Number of cases
Test items and frequency of the intensive follow-up group
Test items and frequency of the control group
Makela et al.
Visit one time every 3 months for the first 2 years and then one time every 6 months later: examine the body, whole blood, fecal occult blood test (FOBT), CEA level, and chest X-ray film. Colonoscopy every year, sigmoidoscope examination every 3 months for the sigmoid colon and rectal cancer patients, and liver ultrasound every 6 months. All the patients will be followed up for 5 years
Visit one time every 3 months for the first 2 years and then one time every 6 months later: examine the body, whole blood, fecal occult blood test (FOBT), CEA level, and chest X-ray film. Barium enema every year. Rigid sigmoidoscope examination every 3 months for the rectal cancer patients. All patients were followed up for 5 years
Ohlsson et al.
Visit one time every 3 months for the first 2 years and then one time every 6 months later: examine the body, rigid sigmoidoscopy, liver function tests, fecal occult blood test (FOBT), CEA level, and chest X-ray film. Colonoscopy at the third, fifth, 30th, and 60th months; CT examination in the third, sixth, 12th, 18th, and 24th months; all patients were followed up for 5 years
No systematic follow-up. Guide the patient to leave the specimens for fecal occult blood test every 3 months at the first 2 years, once every year. all the records of patients will be kept for 5 years
Schoemaker et al.
Visit one time every 3 months for the first 2 years and then one time every 6 months later: examine the body, whole blood, liver function, fecal occult blood test II. Annual chest X-ray inspection and liver CT. Colonoscopy every year
Visit one time every 3 months for the first 2 years and then one time every 6 months later within 5 years: examine the body, whole blood, liver function, fecal occult blood test (FOBT). The CEA test, but not used to start further examination. 94 % of the patients were followed up for 5 years
The CEA test, but not used to start further examination. 94 % of the patients were followed up for 5 years
Pietra et al.
Visit one time every 3 months for the first 2 years and then one time every 6 months in the following 3 years and then once every year; physical examination, liver ultrasound, and CEA level. Annual chest X-ray inspection and CT and colonoscopy. All patients were followed up for 5 years
Visit one time every 6 months for the first year and then one time every year: physical examination, liver ultrasound, CEA level. Annual chest X-ray inspection and colonoscopy. All patients were followed up for 5 years
Kjeldsen et al.
Psychical examination, digital rectal examination, gynecological examination, occult blood test II, whole blood, ESR, liver function, chest X-ray, colonoscopy; visit one time every 6 months for the first 3 years and then one time every 12 months in the following 2 years and then once every year; 79 % of the patients were followed up for 5 years
Psychical examination, digital rectal examination, gynecological examination, occult blood test II, whole blood, ESR, liver function, chest X-ray, colonoscopy in the fifth and tenth years. 73 % of patients were followed up for 5 years
The average time of initial recurrence of the colorectal cancer patients in the intensive follow-up group and the control group (months)
Intensive follow-up group
Makela et al.
Ohlsson et al.
Schoemaker et al.
Pietra et al.
Kjeldsen et al.
Since the diagnostic examination methods for follow-up of all clinical trials are different, i.e., CT or frequent serum detection method CEA or both of them, they possibly have greater impact on the improvement of the survival of the patients with colorectal cancer compared with the direct examination of mucosal lesions (such as colonoscopy) strategy for the early detection of recurrence outside the mucosa (i.e., local pelvic recurrence and isolated liver metastases). The results of subgroup analysis are consistent.
18.104.22.168 Follow-Up and Survival Rate
Whether the intensive follow-up can improve the survival rate of the patients with colorectal cancer is controversial. Sugarbaker et al.  and Safi and Beyer  strongly supported that the intensive follow-up and early intervention can reduce the number of deaths of patients. Cochrane et al.  and Ballantyne et al.  questioned about the value of the follow-up. But they are not proven by randomized clinical trials. Until 1994, Bruinvels et al. [38, 39] provided rational data through meta-analysis of seven nonrandomized studies (more than 3,000 cases). The study showed that in the intensive follow-up group, there were more cases of asymptomatic recurrence and re-resection, but there was no difference in the survival rate between the two groups. But in the test including carcinoembryonic antigen (CEA) analysis, the 5-year survival rate in the intensive follow-up group increased by 9 %, and the author was cautious to explain these data and believed there may be deviation in values. Some studies [40, 41] showed that the intensive follow-up was ineffective and costly.
Northover et al.  randomly divided the patients after radical surgery into the intensive follow-up group and the control group and tested the CEA. In the intensive follow-up group, if the CEA level is elevated, further observation should be conducted; and after an appropriate period, patients should receive another examination. Through the preliminary analysis, there was no difference of the survival rate between two groups.
The studies conducted by Makela et al. , Ohlsson et al. , Schoemaker et al. , and Kjeldsen et al. , respectively, showed that the recurrence rate between the two groups was similar. The tumor recurrence in the intensive follow-up group was 9 months earlier on average, and more patients underwent the secondary radical surgery; but there was no difference of the overall survival rate or tumor-related survival rate between the two groups.
But Andrew et al. concluded that the intensive follow-up can improve the 5-year survival rate after systematic review and meta-analysis on the five groups of randomized clinical trials, although the past clinical trials cannot determined that due to too small samples. They believed that the mortality of patients with the modern follow-up program (including CT or regular serum CEA or both for the detection of recurrence outside of the mucous membrane, i.e., local pelvic recurrence and isolated liver metastasis) was absolutely decreased by 9–13 % compared with the direct examination of mucosal lesions (such as the use of colonoscopy). In contrast, this improvement is more beneficial to the patients of adjuvant chemotherapy in the stage of Dukes C that reduces the mortality rate of 5 %, and it is applicable to different stages of colorectal cancer.
As early as 1999, Howell et al.  also believed that the tests conducted by Makela et al., Ohlsson et al., and Schoemaker et al. may be based on a wrong premise, that is, the intensive follow-up can discover the recurrent tumor in the following radical surgery. However, the above tests showed that although the intensive follow-up can help to observe more asymptomatic recurrence and has more opportunities for surgical resection, there was no difference in the survival rate or the tumor-related survival rate. Howell et al. suggested that since the most frequent part of recurrence and metastasis of the colorectal cancer is the liver, it is necessary to strengthen the follow-up of the liver imaging in the first 3 years in addition to the observation of the local and regional recurrences, so as to discover the effective liver metastasis that can be resected and chemotherapy, to enhance the survival rate.
Therefore, the multidisciplinary treatment of colorectal cancer is strengthened at present, including extensive application of liver resection, the pelvic exenteration for the pelvic cavity recurrence, and the combined therapy for the advanced diseases. All these methods will affect the survival, and on the basis of them, it is more beneficial to strengthen the follow-up.
20.3.2 Develop the Follow-Up Program
The development of the follow-up program of the colorectal cancer patients should be based on the staging, prognosis factors, and whether or not accept postoperative auxiliary treatment. The frequent follow-up will not only waste the medical resources but also increase the psychological burden of patients. So what kind of follow-up is useful?
22.214.171.124 Basis for the Development of the Follow-Up Program
To develop an ideal follow-up plan for the colorectal cancer patients, the physicians shall be aware of (1) which type(s) of colorectal cancer patients are mostly likely to occur recurrence and metastasis, (2) which period that these patients are most likely to occur recurrence and metastasis, and (3) the most likely sites for recurrence and metastasis (see the relevant chapters).
Second, it is required to identify the following: (1) Can the local recurrence and early discovery of metastasis increase the probability of cure (this has been confirmed from the above)? (2) Can the treatment after the follow-up reduce the colorectal cancer mortality or overall mortality? (3) Which kind of examination method is required to achieve the above purpose? Is the costs and efficiency reasonable? (4) To answer the above questions, how does one determine the moral baseline for the design of the control group, particularly under the conditions that the current studies support to improve the living through intensive follow-up?
126.96.36.199 The Development of the Follow-Up Plan
The development of the follow-up plan is easily affected by the individual subjective thinking. Kievet and Bruinvels  proposed four conditions for the practicality of routine follow-up:
At least some lesions can be limited and of curative treatment. The recurrence process includes no lesions observed, subclinical lesions that can be observed, curable symptoms, palliative resection, and unresectable lesions. But the recurrence of curable colorectal cancer is not usually a time-dependent process.
The follow-up should be able to discover the curable recurrence and, under the ideal situation, do not wait until the incurable stage.
Follow-up should help to improve life expectancy and have more curable resection. The follow-up should not produce worthless findings that are incurable, do not improve the mortality rate, and are false-positive results by the re-surgery.
Cost-efficiency ratio should be of assistance for the adjustment of the conventional follow-up methods.
The development of the most effective follow-up plan should refer to a large number of literatures and be based on the multicenter randomized controlled clinical trials. The follow-up contents, intensity, costs, etc., should be described in details, and different results should be compared to obtain the best follow-up plan, but the benefits from the follow-up and excessive unnecessary financial burden of patients should be avoided.
188.8.131.52 Establishment of the Follow-Up Frequency and System
After the initial treatment of colorectal cancer, the discovery of the recurrence through the follow-up still lacks of sufficient and ideal proofs. To obtain follow-up, the efficiency results of effective plan, different methods and intensities, and the multicenter randomized clinical trials should be conducted.
In the early period of postoperative follow-up of colorectal cancer, it is necessary to focus on the postoperative rehabilitation and further treatment plan (including possible adjuvant therapy and stoma treatment), and at this time, patients should receive spiritual comfort and practical medical support. For the patients of colorectal cancer, the importance of the psychological factors remains unclear. But for the patients who underwent Miles and pelvic resection, the acceptance of the artificial anus or urethrostomy will affect the effect of further treatment; at this time, the psychological support is absolutely vital. Besides, the patients should receive the knowledge about the symptoms associated with the tumor recurrence so that they can be treated at the time of relevant symptoms. The patients should also be aware that the risk of recurrence will rapidly drop 2 years after treatment and very small 5 years after treatment; in this way, the patients are comforted in the mind and minimize their psychological pressure.