Neoadjuvant chemoradiation outperforms chemo alone for oesophageal squamous cell carcinoma

Patients with oesophageal squamous cell carcinoma (ESCC) see better survival and safety outcomes after treatment with neoadjuvant chemoradiation therapy (NCRT) as compared with neoadjuvant chemotherapy (NCT) alone, according to a recent meta-analysis.

“NCRT can significantly increase the rates of pathological complete remission rate (pCR) and complete resection and can more significantly improve the long-term survival of patients with ESCC without significantly increasing postoperative complications,” the researchers said.

Eighteen studies were deemed eligible for the quantitative synthesis. The cumulative sample included 2,042 patients treated with NCRT and 1,095 receiving NCT. Outcomes assessed pCR, complete (R0) tumour resection rate, and survival. Studies were retrieved from the online databases of PubMed, Embase, the Cochrane Library, Web of Science, VIP, Wanfang Data, CNKI, and CBM.

Eleven studies compared NCRT and NCT in terms of pCR. Evidence was significantly heterogenous (p=0.008), necessitating a random-effects pooled analysis. Patients who received NCRT were more than five times more likely than their NCT counterparts to achieve pCR (odds ratio [OR], 5.21, 95 percent confidence interval [CI], 2.85–9.50; p<0.00001). [PLoS One 2022;doi:10.1371/journal.pone.0271242]

Similarly, R0 resection was significantly higher in the NCRT arm (OR, 2.31, 95 percent CI, 1.57–3.41; p<0.0001), according to a fixed-effects analysis of 10 studies. Heterogeneity of evidence was not significant (p=0.33).

NCRT likewise yielded significantly better survival outcomes than NCT. At the 1-year follow-up, patients who received NCRT were 50-percent more likely to survive (OR, 1.51, 95 percent CI, 1.11–2.05; p=0.009). Such an effect persisted and even strengthened by the 3-year (OR, 1.73, 95 percent CI, 1.36–2.21; p<0.0001) and 5-year (OR, 1.61, 95 percent CI, 1.30–1.99; p<0.00001) time points.

Despite efficacy advantages, NRCT showed no excess safety concerns as opposed to NCT. Perioperative mortality, for instance, was comparable between the two treatment approaches (OR, 0.97, 95 percent CI, 0.55–1.72).

The same was true for other complications, such as anastomotic leaks (OR, 1.23, 0.84–1.81; p=0.28), pulmonary complications (OR, 1.31, 95 percent CI, 0.88–2.13; p=0.18), cardiac complications (OR, 1.44, 95 percent CI, 0.60–3.47; p=0.42), and chyle leaks (OR, 1.10, 95 percent CI, 0.36–3.31; p=0.87). Incidences of infections (OR, 1.79, 95 percent CI, 0.34–9.58; p=0.49) and bleeding (OR, 0.84, 95 percent CI, 0.16–4.38; p=0.83) also did not differ between NCRT and NCT groups.

“The results of our meta-analysis showed that there was no significant difference between the two neoadjuvant treatments in terms of postoperative complications and perioperative mortality,” the researchers said. “Progress in minimally invasive surgery is bound to reduce postoperative complication rates.”

A key limitation of the present study is the overall lack of trials comparing NCRT with NCT for the treatment of ESCC. Currently, according to the researchers, there are several ongoing studies that seek to determine the optimal treatment regimen for ESCC patients, including the use of concomitant surgery, the type of chemotherapeutic drugs used, and the impacts of disease staging and progression.

“In the era of precision medicine, the treatment of oesophageal cancer should depend on the molecular biological characteristics of tumours and follow the principles of evidence-based medicine to formulate individualized treatment plans in a targeted manner, which will be the main direction of adjuvant radiotherapy and chemotherapy for ESCC in the future,” they said.