In patients with unprovoked VTE, does the addition of FDG PET/CT to a limited occult cancer screening strategy offer good value for money? A cost-effectiveness analysis from the publicly funded health care systems.

INTRODUCTION: Unprovoked venous thromboembolism (VTE) may be the first manifestation of an undiagnosed cancer. We assessed the cost-effectiveness of 18F-Fluorodesoxyglucose Positron Emission/Computed Tomography (FDG PET/CT) plus limited screening and limited screening strategies in patients with unprovoked VTE from the perspectives of the Ontario (Canada) and French health care systems. METHODS: We conducted a cost-effectiveness analysis based on a published randomized controlled trial of 394 patients aged 18 years or older who were diagnosed with unprovoked VTE. We obtained data with respect to efficacy and health care utilization from the published trial. The primary measure of effectiveness was the number of avoided cases of delayed cancer diagnosis and the secondary measure of effectiveness was the quality adjusted life year (QALY) at the end of the study in each group. We used generalized linear models to estimate incremental cost-effectiveness ratios (ICER) while controlling for patient demographic and clinical characteristics. Results were presented as the incremental cost to avoid one case of delayed cancer diagnosis and the incremental cost per QALY gained. The 95% confidence intervals (CIs) were estimated using bootstrap re-sampling procedures with 5000 iterations. RESULTS: Compared to a limited screening strategy, the ICER of limited strategy plus FDG PET/CT scan was C$ 26,840.19 (95% CI: C$ 24,046.51; C$ 34,581.53) per one avoided case of delayed cancer diagnosis from the Ontario health system perspective and €16,370.45 (95% CI: € 9904.48; € 39,578.91) per one avoided case of delayed cancer diagnosis from the French health system perspective. The probabilities that addition of FDG PET/CT to limited screening is cost-effective rose with increasing willingness to pay values. Compared with the limited screening, the extensive screening was associated with C$ 3412.85 per QALY gained (95% CI: 1463.89; -13,935.88) from the Ontario health system perspective and €2162.83 per QALY gained (95% CI 958.78; -10,544.42) from the French health system perspective. CONCLUSION: Addition of a FDG PET/CT for occult cancer diagnosis was associated with better health outcomes (fewer cases of delayed cancer diagnosis and greater QALYs) and a higher cost from the perspective of publicly funded health care systems; the cost-effectiveness results are however highly uncertain.

Pretreatment costs of care and time to initial treatment for patients with cancer of unknown primary.

AIM: Time to treatment and pretreatment costs may be affected by unknown primary tumor site. METHODS: This retrospective study used electronic medical record data from patients in ten US community oncology practices. Eligible patients were ≥18 years, diagnosed with cancer of unknown primary (CUP) or known metastatic solid tumor, and presented between 1 January 2012 and 30 June 2014. RESULTS: Patients with CUP (n = 294) had a longer interval than non-CUP patients (n = 92) from presentation to treatment initiation (1.18 vs 0.49 months, p < 0.0001), and had higher pretreatment costs (US$27,882 vs US$20,449, p = 0.0075). When analyzed as monthly cost, the difference between groups in log-cost per month was nonsignificant. CONCLUSION: Higher pretreatment costs in CUP patients appeared attributable to significantly longer time to initiation of therapy.

Cost-effectiveness of using a gene expression profiling test to aid in identifying the primary tumour in patients with cancer of unknown primary.

We aimed to investigate the cost-effectiveness of a 2000-gene-expression profiling (GEP) test to help identify the primary tumor site when clinicopathological diagnostic evaluation was inconclusive in patients with cancer of unknown primary (CUP). We built a decision-analytic-model to project the lifetime clinical and economic consequences of different clinical management strategies for CUP. The model was parameterized using follow-up data from the Manitoba Cancer Registry, cost data from Manitoba Health administrative databases and secondary sources. The 2000-GEP-based strategy compared to current clinical practice resulted in an incremental cost-effectiveness ratio (ICER) of $44,151 per quality-adjusted life years (QALY) gained. The total annual-budget impact was $36.2 million per year. A value-of-information analysis revealed that the expected value of perfect information about the test's clinical impact was $4.2 million per year. The 2000-GEP test should be considered for adoption in CUP. Field evaluations of the test are associated with a large societal benefit.

Cost-effectiveness of positron emission tomography-CT in the evaluation of cancer of unknown primary of the head and neck.

BACKGROUND: Positron emission tomography (PET)-CT is a useful diagnostic adjunct for cancer unknown primary (CUP) of the head and neck; however, the increased cost has not been justified with an economic evaluation in this patient population. METHODS: A decision tree analysis was performed from the perspective of the third party payer. Primary outcome was cost per life year gained ($/LYG). The 2 comparative groups were: (1) PET-CT followed by panendoscopy versus (2) panendoscopy alone. RESULTS: The incremental cost-effectiveness ratios for N1, N2, and N3 CUP were $369.83/LYG, $329.43/LYG, and $4900.28/LYG, respectively. The sensitivity analysis demonstrated a 96.8%, 97.1%, and 60.1% certainty that PET-CT is cost-effective for CUP with N1, N2, and N3 disease, respectively. CONCLUSION: The use of PET-CT in patients with N1 and N2 CUP is the cost-effective choice. The cost-effectiveness in N3 CUP is questionable and should be used on an individual case basis.

The yield and cost of colonoscopy in patients with metastatic cancer of unknown primary.

BACKGROUND: Although gastroenterologists are asked to perform colonoscopy in patients with metastatic cancer of unknown primary (MCUP), studies evaluating this practice are lacking. AIM: To determine the yield and cost of colonoscopy in patients referred for colonoscopy with an indication of MCUP. METHODS: We prospectively and retrospectively assessed colonoscopies performed from 2000 to 2011 at a county, a university, and a Veterans Administration medical centre to identify patients referred for colonoscopy for the indication of MCUP. Exclusion criteria included overt or occult bleeding, iron-deficiency anaemia, familial-colon-cancer syndrome, prior colon cancer, imaging suggesting colorectal lesion, and palpable rectal mass. Outcomes were the number of primary colon cancers and costs based on 2012 Medicare reimbursements. RESULTS: Two (1%) of the 160 patients meeting enrollment criteria had a primary colon cancer identified, and both died within 1 month after diagnosis without receiving therapy targeted at colon cancer. One patient without colon cancer had a perforation because of colonoscopy, which required surgery and colostomy. The cost of a strategy of routinely performing colonoscopy in patients referred with MCUP was $84 736 per colon primary identified. CONCLUSIONS: Primary colon cancer was rarely identified at colonoscopy in patients with MCUP and no standard indications for diagnostic colonoscopy. Furthermore, the cost to diagnose one additional colon primary was very high. Those with colon cancer had advanced disease and were unable to benefit from targeted therapy. Routine colonoscopy for MCUP cannot be recommended at present.

Epidemiología del cáncer de origen desconocido en Asturias (1992-1996) / Epidemiology of cancer of unknown primary sitye in Asturias (1992-1996)

Propósito: La toma de decisiones diagnósticas en el Cáncer de Origen Desconocido (COD) es un arduo problema médico sujeto a gran variabilidad. La protocolización basada en la evidencia científica, podría evitar gestos sanitarios innecesarios y reducir el sufrimiento del enfermo, sin disminución de la supervivencia. Se describen las características clínico-patológicas y epidemiológicas del COD en Asturias, el nivel de adecuación de las decisiones diagnósticas a un protocolo teórico, su repercusión económica y la supervivencia. Método: Estudio descriptivo longitudinal retrospectivo (1992-96) de los casos de COD diagnosticados en los hospitales de Asturias. Resultados: Se incluyeron 568 casos: edad media 66,9 años; 59,7 por ciento varones; 39,3 por ciento estudiado en Servicios de Medicina Interna; 27,1 por ciento con hallazgo del tumor primario (más frecuente, pulmonar); mediana de la supervivencia 13 semanas. El número de técnicas diagnósticas fue variable y la media de estancia hospitalaria, 24,7 días. Un buen ajuste al protocolo se asoció con un número mayor de primarios conocidos. Conclusiones: Existe variabilidad diagnóstica del COD en Asturias. La protocolización podría evitarla en parte y resultaría beneficiosa para el paciente y el sistema sanitario (AU)

[Cost-effectiveness in diagnosis and treatment of carcinomas of unknown primary origin]. / Analyse Coût/efficacité de la prise en charge diagnostique et thérapeutique des carcinomes d'origine indéterminée.

The aim was to compare, in terms of cost-effectiveness, two diagnostic strategies for finding out the primary site of tumors revealed by metastasis, adopting the hospital's perspective. The observed strategy reflected the usual practices of doctors at the Regional Cancer Center in Toulouse (France), and was based on a sample of 202 patients of this Center. The standardized strategy, which reflected limited diagnostic investigation, was simulated using the same sample of patients to whom we applied the recommendations of local experts. In the low assumption regarding the effectiveness of the standardized strategy, the observed strategy compared to the standardized one raised the life expectancy from 407 to 418 days at an incremental cost of $US 1,236 per patient (1996 values). In this case, one day of additional life induced a cost of $US 112 per patient. In the high assumption, the incremental effectiveness was null and the incremental cost was $US 1,236 per patient. In conclusion, the effectiveness of the observed strategy as compared to the standardized strategy was highly questionable, given that the patients' quality of life was not taken into account.

[Unknown primary cancer: revision of our experience. Preliminary study]. / Cáncer de origen desconocido: revisión de nuestra experiencia. Estudio preliminar.

The unknown primary cancer is a hazardous diagnostic and limited therapeutic medical problem with too much variability. It is possible to design a standard procedure using the world-wide scientific literature, which could be able to decrease patient suffering and to avoid unnecessary sanitary costs, without diminishing survival. First of all we have conducted a retrospective descriptive study including all the patients with unknown primary neoplasms detected in our Internal Medicine service during 1994. We have met 18 cases, most of them adenocarcinoma and undifferentiated carcinoma, and hepatomegaly as clinical presentation. In 8 cases (44%) was the primary tumour site identified, mainly with CT. Only 3 (16%) patients were alive at the end of the study, with a mean survival of 5 months. The mean stay and time until diagnosis were 16.5 and 21.5 days respectively. Further studies will let us to asses the effectiveness of a theoretic diagnostic protocol.

Testing for occult cancer in patients with idiopathic deep vein thrombosis--a decision analysis.

OBJECTIVE: To determine the effectiveness and cost-effectiveness of testing for occult cancer in idiopathic deep vein thrombosis (IDVT). DESIGN: Threshold analysis was performed on the risk-adjusted cancer prevalence in a cost-effectiveness model of ideal testing for selecting cancers with potentially desirable utility (candidate cancers). Decision analysis was employed to compare different testing programs for candidate cancers with that of no testing. Life expectancy (LE) of early- and late-detected cancers and costs of testing were the dimensions of utility. Cost-effectiveness was expressed as marginal cost per year of life saved. The perspective of the third payer was adopted, and a discount rate of 3% was applied to both costs and benefits. DATA SOURCES: Risk of cancer in IDVT, testing policies, test characteristics, and LE were gathered from literature. Costs were provided from our hospital rate book and accounting service. RESULTS: Ideal testing would support a gain of LE of 40 days or more for prostate, colon and bladder cancer in males and for colon, breast and endometrium cancer in females aged from 60 to 69 years. Testing females with colonoscopy and mammography in any sequence provides 70 days of life gained. Testing males with colonoscopy provides 27 days of life gained. Lower and older ages reduce testing effectiveness. The qualitative results are stable over plausible ranges of test characteristics, while variations in the value of benefit for early cancer diagnosis may modify the strategy. Incremental cost-effectiveness ranges from $1,789 to $ 6,979 per year of life gained. CONCLUSIONS: According to the effectiveness criterion adopted, the only worthwhile investigation strategy includes colon and breast cancer in females. Testing for colon cancer in males is desirable at a lower criterion of effectiveness. All the strategies are cost effective.

The need to consider survival, outcome, and expense when evaluating and treating patients with unknown primary carcinoma.

BACKGROUND: Patients who present with unknown primary carcinomas represent 10% to 15% of the patients with cancer who present to medical centers. Despite data in the literature indicating minimal success in determining the location of primary carcinomas, these patients continue to be evaluated exhaustively. Additionally, identification of the location of primary carcinomas does not often affect treatment. Clinical treatment and prognosis are only affected if a reevaluation of the pathologic findings yields a potentially curative diagnosis of an undifferentiated lymphoma, germ cell tumor, or a hormonally sensitive carcinoma. METHODS: Tumor registry files from January 1, 1990, through December 31, 1992, were retrospectively retrieved to identify adult patients who presented with metastasis of an unknown primary site at the H. Lee Moffitt Cancer Center and Research Institute, a 162-bed tertiary care cancer center specialty hospital affiliated with the University of South Florida College of Medicine, Tampa. Medical records were reviewed for age, sex, histologic findings of previous malignant growth, types and duration of symptoms, and mode of presentation. Fifty-six of the 199 patients were included in the study; 31 were men (55.4%) and 25 were women (44.6%), with ages ranging from 33 to 83 years. Diagnostic evaluations were reviewed and included data from procedures conducted at both the H. Lee Moffitt Cancer Center and at outside facilities. Diagnostic studies performed included barium swallow; intravenous pyelogram; mammogram; abdominal ultrasound; chest x-ray film; bone scan; magnetic resonance imaging; computed tomography of the head, chest, abdomen, and pelvis; laparotomy; bronchoscopy; gastroscopy; and colonoscopy. Information for the diagnostic test procedures was taken from the point of initial patient contact until the determination of metastatic disease. RESULTS: The primary cancer site was found in four (7.1%) of the 56 cases in the study and could not be classified as curable by systemic means. The average cost of diagnosis was $17,973, with 19.6% of the patients surviving for more than 1 year. The mean survival period was 8.1 months. A total of 410 tests were performed with only four tests correctly identifying the location of the primary tumor. CONCLUSIONS: Once a potentially curable malignancy has been excluded, there is little justification to support extensive diagnostic evaluation of the patient. Substantial costs are incurred and survival is often not significantly affected. It was estimated that 1.2 million new cancer cases would have occurred during 1994, with approximately 10% of these patients presenting with cancer of unknown primary origin. Based on cost assessments, investigation of these patients would exceed $1.5 billion. This clinical scenario is one where attention to outcome, clinical management, and expense should be carefully considered.

Analysis of a diagnostic strategy for patients with suspected tumors of unknown origin.

PURPOSE: Diagnostic strategies designed to identify the underlying primary malignancies in patients with unknown primary tumors (UPTs) have relied on retrospective analyses. We analyzed 879 consecutive patients referred with suspected UPTs to determine the yield and cost of a limited diagnostic evaluation, assess the contribution of specific studies to diagnosis, and analyze the survival patterns of patients in whom the primary tumor was diagnosed. PATIENTS AND METHODS: Data from patients with a suspected UPT were entered into a computerized data base, and the patients underwent a predefined limited diagnostic evaluation. Primary malignancies were diagnosed by pathologic review alone or by pathologic criteria plus a physical or radiographic finding. Survival was measured from diagnosis, estimated using the Kaplan-Meier method, and compared using the Cox-Mantel log-rank test. RESULTS: A primary tumor was found in 179 of 879 patients (20%). The survival duration of patients in whom the primary tumor was diagnosed was superior to that of patients in whom the primary tumor remained unknown. Specific patient subsets contributed most to the improved survival duration of the group in which the primary tumor was found, including lymphoma patients diagnosed solely by pathologic criteria and female patients with primary breast or ovarian cancer. The cost of diagnosis was mostly due to the extensive use of computed tomography. Except for ovarian cancer, computed tomography rarely identified treatable primary tumors. CONCLUSION: The limited diagnostic evaluation used in this study identified patients with treatable malignancies and increased the survival duration of a population of suspected UPT patients. Primary malignancies with the best survival can be diagnosed through careful pathologic review and focused evaluations for breast and ovarian cancer in women.