Occult cancer‐related first venous thromboembolism is associated with an increased risk of recurrent venous thromboembolism

Abstract

Background Although venous thromboembolism (VTE) is associated with a high recurrence rate, the absolute recurrence rates for cancer-related VTE, particularly occult cancer, are not well known. Objectives To investigate the risk of VTE recurrence in patients with occult and overt cancer-related VTE. Methods Incident VTE events among participants of the first to sixth Tromsø surveys occurring in the period 1994-2012 were included. Occult cancer was defined as cancer diagnosed within a year following a VTE, and overt cancer was defined as cancer diagnosed within the 2 years before a VTE. Results Among 733 patients with incident VTE, 110 had overt cancer and 40 had occult cancer. There were 95 recurrent VTE events during a median of 3.2 years of follow-up. The 1-year cumulative incidence of VTE recurrence was 38.6% in subjects with occult cancer, 15.5% in subjects with overt cancer, and 3.8% in non-cancer subjects. The 1-year risk of recurrence was 12-fold (hazard ratio [HR] 12.4, 95% confidence interval [CI] 5.9-26.3) higher in subjects with occult cancer and four-fold (HR 4.3, 95% CI 2.0-9.2) higher in subjects with overt cancer than in non-cancer subjects. The occult cancers associated with VTE recurrence were typically located at prothrombotic sites (i.e. lung and gastrointestinal) and presented at advanced stages. The majority (69%) of recurrences in subjects with occult cancer occurred before or shortly after cancer diagnosis, and were therefore not treatment-related. Conclusion Our findings suggest that the increased risk of recurrence in patients with occult cancer is mainly attributable to the advanced cancers in these patients.

Prothrombotic genotypes and risk of venous thromboembolism in occult cancer

“…The main strengths of our study include the prospective design with participants recruited from the general population, large number of genotyped subjects, long-term follow-up and thorough assessment of both VTE and cancer. In agreement with previous studies, we confirmed that 5% of the VTE events were related to occult cancer [7][8][9][10][11][12], and similar anatomical sites for cancers [2,5,7,[13][14][15], and degrees of metastatic diseases were found in VTE-patients with occult cancer [5,14,16], which supports a high external validity. Some study limitations must be addressed.…”

“…occult) cancer [4][5][6], and approximately 5% of patients with unprovoked VTE are diagnosed with cancer within the first year following a VTE event [7][8][9][10][11][12]. VTE patients with occult cancer are more often diagnosed with prothrombotic cancers such as pancreatic, lung, gastrointestinal and hematological cancers [2,5,7,[13][14][15], and more advanced stages (higher degree of regional and distant metastasis) at the time of cancer diagnosis [5,14,16].…”

Bidirectional risk between venous thromboembolism and cancer in East Asian patients: synthesis of evidence from recent population-based epidemiological studies

“… 28 The Tromso survey of 733 Norwegians found that the incidence of occult cancer after VTE was 5.5 per 100 patient-years during a 1-year follow-up. 29 The IR of cancer in Taiwanese patients with unprovoked VTE was estimated at 2.2–4.5 per 100 patient-years ( Table 2 ). 10 , 30 …”

Hypercoagulable States and Thrombophilias: Risks Relating to Recurrent Venous Thromboembolism

“…The majority (69%) of recurrences in subjects with occult cancer occurred before or shortly after cancer diagnosis, and was therefore not treatment related. 27 Guidelines from the ACCP (Grade 2C), 7 a guidance document by the International Society on Thrombosis and Haemostasis (ISTH), 28 a guidance document by Anticoagulation FORUM, 29 and an informal suggestion from the American Society of Clinical Oncology (ASCO) 30 recommend the use of LMWH in cancer patients with VTE. The recommendations or suggestions are based on the superior efficacy of LMWH compared with VKAs in patients with cancer and mainly a first VTE.…”