Background It is unclear how frequently unprovoked venous thromboembolism (VTE) reflects the presence of an occult cancer. Methods The California Cancer Registry was used to identify diagnosed cases of 19 common malignancies during a 6-year period. Cases were linked to a hospital discharge database to identify incident VTE events in the year before the cancer diagnosis date. The standardized incidence ratio (SIR) of unprovoked VTE was determined by using the age-, race-, and sex-specific incidence rates in California. Results Among 528 693 cancer cases, 596 (0.11%) were associated with a diagnosis of unprovoked VTE within 1 year of the cancer diagnosis, compared with 443.0 expected cases (SIR, 1.3; 95% confidence interval, 1.2-1.5; P<.001). Among cases with metastatic-stage cancer, the SIR was 2.3 (95% confidence interval, 2.0-2.6; P<.001), whereas for all other stages, the SIR was 1.07 (95% confidence interval, 0.97-1.18; P = .09). The incidence of preceding VTE was increased over that expected only during the 4-month period immediately preceding the cancer diagnosis date (P<.001). Only 7 cancer types were associated with a significantly elevated SIR: acute myelogenous leukemia; non-Hodgkin lymphoma; and renal cell, ovarian, pancreatic, stomach, and lung cancer (SIR range, 1.8-4.2). Conclusions In the year preceding the diagnosis of cancer, the number of cases with unprovoked VTE was modestly higher than expected, and almost all of the unexpected VTE cases were associated with a diagnosis of metastatic-stage cancer within 4 months. Given the timing and advanced stage of the unexpected cases, it is unlikely that earlier diagnosis of these cancers would have significantly improved long-term survival. When a patient develops acute venous thromboembolism (VTE), physicians commonly try to determine whether there is an underlying condition or risk factor associated with the thrombotic event. Patients with a provoking risk factor, such as recent trauma, major surgery, or immobility, have a better long-term prognosis with a lower incidence of recurrent VTE than patients who present with unprovoked VTE.1 In the absence of an obvious provoking risk factor, the presence of an underlying malignancy is often considered.2,3 This is because some types of cancer appear to be able to initiate or trigger a thrombotic diathesis through a number of mechanisms, which have been recently reviewed.4,5 Several cohort studies have suggested that the incidence of cancer among patients who present with unprovoked VTE is more than 3 times higher than among patients with a provoked VTE,6- 12 and there is evidence that more than 40% of these cancers are metastatic at the time of diagnosis.13 It is not clear what percentage of patients with unprovoked VTE harbor an asymptomatic occult malignancy. Several studies have shown that approximately 8% to 12% of patients who presented with acute VTE were diagnosed as having cancer after a relatively simple medical evaluation based on symptoms and routine laboratory testing.6,14 However, these patients did not have truly occult cancers because the malignancies were readily diagnosed. Some recent studies suggest that intensive cancer screening in patients with VTE does lead to the detection of more difficult-to-diagnose cancers,15,16 but it is still not clear whether the incidence of cancer in these patients is higher than expected, nor whether the detection of these occult cancers improves morbidity or survival.17- 19 If patients with unprovoked VTE have a higher-than-expected standardized incidence of cancer in the ensuing year, then patients with cancer would be expected to have a corresponding increase in the standardized incidence of unprovoked VTE in the year before the cancer diagnosis. Using a large cancer registry linked to a comprehensive hospital discharge database, we determined the incidence of unprovoked VTE during the 1-year period immediately preceding the diagnosis of 19 common types of cancer and compared this with the expected incidence of unprovoked VTE in the general population.
