Cancer of the oesophagus is a distressingly common cancer in men and women.

VINAY SHARMA, MD (Rad), MD (Rad Onc), PhD Professor and Consultant, Department of Radiation Oncology, Johannesburg Hospital, University of the Witwatersrand, Johannesburg

Vinay Sharma is in charge of the Head and Neck, and the Oesophagus unit. Dr Sharma's special interest is cancers of the oesophagus, lung and head and neck.

JEFFREY KOTZEN, BSc, MB BCh, MMed Rad(T) Senior Specialist, Department of Radiation Oncology, Johannesburg Hospital and University of the Witwatersrand, Johannesburg

Jeffrey Kotzen's special interests are brachytherapy, paediatric oncology, neuro-oncology, gynaecological oncology, and prostate and colorectal cancer.

Cancer of the oesophagus is the third leading cancer in males, comprising about 5.6% of all cases in males and 4th common in females, comprising 3% of all cancers. The age-adjusted incidence rates are 61/100 000 population in males and 36.8/100 000 in females for the age group 70 - 74 years, steadily increasing from 50 - 54 years. The majority of patients (33%) present in the age group of 65 and above.

The condition is 3.8 times more likely in smokers and the incidence increases if there is alcohol intake in addition to smoking. The age-standardised rates are 37.5/100 000 population in Transkei, Eastern Cape (3 times more) than in other geographical areas, due mainly to consumption of maize, which contains low levels of niacin, riboflavin, vitamin C, zinc, cadmium and magnesium. The incidence is also very high in the black population and forms 13% of all cancers in black males.

Evaluation and investigation

A detailed history of complaints of difficulty in swallowing, cough associated with swallowing, loss of weight, and backache is essential to diagnosis. Weight loss of > 10% in the 6 months preceding treatment has an adverse impact on survival. Investigations include a general physical examination for performance status, including body weight and regional and distant spread, investigations such as barium swallow, endoscopy for histological diagnosis, the length of the lesion and the type of the lesion, a CT scan of the chest and upper abdomen for local extent, extra-oesophageal spread, nodal disease and liver involvement. PET CT has a better sensitivity and specificity than CT alone and changes the management decision in about 20% of cases. Endoscopic ultrasound is optimal for loco regional staging to determine the depth of invasion and loco regional lymph nodes.

The criteria for curative versus palliative treatment should be:

* lesion length of 5 cm or less

* no metastatic disease

* ECOG performance status 0-1.

Curative therapy

Only approximately 20% of patients are suitable for curative therapy. Options for curative therapy include surgical resection, definitive chemoradiation, and chemoradiation followed by surgical resection (trimodality therapy). Postoperative chemotherapy and radiation is only recommended for gastro-oesophageal cancers.

Surgery alone

The aim is to achieve a wide resection with 5 cm margins and a regional lymphadenectomy. The approach may be transthoracic or transhiatal. High lesions (above the aortic arch) require the additional resection of the pharynx and larynx, and are not treated primarily with surgery. About half the patients taken to surgery can be resected, with a 5-year survival of 20 - 35%. The surgery should be performed in a high-volume tertiary referral centre.

Definitive chemoradiation

Chemoradiation has been shown to be superior to radiation alone in an intergroup study. (2) The 2-year survival was 38% versus 10% (p < 0.001), 5-year survival 27% versus nil (p < 0.001).

However, chemoradiation is associated with significant morbidity. Good results have been reported for the rare T1N0M0 lesions with radiation alone. (3) Dose escalation is controversial. The Intergroup randomised patients receiving chemo-radiation to 64.8 or 50.4 Gy with concurrent 5-FU and cisplatin showed no statistically significant difference in recurrence patterns with the higher dose. (4) However, a large proportion of the recurrences are local (about half) so there is a rationale for adding a brachytherapy boost. Hishikawa et al. (5) report 27.9% overall survival at 2 years with high-dose-rate brachytherapy following external beam radiation in comparison to 19.6% with external beam radiation alone. Sharma et al. (6) have reported 22% 5-year survival in a select group of patients with a combination of external beam radiation followed by low-dose-rate brachytherapy along with 5FU radio-sensitisation.

Preoperative chemoradiation

Complete response rates after chemoradiation are approximately 20%. This led to trials comparing preoperative chemoradiation versus oesophagectomy alone. Many of these trials do not report an improvement in overall survival for trimodality therapy. Stahl et al. (7) report no survival benefit with the addition of surgery following chemoradiation although local tumour control (64% versus 41% at 2 years) and the quality of swallowing were improved. A meta-analysis of 9 trials8 has shown that neo-adjuvant chemoradiation improved the 3-year loco regional control (odds ratio 0.88, p = 0.6) and survival (odds ratio 0.66, p = 0.038) at the expense of increased treatment-related mortality.

Palliative therapy

Advanced oesophageal cancer carries a very poor prognosis, with a median survival time that ranges from 2.5 to 6.2 months. (9) Most patients present with an advanced stage of disease and in a poor general condition, where palliation of symptoms is the main aim of treatment. The main symptoms requiring palliation are dysphagia, odynophagia, regurgitation and pain.

Dysphagia appears when the oesophageal lumen is less than 15 mm in diameter. The options for relieving dysphagia include serial dilatations, stenting, external beam radiation, chemotherapy, brachytherapy (low-dose-rate and high-dose-rate), photodynamic therapy or a combination of modalities.

Brachytherapy and stenting

High-dose-rate brachytherapy has an advantage over the low-dose-rate or medium-dose-rate because treatment is quick and therefore the discomfort the patient suffers from having the oesophageal applicator in place for a long period is avoided. Sur et al. (10) have compared brachytherapy schedules of 6 Gy x 3 fractions and 8 Gy x 2 fractions in a multicentre IAEA study and reported similar results for overall survival and dysphagiafree survival. The overall survival was 7.9 months for the whole group (9.1 months for 6 Gy x 3 fractions and 6.9 months for 8 Gy x 2 fractions, p = > 0.05). The dysphagiafree survival for the whole group was 7.1 months (7.8 months for 6 Gy x 3 fractions and 6.3 months for 8 Gy x 2 fractions, p = > 0.05). Due to limited resources, more use of brachytherapy needs to be considered, as this could reduce the waiting period for the patients needing external beam radiation.

A multicentre Dutch study compared a single 12 Gy dose of intraluminal brachytherapy with placement of a stent in 209 patients. (11) Dysphagia improved more rapidly and completely after stent placement but long-term relief of dysphagia (after 3 months) was better after brachytherapy. Stent placement resulted in a higher complication rate than brachytherapy (33% versus 21%) mainly due to increased late haemorrhage. There was no difference in survival between the two groups.

External beam radiation

This is usually given in 5-10 daily fractions (compared with 1 or 2 of brachytherapy), and can achieve palliation of dyphagia in about 66% of patients for 2 months or longer.

REFERENCES

(1.) Mqoqi N, Kellett P, Sitas F, Jula M. Incidence of Histologically Diagnosed Cancers in South Africa, 1998-1999. Johannesburg: National Cancer Registry of South Africa, 2004: 46-48.

(2.) Al-Sarraf M, Martz K, Herskovic A, et al. Progress report of combined chemoradiotherapy versus radiotherapy alone in patients with esophageal cancer: an intergroup study. J Clin Oncol 1997; 15: 1593-1598.

(3.) Ishikawa H, Sakurai H, Yamakawa M, et al, Clinical outcomes and prognostic factors for patients with early esophageal squamous carcinoma treated with definitive radiation. J Clin Gastroenterol 2005; 39: 495-500.

(4.) Minsky BD, Pajak TF, Ginsberg RJ, et al. INT 0123 (Radiation Therapy Oncology Group 94-05) phase III trial of combined-modality therapy for esophageal cancer: high-dose versus standard-dose radiation therapy. J Clin Oncol 2002; 20: 1167-1174.

(5.) Hishikawa Y, Kamikonya N, Tanaka S, Miura T. Radiotherapy of esophageal carcinoma: Role of high dose rate intracavitory irradiation. Radiother Oncol 1987; 9: 13-20.

(6.) Sharma V, Agarwal JP, Dinshaw KA, Mohandas KM, Deshpande RK, Rayabhattnavar S. Late esophageal toxicity using a combination of external beam radiation, intraluminal brachytherapy and 5-fluorouracil infusion in carcinoma of the esophagus. Dis Esophagus 2000; 13: 219-225.

(7.) Stahl M, Stuschke M, Lehmann N, et al. Chemoradiation with and without surgery in patients with locally advanced squamous cell carcinoma (SCC) of the esophagus 2005; 23: 2310-2317.

(8.) Urschel JD, Vasan HA. A meta-analysis of randomized controlled trials that compared neoadjuvant chemoradiation and surgery to surgery alone for resectable esophageal cancer. Am J Surg 2003; 185: 538-543.

(9.) Sur RK, Donde B, Levin CV, Mannell A. Fractionated high dose intra-luminal brachytherapy in palliation of advanced esophageal cancer. Int J Radiat Oncol Biol Phys 1998; 40: 447-453.

(10.) Sur RK, Levin CV, Donde B, et al. A prospective randomized trial of HDR brachytherapy as a sole modality in palliation of advanced esophageal cancer--An IAEA Study. Int J Radiat Oncol Biol Phys 2002; 53: 127-133.

(11.) Homs MyY, Steyerberg EW, Eijkenboom WM, et al. Palliative treatment of esophageal cancer with dysphagia: more favorable outcome from single-dose internal brachytherapy than from the placement of a self-expanding stent; a multicenter randomized study. Ned Tijdschr Geneeskd 2005; 10; 149(50): 2775-2782.

Table I. AJCC staging of cancer of the oesophagus

AJCC Staging (2002)                  AJCC Staging (1978)

Primary tumour (T)                   Primary tumour (T)

TX: Primary tumour cannot be         TX: Primary tumour cannot be
  assessed                             assessed
T0: No evidence of primary tumour    T0: No evidence of primary tumour
Tis: Carcinoma in situ               Tis: Carcinoma in situ
T1: Tumour invades lamina propria    T1: Tumour 5 cm or less, no
  or submucosa                         obstruction, no circumferential
T2: Tumour invades muscularis          involvement, no extra-
  propria                              oesophageal spread
T3: Tumour invades adventitia        T2: Tumour more than 5 cm, any
T4: Tumour invades adjacent            size with obstruction,
  structures                           circumferential involvement and
                                       no extra-oesophageal spread
Regional lymph nodes (n)             T3: any tumour with extra-
                                       oesophageal spread
NX: Regional lymph nodes cannot be
  assessed                           Regional lymph nodes (n)
N0: No regional lymph node
  metastasis                         NX: Regional lymph nodes cannot be
N1: Regional lymph node metastasis     assessed
                                     N0: No regional lymph node
Distant metastasis (m)                 metastasis
                                     N1: Movable unilateral palpable
MX: Distant metastasis cannot be       lymph nodes
  assessed                           N2: Movable bilateral palpable
M0: No distant metastasis              nodes
M1: Distant metastasis               N3: Fixed nodes

Tumours of the lower thoracic        Distant metastasis (m)
oesophagus:
                                     MX: Distant metastasis cannot be
M1a: Metastasis in celiac lymph        assessed
  nodes                              M0: No distant metastasis
M1b: Other distant metastasis        M1: Distant metastasis

Tumours of the midthoracic
oesophagus:

M1a: Not applicable
M1b: Non-regional lymph nodes
  and/or other distant metastasis

Tumours of the upper thoracic
oesophagus:

M1a: Metastasis in cervical nodes
M1b: Other distant metastasis

AJCC stage groupings

Stage 0     Tis, N0, M0
Stage I     T1, N0, M0
Stage IIA   T2, N0, M0
            T3, N0, M0
Stage IIB   T1, N1, M0
            T2, N1, M0
Stage III   T3, N1, M0
            T4, any N, M0
Stage IV    Any T, any N, M1
Stage IVA   Any T, any N, M1a
Stage IVB   Any T, any N, M1b

As the above staging can be done using EUS or, SURGERY, the
AJCC 1978 staging should be applied until facilities for EUS are
available everywhere and patients come in a stage where surgical
staging is possible