Neoadjuvant Chemoradiotherapy for Oesophageal Carcinoma: Real-World Data From Practice Beyond the Chemoradiotherapy for Oesophageal Cancer Followed by Surgery Study (CROSS) Trial.

Background The chemoradiotherapy for oesophageal cancer followed by surgery study (CROSS) protocol, combining neoadjuvant chemoradiotherapy with surgical resection, is the standard of care for patients with locally advanced oesophageal cancer. Real-world patients often don't meet CROSS trial criteria. We evaluated if the trial's positive results apply to patients with large, ineligible lesions. Materials & methods In this retrospective analysis, we included patients with oesophageal cancer treated between November 2022 and November 2025 who received neoadjuvant chemotherapy plus radiotherapy (NACT+RT) at a dose of 41.4 Gray (Gy) delivered in 23 fractions, with concurrent weekly paclitaxel and carboplatin, followed by surgical resection. For study purposes, patients were divided into two groups according to whether they met the CROSS-eligibility criteria. The CROSS-ineligibility criteria were defined as patients with any of the following clinical features, i.e., T4a disease, tumor length >8 cm, or planning target volume length >16 cm. Result Out of 65 cases, 69.2% (n=45) of patients were CROSS-ineligible. Fifty-one cases completed the intended treatment of neoadjuvant chemoradiation followed by surgery. The pathological complete response (pCR) rate was 58.8% (n=30) in the total cohort population (n=51) who underwent NACT+RT followed by surgery. Out of 36 CROSS-ineligible patients, 55.6% (n=20) had a pCR compared to 66.6% (n=10) in CROSS-eligible cases (n=15). Fourteen patients did not undergo surgery after NACT+RT. At a median follow-up of 17 months, the one- and two-year progression-free survival (PFS) rates for the entire cohort were 80% and 68%, respectively. The one-year PFS rate was 90% for CROSS-eligible cases (n=20) versus 80% (p=0.7) for CROSS-ineligible cases (n=45). Similar rates for two-year PFS were 54% and 62% (p=0.7) for CROSS-eligible and CROSS-ineligible cases, respectively. In a subset analysis of the patients who underwent surgery (n=51), the one-year PFS rates were 93% versus 90% (p=0.75) for CROSS-eligible (n=15) and CROSS-ineligible cases (n=36), respectively. Similarly, the two-year PFS rates were 43% versus 70% (p=0.75) for CROSS-eligible (n=15) and CROSS-ineligible cases (n=36), respectively. The one- and two-year overall survival (OS) rates for the entire cohort were 93% and 77%, respectively. The one-year OS rates were 95% for CROSS-eligible cases (n=20) versus 93% (p=0.8) for CROSS-ineligible cases (n=45). Similar rates for two-year OS were 54% and 72% (p=0.8) for CROSS-eligible and CROSS-ineligible cases, respectively. In a subset analysis of patients who underwent surgery (n=51), the one-year OS rates were 93% versus 92% (p=0.78) for CROSS-eligible (n=15) and CROSS-ineligible cases (n=36), respectively. Similarly, the two-year OS rates were 43% versus 70% (p=0.78) for CROSS-eligible (n=15) and CROSS-ineligible cases (n=36), respectively. Conclusion With proper patient selection, the CROSS regimen can be safely extended to CROSS-ineligible patients, demonstrating its safety without compromising survival. We propose that oesophageal cancers presenting with cT4a tumours, tumours measuring greater than 8 cm, and nodal stages N2 and N3 can be safely treated with neoadjuvant chemoradiotherapy followed by surgery, a finding that warrants confirmation in larger prospective studies.