A recent multicenter retrospective analysis published in Scientific Reports has compared the efficacy and safety of neoadjuvant immunochemoradiotherapy (NICRT) versus neoadjuvant chemoradiotherapy (NCRT) in patients with locally advanced esophageal squamous cell carcinoma (ESCC) undergoing radical surgery. The study aimed to evaluate treatment efficacy, perioperative outcomes, treatment-related toxicities, and postoperative complications associated with both approaches.
Comparable pCR Rates with NICRT and NCRT
The study found that the pathological complete response (pCR) rate in the NCRT group was similar to that in the NICRT group. This suggests that the addition of immunotherapy to chemoradiotherapy in the neoadjuvant setting does not significantly improve the pathological response compared to chemoradiotherapy alone. Specifically, the pCR rates for positive lymph nodes and tumor regression grade (TRG) were also similar between the two groups.
Perioperative Outcomes and Toxicities
In addition to pCR rates, the study assessed perioperative outcomes, treatment-related toxicities, and postoperative complications. The analysis revealed no significant differences between the NICRT and NCRT groups in these parameters. Lymph node yield was also comparable between the two groups.
Context and Comparison to Prior Studies
Neoadjuvant chemoradiotherapy is a standard treatment for ESCC. Landmark trials such as the CROSS and NEOCRTEC5010 trials have established its efficacy. The NEOCRTEC5010 trial, for instance, reported a pCR rate of 43.2% with neoadjuvant chemoradiotherapy, aligning with the findings of the current study. The use of immunotherapy in ESCC is supported by the high frequency of mutations, making it potentially responsive to checkpoint inhibitors like anti-PD-1 or PD-L1 therapies. Previous studies, such as the PALACE-1 trial, have explored the combination of pembrolizumab with chemoradiotherapy, reporting promising pCR rates. However, the current study's pCR rate was lower than those reported in PALACE-1 and NCT02844075, possibly due to differences in patient populations and sample sizes.
Postoperative Complications
Contrary to expectations that combining three anti-tumor treatments in the NICRT group might lead to more severe postoperative complications, the study found no significant difference in common complications such as chest complications, cardiac complications, and anastomotic leakage between the NCRT and NICRT groups. However, the incidence of chest complications was higher than reported in some other studies, potentially due to surgical factors or the advanced stage of the patients included.
Implications and Future Directions
While the addition of immunotherapy to neoadjuvant chemoradiotherapy did not demonstrate a superior pathological response, it is important to note that pCR does not always correlate with improved overall survival (OS). Studies suggest that pCR achieved through systemic therapies may translate more effectively into improved OS compared to local therapies like radiotherapy. The potential for immunotherapy to enhance systemic anti-tumor efficacy and improve OS requires further validation through larger, multi-center clinical trials.
Study Limitations
The authors acknowledge several limitations, including the retrospective nature of the study, which may introduce data collection bias. Propensity score matching (PSM) was used to mitigate this bias. Additionally, there was insufficient clinical diagnosis of positive lymph nodes, and the NICRT group had a smaller sample size and shorter follow-up period. Variations in chemotherapy and immunotherapy regimens between the groups may have also influenced the neoadjuvant efficacy.
