In this retrospective study, malignancy was detected in 9.4 % of the patients with idiopathic venous thromboembolism in the first year following thrombosis, compared with 1.9 % in the general population, taking account of age, gender distribution and geographical factors. There was no difference in age, gender or thrombosis location among those in whom occult malignancy was detected and those in whom it was not detected. The limited malignancy screening after detection of idiopathic venous thromboembolism which is used at Bærum Hospital had a high negative predictive value (99 %).
The incidence of occult malignancy in patients with idiopathic venous thromboembolism in our study was of the same order of size as that reported in international literature (3, 6) – (14, 20). As far as we are aware, similar surveys from Norway have not been published previously. In contrast to the findings of a number of other studies, we found no difference in age distribution between those who developed cancer during the first year and those who did not. This indicates that malignancy screening should not only be carried out for the over 60s age group, as some have proposed (6, 21, 22). As we did not find any differences between men and women either, both genders should be screened to the same extent.
Earlier studies have indicated that the location of the thrombosis has a bearing on the the probability of underlying malignancy (22, 23) and that certain types of cancer are more strongly associated with venous thromboembolism than others (4, 21, 24). We found no evidence of this in our material. The number of cases of occult malignancy in our study is so limited that we cannot attach great statistical weight to this, but since the cancer cases are so different, we cannot simply disregard any particular organs.
Extended screening strategy normally implies CT thorax and abdomen in addition to endoscopy. Ultrasound scanning of the abdomen, which was widely used earlier, has proved of limited use in malignancy screening (25). CT scanning of the thorax and abdomen is probably the most useful radiological examination. However, the radiation stress may be substantial, and the scan is resource-intensive for both the health service and the patient (25) – (27).
Thorough cost-benefit analyses of extended malignancy scanning are complicated. Few studies, not including ours, have been conducted to this end, and cost estimates appear to vary from one country to the next (25, 28). The largest and most recent study on the topic concluded that financial results cannot really be made the basis for a cost-benefit analysis (29). The costs are affected by the many false positive findings of extended screening that made further work-up necessary.
False positive findings were made in 98 of the patients in our study. The extra burden this implies should be in focus when determining the extent of the screening that should be chosen (30).
There is sound evidence to indicate that extensive screening for malignancy in cases of idiopathic venous thromboembolism would detect more cases of cancer earlier (6, 28). However, it is still unclear from relevant literature whether such screening has an acceptable cost-benefit ratio when the burden on the whole patient group and the health service is weighed up against the number of patients with an improved prognosis and reduced mortality.
Doubt has been expressed as to whether earlier detection of occult cancer actually yields any prognostic gain, because in most cases the cancer has already reached an advanced stage when idiopathic venous thromboembolism is identified (9, 31). In our study, occult cancer was detected in three patients after limited screening had not revealed signs of malignancy. We cannot exclude the possibility that early diagnosis could have been of significance to the prognosis of some of them, which could weigh in favour of more extensive screening of all patients. However, the large number who would have to be examined, and the radiation strain the whole group would be subjected to, weighs against extensive screening of all patients.
The only randomised study comparing extensive screening with no screening for occult malignancy showed that occult malignancy could be detected at an earlier stage, but provided no clear answer as to whether this was of significance for the prognosis (19). The study raised a number of ethical questions with respect to how the control group should be handled as regards information, and many of the patients in the control group were given more extensive screening than they should have been because some doctors believed it would be unethical not to do so. The study was also discontinued after five years, with 201 included patients of the planned total of 1 000. This means that the results are difficult to interpret.
The high incidence of occult cancer underscores the importance of having an effective malignancy screening plan. It is especially important these days, when more responsibilities are being transferred from the specialist health service to the primary health service as a result of the Coordination Reform, and when new oral anticoagulants are being introduced (9). Both these factors will lead to more outpatient treatment of patients with venous thromboembolism. Many will probably only have one outpatient visit to the hospital in the acute phase before being transferred to the primary health service for further follow-up. Tasks such as malignancy screening will therefore to a large degree have to be taken over by primary doctors.
Our study has its limitations. It was not conducted prospectively with a view to detecting occult cancer. However, screening of patients with idiopathic venous thromboembolism has been described in detail in procedures, and records of the time of diagnosis have been systematically kept by a competent group of doctors and nurses at the Thrombosis Clinic, Bærum Hospital.
We cannot exclude the possibility that those who did not answer the questionnaire on their state of health after having venous thromboembolism may have been found to have cancer without our learning of it. But patients in Asker and Bærum all have Bærum Hospital as their primary hospital, so that most cases of cancer would have been referred there. If there have been more cases of cancer than those we have registered, it means that the incidence of occult cancer is even higher than the 9.4 % we have found, and that the limited screening may have missed cases other than the three we have registered.