CROSS Long-Term Results Support Neoadjuvant Chemoradiation In Oesophageal Cancer

Neoadjuvant chemoradiotherapy significantly extends overall and progression-free survival and reduces locoregional and distant progression in patients with oesophageal or junctional cancer

medwireNews: Neoadjuvant chemoradiotherapy significantly improves survival outcomes and reduces disease recurrence in patients with resectable, locally advanced oesophageal or junctional cancer, according to the long-term results of the CROSS trial.

These findings, after a median of 84 months, are in line with the initial results reported in 2012 after a median 45 months of follow-up, say the researchers, adding that the chemoradiation regimen used in the study followed by surgery “should be regarded as a standard of care” for this patient population.

But in a linked commentary in The Lancet Oncology, Christophe Mariette, from Claude Huriez University Hospital in Lille, France, and co-authors note that although the CROSS trial provides “robust evidence” in support of this treatment modality, all patients had a good WHO performance status of 0 or 1 and 82% had lower third or junctional tumours.

“Whether or not the CROSS trial results are reproducible in patients with poorer performance status or with cancers of the middle and upper third of the oesophagus is unknown”, they add.

The commentators write that further validation of these results is therefore required “before the CROSS regimen can be deemed the gold standard neoadjuvant therapy for this tumour group”.

Median overall survival (OS) was significantly longer for the 178 patients with T1N1M0 or T2–3N0–1M0 disease who were randomly assigned to receive open-label carboplatin plus paclitaxel with concurrent radiotherapy followed by surgery than for their 188 counterparts who were treated with surgery alone, at 48.6 versus 24.0 months.

The OS benefit accorded by neoadjuvant chemoradiation remained significant both in patients with squamous cell carcinomas and those with adenocarcinomas, with median OSs of 81.6 versus 21.1 months and 43.2 versus 27.1 months, respectively.

And progression-free survival (PFS) was similarly significantly extended in the neoadjuvant chemoradiation arm compared with the surgery alone arm, at 37.7 and 16.2 months, respectively. The corresponding values for squamous cell carcinoma and adenocarcinoma patients were 74.7 versus 11.6 months and 29.9 versus 17.7 months.

Treatment with neoadjuvant chemoradiation also resulted in a significantly lower overall incidence of progression (49 vs 66%) compared with patients who received surgery alone, as seen in rates of both locoregional (22 vs 38%) and distant (39 vs 48%) progression.

“The improvement in distant disease control occurred within the first 2 years after initiation of treatment, whereas the improvement in locoregional control continued for a longer period”, report Joel Shapiro, from Erasmus MC – University Medical Centre in Rotterdam, Netherlands, and study co-authors.

They emphasise that “[u]nless convincing results to the contrary become available, strong evidence from the CROSS trial continues to support neoadjuvant chemo radio therapy as a standard of care for both squamous cell carcinoma and adenocarcinoma of the oesophagus or oesophagogastric junction.”


Shapiro J, van Lanschot JJB, Hulshof MCCM,et al.Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol 2015; Advance online publication 5 August. doi:

Mariette C, Robb WB, Piessen G, Adenis A. Neoadjuvant chemoradiation in oesophageal cancer. Lancet Oncol 2015; Advance online publication 5 August. doi:

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