Hypopharyngeal Carcinoma With Synchronous and Metachronous Multiple Malignancies: Clinical Characteristics and Prognosis Analysis of 673 Real World Cases

Abstract

Hypopharyngeal carcinoma (HPC) is one of the most devastating malignancies among head and neck cancers. Our aim is to analyze the clinical characteristics and prognosis of synchronous and metachronous second primary malignancies (SPMs) in patients with hypopharyngeal carcinoma.We retrospectively reviewed 673 patients diagnosed in our institution between May 2009 and October 2019. Endoscopic examination was performed in 97.1% (654/673) of patients before treatment. We defined a synchronous SPM as which developed within 6 months of the index HPC diagnosis, while a metachronous SPM as which developed more than 6 months after initial diagnosis of HPC. The Kaplan-Meier method, propensity score-matched (PSM) and Cox model were used to analyze the data.Within the median follow-up of 66.5 months, 71 (10.5%) patients developed gastric/esophageal tumor in situ (Tis) and 143 (21.2%), patients developed SPMs, consisting of 78 with synchronous SPMs and 75 with metachronous SPMs, respectively, with patient overlap. Among the 143 patients, the most common secondary site was esophagus (n = 85), followed by the head and neck squamous cell carcinoma (HNSCC, n = 36), lung (n = 20) and other cancers (n = 19). The 5-year overall survivals (OS) for non-SPMs (n = 459), SPMs (n = 143) and Tis group (n = 71) were 43.8% vs 37.1% vs 42.9%, respectively. Accordingly, the disease-specific survivals (DSS) were 46.3% vs 56.2% vs 47.8%, respectively. We compared synchronous SPMs and no-SPMs groups, the 5-year OS and DSS were 37.1% and 56.2% for synchronous SPMs group (n = 78), compared with 43.8% (P = 0.093) and 46.3% (P = 0.098) for no-SPMs group (n = 459). We use PSM to balance two arms with the ratio of 1:1, resulting in the number of 62 patients in each group. The adjusted 5-year OS and DSS were 23.6% and 32.7% for synchronous SPMs group (n = 62), compared with 49.8% (P < 0.001) and 52.4% (P < 0.001) for no-SPMs group (n = 62). For synchronous and metachronous SPMs, the 5-year OS and DSS were 27.3% and 40.8% for synchronous SPMs group (n = 78) vs 48.8% (P = 0.001) and 70.7% (P = 0.001) for metachronous SPMs group (n = 75). According to the site of the SPMs, the 5-year OS and DSS were 24.5% and 40.4% for esophagus (n = 85), 51.9% and 66.9% for HNSCC (n = 36), 52.0% and 75.1% for lung (n = 20), 60.7% and 83.9% for others (n = 19). The SPMs in esophagus had worse OS than the other three groups (P<0.05). In multivariable analysis, synchronous SPMs, site of the SPMs, alcohol consumption and N stage were independently significant for OS.Approximately 30% of patients with HPC develop multiple malignancies during the course of disease and the most frequently involved site is the upper aero digestive tract. We should be aware of the possible coexistence of SPMs in HPC. Co-existence of gastric/esophageal tumor in situ does not affect outcome. The OS and DSS for synchronous SPMs are significantly worse than that for metachronous SPMs and no-SPMs. The SPMs in esophagus is the most common site and present the worst outcome than others.