To our knowledge, this was the first study of the role of PTS in the treatment of metastatic HNACC. It was found that removing the primary tumor without resection of distant metastasis can bring survival benefits for patients with metastatic HNACC. Most importantly, our research has identified the optimal candidates for PTS, which contributes to precision medicine.
In our study, the impact of clinicopathological characteristics and PTS on the survival of metastatic HNACC patients was presented. Patients with grade I-II had significantly better prognosis than those with grade III-IV HNACC (P<0.001 for both CSS and OS). Besides, patients with T1-2 stage (P=0.039 for CSS; P=0.009 for OS) and absence of lymph node metastasis (P<0.001 for CSS; P=0.009 for OS) was associated with better survival. Our results were in accordance with previous retrospective studies on ACC, and the grade of pathological differentiation and T stage were independent prognostic factors(17, 18). Of particular note was the marked improvement in survival among patients with PTS, which was undoubtedly good news for head and neck surgeons. The median CSS of patients with PTS and no-PTS were 64.0 months and 22.0 months, respectively. The median OS for the PTS group was 43.0 months; and for the no-PTS groups, it was 16.0 months. In multivariate analyses, PTS was not associated with CSS benefits, whereas it does confer increased OS in metastatic HNACC (HR=0.586, P=0.017). Based on the above findings, PTS should be considered for the treatment of metastatic HNACC. Notably, although the therapeutic value of PTS has been proven in HNACC and other types of cancer(19, 20), there was no consensus on the underlying mechanism of surgical advantages. It has been reported that surgical resection can decrease the risk of weight loss and nutritional depletion(21), or delay the occurrence of anemia, hypoproteinemia and even cachexia by decreasing the tumor burden(22, 23). However, up till now, these hypotheses have not been validated. From this perspective, the mechanism of the surgery-derived merits deserves further investigation.
The secondary purpose of this study was to identify predictive factors for selecting suitable candidates of PTS, which provided more reliable evidence for head and neck surgeons. In our study, PTS was significantly associated with better OS and CSS in patients with T3-4 or N0 stage (all P<0.05), which suggested that PTS may be an effective treatment option for patients with the above clinical characteristics. Specifically, patients with positive regional lymph nodes did not benefit significantly from PTS, but for patients without regional lymph nodes metastasis, patients who received PTS had favorable prognosis than those who did not. Even if metastatic disease exists, PTS may be more suitable for patients with relatively indolent diseases. On the other hand, PTS was shown to be of prognostic value for metastatic patients with T3–T4 stage in our study. We speculated that removal of the primary tumor may reduce the tumor burden and control the local tumor-related symptoms to a certain extent, and ultimately translates into significantly survival benefit. Interestingly, our finding was inconsistent with some retrospective studies(24, 25). In shi xiao et al research, PTS did not confer a survival benefit in patients with T4a-4b stage disease. They considered that aggressive surgical excision was not only unable to bring survival benefits, but was also highly likely to seriously affect the integrity of crucial anatomical structures in the head and neck region(24, 25). This phenomenon may be explained by the inconsistency of the enrolled populations between different study. The tumor heterogeneity could not be ignored. Except for ACC, their research also included some other pathological types of salivary gland tumors (the specific number was unknown). Thus, more well-designed studies are needed to validate the above results.
Despite its advantages, our research had some limitations, most of which were inherent in secondary data analysis of this nature. As a retrospective study, there was inevitably inherent selection bias. Other limitations included the lack of information on clinical symptom, number of metastases, surgical margins and perineural invasion status that could have impact on prognosis. In addition, the subsequent treatment of these patients was unknown, due to the limitation of SEER database. Therefore, further prospective randomized studies are needed to provide evidence that whether this population should be treated with PTS.