Frequency and Risk Factors for Metastasis in Newly Diagnosed Appendiceal Carcinoma

Abstract

BackgroundAppendiceal carcinoma has an insidious clinical presentation, and these tumors are rarely suspected prior to surgery, potentially leading to late diagnosis. The aim of this study is to investigate the prevalence of metastatic disease at initial presentation and potentially associated sociodemographic characteristics. MethodsPatients were identified from the Surveillance, Epidemiology, and End Results (SEER) program using the International Classification of Diseases for Oncology-3 (ICD-O-3) histology/behavior codes between 2010 and 2015. Firth logistic regression was performed to determine the association of metastasis at presentation with tumor subtype, adjusted for age, race, sex, insurance and marital status, tumor grade, and tumor and nodal stage using the 7th edition of the American Joint Committee on Cancer (AJCC) staging system. ResultsWe identified a total of 3,447 patients with known metastatic status. A total of 38.4% had metastatic disease at diagnosis. Compared to colonic-type adenocarcinoma (CA), mucinous adenocarcinoma (MA) and signet ring cell carcinoma (SC) were more likely to present with metastasis at diagnosis (OR: 2.34; 95% CI [1.80-3.06]; OR: 1.93 [1.29-2.89], respectively), however, goblet cell carcinoma (GC) was less likely (OR: 0.59 [0.36-0.93]). Compared to tumors invading the submucosa (T1 stage), tumors invading deeper through the visceral peritoneum or nearby organs (T4 stage) were significantly more likely to present with metastatic disease ). Tumors invading the muscularis propria (T2 stage) or deeper into the subserosa, or the mesoappendix (T3 stage) were less likely to present with metastatic disease (OR: 0.34 [0.16-0.71]); OR: 0.55 [0.34-0.91], respectively). Compared to no regional lymph node spread, four or more regional lymph node involvement (N2 stage) was more likely to present with metastatic disease (OR: 2.19 [1.53-3.16]). Men were less likely to present with metastatic disease (OR: 0.60 [0.48-0.73]). A total of 90.1% of CA, 84.2% of GC, 42.2% of MA, and 78.5% of SC patients with metastasis at diagnosis had extraperitoneal distant metastasis (M1b). ConclusionsA significant proportion of patients with newly diagnosed appendiceal carcinoma presented with metastatic disease, concerning substantial diagnostic delay and potentiating the need for aggressive treatments. Predictors of metastatic disease included female sex, histologic subtype, and significant regional lymph node involvement. Future research should focus on earlier detection and explore tumor biology.

Goblet Cell Adenocarcinoma of the Appendix: A Systematic Review and Incidence and Survival of 1,225 Cases From an English Cancer Registry

“…In studies classifying GCA as local, regional, or metastatic disease, 51%–64% of cases were described as local ( 3 , 16 , 17 , 26 ). While metastases were found in only a relatively small proportion of cases in the registry studies (7%–18.7%) ( 3 , 11 , 12 , 16 – 20 , 23 , 26 ), stage IV disease was more common in retrospective studies and case series ( 7 , 37 , 39 , 44 , 49 , 52 , 58 , 73 ). It is likely that this finding is the result of referral bias, as higher rates of metastatic disease were reported by tertiary centres, with lower rates reported by district general hospitals and national registry studies ( 52 ).…”

“…Only one large registry study reported a median age out of this range at 43 years ( 23 ). GCA is more common in Caucasian patients, who account for 80-90% cases ( 3 , 11 , 12 , 14 – 20 , 25 , 26 ). There was no sex preponderance in most studies ( 3 , 11 , 12 , 14 , 16 , 18 , 20 , 23 , 25 , 26 ); however, this was variable in the smaller retrospective studies and case series.…”

“…GCA is more common in Caucasian patients, who account for 80-90% cases ( 3 , 11 , 12 , 14 – 20 , 25 , 26 ). There was no sex preponderance in most studies ( 3 , 11 , 12 , 14 , 16 , 18 , 20 , 23 , 25 , 26 ); however, this was variable in the smaller retrospective studies and case series. Infection with schistosomiasis was the only potential environmental risk factor identified, although it should be noted that only three cases of combined appendiceal schistosomiasis and GCA were included in this study ( 63 ).…”

“…Authors rarely specified whether staging was based upon index or completion surgery. In larger registry studies using the TNM system, most tumours presented with stage II disease ( 14 , 18 – 20 , 28 , 39 , 52 , 58 ); T3 tumours were found in 49%–60% and N0 in 81%–87% of cases ( 11 , 12 , 23 ). In studies classifying GCA as local, regional, or metastatic disease, 51%–64% of cases were described as local ( 3 , 16 , 17 , 26 ).…”

“…It is likely that this finding is the result of referral bias, as higher rates of metastatic disease were reported by tertiary centres, with lower rates reported by district general hospitals and national registry studies ( 52 ). The most common sites of metastases were the peritoneum, liver, small bowel, and ovaries ( 11 , 28 , 37 , 49 , 52 , 89 , 90 ).…”