Importance of findings on the initial evaluation for cancer in patients with symptomatic idiopathic deep venous thrombosis

Summary

Cancer is known to be a risk factor for deep venous thrombosis of the lower extremities (DVT). Similarly, DVT without obvious precipitating cause may be a marker for unrecognized cancer. How high is the risk of unrecognized cancer in patients with idiopathic DVT? What is the appropriate initial work-up of such patients? What is the subsequent incidence of cancer in these patients, after prevalent cancers have been diagnosed? This retrospective cohort study was designed to look at these issues.

Methods

• Subjects: Patients were chosen in order to compare those with symptomatic, idiopathic DVT to those with suspected DVT ruled out by duplex scanning. Adults who had undergone duplex scanning at Brigham and Women's Hospital (1990-1993) for suspected DVT were eligible.

• Exclusions: Secondary DVT (cancer, surgery, hypercoagulable states, pregnancy, oral contraceptives); duplex scanning for pulmonary emboli.

• Ultrasound: Duplex ultrasound scanning was performed to evaluate for deep venous thrombosis both above and below the knee.

• Data collection: This was a retrospective cohort study. Data was collected from medical records using standardized forms. For all patients, demographic data and smoking history were obtained. For patients hospitalized with DVT, an 86-item form was filled out by chart review that included items from the medical history, physical examination, routine labwork, chest x-ray, and the results of other procedures.

• Follow-up for cancer: Information on cancer incidence during follow-up was obtained primarily from computerized medical record review for members of one large HMO (54%) and from hospital chart review (38%).

• Analysis: Patients with DVT were classified according to the number of components on the initial evaluation (history, physical examination, labwork, chest x-ray) that were suggestive of cancer. Each component was considered suggestive if any of the following were present:
  History: weight loss, fatigue, unusual pain, fever in the absence of infection, change in bowel or bladder habits, abnormal bleeding, recent cough or hoarseness.

  Physical examination:abnormal abdominal examination, cervical lymphadenopathy, abnormal skin examination, abnormal lung auscultation.

  Labwork: anemia (hgb < 11.0 for women, 13.0 for men) or leucocytosis (wbc > 12.0).

  Chest x-ray: presence of mass, effusion or mediastinal lymphadenopathy.

• Patients: Out of 5797 venous ultrasonograms, 4811 were excluded primarily because of risk factors for DVT (3905) or because they were follow-up studies (830). The final cohort included 986 patients, 844 without DVT and 142 with DVT (119 with proximal DVT). Patients with DVT were older (56 vs 52 years), more likely to be male (55% vs 32%), and more likely to be current or former smokers (51% vs 41%).

• Follow-up: Of the 142 patients with DVT, 16 were found to have cancer on the initial hospitalization and 4 were lost to follow-up. The remaining 120 patients with DVT but no cancer on initial evaluation and the 844 patients without DVT were followed for a median of 34 months (95% of patients were followed for more than one year).

• Initial detection of cancer in patients with DVT: Of the 142 patients with DVT, 136 were hospitalized; of these patients, 16 were found to have cancer.

  All 16 patients with cancer had at least one abnormality among the four previously defined components of the initial evaluation (history, physical, laboratory, chest x-ray); 12 out of the 16 had anemia. Only 2 patients had only one abnormal component, 3 had 2 abnormal components and the remainder (11) had 3 or 4 abnormal components. Further work-up included imaging (CT or MRI) in 13 out of the 16 patients.

  None of the 56 patients who were negative for all four components were found to have cancer during the initial evaluation.

• Incidence of cancer during follow-up: During 34 months median follow-up, cancer incidence was 2.5% in patients with DVT and 2.7% in patients without a diagnosis of DVT.

  Since the patients with DVT had a much more detailed initial clinical evaluation than patients without DVT, some "incident" cases in the latter group might have been picked up earlier had they undergone the same investigations. Such cancers, which would have been picked up on initial evaluation, would be more likely to become apparent early during follow-up. To look at this possible source of bias, the authors also examined their numbers excluding patients without DVT whose cancers developed during the first 12 months of follow-up. This did not materially alter their results. Finally, the incidence of cancer in the two groups was found to be very close to that predicted for the age- and sex-matched US population at large.

The authors conclude that, based on their results (and on other data and consensus guidelines), the appropriate initial work-up for patients with idiopathic deep venous thrombosis of the legs should include a detailed history, physical examination, routine labwork, chest x-ray, urinalysis, stool for occult blood and mammography (where appropriate). More extensive investigation should be limited to and guided by abnormalities found on the above evaluation. They also conclude that, once prevalent cancers have been detected by the above work-up, the incidence of cancer during follow-up is not greater than in the general population.

They compare their results to other studies. A Scandinavian study of 1383 patients with DVT confirmed their finding that simple clinical and diagnostic methods were sufficient to detect prevalent cancers, but found that the incidence of cancer was higher during follow-up. A smaller cohort study, on the other hand, confirmed their finding that the incidence of subsequent cancer was not higher in patients with DVT. Several other studies did not confirm these results, however. The authors feel that these discrepancies may be due to improper selection of controls, to a heightened awareness of physicians in their study group of the association between DVT and cancer (leading to more careful clinical screening), and to a lack of adjustment for smoking in some of the other studies (patients who smoke have both a higher incidence of cancer and of DVT).

Comment

The second comment relates to the results themselves. Only 56 out of 142 patients with DVT had no abnormalities on the four components of the initial evaluation. This means that, based on this study, only 39% of patients with DVT would be eligible for "no further work-up". Over 60% would require further evaluation. This represents a fairly large number of patients.

Finally, on a more philosophical note, we live in a time when the cry of "where's the evidence?" meets the cost-cutting imperatives of managed care. Studies demonstrating that expensive diagnostic tests are not supported by evidence are increasingly in vogue, and we can expect to see more of them in the future. We need to subject them to the same scrutiny as those reporting a benefit from new, expensive, diagnostic and therapeutic strategies.

November 26, 1996

Reader comments

The following responses were submitted by Dr. Jacques Cornuz, first author of the article:

1. Methodological standpoint

The four items were designed before the study was carried out. However, we do believe that our results must be confirmed by a prospective study.

2. Results

I agree that, based on our study, about 60% of patients with DVT would be eligible for further workup. However, 60% is considerably less than all patients, i.e. 100%.

3. Philosophical note

I do agree with this point. However, in the recent past, scrutiny was not always met in clinical cancer screening, e.g., in screening for prostate cancer with prostatic specific antigen.

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