Delayed regional metastases, distant metastases, and second primary malignancies in squamous cell carcinomas of the larynx and hypopharynx

Objective: To determine the impact of delayed regional metastases, distant metastases, and second primary tumors on the therapeutic outcomes in squamo us cell carcinomas of the larynx and hypopharynx Study Design Chart review and statistical analysis. Methods: A retrospective tumor registry analysis was made of patients with squamous cell carcinomas of the larynx and hypoph arynx who were treated with curative intent in the Department of Otolaryngo logy - Head and Neck Surgery and the Radiation Oncology Center of the Washi ngton University School of Medicine (St. Louis, MO), between January 1971 a nd December 1991 and developed delayed regional metastases (2 y after treat ment), distant metastases, and second primary malignancies. Results: In 255 0 patients, the mean age (59.8 y), sex (8.5 male patients and 1 female pati ent), and tumor differentiation did not affect the incidence of delayed dis tant, regional, or second primary malignancies. The overall incidence of de layed regional metastases was 12.4% (317/2550 patients); distant metastases , 8.5% (217/ 2550); and second primary tumors, 8.9% (228/2550), with a 5 ye ar disease-specific survival of 41%, 6.4%, and 35%, respectively. Second pr imary malignancies were not statistically related to the origin of the prim ary tumor, tumor staging, or delayed regional and distant metastases (P = . 98). Delayed regional metastases and distant metastases were related to adv anced primary disease (T4 stage), lymph node metastases (node positive [N+] ), tumor location (hypopharynx), and locoregional tumor recurrence (P less than or equal to .028). Advanced regional metastases at initial diagnosis ( N2 and N3 disease) increased the incidence of delayed and distant metastase s threefold (P = .017). These two metastatic parameters were significantly greater in hypopharyngeal tumors than in laryngeal tumors (P = .037). The i ncidences of delayed regional metastases by anatomical location of the prim ary tumor were as follows: glottic, 4.4%; supraglottic, 16%; subglottic, 11 .5%; aryepiglottic fold, 21.9% pyriform sinus, 31.1%; and posterior hypopha ryngeal wall, 18.5%. The incidences of distant metastases were as follows: glottic, 4%; supraglottic, 3.7%; subglottic, 14%; aryepiglottic fold, 16%; pyriform fossa, 17.2%; and posterior hypopharyngeal wall, 17.6%. Seventeen hypopharyngeal tumors (2%) presented with Mi disease. Delayed regional meta stases to the ipsilateral treated neck had a significantly worse survival p rognosis than delayed metastases to the contralateral nontreated neck (P = .001). Conclusions: Conclusions are as follows: 1) The incidence of second primary tumors is independent from the primary tumor staging and distant an d delayed regional metastases. The highest incidence occurred in patient gr oups with the highest disease-free survival rates (P = .0378). 2) Highest i ncidence of delayed and distant metastases occurred in hypopharyngeal tumor s and was three times greater than in laryngeal cancers (P = .028). 3) Salv age therapeutic rates were poor for delayed metastases to the ipsilateral t reated nodes and distant metastases as compared with contralateral neck met astases and second primary tumors (P = .001). 4) Delayed and distant lymph node metastases were significantly higher in advanced primary disease (T4 s tage), locoregional recurrences, and regional disease (N2 and N3) (P = .028 ) in both the larynx and hypopharynx 5) The higher incidence of delayed and distant metastatic disease was related to more advanced initial tumor pres entation in hypopharyngeal cancer as compared with laryngeal cancer (P = .0 39). 6) Incidence of distant metastases was greatest between 1. 5 and 6 years after initial treatment with a mean incidence being less than or equal to 3.2 years.