Synopsis of new findings
Our cohort study assessed 74 patients with laCSCC or reCSCC of head and neck region, with a median follow-up of 35.8 months; 50% showed parotid and/or neck metastasis, much higher than the 20%-39% range of literature, explained by health system failures and the continental size of country located in tropical area 18,30,31. The majority of the patients were men, median age of 67 y, explained by prolonged sun occupational exposure.
In our cases, the prevalent location of the primary CSCC was the auricular and eyelid region, almost 67.5% were T2 and T3, some T1 reCSCC evolved with parotid metastasis, probably due immunosuppression condition, contrary to some authors (Table 1 )30,32. In univariate and multivariate analysis, primary tumor site, histopathological characteristics and margins did not affect the OS, attributed to retrospective data bias33-35. Interestingly, our study found 90.5% of patients with comorbidities (20% immunosuppressed due transplant organ), having main role on developing progressively metastases from primary to parotid/neck 36-38.
In 75% of patients, the main surgery was total primary resection with reconstruction followed by exenteration and temporalectomies, showing an aggressive presentation, similar to other developing countries35. Our data did not find an association between the type of primary surgery and survival, unusual since such a correlation is expected, however, there is comparable studies34,38,39.
The margins was compromised in 43.3% in the PM group and only 16.2% in the WPM group, expected in advanced cases, with no impact on survival. Majority of PM group patients had clinical T3/T4 (86.4%) tumors (most laCSCC) instead the WPM group (most reCSCC) showed T1/T2 (86.4%); this biological behavior difference has impacted on survival (T1 x T4) curves, with clearly negative impact on the clinical T stage survival, p = 0.028 (Figure 1) .
The parotid metastasis from CSCC has an unfavorable prognosis17,18,21,42. Our study reported a 50% incidence of parotid metastasis in laCSCC and reCSCC, 32.4% showed parotid extracapsular spread, with 29.7% compromised margins, denoting a difficulty to achieve an adequate surgical treatment10,14,21,36,43-46; otherwise, our isolated occult parotid metastasis rate was only 2.7%, meaning that probably is safe to observe the clinically and radiologically negative parotid gland lymph node cases (Table 2 and Table3 ).
This is very controversial, although no difference was observed between types of parotid surgery, our overall recurrence rate was 22.9%, the most frequent in parotid surgical bed (21.6%).
Our overall rate of occult neck metastasis was 13.5%; in PM group, 51.3% presented clinical neck metastasis, and 37.8% of these, extracapsular spread; demonstrating the path of tumor behavior; once it has the positive parotid gland metastasis, rapidly evolves to a positive neck metastasis; in fact, 64.8% of PM group has the N1-N2 neck compared to the 13.5% N1-N2 necks in the WPM group (Table 2 ); notably, the risk of a positive parotid metastasis evolving into positive neck metastasis was 37.6, with p=0.001 (Table 4 ).
Our OS curve (Figure 2 ) demonstrated negative survival for the PM group, with worst predictors (p=0.0283). Once the parotid shows clinical positive metastasis (P1-3 stages) the disease-specific survival is progressively and severely impacted (Figure 3) (p=0.016), findings similar to others 18,31,32,36,40,42,43,45-48.
Although 72.9% of our patients underwent to adjuvant radiochemotherapy, there have not impacted on survival, maybe due the poor response of CSCC to chemoradiation (Table 4) 10,32,35,36,46, but the radiochemotherapy is still the adjuvant treatment in multiple guidelines 12,21,31,32,36,49.
The Table 5 show the review of literature in 20 years regarding overall survival, and parotid and neck metastasis in CSCC, including our data.