The impact of stage, grade, and mucinous histology on the efficacy of systemic chemotherapy in adenocarcinomas of the appendix: Analysis of the National Cancer Data Base

Abstract

Background Adenocarcinomas of the appendix represent a heterogeneous disease depending upon the presence of mucinous histology, histologic grade, and stage. We sought to explore the interplay of these factors with systemic chemotherapy in a large population dataset. Methods Patients in the National Cancer Data Base (NCDB) with mucinous, non-mucinous and signet-ring cell type appendiceal neoplasms from 1985-2006 were selected. Multivariable Cox proportional hazards regression models were developed. Results 11,871 patients met our inclusion criteria: 50.3% mucinous, 40.5% non-mucinous and 9.2% signet-ring cell. 5-year overall survival (OS) stratified by grade was similar across stage I-III disease but not for stage IV disease. Median OS for stage IV mucinous and non-mucinous histology was 6.4 and 2.3 years for well differentiated (p<0.0001) and 1.5 and 0.8 years for poorly differentiated (p<0.0001), respectively. In multivariable modeling for stage I-III disease, adjuvant chemotherapy improved OS for both mucinous and non-mucinous histologies: HR of 0.78 (0.68-0.89; p=0.0002) and 0.83 (0.74-0.94;p=0.002) respectively. For stage IV disease systemic chemotherapy was significant for non-mucinous 0.72 (0.64-0.82; p<0.0001) but not mucinous 0.95 (0.86-1.04; p=0.2) histologies, though this was grade dependent. Median OS for chemotherapy vs. no chemotherapy was 6.4 versus 6.5 years. (p=not significant) for mucinous well differentiated and 1.6 versus 1.0 years. (p=0.0007) for mucinous poorly differentiated. Conclusions Adjuvant chemotherapy demonstrated a significant OS benefit regardless of histology. However, for stage IV disease the benefit of systemic chemotherapy varied by histology and grade, with well differentiated mucinous appendiceal adenocarcinomas deriving no survival benefit from systemic chemotherapy.

Retrospective study of non-mucinous appendiceal adenocarcinomas: Role of systemic chemotherapy and cytoreductive surgery.

“…Interestingly, the efficacy of systemic chemotherapy did not differ by histological grade; patients with moderately and poorly differentiated tumors had similar outcomes. Our observations of systemic chemotherapy activity in nonmucinous AA is consistent with a report based on NCDB data showing that systemic chemotherapy improved OS in patients with stage IV nonmucinous AA [3].…”

“…Approximately two-thirds are adenocarcinomas, and are histologically classified into mucinous and nonmucinous subtypes. Recent observational studies of data from both the Surveillance, Epidemiology, and End Results (SEER) database and the National Cancer Data Base (NCDB) have shown similar overall survival (OS) and cancerspecific survival (unadjusted for grade and stage) for patients with mucinous and nonmucinous appendiceal tumors [2,3]. However, when patients were stratified by histological grade and disease stage, marked differences in outcomes were noted.…”

“…Particularly, the 5-year OS rate for patients with stage IV disease was significantly lower for those with nonmucinous (15%) than for those with mucinous tumors (41%). The differences were even more pronounced when well-differentiated stage IV appendiceal adenocarcinomas (AAs) were compared by histologic type: patients with nonmucinous welldifferentiated stage IV disease had worse median OS (2.2 years) than those with mucinous (6.4 years) disease [3]. These findings suggest that nonmucinous and mucinous AAs may have differences in tumor biology, but observational data cannot evaluate the impact of treatment across these histological subtypes.…”

“…Similarly, the efficacy of systemic chemotherapy in the treatment of AAs is uncertain, as the benefits appear to differ depending on histology (mucinous vs. nonmucinous) and tumor grade. A population-based study using the NCDB demonstrated no benefit from systemic chemotherapy for stage IV mucinous tumors but did show a benefit for the nonmucinous subtype (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.65-0.83; p < 0.0001) [3]. Though several other retrospective studies [9][10][11][12] have examined systemic chemotherapy in AA, none have described outcomes specifically in patients with nonmucinous AA.…”

The Management and Prognostic Prediction of Adenocarcinoma of Appendix

“…However, in stage IV patients, the benefit of systematic therapy has been reported to be influenced by tumour grade and histology. In addition, mucinous and well-differentiated adenocarcinomas did not appear to benefit from systemic chemotherapy20. In our study, due to the limitations of the SEER database, we could not obtain information regarding the administration of chemotherapy in patients with adenocarcinoma of the appendix.…”