Close/Positive Surgical Margins in Salivary Gland Cancer Linked With Poor Outcomes, But Low-Risk Disease May Be Watched

Close or positive surgical margins in salivary gland cancer appear to be associated with an increased risk of poor local control and survival, although when controlling for tumor stage, histologic risk, and adjuvant radiotherapy use, it did not appear to be an independent factor for poor outcomes, according to a study published in JAMA Otolaryngology Head and Neck Surgery.

Additionally, investigators noted that observation may be a safe post-surgery option for patients with close margins and low histologic risk and low-stage disease.

The 5-year disease-specific survival (DSS) for patients with major salivary gland tumors who achieved negative margins was 85.0%, close margins was 70.0%, and positive margins was 63.5%. A 2.7-fold increase in risk of disease-specific death was observed among patients with positive margins (HR, 2.69; 95% CI, 1.53-4.77) compared with patients who had negative margins. Additionally, those with close margins had a 1.8-fold increase in risk of disease-specific death (HR, 1.84; 95% CI, 0.97-3.48).

The 5-year DSS rate among those with minor salivary gland tumors with negative margins was 95.5%. Patients with close and positive margins had a 5-year DSS rate of 91.4% and 92.7%, respectively. Those with positive margins had a 2.4-fold increased risk of disease-specific death (HR, 2.38; 95% CI, 1.26-4.52), and those with close margins had a 1.8-fold increased risk of death (HR, 1.84; 95% CI, 0.84-4.03).

A total of 837 patients enrolled on the study with a median follow-up up of 57 months. The median age at initial surgery was 58 years. Additionally, 49.1% of patients reported having ever used tobacco and 61.4% used alcohol. A total of 52.3% of patients had minor salivary gland tumors, and 47.7% had major salivary gland tumors, with the most common types of cancer being mucoepidermoid cancer (35.8%) and adenoid cystic cancer (21.1%). Of the patients included in the research, positive surgical margins were identified in 30.1%, with the most common sites being nasal cavity or paranasal sinuses and trachea or larynx. Adjuvant radiotherapy was given to 30.7% of patients with negative margins, 58.8% of those with close margins, and 80.5% of patients with positive margins.

In terms of histologic risk group distribution, 50.4% of patients were low, 17.7% were intermediate, and 31.5% were high. Additionally, 46.1% of patients had T1 lesions, and T3 to T4 tumors were identified in 27.8% of patients. Seventeen percent of patients had regional lymph node metastases. Moreover, 15.4% of patients had lymphovascular invasion, 36.2% had perineural invasion, and 9.1% had extranodal extension. Additionally, the overall patient population had a 5-year overall survival rate of 79% and a DSS rate of 86%.

Negative margins were observed in 45.6% of patients, 30.1% had positive margins, and 24.3% had close margins. A total of 54.5% patients underwent surgery alone, and adjuvant radiotherapy was used in 40.6% of patients. An additional 41 patients needed adjuvant radiotherapy with systemic therapy. A median dosage of adjuvant radiotherapy was received at 62 Gy.

Among the patients with perineural invasion (n = 144), 47.9% had positive margins, and negative margins were seen in 51.0% patients in the low-risk histologic group, 55.2% in those with pT1, and 46.7% in those with pN0. In total, 30.7% of those with negative margins received adjuvant radiotherapy vs 58.8% of patients who had close margins, and 80.5% of those with positive margins (P <.001). Among those with minor salivary gland tumors, disease of the nasal or paranasal sinuses (n = 36) were most susceptible to margin involvement, with 58.3% of patients having positive margins.

At 5-years, the local recurrence–free survival (LRFS) for patients with major salivary glands was 94.1% for negative margins, 89.6% for close margins, and 74.8% for positive margins. A 1.43-fold increase in risk of local recurrence was observed for those with close margins (HR, 1.43; 95% CI, 0.48-4.25), and positive margins had a 4.01-fold increased risk (HR, 4.08; 95% CI, 1.74-9.61).

In the univariate analysis, patients with close margins had a 1.34-fold increase in local recurrence compared with those who had negative margins (HR, 1.34; 95% CI, 0.41-4.410). Adjuvant radiotherapy was also a significant independent estimator in the multivariate analysis (HR, 0.34; 95% CI, 0.13-0.89). 

For those with minor salivary glands, the 5-year LRFS for negative margins was 94.3%, close margins was 89.4%, and positive margins was 87.2%. A 2.63-fold increase in risk of local recurrence was seen for those with close margins (HR, 2.63; 95% CI, 1.11-6.23), and positive margins had a 2.93-fold increase (HR, 2.93; 95% CI, 1.37-6.72). Those receiving adjuvant radiotherapy had improved local control (HR, 0.37; 95% CI, 0.14-1.00).

A subgroup analysis was conducted in 203 patients with close margins, 58.1% of whom had low-risk or intermediate-risk histologic group stage I or stage II disease. The low-risk group had 90 patients, 21.1% of whom had received adjuvant radiotherapy and 2 patients experienced local recurrence during follow-up. A univariable analysis showed tumor site, histologic risk group, overall stage, and adjuvant radiotherapy were not associated with LRFS, and adjuvant radiotherapy was not associated with improved local control (HR, 0.66; 95% CI, 0.07-6.34).

A total of 62 patients with positive margins did not receive adjuvant radiotherapy. Within this group, 61.3% were low risk, 9.7% were intermediate risk, and 29.0% were high risk. Of these patients, 72.6% had T1 or T2 tumors. Additionally, within this group, investigators reported 8 local recurrences, 4 distant recurrences, and 5 regional recurrences. These patients had an overall DSS rate of 79.8% and an LRFS rate of 77.8%.

The 10-year DSS for the low-risk histologic group was 100% and 88.6% for local control. Poor survival was seen for patients in the high-risk histologic group, with a 10-year DSS of 30%, as well as those with stage III disease, who had a 10-year DSS rate of of 50%.

Reference

Hanson M, McGill M, Mimica X, et al. Evaluation of surgical margin status in patients with salivary gland cancer. JAMA Otolaryngol Head Neck Surg. 2021;e213459. doi:10.1001/jamaoto.2021.3459