Introduction

Major salivary gland cancer is a rare malignancy that accounts for 5 % of head and neck cancers, with an annual incidence of 0.5–16 per 1,000,000 population . According to the 5th WHO classification, there are more than 20 histological types of salivary gland cancers, including mucoepidermoid carcinoma (MEC), adenoid cystic carcinoma (AdCC), acinic cell carcinoma (ACC), salivary duct carcinoma (SDC), carcinoma ex pleomorphic adenoma (CXPA), squamous cell carcinoma (SCC), and adenocarcinoma not otherwise specified (NOS), which have different clinical behaviors and different prognoses . Although there are exceptions, most MEC, ACC, and CXPA (intracapsular/minimally invasive type) tumors are classified as low-grade malignancies, AdCC (cribriform/tubular types) as intermediate-grade malignancies, and AdCC (solid type), CXPA (invasive type), SDC, and SCC as high-grade malignancies . According to the ESMO clinical practice guideline for salivary gland cancer, surgery is the standard treatment for resectable salivary gland cancer . Previous studies have shown that older age, high-grade histology, higher T classification, positive surgical margin, perineural invasion, and positive lymph node (LN) metastasis are risk factors for recurrence and a poor prognosis . Postoperative radiotherapy (PORT) reduces the risk of recurrence and improves the prognosis in patients with high to intermediate risk characteristics for recurrence . Although there have been many reports of the predictors of recurrence and survival after surgery, they often involved relatively small cohorts with a variety of histological types. To clarify the most important predictive factors for recurrence and survival in a large number of patients, a multicenter, retrospective study that included more than 500 patients who underwent surgery for salivary gland cancers was performed. All 13 university hospitals and cancer centers in the northern area of Japan with a population of 14 million people participated in this study, and factors affecting recurrence and survival were analyzed statistically.

Materials and methods

Results

A total of 543 patients with salivary gland cancer underwent surgery for curative intent at the 13 participating hospitals from January 2012 to December 2022. The clinical characteristics of the patients are shown in Table 1 . The most common histological type was SDC, followed by AdCC, MEC, CXPA, SCC, adenocarcinoma NOS, and ACC.

The postoperative characteristics are shown in Table 2 . There were 165 (31.2 %) patients with positive surgical margins, and 185 (34.1 %) patients with LN metastasis, including 59 (10.8 %) patients with ENE. During a median follow-up period of 39 months, 190 (34.9 %) patients had recurrence of local, LN, or distant metastases.

The Kaplan-Meier curves for DFS are shown in Fig. 1 , and 3 to 5-year DFS is summarized in Supplemental Table 2 . Patients over 65 years of age had significantly poorer DFS than the others (p < 0.0001, Fig. 1 A). Male patients had significantly poorer DFS than female patients (p < 0.0012, Fig. 1 B). Patients with submandibular cancer had significantly poorer DFS than those with parotid cancer (p = 0.0018, Fig. 1 C). There were significant differences in DFS among histological types (p < 0.0001, Fig. 1 D) and depending on pathological T status (p < 0.0001, Fig. 1 E). Patients with positive surgical margins had significantly poorer DFS than those with negative margins (p = 0.0097, Fig. 1 F). There was a significant difference in DFS depending on LN metastasis and ENE (p < 0.0001, Fig. 1 G). Patients who received PORT had significantly poorer DFS than those who did not (p = 0.023, Fig. 1 H).

Kaplan-Meier curves of disease-free survival (DFS). Differences in each factor were compared using the log-rank test. A) Patients over 65 years of age have significantly poorer DFS than younger ones (p < 0.0001). B) Male patients have significantly poorer DFS than female patients (p < 0.0012). C) Patients with submandibular cancer have significantly poorer DFS than those with parotid cancer (p = 0.0018). D) There is a significant difference in DFS among histological types (p < 0.0001). E) There is a significant difference in DFS depending on pathological T status (p < 0.0001). F) Patients with positive surgical margins have significantly poorer DFS than those with negative margins (p = 0.0097). G) There is a significant difference in DFS depending on lymph node (LN) metastasis and extranodal extension (ENE) (p < 0.0001). H) Patients who received postoperative radiotherapy (PORT) have significantly poorer DFS than those who did not (p = 0.023).

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