Tumor Marker Evolution: Comparison with Imaging for Assessment of Response to Chemotherapy in Patients with Colorectal Liver Metastases

Abstract

BackgroundAs the real clinical significance of carcinoembryonic antigen (CEA) and carbohydrate antigen 19.9 (CA19.9) evolution during preoperative chemotherapy for colorectal liver metastases (CLM) is still unknown, we explored the correlation between biological and radiological response to chemotherapy, and their comparative impact on outcome after hepatectomy.MethodsAll patients resected for CLM at our hospital between 1990 and 2004 with the following eligibility criteria were included in the study: (1) preoperative chemotherapy, (2) complete resection of CLM, (3) no extrahepatic disease, and (4) elevated baseline tumor marker values. A 20% change of tumor marker levels while on chemotherapy was used to define biological response (decrease) or progression (increase). Correlation between biological and radiological response at computed tomography (CT) scan, and their impact on overall survival (OS) and progression-free survival (PFS) after hepatectomy were determined.ResultsAmong 119 of 695 consecutive patients resected for CLM who fulfilled the inclusion criteria, serial CEA and CA19.9 were available in 113 and 68 patients, respectively. Of patients with radiological response or stabilization, 94% had similar biological evolution for CEA and 91% for CA19.9. In patients with radiological progression, similar biological evolution was observed in 95% of cases for CEA and in 64% for CA19.9. On multivariate analysis, radiological response (but not biological evolution) independently predicted OS. However, progression of CA19.9, but not radiological response, was an independent predictor of PFS.ConclusionsIn patients with CLM and elevated tumor markers, biological response is as accurate as CT imaging to assess “clinical” response to chemotherapy. With regards to PFS, CA19.9 evolution has even better prognostic value than does radiological response. Assessment of tumor markers could be sufficient to evaluate chemotherapy response in a nonsurgical setting, limiting the need of repeat imaging.

Surgery for colorectal liver metastases: The evolution of determining prognosis

“…Patients with a larger intrahepatic tumor burden are most at risk for an R1 margin; it is these patients who also have worse overall tumor biology and overall recurrence. To this point, de Haas et al [23] did not find a difference in OS among patients undergoing an R0 vs R1 resection. These data may suggest that, in an era of more effective chemotherapy options, leaving microscopic disease behind may result in increased local failure but not necessarily a worse OS.…”

“…Among many patients, CEA can be an effective marker to monitor for recurrence, as well as to assess response to systemic therapy [18,21] . CEA levels can correlate with the radiological response to preoperative chemotherapy; however, other data have suggested that the absolute change in CEA level with chemotherapy may not correlate with long-term outcome [23] . As a pre-operative prognostic factor, Mann et al [12] reported that CEA levels did correlate with 5-year survival (CEA levels < 200 ng/mL: 48.9% vs > 200 ng/mL: 0.0%).…”

“…The impact of margin status on outcomes may therefore be influenced by patient and tumor factors, as well as the utilization of chemotherapy [61] . Regardless of the impact of margin status on prognosis, complete macroscopic and microscopic removal of all lesions with negative resection margins should remain the gold standard in the surgical treatment of CRLM [23] .…”

CA 19-9: handle with care

“…It is worth mentioning the study of de Haas et al [ 68 ] who evaluated both CEA and CA 19-9 in comparison with the radiological response (TAC) to chemotherapy after complete resection for metastases of CRC, considering a change in levels of at least 20% as significant. Serial determinations of CEA and CA 19-9, respectively, were available for 113 and 68 patients: the patterns of these markers, or biological evolution, was similar to the radiological evidence of response in 94% of cases for CEA and in 91% of cases CA 19-9, and in patients with radiologic progression the correlation with the performance of the serum markers was, respectively, 95% and 64%.…”

Paradoxical Reductions in Serum Anti-p53 Autoantibody Levels by Chemotherapy in Unresectable Colorectal Cancer: An Observational Study

“…A previous study reported that changes in CEA levels were parallel with radiological tumor responses in frontline chemotherapy in CRC patients with liver-only metastatic disease [33]. On the other hand, recent studies showed that the concordance rate between changes in CEA levels and tumor responses to therapy was only 50-60% in CRC with metastases in various organs [34,35].…”