Table 3.
CEA and follow-up after CRC: outcome measures in selected studies
| Trial | Type of regimen | Time to first recurrence (mo) | Proportion of recurrences | Overall 5-year survival | Outcome summary |
|---|---|---|---|---|---|
| Treasure (CEASL) [12] | All patients had clinical review 3/12 for 2 years and 6/12 for the next 3 years. CEA was measured monthly for the first 3 years and 3/12 for the next 2 years. | Median time from primary surgery to CEA increases and randomization was 403 days (range, 103–1,754) | Conventional: 82%; aggressive: 77% | Not reported. End of trial figures below | Second look laparotomy in the event of CEA elevation did not improve survival. |
| Patients were randomized if the CEA became elevated (≥10 ng/mL). | Conventional: 82% died | ||||
| 216 Patients were randomized. | Aggressive: 84% died | ||||
| Conventional: Continued clinical monitoring with clinicians blinded to increased CEA. | |||||
| Aggressive: Clinician screen for widespread metastatic disease examinations and CXR. If not found, patient had a laparotomy to look for recurrence. | |||||
| Makela [72] | Clinic review for all 3/12 for 2 years, the 6/12 for 3 years with history, examination, complete blood cell counts, faecal occult bloods, CEA and CXR. | Conventional: 15 ± 10; intensive: 10 ± 5 | Conventional: 39%; intensive: 42% | Conventional: 54%; intensive: 59% | Intensive follow-up leads to earlier detection of recurrence. |
| USS liver every 6/12 and CT every year. | Most common sign indicating recurrence was CEA elevation in both groups. | ||||
| In addition: Conventional: rigid sigmoidoscopy at each visit for those who had undergone surgery for rectal and sigmoid cancers, and a barium enema was done for all patients at 12 months and once a year thereafter; Intensive: colonoscopy 3 months after the surgery to ensure a clean colon and once a year thereafter on allpatients | |||||
| Ohlsson [20] | None/Control: No FU | - | Control: 33%; intensive: 32% | Control: 67%; intensive: 75% | Intensive follow-up did not improve survival. |
| Intensive: clinical exam, rigid sig, colonoscopy, CT pelvis (in patients with APR), pulmonary X-ray, liver function tests, CEA and faecal hemoglobin at 3-, 6-, 9-, 12-, 15-, 18-, 21-, 24-, 30-, 36-, 42-, 48-, and 60-month intervals | |||||
| Pietra [21] | Conventional: clinical exam + CEA and USS at 6/12 intervals for 1 year then annually thereafter. | Conventional: 20.2 ± 6.1; iIntensive: 10.3 ± 2.7 | Conventional:19.4%; intensive: 25.2% | Conventional: 58.3%; intensive: 73.1% | Intense follow-up leads to earlier detection of recurrent disease and improved survival. |
| All patients received yearly CXR, colonoscopy and CT. | |||||
| Intensive: As above, but with intervals 3/12 for 2 years then 6/12 for 3 years | |||||
| Primrose (FACS) [15] | Control: CT at 12–18 months or if symptomatic | - | Cancer recurrence in 16.6% of patients, 5.9% of these surgically treated with curative intent | Intensive follow-up (any group) detected recurrence earlier and increased rate of curative surgical treatment. No advantage when using CT and CEA in combination. Could not demonstrate survival advantage. | |
| Intensive: CT: Scan of the chest, abdomen, and pelvis every 6 months for 2 years, then annually for 3. CEA: CEA every 3 months for 2 years, then every 6 months for 3 years, with a single CT scan at 12 to 18 months if requested at study entry by hospital clinician. CT and CEA: Both of the regimes combined. | |||||
| All had colonoscopy at 2 and 5 years | |||||
| Rosati (GILDA) [18] | Control: Clinical review and CEA every 3 months for 2 years, then every 6 months for 3 years. Colonoscopy at 1 year. Liver USS at 4 months and 16 months. | Intensive surveillance had earlier detection of 5.9 months (95% CI, 2.71–9.11) | Overall recurrence rate: 20.4%; control: 18.7%; intensive: 22% | Control: 52.7%; intensive: 47.8% | Intensive surveillance detected recurrences earlier, but there was no difference in overall survival. Quality of life was not affected by surveillance strategy. |
| Intensive: Clinical review and CEA as per control group. CBC and CA 19-9 included with CEA. Colonoscopy and CXR every 12 months. Liver USS every 4 months for 16 months, then yearly | |||||
| Verberne (CEAWatch) [23] | Control: 5-year follow-up. Clinic every 6/12 for 3 years, then annually thereafter. Liver USS and CXR at each visit. CEA every 3 to 6 months for 3 years and annually thereafter. | Specific time interval not given; however, the authors stated that the time to diagnosis of recurrent disease decreased with the intensive follow-up protocol as compared to the control protocol (HR, 1.45; 95% CI, 1.08–1.95; P = 0.013) | Overall recurrence rate: 7.5%; control: 3.6%; intensive: 4.4% | No difference in OS or DFS between 2 arms. Survival significantly worse when detected by patients self-report rather than CEA or imaging. | An intensified protocol with CEA monitoring and assessment of CEA rise rather than absolute value detected recurrences earlier than the standard protocol. This does not affect overall or disease-free survival. |
| Intensive: bimonthly CEA and yearly imaging for 3 years. CEA every 3/12 for next 2 years. Annual clinic review with imaging of chest and abdomen for 3 years. If 20% increase in CEA, another blood sample was drawn 4 weeks later. If a consecutive rise, CT scan of chest and abdomen was advised. Normal value was considered to be ≤2.5 ng/mL | |||||
| Wille-Jørgensen (COLOFOL) [13] | Nonintensive: CT scan of liver and lungs (or CT of liver + plain X-ray of lungs) + CEA after 12 and 36 months. | - | - | - | Recruitment ended 2015. Results awaited. |
| Intensive: CT scan of liver and lungs (or CT of liver + plain X-ray of lungs) + CEA after 6, 12, 18, 24, and 36 months | |||||
| Lepage (PRODIGE 13) [14] | Standard: Abdo USS every 3/12 for 3 years, 6/12 for 2 years, then annually. CXR ever 6/12 for 3 years, then annually. | - | - | - | Recruitment ended. Results awaited |
| Intensive: A CT thorax/abdominal/pelvis alternating with abdominal USS every 3/12 for 3 years, then every 6/12 for 2 years. CEA every 3/12 for 3 years, then 6/12 2 years |
FACS, Follow-up After Colorectal Surgery; GILDA, Gruppo Italiano di Lavoro per la Diagnosi Anticipata; CEAWatch, Carcino-Embryonic Antigen Watch; CEA, carcinoembryonic antigen; CRC, colorectal cancer; CT, computed tomography; FU, follow-up; CXR, chest X-Ray; USS, UltraSound Scan; CBC, complete blood count; CI, confidence interval; HR, hazard ratio; OS, overall survival; DFS, disease-free survival.