Survival Outcomes in Asymptomatic Patients With Normal Conventional Imaging but Raised Carcinoembryonic Antigen Levels in Colorectal Cancer Following Positron Emission Tomography-Computed Tomography Imaging

Abstract

Background: This study had two aims: (a) to evaluate the utility of fluorine 18-fluorodeoxyglucose (FDG) positron emission tomography (PET)-computed tomography (CT) in detecting occult disease recurrence with raised carcinoembryonic antigen (CEA) and (b) to establish the prognostic effects of early detection of disease recurrence in patients with colorectal cancer (CRC).

Patients and methods: Clinico-pathological data were obtained from all consecutive patients undergoing CRC surveillance from 2004 to 2010 who had an elevated CEA level (>3 ng/mL in nonsmokers, >5 ng/mL in smokers) but normal or equivocal conventional investigations. Histopathological confirmation or a minimum of 12 months' clinical and radiological follow-up were required to ascertain disease relapse.

Results: A total of 1,200 patients were screened; of those, 88 (59% men; mean age, 66 years [SD, 9.6]) eligible patients (67 with normal and 21 with equivocal results on conventional investigations) were identified. Recurrent disease was detected in 56 of 88 patients (64%). The sensitivity of FDG PET-CT to detect recurrence was 49 of 56 (88%; 95% confidence interval [CI], 76%-95%) and specificity was 28 of 32 (88%; 95% CI, 71%-97%). Twenty-seven of 49 (55%) patients with PET-CT-detected relapsed disease were deemed eligible for further curative therapy; 19 (70%) went on to receive potentially curative therapy. The median time to progression (8.8 months [interquartile range (IQR), 4.5-19.1 months] vs. 2.2 months [IQR, 0.7-5.6]), median overall survival (39.9 months [IQR, 23.6-65.4 months] vs. 15.6 months [IQR, 7.3-25.7 months]), and 5-year survival (36.8% [95% CI, 16.5%-57.5%] vs. 6.1% [95% CI, 1.1%-17.6%]; p ≤ .001) were higher in patients who received potentially curative therapy than in those who received noncurative therapy.

Conclusion: FDG PET-CT is a highly sensitive and specific tool for the detection of occult CRC recurrence. In >50% of patients, recurrent disease may still be potentially amenable to curative therapy. Long-term survival can be achieved in such patients.

Implications for practice: Colorectal cancer (CRC) patients who, on follow-up, have normal or equivocal results on clinical investigations but raised carcinoembryonic antigen (CEA) levels pose a significant challenge to treating physicians. This study supported the notion that the early use of fluorodeoxyglucose (FDG) positron emission tomography (PET)-computed tomography (CT) may have predictive and prognostic value in management of such patients. Long-term disease control and cure can be achieved in a subgroup of this patient population with low-volume disease relapse who are amenable to potentially curative treatment strategies. Reassuringly, the sensitivity and specificity for recurrence did not significantly vary as a function of the CEA level, suggesting that even with a minimal CEA rise, benefit can be attained by conducting FDG PET-CT in a timely manner.

Keywords: Carcinoembryonic antigen; Colorectal cancer; Conventional investigations; FDG PET-CT.

Figure 1.

Imaging results of a 68-year-old man who presented with a rising carcinoembryonic antigen level (from 2 to 4 ng/mL) 18 months after surgery and adjuvant chemotherapy for a Duke’s C colon adenocarcinoma. (A): Contrast-enhanced CT demonstrated no evidence of recurrence. (B): FDG PET-CT demonstrated an isolated liver lesion, subsequently confirmed on Tesla MRI (C, D). He proceeded to undergo surgical resection of the liver metastasis. Abbreviations: CT, computed tomography; FDG, fluorine 18-fluorodeoxyglucose; MRI, magnetic resonance imaging; PET, positron emission tomography.

Figure 2.

Imaging results of a 70-year-old woman who had previously undergone surgery alone for a carcinoma of the ascending colon and was investigated for a carcinoembryonic antigen level that had increased from 2 to 9 ng/mL. (A): The CT scan was reported as normal. (B): FDG PET-CT showed peritoneal FDG uptake within the pelvis, confirmed on pelvic MRI (C, D). With the guidance of FDG PET-CT, a subtle abnormality was seen in retrospect at this site on the original CT scan (as shown by arrows). This recurrence was treated with palliative chemotherapy. Abbreviations: CT, computed tomography; FDG, fluorine 18-fluorodeoxyglucose; MRI, magnetic resonance imaging; PET, positron emission tomography.