A Chinese research team has reported encouraging results for a novel treatment approach combining immunotherapy with chemotherapy for patients with borderline resectable esophageal squamous cell carcinoma (BR-ESCC), a challenging cancer subtype where optimal treatment strategies remain controversial.
The retrospective study, conducted at the Affiliated Hospital of North Sichuan Medical College, analyzed 40 patients with BR-ESCC who received induction immunochemotherapy between January 2020 and July 2023. The treatment protocol combined PD-1 inhibitors (Sintilimab, Camrelizumab, or Tislelizumab) with platinum-based chemotherapy regimens.
Treatment Outcomes and Conversion Rates
The study achieved a conversion surgery rate of 67.5% (27 of 40 patients), with 57.5% of all patients ultimately achieving R0 resection - complete tumor removal with negative microscopic margins. Among the 28 patients who underwent surgery, the R0 resection rate was 85.2%, representing a substantial improvement over historical outcomes.
"For conversion therapy in advanced esophageal squamous cell carcinoma, improving the R0 resection rate is crucial for patient prognosis," the researchers noted, highlighting the clinical significance of their findings.
The pathological complete remission (pCR) rate reached 27.5% overall, with 40.7% of surgical patients achieving complete pathological response. This compares favorably to conventional chemotherapy regimens, which typically achieve pCR rates of 14.8-18.5% in similar patient populations.
Safety Profile and Toxicity Management
One of the most striking findings was the improved safety profile of the immunochemotherapy approach. The incidence of grade 3-4 adverse events was only 10%, dramatically lower than the 31.9-79.4% reported with conventional induction regimens. Neutropenia was the most common severe adverse event, affecting 10% of patients, followed by leukopenia at 5%.
The most frequent mild-to-moderate side effect was anemia, occurring in 45% of patients. This favorable toxicity profile represents a significant advantage over traditional DCF (docetaxel, cisplatin, 5-fluorouracil) regimens, which have been associated with up to 79.3% grade 3-4 hematologic toxicity.
Survival Outcomes and Clinical Significance
With a median follow-up of 23.6 months, the study demonstrated one-year overall survival and progression-free survival rates of 77.7% and 71.8%, respectively. Patients who underwent surgery showed superior outcomes compared to those who did not, with one-year progression-free survival rates of 76.0% versus 49.4%.
Particularly noteworthy was the finding that patients achieving clinical downstaging after induction therapy experienced significantly better survival outcomes. This group showed superior overall survival (P = 0.004) and progression-free survival (P = 0.0016) compared to patients without downstaging.
Mechanistic Advantages of Combination Therapy
The researchers explained that the combination approach leverages complementary mechanisms of action. Chemotherapeutic agents induce tumor cell death and release tumor-associated antigens that activate the immune system, while PD-1 inhibitors alleviate tumor-mediated immune suppression and enhance T cell-mediated tumor killing.
"This innovative strategy combines the direct cytotoxic effects of conventional chemotherapy with the immune-modulating ability of immunotherapy, which enhances both tumor sensitivity to treatment and patient immune response," the study authors explained.
Comparison with Historical Controls
The results compare favorably to previous studies using conventional approaches. Historical data from CF (cisplatin, 5-fluorouracil) regimens combined with radiotherapy showed conversion success rates of only 54% with R0 resection rates of 81.5%. While DCF regimens achieved higher conversion rates of 84.4%, they came with significantly higher toxicity burdens.
Recent studies by Fan et al. and Li et al. using similar immunochemotherapy approaches reported conversion rates of 75% and 74.1%, respectively, supporting the reproducibility of these encouraging results across different institutions.
Clinical Implications and Future Directions
The study addresses a critical unmet need in esophageal cancer treatment. Borderline resectable esophageal squamous cell carcinoma represents a particularly challenging subset where tumors have suspicious but not definitive invasion of adjacent organs, making treatment decisions complex.
Traditional approaches using definitive chemoradiotherapy may deny patients the opportunity for potentially curative surgery, even when tumors respond well to treatment. Conversely, conventional neoadjuvant chemotherapy alone often yields insufficient response rates for successful conversion to resectable disease.
However, the researchers noted several important limitations. The study was a single-center retrospective analysis with a relatively small sample size, and longer follow-up periods are needed to determine whether the promising short-term outcomes translate into sustained survival benefits.
Safety Considerations
While the overall safety profile was favorable, the study identified some areas requiring careful monitoring. Postoperative pulmonary infections occurred in 33.3% of surgical patients, which was higher than some previous reports. One patient developed immune-related pneumonia during postoperative maintenance therapy with Camrelizumab and died 10.6 months after surgery.
The researchers emphasized the need for phase III clinical trials to definitively establish whether immunotherapy addition increases postoperative pulmonary complications and immune-related adverse events.
The findings suggest that conversion surgery following induction immunochemotherapy represents a promising new treatment paradigm for borderline resectable esophageal squamous cell carcinoma, offering the potential for improved outcomes with reduced toxicity compared to conventional approaches. However, larger prospective studies are needed to validate these encouraging preliminary results.
