Primary Salivary Gland Malignancy: A Review on Post-Operative Follow-Up Duration and Investigations

Follow-up

Studies across SGCs share similar challenges, primarily being heterogeneous histological groups with variable biological behavior. The limited data, largely retrospective study designs, inconsistent integration of radiotherapy, short follow-up duration, and lack of post-operative investigation make it particularly difficult to establish a standard post-operative guideline. Follow-up after initial treatment was designed to identify locoregional recurrence and/or distant metastases. Distant metastases following primary SGCs have long time.² The relative risk of frequent recurrence and/or distant metastases depends on the tumor site, size, histology, and staging.^4,5 Shigeishi et al. demonstrated the importance of tumor resection before it increases in size (>4 cm) as delayed tumor resection is associated with higher mortality. This is known as ‘the 4 cm rule’.³

Surgery with or without post-operative radiotherapy remains the cornerstone of treatment for most resectable SGCs.^8,10,12–14 In addition, neck dissection is reserved for nodal disease, whereas adjuvant chemotherapy is only used for palliation.^4,6 In an extensive study on the outcomes of current major SGCs management, post-operative radiotherapy only reduced the risk of locoregional recurrence, but not distant metastases.^15,18 However, primary tumors of the parotid gland constitute the majority of their study population, despite primary tumors of the submandibular gland representing a significantly higher relative incidence of distant metastases.^19,20 In terms of demographic prognostic factors, this review did not find a sex predilection for survival or failure patterns.^18,19

In a more recent retrospective study by Shabani et al., the average times for locoregional recurrence and distant metastases were approximately 5 and 11 years, respectively. However, their study did not include high-grade tumors. Comparatively, Mimica et al. explored the recurrence of high-grade tumors and showed a median time of 20 months (1.6 years) to diagnose distant metastases after the completion of primary treatment. These data are also reflected in a Korean study focusing on post-treatment outcomes of diverse histologic grade tumors, specifically mucoepidermoid carcinoma (MEC).¹⁷ The average time for locoregional recurrence or distant metastases was 21 months (1.8 years). The team followed up the patients more frequently in the first 2 years after the initial treatment and biannually thereafter. The poor prognosis of high-grade tumors emphasizes the need for more aggressive treatment approaches and frequent follow-up in the initial years post treatment.

Our review showed that the development of distant metastases is possible after several years despite adequate local control.² The most predominant site of distant metastases is the lung, although metastasis can also be seen in the bone, liver, brain, and skin.¹ Ohta et al. showed that distant metastasis to the lung can occur as late as 20 years after initial treatment, using an example case of primary AdCC. It can be argued that the high-grade nature of AdCCs requires a longer follow-up period. Interestingly, although rare, polymorphous adenocarcinoma (PAC), a tumor with low-grade histology with a relatively indolent clinical course and excellent prognosis, has been reported to present with distant metastasis 20 years after initial diagnosis.¹⁰ Although no study has concretely suggested an upper limit for the follow-up period, this study recommends a minimum of 15-20 years.

Investigations

The main reason for treatment failure and eventual death is distant metastases in patients with primary SGC.^13,14,16 This further emphasizes the need for a longer follow-up duration and adequate imaging to detect local recurrence and/or distant metastases. The heterogeneous histology and variable biological behavior of SGC impose significant challenges for clinicians. The establishment of uniform post-operative guidelines is dependent on previous studies and scarce data.

Currently, magnetic resonance imaging (MRI) is the investigation of choice, and the value of functional MRI techniques pre-operatively are being further investigated; however, few studies have evaluated post-operative imaging.²¹ As discussed, follow-up is in place to detect disease recurrence and/or distant metastasis. One study has recommended MRI for local recurrence and chest computed tomography (CT) for lung metastases to be included as part of follow-up investigations.¹⁴ This recommendation is in accordance with lung being the most common site of distant metastases.^2,3,12 There is no consensus on the benefit of positron emission tomography for assessing local recurrence compared with conventional imaging.¹⁴

The United Kingdom National Multidisciplinary Guidelines agree that despite ultrasound being an accurate imaging modality for local recurrence, a quarterly baseline MRI is required for useful comparison.³ The frequency of MRI is then reduced to six monthly from the third to the fifth year post-operatively and then annually thereafter.¹⁴ No follow-up protocols have been established for the detection of abdominal or rare distant metastatic sites.²² Although rare, distant metastatic sites that are anecdotal mandate higher clinical suspicion for diagnosis.