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Page 6 of 9 Oo et al. Mini-invasive Surg 2019;3:13 I http://dx.doi.org/10.20517/2574-1225.2019.02

or without radiation therapy in addition to surgery. The multimodality treatment has now become the
standard of care for advanced GEJ cancers. However, the best approach to multimodality treatment for GEJ
cancers is not established yet as GEJ tumours represent only a small subset of cohort in most of clinical
trials [50-53] . Even though adjuvant chemotherapy has been proven to be beneficial and improve survival
outcomes compared to surgery alone in gastric cancers, the role of adjuvant chemotherapy in GEJ tumours
is still unclear as there are no large trials conducted for GEJ cancers specifically and are often categorised
under the subset of gastric cancers [54,55] .

Adjuvant chemoradiotherapy is one possible option for patients with GEJ tumours who didn’t receive the
[53]
preoperative treatment with survival benefit demonstrated in US intergroup 0116 trial . This regimen also
known as the “Macdonald regimen” is the current standard of adjuvant treatment for patients with gastric
cancer. Of the 559 patients recruited in this trial only 20% had GEJ cancers. Adjuvant chemoradiotherapy
produced substantial reduction in both overall relapse and locoregional relapse as well improved overall
[53]
survival, hazard ratio (HR) 1.32 (95%CI: 1.10-1.60; P = 0.0046) . One major criticism of the study was that
only 10% of patients had received D2 lymphadenectomy and therefore the improvement in relapse rates
and survival could be due to potential compensation of an oncologically inadequate surgery.

Neoadjuvant or perioperative chemotherapy with or without radiation therapy have proven to be effective
in improving survival. The MAGIC trial compared patients who underwent surgery alone to surgery plus
perioperative chemotherapy (3 cycles of preoperative and 3 cycles of postoperative epirubicin, cisplatin and
[50]
infusional flurouracil) . Of the 503 patients recruited only 11% had GEJ tumours. Compared to surgery
alone group, the perioperative chemotherapy group had higher overall survival (HR for death, 0.75; 95%CI:
0.60-0.93; P = 0.00936 percent vs. 23 percent) and progression-free survival (HR for progression, 0.66;
95%CI: 0.53-0.81; P < 0.001).

The Dutch Chemoradiotherapy for Esophageal Cancer Followed by Surgery Study (CROSS) trial included
22%of patients with GEJ cancers and compared the effectiveness of neoadjuvant chemoradiation over
[52]
surgery alone . Overall survival was significantly better in the neoadjuvant chemoradiotherapy group
(HR, 0.657; 95%CI: 0.495-0.871; P = 0.003). The survival benefit in chemoradiation group was persistent in
[56]
the long term with median follow up of 86.4 months .

The Preoperative therapy in Esophagogastric adenocarcinoma Trial (POET) was the only trial which
[57]
compared neoadjuvant chemotherapy versus chemoradiotherapy in locally advanced GEJ adenocarcinoma .
Although the study ended prematurely due to lower accrual, there was a trend observed towards improved
3-year survival in the chemoradiation group (47.4% vs. 27.7%; P = 0.07). The long-term follow-up of the patients
also showed a trend in improved overall 5-year survival in favor of preoperative chemoradiotherarpy (HR
0.65, 95%CI: 0.42-1.01, P = 0.055).

A meta-analysis including 24 studies concluded that there was strong evidence for survival benefit of
neoadjuvant chemoradiotherapy or chemotherapy over surgery alone in patients with esophageal carcinoma
[58]
including GEJ cancers . However, there was no clear advantage of neoadjuvant chemoradiotherapy over
neoadjuvant chemotherapy according to the study.

CONCLUSION
The management of GEJ junction tumours is challenging and there is no one-size-fit-all strategy. The
endoscopic option can be considered for early tumours especially for those patients with high risk for
surgery. The surgical approach for advanced GEJ cancers should be tailored according to the histological
subtype, extent of oesophageal and/or gastric invasion, clinical and radiological lymph node involvement,
achievement of negative resection margins with R0 resection as well as achievement of safe anastomosis for