Cost effectiveness of a 92-gene assay for the diagnosis of metastatic cancer

Figures & data

Figure 1. The 92-gene assay model schematic. (a) Primary model. (b) Early model. (c) Late model. (d) Clinically simplified model. H&E, hematoxylin and eosin; IHC, immunohistochemistry; MIBG, iodine-131-meta-iodobenzylguanidine scintiscan.

Table 1. The 92-gene assay model: event probabilities, costs, and utility weights.

	Estimate^a	Source
Event Probabilities
Diagnostic result in cases of uncertain diagnosis following initial workup and pathology/IHC review^b (%)	22–29	18
Correct treatment (%), following:
Diagnosis (following clinical workup, oncology consultation)	83	Expert opinion^c
Diagnosis (following physician agreement)	87	14
Diagnosis and suspected primary site (all other instances)	66	4
Treatment for suspected primary site (%)	45–75	Expert opinion^c
Empiric treatment (%)	10–25	Expert opinion^c
Further workup (%)	15–25	Expert opinion^c
Physician agreement with the 92-gene assay^d (%)	84	18
Diagnostic Costs^e
IHC stain	$359	38
Further clinical workup^f	$9377	24,25,38
Further pathology consultation^g	$2518	38
Further oncology consultation	$453	38
The 92-gene assay	$3950	bioTheranostics (list price)
Cancer Treatment Costs^e,h
Breast cancer	$38,101–$58,636	26
Colon and rectum cancer	$68,409–$77,298	26
Kidney and renal pelvis cancer	$58,711–$73,185	26
Liver and intrahepatic bile duct cancer	$78,397–$93,032	26
Lung and bronchus cancer	$57,276–$89,551	26
Ovarian cancer	$76,552–$77,809	26
Pancreatic cancer	$78,577–$100,596	26
Prostate cancer	$17,069–$50,150	26
Empiric treatment	$37,128–$49,860	26,27
Utility Weights^i
Breast cancer	0.44–0.72	32
Colon and rectum cancer	0.63–0.77	33
Kidney and renal pelvis cancer	0.36–0.80	34
Liver and intrahepatic bile duct cancer	0.44–0.63	28,36
Lung and bronchus cancer	0.47–0.65	35
Ovarian cancer	0.48–0.69	29,36
Pancreatic cancer	0.46–0.65	30,36
Prostate cancer	0.53–0.76	31,36
Empiric treatment	0.55	36

IHC, immunohistochemistry.

^aRanges reflect values used across different points in the model.

^bOne primary site identified.

^cEstimated based on consultations with various practicing clinical oncologists.

^dAgreement with the 92-gene assay diagnosis and treated accordingly; physicians of all other patients undergoing 92-gene assay testing are assumed to disagree with the result and proceed with further workup.

^eCosts were inflated to 2012 USD.

^fProcedures include those in National Comprehensive Cancer Network (NCCN) guidelines and those recommended by experts.

^gIncludes fee for pathology consultation and report on referred material requiring preparation of slides as well as cost of performing six IHC stains.

^hRanges reflect costs for the first 12 months after diagnosis and the final 12 months of life. For all cancers, the cost for the months between the initial and last year of life phases averaged $6022 and ranged from $3433 (prostate cancer) to $11,108 (liver and intrahepatic bile duct cancer).

ⁱRanges reflect utilities for incorrect (lower bound) and correct treatment (upper bound).

Figure 2. Distribution of treatment by use of 92-gene assay in the primary, early, and late models.

Table 2. The 92-gene assay model: base case results.

	Costs^a		Survival (mo)		Survival (QA mo)		Incremental CE Ratio
	Lifetime	Δ	Lifetime	Δ	Lifetime	Δ	$/LY	$/QALY
Primary Model^b
Standard care methods	$72,080	–	14.64	–	9.20	–	–	–
92-gene assay	$76,884	$4804	15.56	0.92	10.34	1.15	$62,451	$50,273
Early Model^c
Standard care methods	$72,915	–	14.75	–	9.33	–	–	–
92-gene assay	$78,388	$5473	15.60	0.85	10.35	1.03	$77,501	$63,972
Late Model^d
Standard care methods	$69,915	–	14.56	–	9.09	–	–	–
92-gene assay	$75,954	$6038	15.47	0.91	10.23	1.14	$79,269	$63,796
Clinically Simplified Model^e
Standard care methods	$53,353	–	13.13	–	7.22	–	–	–
92-gene assay	$77,582	$24,229	15.78	2.65	10.62	3.40	$109,749	$85,584

CE, cost effectiveness; LY, life year; mo, months; QA, quality-adjusted; QALY, quality-adjusted life-year.

^aCosts were inflated to 2012 USD.

^bThe primary model begins with patients with confirmed metastatic cancer with an uncertain site of tumor origin based on initial oncology consultation, a hematoxylin and eosin (H&E) stain, and an initial set of six IHC stains.

^cThe early model assessed the 92-gene assay when it was used before the first set of six IHC stains in the patient population entering the model.

^dThe late model assessed the 92-gene assay when it was used after the second set of six IHC stains in patients who were still undiagnosed at this point.

^eThe clinically simplified model compared an approach using the 92-gene assay and treating immediately based on the assay result with an empiric chemotherapy treatment approach.

Figure 3. Primary model. (a) One-way sensitivity analyses. Each parameter varied ±25%. (b) Probabilistic sensitivity analyses. Individual dots represent ICERs when all parameters are varied simultaneously for 1000 model simulations. The dotted circular line represents 95% confidence ellipse. IC, incremental cost, ICER, incremental cost-effectiveness ratio; IE, incremental effectiveness; QALY, quality-adjusted life-year.

Appendix Table 1. Mean Survival for Eight Primary Cancer Sites by Histologic Subtype.

Primary Cancer Site and Histologic Subtype	SEER Analysis^a,b (mo)	Correct Treatment^c (mo)	Incorrect Treatment^c (mo)
Breast
Adenocarcinoma, NOS	30.70	33.84	24.64
Squamous cell	15.15	16.70	12.16
Neuroendocrine	12.32	13.58	9.89
Colon and rectum
Adenocarcinoma, NOS	18.25	20.12	14.65
Squamous cell	12.72	14.03	10.21
Neuroendocrine	8.74	9.64	7.02
Kidney and renal pelvis
Adenocarcinoma, NOS	10.60	11.69	8.51
Squamous cell	6.56	7.24	5.27
Neuroendocrine	3.56	3.93	2.86
Liver and intrahepatic bile duct
Adenocarcinoma, NOS	4.26	4.69	3.41
Squamous cell	n/a	n/a	n/a
Neuroendocrine	2.89	3.18	2.32
Lung and bronchus
Adenocarcinoma, NOS	7.19	7.93	5.77
Squamous cell	7.53	8.30	6.04
Neuroendocrine	8.40	9.26	6.74
Ovary
Adenocarcinoma, NOS	22.60	24.91	18.13
Squamous cell	6.91	7.62	5.55
Neuroendocrine	4.23	4.66	3.39
Pancreas
Adenocarcinoma, NOS	4.95	5.45	3.97
Squamous cell	5.41	5.96	4.34
Neuroendocrine	13.91	15.33	11.16
Prostate
Adenocarcinoma, NOS	56.81	62.61	45.58
Squamous cell	19.48	21.47	15.63
Neuroendocrine	14.86	16.38	11.92

n/a, not available; NOS, not otherwise specified; SEER, Surveillance Epidemiology and End Results.

^aUnless otherwise noted, source: SEER Survival Analysis, Hainsworth 2012.

^bStage IV, IV NOS, IVA, IVB, IVC patients only.

^cSEER column used to calculate correct and incorrect survival for use in the model, adjusted for based on published survival estimates associated with site-specific versus empiric therapy.

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