Cost-Effectiveness Analysis of Diagnostic Tests for Para-Aortic Lymph Node Detection in Locally Advanced Cervical Cancer

Figures & data

Figure 1 Decision tree of para-aortic lymph node detection with the first approach: without laparoscopic lymphadenectomy.

Abbreviations: CT, computed tomography; MRI, magnetic resonance imaging; PET/CT, positron emission tomography/computed tomography; PALN, para-aortic lymph node; CCRT, concurrent chemoradiation; EFRT, extended-field radiation therapy; M, Markov model.

Figure 2 Decision tree of para-aortic lymph node detection with the second approach: laparoscopic lymphadenectomy.

Abbreviations: CT, computed tomography; MRI, magnetic resonance imaging; PET/CT, positron emission tomography/computed tomography; PALN, para-aortic lymph node; CCRT, concurrent chemoradiation; EFRT, extended-field radiation therapy; LL, laparoscopic lymphadenectomy; M, Markov model.

Figure 3 The schematic diagram of the Markov model.

Table 1 Clinical Parameters

Parameters	Mean (95% Confidence Interval)			Reference
Incidence of PALN (stage IB–IVA)	0.16 (0.13–0.18)			[^Citation4]
Diagnostic test accuracy	CT	MRI	PET/CT
True negative (TN)	0.91 (0.89 −0.93)	0.93 (0.91–0.95)	0.97 (0.98–0.96)	[^Citation24]
True positive (TP)	0.57 (0.47–0.67)	0.54 (0.44–0.64)	0.66 (0.57–0.75)	[^Citation24]
False negative (FN)	0.43 (0.33–0.53)	0.46 (0.36–0.56)	0.34 (0.25–0.43)	[^Citation24]
False positive (FP)	0.09 (0.07–0.11)	0.07(0.05–0.09)	0.03 (0.02–0.04)	[^Citation24]
Survival data at 5 years (disease-free survival)
No investigation ➔ CCRT		0.63 (0.55–0.71)		[^Citation25]
Diagnostic test with no LL when suspected disease at PALN
- no suspected disease at PALN (TN) ➔ CCRT		0.65 (0.57–0.73)		[^Citation26]
- no suspected disease at PALN (FN) ➔ CCRT		0.06 (0.02–0.10)		[^Citation23]
- suspected disease at PALN (TP and FP) ➔ EFRT		0.46 (0.32–0.60)		[^Citation17]
Diagnostic test with LL when suspected disease at PALN
- disease (TP) ➔ EFRT		0.29 (0.16–0.42)		[^Citation19]
- no disease (FP) ➔ CCRT		0.65 (0.57–0.73)		[^Citation26]
Overall survival rate after when disease progression		0.10 (0.05–0.15)		[^Citation23]
Severe late side effect rates (grades 3–5)
- gastrointestinal system from CCRT ± LL		0.06 (0.02–0.10)		[^Citation26]
- genitourinary system from CCRT ± LL		0.17 (0.11–0.23)		[^Citation26]
- gastrointestinal system from EFRT		0.06 (0.02–0.10)		[^Citation26]
- genitourinary system from EFRT		0.17 (0.11–0.23)		[^Citation26]
- gastrointestinal system from LL + EFRT		0.11 (0.02–0.20)		[^Citation19]
- genitourinary system from LL + EFRT		0.19 (0.08–0.30)		[^Citation19]
- death from CCRT ± LL		0.01 (0–0.03)		[^Citation26]
- death from CCRT + EFRT		0.01 (0–0.02)		[^Citation17]
- death from LL + EFRT		0.02 (0–0.06)		[^Citation19]

Abbreviations: PALN, para-aortic lymph node; FN, false negative; FP, false positive; TN, true negative; TP, true positive; CT, computed tomography; MRI, magnetic resonance imaging; PET⁄CT, fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography; CCRT, concurrent chemoradiation therapy; LL, laparoscopic lymphadenectomy; EFRT, extended-field radiation therapy.

Table 2 Cost and Utility Parameters

Parameters	Mean (US$/THB)	Range (US$/THB)
Direct Medical Costs
CT whole abdomen	599/19,155	449–748/14,367–23,945
MRI whole abdomen	917/29,340	688–1146/22,005–36,675
PET/CT	3056/97,800	2292–3820/73,350–122,250
Laparoscopic lymphadenectomy	2116/67,712	1587–2645/50,784–84,640
Concurrent chemoradiation therapy	4291/137,312	3218–5364/102,984–171,640
Extended-field radiation therapy	4952/158,452	3714–6190/118,839–198,065
Palliative treatment	9665/309,277	7249–12,081/231,958–386,596
Treatment grades 3–4 of late GI side effect	6750/216,000	5063–8438/162,000–270,000
Treatment grades 3–4 of late GU side effect	8558/273,861	6419–10,698/205,396–342,326
Direct non-medical costs
Treatment period
Concurrent chemoradiation therapy	1033/33,063	775–1292/24,798–41,330
Extended-field radiation therapy	3046/97,463	2284–3807/73,097–121,828
Follow-up period
No disease and no severe side effects	1113/35,629	835–1392/26,722–44,536
No disease with grades 3–4 GI side effects	1532/49,040	1149–1916/36,780–61,300
No disease with grades 3–4 GU side effects	1253/40,096	940–1566/30,072–50,121
Disease progression	2158/69,074	1619–2698/51,806–86,343
Utility		95% confidence interval
Treatment period to first six months	0.89	0.86–0.92
Follow-up period
No disease and no severe side effects	0.93	0.91–0.95
No disease with grades 3–4 GI side effects	0.86	0.81–0.89
No disease with grades 3–4 GU side effects	0.89	0.84–0.94
Disease progression	0.72	0.64–0.80

Abbreviations: THB, Thai baht; CT, computed tomography; MRI, magnetic resonance imaging; PET⁄CT, fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography; GI, gastrointestinal system; GU, genitourinary system.

Table 3 Outcomes of Cost-Effectiveness Analysis Comparing Seven Approaches (No Investigation and Six Strategies)

Outcomes	Approaches
	1. No Investigation	2. CT without LL	3. CT with LL	4. MRI without LL	5. MRI with LL	6.PET/CT without LL	7.PET/CT with LL
Cost (US$/THB)
Provider	8026/256,829	9643/308,569	9619/307,814	9852/315,272	9874/315,983	11,862/379,588	12,051/385,624
Society	11,444/366,202	13,279/424,927	13,179/421,724	13,466/430,918	13,431/429,796	15,446/494,270	15,620/499,824
QALY	3.70	3.63	3.62	3.63	3.62	3.65	3.63
ICER (US$ per QALY/THB per QALY)		−29,679/−949,740	−23,505/−752,152	−32,536/−1,041,160	−26,340/−842,864	−87,656/−2,804,992	−60,586/−1,938,750
Dominant		Dominated	Dominated	Dominated	Dominated	Dominated	Dominated

Abbreviations: CT, computed tomography; MRI, magnetic resonance imaging; PET/CT, fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography; LL, laparoscopic lymphadenectomy; THB, Thai baht; QALY, quality-adjusted life year; ICER, incremental cost-effectiveness ratio.

Table 4 Outcomes of Cost-Effectiveness Analysis in Terms of Cost per One Case of Para-Aortic Lymph Node Detection

Outcomes (US$/THB)	CT	MRI	PET/CT
Incidence of PALN metastasis of 16%
- Cost per case detected	154,858/4,955,443	167,144/5,348,619	157,014/5,024,438
- ICER	146,832/4,698,614	159,118/5,091,789	148,988/4,767,609
Incidence of PALN metastasis of 30%
- Cost per case detected	82,591/2,642,903	89,114/2,852,597	83,741/2,679,700
- ICER	74,565/2,386,074	81,118/2,595,767	75,715/2,422,871

Abbreviations: PALN, para-aortic lymph node; CT, computed tomography; MRI, magnetic resonance imaging; PET⁄CT, fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography.

Figure 4 One-way sensitivity analysis (Tornado diagram) for the top ten most influential parameters.

Abbreviations: GI, gastrointestinal; GU, genitourinary; CT, computed tomography; LL, laparoscopic lymphadenectomy; PALN, para-aortic lymph node; FP, false positive; TN, true negative; TP, true positive; DMC, direct medical cost; CCRT, concurrent chemoradiation; EFRT, extended-field radiation therapy; NoIx, no investigation; ICER, incremental cost-effectiveness ratio; CI, confidence interval.

Figure 5 Cost-effectiveness acceptability curves of using different approaches for para-aortic lymph nodes detection in locally advanced cervical cancer patients with a willingness-to-pay threshold of Thailand.

Abbreviations: CT, computed tomography; MRI, magnetic resonance imaging; PET⁄CT, fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography; LL, laparoscopic lymphadenectomy.

Figure 6 Cost-effectiveness planes with the threshold willingness-to-pay (WTP) of US$5000 or THB 160,000 per quality-adjusted life year for all approaches in (A), comparing no investigation and CT in (B), comparing no investigation and MRI in (C), and comparing no investigation and PET/CT in (D).

Abbreviations: CT, computed tomography; MRI, magnetic resonance imaging; PET⁄CT, fluorine-18-fluorodeoxyglucose positron emission tomography/computed tomography; LL, laparoscopic lymphadenectomy; QALY, quality-adjusted life year; WTP, willingness-to-pay.

Berman ML, Keys H, Creasman W, Disaia P, Bundy B, Blessing J. Survival and patterns of recurrence in cervical cancer metastatic to periaortic lymph nodes (a Gynecologic Oncology Group study). Gynecol Oncol. 1984;19:8–16. doi:10.1016/0090-8258(84)90151-3

 PubMed Web of Science ®Google Scholar

Liu B, Gao S, Li S. A comprehensive comparison of CT, MRI, Positron Emission Tomography or Positron Emission Tomography/CT, and diffusion weighted imaging-MRI for detecting the lymph nodes metastases in patients with cervical cancer: a meta-analysis based on 67 studies. Gynecol Obstet Invest. 2017;82:209–222. doi:10.1159/000456006

 Web of Science ®Google Scholar

Katanyoo K, Tangjitgamol S, Chongthanakorn M, et al. Treatment outcomes of concurrent weekly carboplatin with radiation therapy in locally advanced cervical cancer patients. Gynecol Oncol. 2011;123:571–576. doi:10.1016/j.ygyno.2011.09.001

 PubMed Web of Science ®Google Scholar

Pearcey R, Brundage M, Drouin P, et al. Phase III trial comparing radical radiotherapy with and without cisplatin chemotherapy in patients with advanced squamous cell cancer of the cervix. J Clin Oncol. 2002;20:966–972. doi:10.1200/JCO.2002.20.4.966

 PubMed Web of Science ®Google Scholar

Kitagawa R, Katsumata K, Shibata T, et al. Paclitaxel plus carboplatin versus paclitaxel plus cisplatin in metastatic or recurrent cervical cancer: the open label randomized phase III trial (JCOG0505). J Clin Oncol. 2015;33:2129–2135. doi:10.1200/JCO.2014.58.4391

 PubMed Web of Science ®Google Scholar

Jung J, Park G, Kim YS. Definitive extended-field intensity-modulated radiotherapy with chemotherapy for cervical cancer with para-aortic nodal metastasis. Anticancer Res. 2014;34:4361–4366.

 Web of Science ®Google Scholar

Marnitz S, Schram J, Budach V, et al. Extended field chemoradiation for cervical cancer patients with histologically proven para-aortic lymph node metastases after laparoscopic lymphadenectomy. Strahlenther Onkol. 2015;191:421–428. doi:10.1007/s00066-014-0785-z

 Web of Science ®Google Scholar