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

Purpose: Several 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.

Objective: We aimed to assess the clinical and economic value of primary tumour identification in CUP using a retrospective matched cohort study.

Methods: We 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.

Results: Of 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.

Conclusion: Identifying the primary tumour in CUP patients might enable the use of more effective therapies, improve OS and allow more efficient allocation of healthcare resources.

Fig. 1

Overall survival analyses comparing patients with cancer of unknown primary tumour (CUP) with patients with cancer from a known primary tumour (CKP)

Fig. 2

Cost of healthcare utilization for 5839 patients diagnosed with metastatic cancer by diagnostic status of their primary tumour and cost category and phase of care. Mean net cost of an entire phase of care = (mean cost per day in that phase of care − mean cost per day in the “usual care before the onset of signs of illness” phase) × average number of days spent in that phase of care. Since all patients included in our study survived at least 6 months following their initial cancer diagnosis, the three patient groups spent 2.5 years in the “usual care before the onset of signs of illness” phase and 6 months in the “initial diagnostic workup before diagnosis” phase. In the “continuing diagnostic workup after diagnosis and initial cancer care” phase, CUP patients, matched CKP patients and all patients with CKP spent an average of 144 days, 154 and 156 days, respectively. In the “continuing cancer care” phase, CUP patients, matched CKP patients and all patients with CKP spent an average of 260, 310 and 301 days, respectively. In the “last 6 months of life” phase, CUP patients, matched CKP patients and all patients with CKP spent an average of 108, 95 and 97 days, respectively. Asterisk We used the resource intensity weights [36, 37] recorded for inpatient stays and day procedure group weights [36, 37] recorded for day procedure stays to reflect the resources consumed during hospital contacts. We converted these weights into Canadian dollars using a multiplier known as the cost per weighted case [36, 37]. CKP cancer from a known primary tumour, CUP cancer of unknown primary tumour

Fig. 2

Cost of healthcare utilization for 5839 patients diagnosed with metastatic cancer by diagnostic status of their primary tumour and cost category and phase of care. Mean net cost of an entire phase of care = (mean cost per day in that phase of care − mean cost per day in the “usual care before the onset of signs of illness” phase) × average number of days spent in that phase of care. Since all patients included in our study survived at least 6 months following their initial cancer diagnosis, the three patient groups spent 2.5 years in the “usual care before the onset of signs of illness” phase and 6 months in the “initial diagnostic workup before diagnosis” phase. In the “continuing diagnostic workup after diagnosis and initial cancer care” phase, CUP patients, matched CKP patients and all patients with CKP spent an average of 144 days, 154 and 156 days, respectively. In the “continuing cancer care” phase, CUP patients, matched CKP patients and all patients with CKP spent an average of 260, 310 and 301 days, respectively. In the “last 6 months of life” phase, CUP patients, matched CKP patients and all patients with CKP spent an average of 108, 95 and 97 days, respectively. Asterisk We used the resource intensity weights [36, 37] recorded for inpatient stays and day procedure group weights [36, 37] recorded for day procedure stays to reflect the resources consumed during hospital contacts. We converted these weights into Canadian dollars using a multiplier known as the cost per weighted case [36, 37]. CKP cancer from a known primary tumour, CUP cancer of unknown primary tumour