Pre-operative chemoradiation versus peri-operative chemotherapy for oesophageal cancer

Pre-operative chemoradiation and peri-operative chemotherapy are 2 treatment options for patients with lower oesophageal adenocarcinoma (OAC) and gastroesophageal junction adenocarcinoma (GEJAC). The latest evidence on this topic was discussed by Prof. Karyn Goodman (Icahn School of Medicine at Mount Sinai, NY, USA) [1].

“The R0 resection rate in patients with OAC or GEJAC is only 60%,” said Prof. Goodman. “However, pre-operative chemoradiation has demonstrated to improve R0 resection rates.” The CROSS trial showed that neoadjuvant chemoradiation delivered higher R0 resection rates (88%) compared with surgery alone (59%) in patients with OAC or GEJAC [2]. Notably, the overall risk of distant relapse was lower in the chemoradiation arm at 10 years follow-up, but the rate of isolated distant recurrences was similar between the 2 arms, suggesting that the low-dose chemotherapy of this regimen did not exert full control.

“The FLOT4 trial showed that peri-operative chemotherapy with FLOT delivered an R0 resection rate of 85% in patients with GEJAC or gastric cancers,” continued Prof. Goodman [3]. The 5-year overall survival rates of the 2 regimens in FLOT4 (45%) and the CROSS trial (43%) appear similar. However, the populations of these trials were very different. FLOT4 included patients with gastric cancer (44%) and GEJ cancer (56%), whereas CROSS included patients with GEJ cancer (22%) and oesophageal cancer (74%) with mixed histologies (adenocarcinoma and squamous cell carcinoma). Interestingly, 95% of the patients completed the CROSS regimen but only 46% completed the post-operative FLOT regimen, mostly due to grade 3 or 4 neutropaenia.

A direct comparison between chemoradiation and FLOT suggested similar efficacy of the 2 regimens in patients with oesophageal or GEJ cancer [4]. However, adjuvant immunotherapies may improve the outcomes of neoadjuvant chemoradiation [5]. “Given the current evidence, I would recommend neoadjuvant chemoradiation in patients with Siewert 1 or 2 OAC or GEJAC, patients with bulky tumours, or patients with contraindications to FLOT. For patients with gastric or Siewert 3 GEJ tumours, patients with contraindications to radiotherapy, or those with diffuse/signet ring cell histology, I would recommend peri-operative chemotherapy. To improve outcomes, we need to tailor neoadjuvant chemotherapy to the tumour biology. PET-directed therapy may be used for this purpose. All in all, I think that induction chemotherapy addresses micrometastatic disease, whereas radiotherapy exerts local control in patients OAC and GEJAC, offering the best of both worlds.”

1. Goodman KA, et al. Preoperative Chemoradiation Versus Perioperative Chemotherapy for Lower Esophageal and Gastroesophageal Junction Adenocarcinoma. Controversial Issues in Localized Gastroesophageal Cancer. ASCO GI 2022, 20–22 January.
2. Van Hagen P, et al. N Engl J Med 2012;366:2074–2084.
3. Al-Batran SE, et al. 2019;393(10184):1948–1957.
4. Reynolds JV, et al. Abstract 4004, ASCO 2021, 4–8 June.
5. Kelly RJ, et al. N Engl J Med 2021;384:1191–1203.

 

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Posted on 21 March, 202227 March, 2024