Economic burden of the management of metastatic castrate-resistant prostate cancer in Italy: a cost of illness study

Figures & data

Table 1 Characteristics of the analysis

Target population	Patients affected by mCRPC
Approach	Prevalence
Time horizon	1 year
Perspective	Italian National Health Service
Costs	Direct health costs
Discount rate	None
Costing approach	Bottom-up

Abbreviation: mCRPC, metastatic castrate-resistant prostate cancer.

Table 2 Market shares per line of treatment

Treatment	Patients in first-line, %*	Patients in second-line, %*
Abiraterone	31.3	34.0
Cabazitaxel	0.0	11.0
Docetaxel	39.5	24.0
Enzalutamide	20.2	8.0
Radium-223	9.0	24.0

Note:

* Estimates from Verzoni et al.⁴⁶

Table 3 Incidence of adverse events and skeletal-related events per treatment

Notes: The rate of events was taken from randomized trials that compared the efficacy of the experimental drug with that of placebo.²⁷ Incidence values considered when N/A: for anemia a mean value of 8.77%, a minimum value of 5.00%, a maximum value of 12.67%; for thrombocytopenia a mean value of 2.86%, a minimum value of 1.00%, a maximum value of 6.50%; for neutropenia a mean value of 23.22%, a minimum value of 0.13%, a maximum value of 81.67%; for febrile neutropenia a mean value of 2.12%, a minimum value of 0.17%, a maximum value of 7.55%; for nausea a mean value of 1.57%, a minimum value of 0.00%, a maximum value of 2.15%; for vomiting a mean value of 1.77%, a minimum value of 0.00%, a maximum value of 2.65%; for pathological fracture a mean value of 4.50%, a minimum value of 3.00%, a maximum value of 6.00%; for radiation to bone a mean value of 23.00%, a minimum value of 22.00%, a maximum value of 24.00%; for spinal cord compression a mean value of 5.80%, a minimum value of 2.10%, a maximum value of 8.00%; for surgery to bone a mean value of 1.35%, a minimum value of 1.00%, a maximum value of 1.70%.

* Due to lack of second-line evidence, the same value as first-line was considered.

Abbreviation: N/A, not available.

Table 4 Treatments costs considered

Treatment	Total treatment cost per patient, per treatment, €*		Data source (references)
	Gross	Including negotiating agreements
Abiraterone (first-line)	33,428	26,762	^Citation52
Abiraterone (second-line)	22,290	18,995	^Citation52
Cabazitaxel	16,374	16,374	^Citation52
Docetaxel	3,600	3,600	^Citation53
Enzalutamide (first-line)	28,389	28,389	^Citation52
Enzalutamide (second-line)	19,635	19,635	^Citation52
Radium-223	17,012	17,012	^Citation53
External beam radiotherapy	2,702	2,702	^Citation41
Denosumab	420.00a	420.00	^Citation54
Zoledronic acid	680.40b	680.40b	^Citation55
Goserelin acetate	2,311,68c	2,311.68c	^Citation56
Leuprorelin acetate	1,432.80d	1,432.80d	^Citation57, ^Citation58
	1,146.24e	1,146.24e
Degarelix acetate	1,715.28f	1,715.28f	^Citation59

Notes:

* Total cost inclusive of support therapies (ie, prednisone) and administration (ie, 10% of DRGs 410–409), considering a body surface of 1.8 m². If the median treatment duration is above 12 months, the cost of 12 months of administration was considered. Cost considered for the following:

a Two doses of 60 mL (one every 6 months);

b 12 doses of 4 mg;

c 12 doses of 3.6 mg;

d 12 doses of 3.75 mg;

e 12 doses of 7.5 mg;

f 12 doses of 80 mg. Goserelin acetate, leuprorelin acetate, and degarelix acetate were considered within “other costs” category.

Abbreviation: DRGs, diagnosis related groups.

Table 5 Costs of adverse events and skeletal-related events

Events	Management cost per episode, €	Source	Notes
Anemia	1,238.76	Restelli et al^Citation47	Epoetin alfa + blood transfusion (blood transfusion in 10% of patients)
Thrombocytopenia	20.69	Restelli et al^Citation47	Specialist visit
Neutropenia	413.02	Restelli et al^Citation47	Antibiotics + granulocyte – colony-stimulating factor
Febrile neutropenia	782.34	Restelli et al^Citation47	Granulocyte – colony stimulating factor + hospitalization in 10% of patients (DRG 574)
Diarrhea	20.69	Restelli et al^Citation47	Specialist visit
Nausea	226.23	Restelli et al^Citation47	Antiemetic therapy
Vomiting	226.23	Restelli et al^Citation47	Antiemetic therapy
Fatigue	1,236.18	Restelli et al^Citation47	Epoetin alfa
Non-vertebral fracture	2,295	Hechmati et al^Citation41	–
Vertebral fracture	2,356	Hechmati et al^Citation41	–
Radiation to bone	2,706	Hechmati et al^Citation41	–
Spinal cord compression	5,371	Hechmati et al^Citation41	–
Surgery to bone	3,682	Hechmati et al^Citation41	–

Abbreviation: DRGs, diagnosis related groups.

Table 6 Monitoring activity costs

Monitoring activity	Cost per monitoring activity, €	Notes
Abdominal computed tomography	79.50	Italian national nomenclature tariff 88.01.3; twice a year
Total body bone scintigraphy	113.10	Italian national nomenclature tariff 92.18.2; twice a year
Prostate-specific antigen level	7.41	Italian national nomenclature tariff 90.56.5; four times a year
Testosterone level	9.78	Italian national nomenclature tariff 90.41.3; four times a year
Renal function	6.03	Italian national nomenclature tariffs 90.16.3, 90.16.4, 90.44.1, 90.44.3; every month
Liver function	12.10	Italian national nomenclature tariffs 90.04.5, 90.09.2, 90.23.5, 90.05.1, 90.10.4, 90.25.5, 90.29.2, 90.75.4, 90.14.4; every month
Blood test	3.17	Italian national nomenclature tariff 90.62.2; every month
Lactate dehydrogenase	1.13	Italian national nomenclature tariff 90.29.2; every month
Alkaline phosphatase	1.04	Italian national nomenclature tariff 90.23.5; every month

Table 7 Cost of mCRPC management and treatment in Italy

Treatment	Patients (n)	Cost (thousands of €)
		Treatment		Adverse events			SREs			Other costs*			Total cost – net treatments			Total cost – gross treatments
		Net	Gross	Mean values	Min values	Max values	Mean values	Min values	Max values	Mean values	Min values	Max values	Mean values	Min values	Max values	Mean values	Min values	Max values
Abiraterone (first-line)	2,034	54,433.4	67,992.2	456.6			2,529.8			6,683.8	5,655.1	8,025.6	64,103.5	63,075.8	65,446.4	77,662.4	76,634.7	79,005.2
Abiraterone (second-line)	1,083	20,571.6	24,140.1	153.4			1,347.0			3,558.3	3,011.1	4,273.2	25,630.8	25,083.6	26,345.7	29,199.2	28,652.0	29,914.2
Cabazitaxel (second-line)	346	5,665.4		206.6			376.6	281.9	443.3	1,136.8	962.0	1,365.2	7,385.6	7,116.1	7,680.8	7,385.6	7,116.1	7,680.8
Docetaxel (first-line)	2,566	9,237.6		700.9	661.7	809.9	2,792.7	2,090.8	3,287.9	8,430.7	7,134.3	10,124.8	21,163.1	19,125.5	23,461.3	21,163.1	19,125.5	23,461.3
Docetaxel (second-line)	762	2,743.2		208.1	196.5	240.5	829.3	620.9	976.4	2,503.6	2,118.6	3,006.7	6,284.6	5,679.5	6,967.1	6,284.6	5,679.5	6,967.1
Enzalutamide (first-line)	1,312	37,245.9		378.4	113.9	889.6	1,530.5	1,484.8	1,576.3	4,310.7	3,647.8	5,176.8	43,466.1	42,492.9	44,889.3	43,466.1	42,492.9	44,889.3
Enzalutamide (second-line)	250	4,908.8		72.2	21.7	169.6	291.6	282.9	300.4	821.4	695.1	986.4	6,094.0	5,908.6	6,365.2	6,094.0	5,908.6	6,365.2
Radium-223 (first-line)	585	9,951.9		132.2			500.0	476.7	523.4	1,922.1	1,626.5	2,308.3	12,506.4	12,187.5	12,916.0	12,506.4	12,187.5	12,916.0
Radium-223 (second-line)	762	12,963.0		172.1			651.3	620.9	681.8	2,503.6	2,118.6	3,006.7	16,290.4	15,874.9	16,823.9	16,290.4	15,874.9	16,823.9
Total first-line	6,497	110,868.8	124,427.6	1,668.1	1,364.4	2,288.3	7,353.1	6,582.0	7,917.4	21,346.3	18,063.7	25,635.5	141,239.1	136,881.7	146,712.9	154,798.0	150,440.6	160,271.8
Total second-line	3,203	46,851.9	50,420.4	812.5	750.5	942.3	3,495.8	3,153.6	3,748.8	10,523.7	8,905.3	12,638.2	61,685.3	59,662.7	64,182.7	65,253.8	63,231.2	67,751.2
Total	9,700	157,720.8	174,848.1	2,480.6	2,114.9	3,230.6	10,848.9	9,735.5	11,666.2	31,869.9	26,968.9	38,273.7	202,924.5	196,544.4	210,895.6	220,051.8	213,671.7	228,022.9

Notes:

* External beam radiotherapy, denosumab, zoledronic acid, monitoring activity, androgen deprivation therapy.

Abbreviations: SREs, skeletal-related events; mCRPC, metastatic castrate-resistant prostate cancer; min, minimum; max, maximum.

Table S1 Per capita cost

Treatment	Total cost – net treatments (€)			Total cost – gross treatments (€)
	Mean values	Min values	Max values	Mean values	Min values	Max values
Abiraterone (first-line)	31,516	31,011	32,176	38,182	37,677	38,842
Abiraterone (second-line)	23,666	23,161	24,327	26,961	26,456	27,622
Cabazitaxel (second-line)	21,346	20,567	22,199	21,346	20,567	22,199
Docetaxel (first-line)	8,248	7,453	9,143	8,248	7,453	9,143
Docetaxel (second-line)	8,248	7,453	9,143	8,248	7,453	9,143
Enzalutamide (first-line)	33,130	32,388	34,214	33,130	32,388	34,214
Enzalutamide (second-line)	24,376	23,634	25,461	24,376	23,634	25,461
Radium-223 (first-line)	21,378	20,833	22,079	21,378	20,833	22,079
Radium-223 (second-line)	21,378	20,833	22,079	21,378	20,833	22,079

Abbreviations: min, minimum; max, maximum.

Table S2 Sensitivity analysis results

Variables	Total cost – net treatments (thousands of €)			Total cost – gross treatments(thousands of €)
	Mean values	Min values	Max values	Mean values	Min values	Max values
Base case	202,924.5	196,544.4	210,895.6	220,051.8	213,671.7	228,022.9
Abiraterone (+10%)	206,524.9	200,215.0	214,421.9	225,361.2	219,051.3	233,258.3
Abiraterone (−10%)	199,280.7	192,831.3	207,325.0	214,689.0	208,239.6	222,733.2
Cabazitaxel (+10%)	203,024.2	196,637.7	210,999.0	220,108.6	213,722.2	228,083.4
Cabazitaxel (−10%)	202,854.4	196,479.5	210,823.5	220,024.6	213,649.6	227,993.7
Docetaxel (+10%)	196,132.9	189,682.9	204,140.0	212,261.6	205,811.6	220,268.7
Docetaxel (−10%)	209,731.8	203,420.0	217,669.3	227,847.8	221,535.9	235,785.3
Enzalutamide (+10%)	204,933.0	198,537.9	212,952.6	221,680.8	215,285.7	229,700.3
Enzalutamide (−10%)	200,923.6	194,557.4	208,847.6	218,420.5	212,054.4	226,344.5
Radium-223 (+10%)	203,087.7	196,724.1	211,041.9	219,963.0	213,599.4	227,917.2
Radium-223 (−10%)	202,722.6	196,325.5	210,711.1	220,091.9	213,694.9	228,080.5
Patients treated in first-line (+10%)	217,054.9	210,238.7	225,574.0	235,535.4	228,719.2	244,054.6
Patients treated in first-line (−10%)	188,782.5	182,838.2	196,206.3	204,550.0	198,605.6	211,973.7
Patients treated in second-line (+10%)	209,118.2	202,534.6	217,340.4	226,601.3	220,017.8	234,823.6
Patients treated in second-line (−10%)	196,736.8	190,559.4	204,457.7	213,504.9	207,327.5	221,225.8
Patients treated with external beam radiotherapy (+100%)	205,549.8	199,169.7	213,520.9	222,677.1	216,297.0	230,648.2
Patients treated with denosumab (+100%)	203,739.3	197,359.2	211,710.4	220,866.6	214,486.5	228,837.7
Patients treated with zoledronic acid (+10%)	203,452.5	197,072.4	211,423.6	220,579.8	214,199.7	228,550.9
Patients treated with zoledronic acid (−10%)	202,396.5	196,016.5	210,367.6	219,523.8	213,143.8	227,494.9
Patients treated with ADT (−10%)	201,322.5	195,432.6	208,653.3	218,449.8	212,559.9	225,780.6

Abbreviations: min, minimum; max, maximum; ADT, androgen deprivation therapy.

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