Clinical response evaluations via bite-on-bite biopsies and endoscopic ultrasonography with fine needle aspiration for lymph nodes were accurate in detecting locoregional residual disease following treatment with neoadjuvant chemoradiotherapy in patients with esophageal squamous cell carcinoma (ESCC), according to findings from the observational preSINO trial (NCT03937362) presented during the 2024 ASCO Breakthrough Conference.1,2
Bite-on-bite biopsies and endoscopic ultrasonography with fine needle aspiration displayed a false-negative rate of 13.5% (95% CI, 8.7%-20.4%) among patients with ESCC who had TRG3-4 or TRG1-2 with ypN-positive residual tumor cells after neoadjuvant chemoradiotherapy (n = 133). Additionally, the positivity rates of bite-on-bite biopsies and endoscopic ultrasonography with fine needle aspiration in patients with TRG3, TRG4, and TRG1/2-ypN-positive residual tumor cells were 88.9% (n = 32/36), 92.6% (n = 63/68), and 69% (n = 20/29), respectively.1
“Our study is important because it addresses whether we can accurately and safely evaluate residual tumors in ESCC after neoadjuvant treatment,” Zhigang Li, MD, PhD, deputy chief, Division of Thoracic Surgery, and director, Esophageal Surgery Section, at Shanghai Chest Hospital in China, said in a news release.2 “Our preSINO study adapted methods from the previous European preSANO trial in esophageal adenocarcinoma to ESCC in Asia and explored circulating tumor DNA [ctDNA] testing to enhance accuracy. This research helps expand the use of an active surveillance strategy for ESCC to optimize treatment approaches.”
preSINO was a multicenter, diagnostic trial that enrolled patients with locally advanced ESCC who received neoadjuvant chemoradiotherapy with the CROSS regimen followed by standard surgical resection. Eligible patients underwent the first clinical response evaluation via bite-on-bite biopsies 4 to 6 weeks following completion of neoadjuvant chemoradiotherapy; those without locoregional residual tumor and distant metastases underwent surgery immediately. Patients with a clinical complete response at the first clinical response evaluation underwent a second clinical response evaluation at 10 to 12 weeks after the completion of neoadjuvant chemoradiotherapy via PET-CT, bite-on-bite biopsies and endoscopic ultrasonography with fine needle aspiration for suspicious lymph nodes.
All patients underwent surgery regardless of the outcome of the second clinical response evaluation in the absence of distant metastases. ctDNA analyses were performed at baseline and after clinical response evaluation based on a tumor-informed assay.
The primary end point was the combined accuracy of the clinical response evaluations for detecting TRG3-4 or TRG1-2 with ypN-positive residual tumor cells in the resected specimen, with a false negative threshold of 19.5% or less. Secondary end points included accuracy of the clinical response evaluations at detecting any residual tumor cells, the value of PET-CT, and the sensitivity, specificity, negative predictive value, and positive predictive value of the clinical response evaluations. Investigators also evaluated ctDNA for minimal residual disease as an exploratory end point.
At baseline, patients in the per-protocol cohort (n = 242) had a median age of 65 years (IQR, 59-70). Most patients were male (86.4%), had clinical stage cT3 disease (84.7%), had clinical N stage cN1 disease (50.8%), and a middle tumor location (52.9%). Patients had a pathological response of TRG1 ypN0 (30.2%), TRG2 ypN0 (14.9%), TRG3-4 (43.0%), or TRG1-2 ypN-positive (12.0%) following neoadjuvant chemoradiotherapy.
Additional findings from the analysis revealed that the diagnostic sensitivity and specificity of bite-on-bite biopsies and endoscopic ultrasonography with fine needle aspiration in terms of predicting a TRG2-4 or ypN-positive vs TRG1-ypN0 response were 81.7% (95% CI, 75.1%-86.8%) and 93.2% (95% CI, 84.9%-97.0%), respectively. The respective negative and positive predictive values were 68.7% (95% CI, 59.0%-77.0%) and 96.5% (95% CI, 92.1%-98.5%). PET-CT detected interval distant metastases in 4.9% (n = 13) of evaluable patients prior to surgery (n = 268).
Data from an exploratory analysis demonstrated that positive ctDNA status at clinical response evaluation prior to surgery was associated with an increased risk of systemic metastases. In the ctDNA cohort (n = 132), among patients with positive ctDNA at clinical response evaluation (n = 75), 28.0% had distant metastases and 72.0% did not. Among patients with negative ctDNA at clinical response evaluation (n = 57), 5.3% had distant metastases and 94.7% did not.
Patients with a positive clinical response evaluation following bite-on-bite biopsies and endoscopic ultrasonography with fine needle aspiration who tested positive for ctDNA (n = 54) had distant metastases and no distant metastases at rates of 31.5% vs 68.5%, respectively. Those with a negative clinical response evaluation following bite-on-bite biopsies and endoscopic ultrasonography with fine needle aspiration who tested positive for ctDNA (n = 21) had distant metastases and no distant metastases at rates of 19.0% vs 81.0%, respectively.
“The preSINO trial is a novel prospective study demonstrating the importance of clinical response evaluation after neoadjuvant chemoradiation in patients with ESCC,” Vishwanath Sathyanarayanan, MD, MBSS, DM, medical oncologist, Apollo Hospitals, in Bangalore, India, added in the news release.2 “Combining PET/CT and bite-on-bite biopsy with ctDNA-based MRD detection demonstrated improved accuracy in identifying patients with an increased risk of distant metastases and can help support clinicians in determining whether to escalate or de-escalate treatment.”
References
- Li Z, Yang Y, Liu Z, et al. Accuracy of detecting residual disease after neoadjuvant chemoradiotherapy for esophageal squamous cell carcinoma (preSINO trial): a prospective multicenter diagnostic cohort study in Asia. J Clin Oncol. 2024;42(suppl 23):196. doi:10.1200/JCO.2024.42.23_suppl.196
- ASCO breakthrough to highlight advances in esophageal, nasopharyngeal, lung cancers new treatment approaches help improve survival, quality of life. News release. ASCO. August 5, 2024. Accessed August 6, 2024.
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