Page 19 - JCTR-11-4

Journal of Clinical and
Translational Research Hidden cancer after VTE

follow-up, malignancy was diagnosed in 3.7% and 5.0% of that compared extensive versus limited screening for
the extensive and limited screening groups, respectively. occult malignancy after an unprovoked VTE, as well as
In the extensive screening group, 26 patients (7.6%) died five observational prospective studies that evaluated a
compared with 24 (8.3%) in the limited screening group comprehensive strategy lacking a control group. 20-22,24,25
(hazard ratio [HR]: 1.22; 95% CI: 0.6 – 2.2). Among these Among 2621 patients included, we estimated the
deaths, 17 (5.0%) in the extensive screening group and 24-month prevalence of occult cancer detection to be 8.2%.
8 (2.8%) in the limited screening group were cancer-related About two-thirds of these cases were detected by screening
(HR: 1.79; 95% CI: 0.7 – 4.3). tests, whereas the remaining one-third became clinically
In a pilot study, the use of PET/CT to screen for occult overt during follow-up. The pooled analysis of the RCTs
malignancy in 40 patients with unprovoked VTE was demonstrated that the probability of a cancer diagnosis
prospectively investigated . All patients were initially was strongly associated with extensive screening. At initial
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screened for occult malignancy with a focused history, screening, a comprehensive strategy detected more than
physical, and laboratory evaluation. Patients underwent twice as many occult cancer cases compared to a limited
whole-body PET/CT and were followed for up to 2 years. test. Moreover, there was a strong trend towards a diagnosis
PET/CT imaging identified abnormal findings requiring of early-stage cancer in the extensive screening group
additional assessment in 62.5% of patients (25 out of when data from RCTs was analyzed separately. However,
40 patients). Among them, only one patient had confirmed no statistically significant difference was observed in
cancer. No patients with a negative PET/CT were diagnosed cancer- and overall-related mortality.
with malignancy during the follow-up. Early detection of an occult malignancy after a
In the Alfonso et al. study, patients ≥50 years old with diagnosis of unprovoked VTE might be translated to
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a first unprovoked VTE episode underwent screening for a better prognosis for these patients; nevertheless, the
occult cancer with PET/CT, which was performed 3 – optimal screening strategy remains unclear. At present,
4 weeks after the VTE event. Clinical follow-up continued there is no evidence that testing for undiagnosed cancer
for 2 years. The PET/CT was negative in 68 out of in patients with a first episode of unprovoked VTE is
99 patients (68.7%), while suspicious uptake was detected effective in reducing cancer- and overall-related mortality
in 31 out of 99 patients (31.3%). Additional diagnostic or which tests for cancer are most helpful. On the other
work-up confirmed a malignancy in 7 out of 31 patients hand, two rules have been developed for occult cancer
(22.6%), with six at an early stage. During follow-up, screening in patients with VTE: The RIETE and SOME
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two patients with negative PET/CT were diagnosed with scores. Jara-Palomares et al. identified six independent
cancer. The sensitivity, positive predictive value, and predictors (RIETE score) of occult cancer between 30 days
negative predictive value of PET/CT were 77.8%, 22.6%, and 24 months after experiencing the VTE (provoked
and 97.1%, respectively. or unprovoked): male sex, age >70 years, chronic lung
disease, anemia (hemoglobin levels <13 g/dL for men
In these studies, 3.6% (35 out of 977) of patients and <12 g/dL for women), elevated platelet count (≥350,000
were diagnosed with cancer at initial screening, and 36 platelets/mm ), prior VTE, and recent surgery. Ihaddadene
3
additional cases (3.7%) were detected during follow-up. et al. performed a post hoc analysis of the SOME trial.
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In the analysis of the studies with available data, cancer- They found that age ≥60 years, previous provoked VTE,
related mortality was 2.7% (25 out of 926), and the overall and current smoker were associated with occult cancer
mortality rate was 8.4% (69 out of 819). detection within 1 year of a diagnosis of unprovoked
Regarding the risk of bias, only the study by Van VTE. These rules are a potentially attractive strategy for
Doormaal et al. included a cohort of unexposed patients occult cancer screening in patients with VTE; however,
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(limited tests). The studies by Jara-Palomares et al. and both scores’ predictive performance was poor in external
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Rieu et al. were considered unrepresentative of the case validation studies. 28-32
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sample as they included only patients with PE and aged over The results of our study are in accordance with previous
70 years, respectively. Therefore, all studies were considered meta-analyses. 11,33,34 Klein et al. and Robertson et al. did
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to have a moderate risk of bias, except the study by Van not include the observational prospective studies in their
Doormaal et al., which was regarded as low risk (Table 5). meta-analysis, and in another meta-analysis of individual
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11
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4. Discussion patient data, the trial conducted by Piccioli et al. was
not included. Our study strengthens the results of previous
This systematic review compiled four RCTs. 16-19 and one meta-analyses, yet, it is more extensive and includes more
prospective open-label study without randomization studies and patients.
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Volume 11 Issue 4 (2025) 13 doi: 10.36922/jctr.24.00069