The impact of routine ultrasonography on nodal metastasis in head and neck cutaneous squamous cell carcinoma: A retrospective multicentre cohort study

Dear Editor, Cutaneous squamous cell carcinoma (cSCC) is the second most prevalent skin cancer, with a metastasis rate of 2%– 5%, significantly lowering survival rates.1– 3 Early detection of lymph node metastasis (LNM) may contribute to higher survival rates.4 We performed a retrospective, multicentre study investigating whether early detection of LNM by routine ultrasonography results in lower disease morbidity, compared to clinically detected LNM. All patients diagnosed between 01 January 2010 and 01 September 2019 with cSCC LNM in the head and neck region among four university hospitals were identified via the Nationwide Network and Registry of Histopathology and Cytopathology (PALGA). The primary outcome was the clinical Nstage distribution according to the AJCC8 between patients with LNM detected by routine ultrasound evaluation versus clinical examination. As secondary outcomes, we compared the size of the largest LNM, the occurrence of extranodal growth and the lymph node ratio. To detect a difference in clinical Nstage of 3% (power 80%, twosided alpha level 0.05), 174 patients per group were required. Pearson chisquare or Fisher's exact tests were used to compare categorical data and Mann– Whitney U tests for nonnormally distributed continuous data. To account for multiple comparisons, a 2sided pvalue of less than 0.05 was adjusted for statistical significance using the false discovery rate method.5 Among the 276 eligible patients, 244 (88%) had LNM found by clinical evaluation, of which 171 (70%) by selfexamination, while 32 (12%) were detected by routine ultrasonography (Figure 1). The majority of clinically detected metastatic patients were found during followup (218/244, 89%), whereas the ultrasounddetected metastatic patients (25/32, 78%) were mainly detected at baseline. There were no relevant differences in patient characteristics between the two groups (Table 1). Patients with routine ultrasounddiagnosed LNM had more highrisk tumour features, including larger tumour sizes, deep invasion and higher Tstages. Patients with routine ultrasounddiagnosed LNM also received more postoperative radiotherapy (34.3% vs. 13.9%, p < 0.01) (data not shown). A third (33%) of the LNM developed from T1 primary tumours, of which almost all (75/76, 99%) were discovered by clinical examination and (61/75, 81%) by selfexamination. Clinically detected LNM were more frequently staged as N3 compared to ultrasounddetected LNM (13.5% vs. 3.1%), but the difference was not statistically significant (p = 0.296). Patients with clinically detected LNM had larger lymph nodes on ultrasound than patients with ultrasounddetected LNM (17.0 mm IQR [12.0– 24.0] vs. 9.6 mm IQR [7.1– 19.0], p = 0.002). Neither the number of radiologically suspected nodes nor the pathological Nstage differed between the groups. Patients with ultrasounddetected LNM had smaller lymph nodes after surgery (15.0 mm IQR [12.8– 29.8] versus 25.0 mm IQR [16.0– 35.0], p = 0.08). The median time from index cSCC diagnosis to LNM diagnosis was 7 months (IQR 3– 16) in clinically detected patients. The median time from primary cSCC diagnosis to LNM diagnosis was 6 months longer compared to recurrent cSCC (7.0 IQR (3– 15) vs. 1.0 IQR (0– 9), p < 0.001) (data not shown). This study demonstrates that with a screening ultrasound investigation at baseline, only few LNM are detected, while most metastasis are found by clinical examination, usually selfexamination, during followup. Because the group with clinically detected LNM was much larger than expected, our study was underpowered to evaluate the impact of routine ultrasound investigation on clinical Nstage. There was a trend towards larger lymph nodes in patients with clinically detected LNM. Interestingly, we found that onethird of all LNM originated from primary lowrisk cSCC. Based on the median time of 6 months to the diagnosis of LNM, a prospective study evaluating the value and timing of routine ultrasound versus appropriate instructions for selfexamination in cSCC, as well as providing information to patients on regular selfexamination, seem like important next steps. Received: 22 December 2022 | Accepted: 17 April 2023