Cancer of the Larynx-20-Year Comparative Survival and Mortality Analysis by Age, Sex, Race, Stage, Grade, Cohort Entry Time-Period, Disease Duration and ICD-O-3 Topographic Primary Sites-Codes C32.0-9: A Systematic Review of 43,103 Cases for Diagnosis Years 1975-2017: (NCI SEER*Stat 8.3.9).

Background: .-Laryngeal malignancy, "voice box" cancer, is uncommon with 12,620 estimated new cases and 3770 deaths in the United States in 2021,1 and represents only 6.2% of all respiratory system malignancies. The most significant risk factors are alcohol and tobacco consumption. Almost all cases (98%) of laryngeal cancer arise in the squamous epithelium, and in this analysis more than 75% are of well-or-moderately differentiated histopathology (Grades I&II). Local stage cancer (SEER Historic Staging) was more common than regional and distant stages combined (55.3% vs 44.7%). Tumors may arise above, below or at the level of the vocal folds and are described as supraglottic (encompassing the epiglottis, false vocal cords, ventricles, aryepiglottic fold and arytenoids), the glottis (encompassing the true vocal cords and the anterior and posterior commissures), and the subglottic region. In the National Cancer Institute's Surveillance, Epidemiology, End-Results (NCI-SEER) Data Research, 9 Registries, Nov 2019 Sub (1975-2017),2 laryngeal cancer occurred more commonly in men than in women, 80.7% vs 19.3%, respectively with a 4.2 to 1 ratio. Additionally, there are racial disparities with African Americans presenting at a younger age and having a higher incidence and mortality than Caucasians. In the 1975-2017 period, overall median patient age was 64.4 years with White Americans-64.8 years and Black Americans-61.5 years. Unfortunately, the 5-year relative survival rate has declined 4%, and excess death rate has risen 13% since 1975 with overall incidence declining.As a consequence, observed median survival is approximately 6.5-years for the total study-period pinpointing the need for further specialty research. This study follows the World Health Organization International Classification of Diseases for Oncology-3rd Edition (ICD-O-3)3 topographical identification, coding, labeling and listing of 43,103 patient-cases accessible for analysis in the United States National Cancer Institute's Surveillance, Epidemiology and End Results program (NCI SEER Research Data, 9 Registries, 1975-2017). These are located in 6 primary anatomical sites: C32.0-Glottis, C32.1-Supraglottis, C32.2-Subglottis, C32.3-Laryngeal cartilage, C32.8-Overlapping lesion of larynx, C32.9-Larynx, NOS.

Objectives: .-To update short- and long-term mortality and survival indices, and identify changing risk patterns for laryngeal cancer patients in a retrospective US population-based analysis, 1975-2017, using prognostic data stratified by ICD-O-3 Primary Site, age, sex, race, stage, histologic grade, two cohort entry time-periods (1975-1996 to 1997-2017), and disease duration to 20-years.

Methods: .-SEER*Stat v8.3.94 software (built March 12, 2021) was used to access SEER Research Data, 9 Registries, Nov. 2019 submission (1975-2017). For displaying risk, general methods and standard double decrement life table methodologies for converting and displaying ICD-O-3 coded laryngeal cancer primary site annual data to aggregate average annual mortality and survival units in durational-intervals of 0-1, 1-2, 2-5, 0-5, 5-10, 10-15, and 15-20 years were employed. The reader is referred to the "Registrar Staging Assistant (SEER*RSA)" for local-regional-distant Extent of Disease (EOD) sources used in the development of staging descriptions, and Summary Stage 2018 Coding Manual v2.0 released September 1, 2020. Cancer staging & grading procedural explanations, statistical significance and 95% confidence levels5 are described in previous Journal of Insurance Medicine articles6,7 and other publications.8,9 Poisson confidence intervals at the 95% level based on the number of observed deaths are used in this study but not displayed here to conserve space on the mortality tables. Excluded were all death certificate only and those alive with no survival time.

Results: .-Total SEER annual age-adjusted incidence rates from 1980 to 2017 have diminished from 5.25 patient-cases/100,000/year to 2.59/100,000 per year, and in the same period annual age-adjusted US death rates declined from 1.61 deaths/100.000/year to 0.91 deaths/100,000/year (Ref. 10, CSR Tables 12.5-6), However, in the 0-5-year disease durational interval for all staged cases in both cohort time-periods (Table 5), excess death rates (EDR) rose from 80 per 1000 persons per year in the 1975-96 cohort, to 89 per 1000 persons per year in the 1997-17 cohort, (a 10% rise in excess mortality in 42 years). Further, in the 5-10-year disease durational interval, EDR rose from 39 per 1000 persons per year to 45 per 1000 persons per year with corresponding cohort declines in cumulative survival ratios (SR), and overall declines in median observed and relative survival times in the later cohort (not shown). The epidemiologic burden of malignancy is >4-fold higher in males and increases in parallel with aging, peaking after 65 years. The most significant risk factors for laryngeal cancer are tobacco and alcohol consumption.

Conclusion: .-Although annual incidence and mortality rates from 1980 to 2017 have diminished, there is no concomitant improvement in larynx cancer survival (SR) and mortality (EDR) indices, with rising mortality and diminishing survival in all staged cases at 5-years disease duration between the 1975-96 and 1997-2017 analytic cohorts. Larynx cancer remains a burdensome clinical, social, and public health challenge.