Background: Appendiceal adenocarcinoma (AA) is a rare gastrointestinal cancer that frequently presents with peritoneal metastases; the standard of care for resectable peritoneal metastases from AA limited to the peritoneum is cytoreductive surgery (CRS) followed by hyperthermic intraperitoneal chemotherapy (HIPEC). Three serum tumor markers (TMs)-carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and cancer antigen 125 (CA125)-may play a role in preoperative and postoperative risk estimation and decision-making in patients undergoing CRS-HIPEC. Objective: To evaluate the association of preoperative and postoperative serum TM levels with outcomes in patients with AA or goblet cell adenocarcinoma (GCA) undergoing CRS-HIPEC. Design, Setting, and Participants: This retrospective cohort study was conducted in a single quaternary referral cancer center. Software was used to query the MD Anderson internal patient database of patients with AA or GCA to identify a cohort receiving CRS with or without HIPEC between March 2016 and August 2024, with median postoperative follow-up of 35.6 months (range, 1.4-100.5 months). Data were analyzed from June 2024 to March 2025. Exposure: Preoperative and postoperative levels of CEA, CA19-9, and CA125. Main Outcomes and Measures: Association of preoperative and postoperative serum TM levels with tumor burden and likelihood of complete CRS, disease-free survival (DFS), and overall survival (OS). Results: A total of 421 CRSs were included in the study, 376 (89.3%) of which were performed in patients with AA (229 60.9% in females; median age at surgery, 56 IQR, 47-64 years; 290 77.1% were complete CRS). In AA, greater vs lesser preoperative tumor burden was associated with increased median serum TM levels (CEA: 9.5 IQR, 3.7-42.3 ng/mL vs 3.0 IQR, 2.1-5.9 ng/mL; CA19-9: 31.1 IQR, 10.0-102.3 U/mL vs 15.0 IQR, 6.1-25.5 U/mL; CA125: 28.7 IQR, 13.9-58.5 U/mL vs 11.5 IQR, 8.0-17.3 U/mL; all P < .001), and after CRS vs before, percentages of patients with TM elevation were significantly lower (CEA: 77 of 223 34.5% vs 222 of 340 65.3%; CA19-9: 45 of 194 23.2% vs 117 of 324 36.1%; CA125: 13 of 203 6.4% vs 98 of 325 30.2%; all P < .001). However, complete vs incomplete CRS was associated with normalized TM levels in a greater percentage of patients (55 of 90 61.1% vs 7 of 52 13.5%; P < .001). Elevated vs normal preoperative TM levels were associated with increased rate of incomplete CRS (30 of 193 15.5% vs 1 of 95 1.1%; P < .001) and shorter DFS (hazard ratio HR, 2.30; 95% CI, 1.46-3.64; P < .001) but not shorter OS (HR, 1.36; 95% CI, 0.71-2.60; P = .36). Postoperative TM elevation was associated with shorter DFS (HR, 3.73; 95% CI, 2.33-5.95; P < .001) and OS (HR, 4.10; 95% CI, 2.02-8.31; P < .001) in univariate analyses and also in multivariate analyses (HR, 3.34; 95% CI, 1.44-7.75; P = .005), whereas postoperative normalization of all TMs was associated with improved DFS (HR, 3.54; 95% CI, 2.01-6.23; P < .001) and OS (HR, 6.00; 95% CI, 2.06-17.46; P = .001) in univariate analyses and also in multivariate analyses (HR, 4.21; 95% CI, 1.33-13.35; P = .02). Conclusions and Relevance: In this cohort study of CRS in patients with AA, elevated serum TM levels were associated with worse outcomes, suggesting that patients with postoperative TM elevation after complete CRS may represent a cohort with residual tumor that requires more cautious surveillance and that both preoperative and postoperative levels of CEA, CA19-9, and CA125 should be assessed in clinical practice.
Pattalachinti et al. (Mon,) studied this question.