© Borgis - New Medicine 4/2005, s. 57-59
Eryk Chrapowicki, Grzegorz Krasowski
Follow-up of patients with curatively resected colorectal cancer – a literature review
General Surgery Department Wolski Hospital Warsaw, Poland
Head of Department: Marek Kruk, MD, PhD
Follow-up of patients with curatively resected colorectal cancer is an integral part of the total long-term treatment of this group of patients. In this review current recommendations of oncologists and surgeons concerning postoperative management and controversial opinions of specialists interested in the therapy of patients with colorectal cancer published in the literature are described.
Colorectal cancer is one of the most frequent cancers in Poland, but it is often discovered relatively late. During the past 60 years colon cancer incidence in Poland has increased threefold. According to the latest figures of the Oncology Institute in Warsaw, it takes the third position among neoplasm-connected mortality causes both in males and in females. Approximately 11 thousand new cases are diagnosed in Poland annually (in EU countries approx. 220 thousand.). The morbidity increases with age (above 50 years old). The number of deaths due to this disease reaches 8 thousand in Poland (in the EU approx. 112 thousand) . Recurrence of the disease is estimated to occur in 40% of operated patients. This index reveals the low efficacy of treatment, especially as the number of operated subjects surviving more than 5 years is 25% maximum . The problem of proper monitoring after colorectal cancer resection has been widely discussed in recent years. Firstly, properly performed post-operative monitoring allows a recurrence of the disease to be discovered and treated early enough or the chemotherapy treatment to be changed. It also enables patients in advanced stages of the disease to be selected and palliative care to be started. What is also important, such postoperative monitoring allows metachronous cancer foci to be discovered and any residual or new polyps in the colon to be observed. It also plays an important role in discovering other types of cancer, which has been proved to occur more frequently in patients with colon cancer. However, the high costs connected with carrying out many specialist procedures and the limited usefulness of some of them are obvious. Consequently, the determination of standards based on EBM rules that might be used in daily clinical practice has become essential.
The aim of this work is to describe current ASCO (American Society of Clinical Oncology) and ESMO (European Society for Medical Oncology) recommendations with modifications and opinions published in the literature of experts and clinicians interested in the subject.
Material and method
Cochrane, Medline and Medscape 2000-2005 data were searched using such terms as colon cancer, follow-up, monitoring, clinical recommendation; and metaanalysis and prospective clinical trials were chosen.
Results and discussion
According to the ASCO expert panel recommendations, the ideal test should be:
1) sensitive enough to detect a neoplasmatic change that could be treated radically,
2) reliable and credible,
4) easy to perform.
The basic question is still the frequency and intensiveness of the recommended examinations.
The available prospective clinical trials assessing the influence of accessory follow-up examinations did not show (besides one) a higher survival rate. The meta-analyses that have been carried out so far show slightly more positive results where the higher frequency of check-up examinations correlated with a slightly higher survival rate . The presently valid control schemes should take into account the difference in the biology of rectal and colon cancers – their different dynamics, the type of recurrence and localization of primary metastases. The well-known facts prove that distant metastases occur more often in colon cancer, whereas local recurrence occurs more often in rectal cancer. Metastases should be searched in the liver in the former and in the vertebrae or lungs (via paravertebral veins) in the latter. It is also known that preoperative radiotherapy improves the results of therapy in rectal cancer, reducing the number of endoscopic examinations that have to be carried out after the operation. The economical aspect is also important. No randomized prospective trials concerning this problem have been found. However, the reports of Graham et al.  concerning the costs of treating post-resection recurrence should be taken into consideration. The cheapest of all diagnostic tests was certainly CEA assay ($5500 for one recurrence vs colonoscopy $45,000) . In all cases the most frequent, the cheapest and most based on GCP (good clinical practice) method of post-resectional follow-up procedure is cyclic physical examination and medical history. Despite the lack of evidence in the literature that clinical investigation alone improves the detectability of recurrences, both ASCO and ESMO guidelines underline its importance as the indispensable factor making possible the coordination of other tests and examinations executed in the patient, more than once contributing to detection of other diseases (also neoplasms). Regular visits also improve the patient´s frame of mind and encourage further, regular inspections. Among all blood tests, morphology, aminotransferase level and standard biochemical assays are useless in early detection of metastases and consequently should not be performed as a routine.  ASCO recommends monitoring CEA level every 2-3 months for the first 2 years after operation, and thereafter once a year. The European recommendations are somewhat different: CEA level monitoring every 3-6 months for the first 3 years after the operation and every 6-12 months later on. Despite this, the real value of this most widely used test is still controversial. Based on results of examinations from years 1999-2002, CEA seems to be the cheapest and most effective laboratory test.  Thus it can detect a recurrence of the disease much earlier than other tests and examinations. Unfortunately, the progression of the recurrence does not allow for R0 operation (trial NT 0089). Consequently, it does not result in prolonging the survival time. The Langerbrot examination authors tried to estimate the number of patients in whom the R0 operation was still possible. The estimated number was not higher than 12% of all observed patients. Unfortunately, the examiners did not follow the further history of these patients. It should also be underlined that around 30% of recurrences do not cause elevation of CEA level at all, and this happens especially in the group of low-differentiated tumours (G3). However, CEA assay is still the least controversial of all the recommendations and its elevation is an indication for more advanced diagnostic procedures, which means radiological methods first of all. Both ASCO and ESMO recommendations underline abdomen CT efficacy in recurrence diagnosis in patients with elevated CEA level. The experts are also strongly against the routine use of CT in order to detect recurrence. The available examination results show that the percentage of tumours which were primarily resective based on CT results was not higher than 12%. Shoemaker et al.  proved that yearly abdomen CT leads to higher asymptomatic tumour detection but similarly leads to partial liver resection in a similar number of patients as in the group where screening was done based on CEA level. The next group is endoscopic examinations. However, endoscopic follow-up after colon resection and anterior rectal resection should be distinguished. In the former group recurrences in the anastomosis site are rare and the examination important for metachronous cancer and polyp detection; in the latter group local recurrence is relatively frequent. ASCO experts recommend colonoscopy in all the patients every 3-5 years after the operation. Ideally, the first one should be performed either before the treatment or intraoperatively, which enables better operation planning (increase of operation range). In other cases it should be carried out within 6 months after the operation. According to examination results, it is sufficient to perform colonoscopy every 5 years. Then the percentage of detected changes is exactly the same as in the cases when colonoscopy is carried out every 3 years . Nevertheless, the danger of metachronous cancer development in the remaining colon part is low – around 0.35% per year , in contrast with metachronous polyp development (more than 50% as estimated by Chen and Stuart) . In patients cured of colorectal cancer the risk of developing metachronous cancer increases. It can develop for 10-12 years in 2-4% of patients . Some authors recommend yearly endoscopic examinations if villosum adenoma larger than 1 cm is detected . Whether to carry out proctoscopy or not after rectal resection is still controversial. It was thought that this examination should be performed often, even every half a year. However, this procedure turned out not to prolong survival time. Endoanal ultrasonography is supposed to raise the sensitivity of diagnosis. Along with the development of oncology and surgical procedures that use preoperative irradiation and TME (Total Mesorectal Excision) technique as a rule, the ASCO  experts believe that regular colonoscopy performed as often as in the case of colon operations should be sufficient. ESMO standards  however are much stricter and recommend performing rectosigmoidoscopy every 6 months for the first 2 years after the operation.
Despite many schemes of postoperative monitoring, there are still many controversies. The exact type and number of examinations that should be carried out is still a problem. Moreover, the coexistence of other diseases and the age of the patients is not usually considered. There are no prospective trials on representative groups of patients that could evaluate how useful such tests as determination of monoclonal antibodies or PET techniques could be in this case. What the indication for using such expensive tests should be and whether they really prolong survival after colorectal cancer operations is still questionable. Independently of the hopes connected with the continually developing possibilities of the oncological and surgical treatment of distant metastases, the question of the most effective systematic postoperative monitoring is not answered and is even becoming more and more pressing.
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