Macrocytosis as a risk factor for secondary esophageal cancer in hypopharyngeal cancer patients: a multicenter case–control study

BACKGROUND: Identification of hypopharyngeal cancer (HPC) patients at heightened risk for developing metachronous second primary esophageal cancer (MSPEC) is crucial for the optimization of screening protocols and thus survival improvement. Although mean corpuscular volume (MCV) is recognized as a biomarker for esophageal cancer, its association with MSPEC among HPC patients remains unexplored.

OBJECTIVE: This study aimed to investigate the predictive value of MCV for MSPEC in HPC patients.

DESIGN: In this 19-year retrospective, nested case-control study, HPC patients from the Chang Gung Research Database between January 2001, and December 2019, were examined.

METHODS: A total of 114 HPC patients who developed MSPEC were matched with 1895 non-MSPEC controls in a 1:3 propensity score-matched analysis. Logistic regression models were deployed to assess the odds of MSPEC manifestation in relation to MCV levels.

RESULTS: Matching for clinical characteristics and follow-up periods yielded 96 MSPEC patients and 288 matched controls. Elevated MCV levels were associated with an increased risk of MSPEC, indicating a dose-response relationship. Specifically, MCV ranges from 95 to 100 femtoliters (fL) and ⩾100 fL correlated with adjusted odds ratios for MSPEC of 2.37 (95% confidence interval (CI): 1.33-4.24) and 4.84 (95% CI: 2.62-8.95), respectively. Notably, an MCV ⩾100 fL was a more pronounced predictor of MSPEC among younger patients and those with advanced disease stages. Within the initial cohort of 2009 HPC patients, 31 (2.9%) of 1052 patients with MCV <95 fL developed MSPEC, and 46 (11.5%) of 401 patients with MCV ⩾100 fL experienced MSPEC.

CONCLUSION: Macrocytosis at HPC diagnosis is indicative of an escalated MSPEC risk, underscoring the imperative for intensive surveillance.