied. There are no randomised trials comparing chemoradiotherapy or chemotherapy to surgery alone in the adjuvant setting. Non randomised prospective and retrospective data indicates that there is a survival advantage and results from neoadjuvant studies are often used as evidence for a benefit in the adjuvant setting.

Unresectable or Metastatic Thoracic Oesophageal Cancer

The main aims of treatment are to prolong high-quality life. This is accomplished by:

  • Restoring normal swallowing as far as able
  • Controlling metastatic disease

Patients with metastatic disease typically have a life expectancy of under 6 months and treatment options must be tailored around this.


Surgery is rarely used in the unresectable or metastatic setting. In unresectable patients, outcomes are likely to be equivalent with the use of chemoradiotherapy and major surgery is avoided. In patients with metastatic disease, limited survival means that patient will often not be able to recover fully from their operation before they are struck down by metastatic complications.
Stenting remains a viable option for these patients. It can be used in several situations:

  • When dysphagia is so severe at presentation that it can not wait for chemoradiotherapy to resolve it
  • In patients unable to receive chemoRT
  • In patients with stricture after radiotherapy
  • In patients with recurrence after radiotherapy


Radiotherapy alone provides symptomatic relief for dysphagia in most patients, and half of patients die before dysphagia recurs. Radiotherapy alone is less viable when long term survival is expected (ie. non-metastatic disease) and concurrent chemoradiotherapy should be attempted if at all possible. Long term survival has been reported but is low (1-2%). In metastatic cases with limited survival, the radiotherapy dose is often hypofractionated to reduce the time spent in the department (eg. 30 Gy in 10 fractions).


Chemotherapy alone is often used for palliation to extend life but has less impact on local symptoms. Multiple regimens have been evaluated and there are similarities between those used for gastric and oesophageal cancers. Epirubicin, oxaliplatin and capecitabine (EOX) is a good choice (survival ~ 11 months vs 10 months for ECF).


Chemoradiotherapy was evaluated in the RTOG 85-01 trial and shown to be significantly better than escalated radiotherapy alone. This now forms the mainstay of treatment for unresectable disease (50.4 Gy with concurrent 5-FU 1000 mg/m^2 and cisplatin 75 mg/m^2). Higher doses of radiotherapy were ineffective even when combined with chemotherapy. Median survival was improved in RTOG 85-01 from 9 to 14 months.

Cervical Oesophageal Cancer

Cervical oesophageal tumours present a different scenario to the thoracic oesophagus. Surgery is generally extensive, with total oesophagectomy, gastric pull-up, laryngectomy, tracheostomy and bilateral neck dissections. This makes it a less attractive option. Most tumours of the cervical oesophagus are squamous cell carcinomas, and they have a very similar pattern of disease to mucosal tumours of the head and neck. Chemoradiotherapy is generally recommended for these patients. The beam arrangement is different due to the anterior position of the oesophagus in the neck relative to the thorax.

Gastro-oesophageal Junction Cancer

This is the most controversial of the controversies! The gastro-oesophageal junction usually develops adenocarcinoma, and it has been included in numerous trials exploring neo-adjuvant and adjuvant therapies for both oesophageal and gastric carcinomas. This means that treatment options for both sites are applied to this region.


For staging purposes, the AJCC stages gastro-oesophageal (and proximal 5 cm of stomach) tumours are oesophageal tumours if they involve the gastro-oesophegeal junction or distal oesophagus.

Treatment Options

From oesophageal cancer trials:

  • Surgery alone (20% 5 year survival except for T1 lesions)
  • Neoadjuvant chemoradiotherapy (30% 5 year survival)
    • 50.4 Gy with concurrent 5-FU (1000 mg/m2) and cisplatin (75 mg/m2)

From gastric cancer trials:

  • Surgery alone for T1 lesions
  • Neo-adjuvant and adjuvant chemotherapy (MAGIC trial) with ECF
  • Adjuvant chemotherapy and chemoradiotherapy (Intergroup 0116/MacDonald protocol) 50.4 Gy with concurrent 5-FU.

The option chosen will depend greatly on the local pattern of care as there is no proven superior option. For a good review of all options, see the Yu and Ilson article here.

  • In summary, most options will improve survival by 10-15%
  • Chemoradiotherapy was superior to chemotherapy alone in the POET trial
  • Chemoradiotherapy was non-significantly superior to chemotherapy alone in the Sjoquist meta-analysis
  • Chemoradiotherapy has much higher rates of complete pathological response than chemotherapy alone (17% vs 2%)

Future randomised trials may resolve these questions - for instance, the TOP GEAR study (trial of perioperative therapy for gastric and oesophagogastric junction adenocarcinoma) will evaluate the MAGIC protocol against a MAGIC + neoadjuvant chemoradiotherapy protocol (3rd neoadjuvant cycle of MAGIC replaced with 45 Gy + concurrent 5-fluorouracil).