The Potential Clinical and Economic Value of Primary Tumour Identification in Metastatic Cancer of Unknown Primary Tumour: A Population-Based Retrospective Matched Cohort Study

Abstract

PurposeSeveral genomic tests have recently been developed to identify the primary tumour in cancer of unknown primary tumour (CUP). However, the value of identifying the primary tumour in clinical practice for CUP patients remains questionable and difficult to prove in randomized trials.ObjectiveWe aimed to assess the clinical and economic value of primary tumour identification in CUP using a retrospective matched cohort study.MethodsWe used the Manitoba Cancer Registry to identify all patients initially diagnosed with metastatic cancer between 2002 and 2011. We defined patients as having CUP if their primary tumour was found 6 months or more after initial diagnosis or never found during the course of disease. Otherwise, we considered patients to have metastatic cancer from a known primary tumour (CKP). We linked all patients with Manitoba Health databases to estimate their direct healthcare costs using a phase-of-care approach. We used the propensity score matching technique to match each CUP patient with a CKP patient on clinicopathologic characteristics. We compared treatment patterns, overall survival (OS) and phase-specific healthcare costs between the two patient groups and assessed association with OS using Cox regression adjustment.ResultsOf 5839 patients diagnosed with metastatic cancer, 395 had CUP (6.8%); 1:1 matching created a matched group of 395 CKP patients. CUP patients were less likely to receive surgery, radiation, hormonal and targeted therapy and more likely to receive cytotoxic empiric chemotherapeutic agents. Having CUP was associated with reduced OS (hazard ratio [HR] 1.31; 95% confidence interval 1.1–1.58), but this lost statistical significance with adjustment for treatment differences. CUP patients had a significant increase in the mean net cost of initial diagnostic workup before diagnosis and a significant reduction in the mean net cost of continuing cancer care.ConclusionIdentifying the primary tumour in CUP patients might enable the use of more effective therapies, improve OS and allow more efficient allocation of healthcare resources.Electronic supplementary materialThe online version of this article (doi:10.1007/s41669-017-0051-2) contains supplementary material, which is available to authorized users.

Healthcare Costs Before and After Diagnosis of Cancer of Unknown Primary Versus Ovarian Cancer in Australia

“…Few studies have documented the costs of CUP during the diagnosis phase. In a Canadian study, healthcare costs were significantly higher 6 months prior to diagnosis across most resource types in those with CUP compared with a mixed and matched sample of patients with known primary cancers, yet treatment costs after diagnosis were lower [ 6 ]. Our findings contradict these results in the treatment phase where cancer therapy costs appear to be higher and MBS costs similar for CUP patients (Table 2 ).…”

“…Our findings contradict these results in the treatment phase where cancer therapy costs appear to be higher and MBS costs similar for CUP patients (Table 2 ). However, our study compared patients with CUP to women with ovarian cancer, with all patients having stage III or IV disease, unlike the mixed cancer sample used in the Hannouf et al (2018) study [ 6 ]. Australian studies in older patients with CUP have shown higher use of general practitioner consultations, palliative care services, hospitalisations and emergency department visits 3 months before and after diagnosis, compared with metastatic cancer of known primary site [ 9 , 16 ].…”

“…MBS data were aggregated for the period 6 months prior to diagnosis date when most diagnostic services are concentrated [ 6 ]. Total costs to government prior to diagnosis were aggregated for five of the seven major categories on the MBS that are most relevant to diagnosis: doctor consultations, diagnostics, imaging, pathology and therapeutic procedures (allied health and oral and maxillofacial services were excluded, as were PBS medicines).…”

“…Avoiding delays in diagnosis of CUP will not only potentially improve patient outcomes, but also contribute to more efficient use of healthcare resources and costs. There are few studies on the economic and clinical value of diagnostic tests for CUP [6][7][8]. Therefore, to inform resource planning and allocation, there is a need to evaluate both the cost of diagnosing and treating CUP in addition to cost-effective treatments.…”

Therapeutic Actionability of Circulating Cell-Free DNA Alterations in Carcinoma of Unknown Primary

“…1,2 Patients with CUP are often treated with empiric chemotherapies such as taxanes and platinum-containing regimens. 3,4 Median overall survival (OS) remains dismal, ranging from 6 to 15 months. [5][6][7][8][9] Initial work-up, as recommended by the National Comprehensive Cancer Network guidelines, includes a history and physical examination, basic laboratory tests, computed tomography scans, clinically directed endoscopy, and microsatellite instability/mismatch repair gene testing.…”