In the Journals

Endoscopic biopsy, EUS inadequate for detecting residual esophageal cancer after neoadjuvant chemoradiotherapy

Endoscopic biopsy and endoscopic ultrasound did not perform with sufficient accuracy in detecting pathologic complete response in patients with esophageal cancer after neoadjuvant chemoradiotherapy, according to the results of a systematic review and meta-analysis.

“The clinical value and accuracy of endoscopic biopsy and EUS for predicting residual cancer after [neoadjuvant chemoradiotherapy] remains controversial because of varying study designs and methodologic quality, heterogeneous patient populations and conflicting results among individual studies in the current literature,” Peter D. Siersema, MD, PhD, and colleagues from University Medical Center Utrecht in the Netherlands wrote.

Peter D. Siersema

“In order to critically appraise and potentially overcome shortcomings of individual studies, the aim of this study was to systematically review and meta-analyze the diagnostic performance of endoscopic biopsy and EUS after [neoadjuvant chemoradiotherapy] in esophageal cancer for detecting residual cancer at the primary tumor site ... and regional lymph nodes ... as opposed to a pathologic complete response. ... We were specifically interesting in determining how accurately the endoscopic absence of malignant abnormalities rules out the presence of residual cancer (ie, the negative predictive value).”

They searched relevant literature for diagnostic studies published through July 15, 2015, and included 23 studies in their final analysis: 12 of which evaluated endoscopic biopsy after neoadjuvant chemoradiotherapy (nCRT; n = 1,281), 11 of which evaluated EUS after nCRT for detecting residual primary cancer (n = 593) and 10 of which evaluated EUS after nCRT for detecting residual lymph node metastasis (n = 602). They used bivariate random-effects models to estimate pooled sensitivities and specificities, and histopathology served as the reference standard. In most of the studies, nCRT was based on cisplatin and 5-fluorouracil with total radiation doses ranging from 30 Gy to 50.4 Gy.

Endoscopic biopsy performed with 34.5% sensitivity (95% CI, 26-44.1) and 91% specificity (95% CI, 85.6-94.5) for the detection of residual esophageal cancer. EUS performed with 96.4% sensitivity (95% CI, 91.7-98.5) and 10.9% specificity (95% CI, 3.5-29) for detecting residual primary cancer, and with 62% sensitivity (95% CI, 46-75.7) and 56.7% specificity (95% CI, 41.8-70.5) for detecting residual lymph node metastasis.

Subgroup analyses showed that endoscopic biopsy performed with higher sensitivity in studies of patients with mainly squamous cell carcinoma vs. adenocarcinoma (P < .001), and that EUS for N-restaging performed with higher sensitivity for squamous cell carcinoma vs. adenocarcinoma studies (P < .001). Expectedly, EUS performed with higher specificity but lower sensitivity for N-restaging when lymph nodes 10 mm or larger rather than 5 mm or larger were considered positive (P < .001).

There was some unexplained heterogeneity between studies, the researchers wrote.

“Based on the current evidence with reasonable methodologic quality, endoscopic biopsy after nCRT is a specific but not sensitive method for detecting residual esophageal cancer,” the researchers concluded. “Although EUS after nCRT yields a high sensitivity, the number of patients with negative findings on EUS is limited, whereas a considerable proportion of these patients with negative results turn out to have residual cancer (ie, false negatives). Therefore, endoscopic biopsy and EUS should currently not be used in routine clinical practice after nCRT to triage test-negative patients for withholding surgery.” – by Adam Leitenberger

Disclosure: The researchers report no relevant financial disclosures.

Endoscopic biopsy and endoscopic ultrasound did not perform with sufficient accuracy in detecting pathologic complete response in patients with esophageal cancer after neoadjuvant chemoradiotherapy, according to the results of a systematic review and meta-analysis.

“The clinical value and accuracy of endoscopic biopsy and EUS for predicting residual cancer after [neoadjuvant chemoradiotherapy] remains controversial because of varying study designs and methodologic quality, heterogeneous patient populations and conflicting results among individual studies in the current literature,” Peter D. Siersema, MD, PhD, and colleagues from University Medical Center Utrecht in the Netherlands wrote.

Peter D. Siersema

“In order to critically appraise and potentially overcome shortcomings of individual studies, the aim of this study was to systematically review and meta-analyze the diagnostic performance of endoscopic biopsy and EUS after [neoadjuvant chemoradiotherapy] in esophageal cancer for detecting residual cancer at the primary tumor site ... and regional lymph nodes ... as opposed to a pathologic complete response. ... We were specifically interesting in determining how accurately the endoscopic absence of malignant abnormalities rules out the presence of residual cancer (ie, the negative predictive value).”

They searched relevant literature for diagnostic studies published through July 15, 2015, and included 23 studies in their final analysis: 12 of which evaluated endoscopic biopsy after neoadjuvant chemoradiotherapy (nCRT; n = 1,281), 11 of which evaluated EUS after nCRT for detecting residual primary cancer (n = 593) and 10 of which evaluated EUS after nCRT for detecting residual lymph node metastasis (n = 602). They used bivariate random-effects models to estimate pooled sensitivities and specificities, and histopathology served as the reference standard. In most of the studies, nCRT was based on cisplatin and 5-fluorouracil with total radiation doses ranging from 30 Gy to 50.4 Gy.

Endoscopic biopsy performed with 34.5% sensitivity (95% CI, 26-44.1) and 91% specificity (95% CI, 85.6-94.5) for the detection of residual esophageal cancer. EUS performed with 96.4% sensitivity (95% CI, 91.7-98.5) and 10.9% specificity (95% CI, 3.5-29) for detecting residual primary cancer, and with 62% sensitivity (95% CI, 46-75.7) and 56.7% specificity (95% CI, 41.8-70.5) for detecting residual lymph node metastasis.

Subgroup analyses showed that endoscopic biopsy performed with higher sensitivity in studies of patients with mainly squamous cell carcinoma vs. adenocarcinoma (P < .001), and that EUS for N-restaging performed with higher sensitivity for squamous cell carcinoma vs. adenocarcinoma studies (P < .001). Expectedly, EUS performed with higher specificity but lower sensitivity for N-restaging when lymph nodes 10 mm or larger rather than 5 mm or larger were considered positive (P < .001).

There was some unexplained heterogeneity between studies, the researchers wrote.

“Based on the current evidence with reasonable methodologic quality, endoscopic biopsy after nCRT is a specific but not sensitive method for detecting residual esophageal cancer,” the researchers concluded. “Although EUS after nCRT yields a high sensitivity, the number of patients with negative findings on EUS is limited, whereas a considerable proportion of these patients with negative results turn out to have residual cancer (ie, false negatives). Therefore, endoscopic biopsy and EUS should currently not be used in routine clinical practice after nCRT to triage test-negative patients for withholding surgery.” – by Adam Leitenberger

Disclosure: The researchers report no relevant financial disclosures.