Thromboembolic events in metastatic testicular cancer treated with cisplatin-based chemotherapy

Table 1 Characteristics of patients with testicular germ cell tumors at our Institution

Metric		Number of patients (n = 68)
Demographics
Mean age at orchiectomy (yr)		31 (16-53)
Mean BMI at 1st medical oncology visit, n (%)		29 (18.6-58.4)
Cigarette smoker or ex-smoker		35 (51)
Current cannabis user, n (%)		16 (23.5)
Clinicopathologic characteristics
Histology, n (%)	Seminoma	19 (28)
	Non-seminoma	49 (72)
Pathologic stage, n (%)	IA	1 (1.5)
	IB	1 (1.5)
	IS	6 (9)
	IIA	31 (45.5)
	IIB	10 (14.5)
	IIC	8 (11.5)
	III	1 (1.5)
	IIIA	2 (3)
	IIIB	4 (6)
	IIIC	4 (6)
Laterality, n (%)	Left	35 (52)
	Right	33 (48)
RPLN ≥ 3.0 cm before chemotherapy, n (%)	Yes	18 (26)
	No	50 (74)
Type of chemotherapy	BEP	58 (85.3%)
	EP	4 (5.9%)
	BEP + EP	6 (8.8%)
Cycles of chemotherapy	1	1 (1.5%)
	2	3 (4.4%)
	3	49 (72.0%)
	4	13 (19.1%)
	6	1 (1.5%)
	7	1 (1.5%)
RPLND	Yes	18 (26.5%)
	No	50 (73.5%)
Recurrence after initial chemotherapy	Yes	5 (7.4%)
	No	63 (92.6%)

BMI: Body mass index; BEP: Bleomycin, etoposide, and cisplatin; EP: Etoposide and cisplatin; RPLN: Retroperitoneal lymph node; RPLND: Retroperitoneal lymph node dissection.

Table 2 Thromboembolic events in patients with testicular germ cell tumors who underwent cisplatin-based chemotherapy at our Institution (n = 19)

Type/pathologic stage of testicular tumor	RPLN ≥ 3.0 cm before chemotherapy	Type/number of cycles of chemotherapy	PE/DVT	Timing of PE/DVT in relation to chemotherapy	Anticoagulant	Hospitalization
Seminoma IIB	Yes	BEP (2 cycles), EP (1 cycles)	DVT	Same day immediately prior to Cycle 1	Fondaparinux sodium	Yes
Seminoma IIA	No	EP (3 cycles)	DVT1	During (Cycle 1)	Heparin → apixaban	Yes
Seminoma IIIB	No	EP (4 cycles)	PE + DVT2	3 yr after initial chemotherapy, recurrent disease	Enoxaparin sodium	Yes
Non-seminoma IIB	Yes	BEP (2 cycles)	DVT2	During (Cycle 2)	Warfarin →enoxaparin sodium	Yes
Non-seminoma IIB	No	BEP (3 cycles)	PE	During (Cycle 2)	Heparin → enoxaparin sodium → rivaroxaban → apixaban	Yes
Non-seminoma IIC	Yes	EP (4 cycles)	PE + DVT	1 wk before Cycle 1	Heparin (lovenox) → warfarin	Yes
Non-seminoma IIA	No	BEP (3 cycles)	DVT2	During (Cycle 2)	Fondaparinux sodium	No
Non-seminoma IIB	Yes	BEP (3 cycles)	PE1	During (Cycle 3)	Fondaparinux sodium → warfarin	No
Seminoma IIA	No	BEP (3 cycles)	DVT2	During (Cycle 3)	None	No
Seminoma III	No	BEP (3 cycles)	PE	During (Cycle 3)	Enoxaparin sodium	No
Non-seminoma IIIC	Yes	BEP (4 cycles)	PE	During (Cycle 4)	Enoxaparin sodium	No
Non-seminoma IIIC	Yes	BEP (4 cycles)	DVT	During (Cycle 3)	Enoxaparin sodium	No
Non-seminoma IIA	No	BEP (3 cycles)	PE	During (Cycle 3)	Heparin → rivaroxaban	Yes
Non-seminoma IIA	No	BEP (2 cycles)	PE	During (Cycle 2)	Enoxaparin sodium	No
Seminoma IIC	Yes	BEP (3 cycles)	PE	1 mo after chemotherapy ended	Heparin → enoxaparin sodium	Yes
Seminoma IIA	No	BEP (3 cycles)	PE + DVT	During (Cycle 2)	Heparin → enoxaparin sodium	Yes
Non-seminoma IIB	No	BEP (3 cycles)	DVT	1 d prior to Cycle 1	Heparin → fondaparinux sodium	Yes
Non-seminoma IIIA	No	BEP (3 cycles)	PE	2 wk after chemotherapy ended	Warfarin + enoxaparin sodium	No
Seminoma IIC	Yes	EP (4 cycles)	DVT2	During (Cycle 2)	Enoxaparin sodium → fondaparinux	Yes

¹Infusaport.

²Peripherally inserted central catheter line. PE: Pulmonary embolism; BEP: Bleomycin, etoposide, and cisplatin; DVT: Deep vein thrombosis; EP: Etoposide and cisplatin.

Table 3 Comparison of metrics between patients with testicular germ cell tumors at our Institution stratified by those who experienced a thromboembolic event and those who did not

	Thromboembolic event
Metric	No (%)	Yes (%)	P value
n	49	19
Age [mean (SD)]	30.9 (7.86)	30.79 (8.67)	0.909
BMI [mean (SD)]	27.87 (6.38)	30.22 (9.25)	0.237
Cigarette smoker = Yes (%)	27 (55.1)	8 (42.1)	0.421
Marijuana use = Yes (%)	13 (26.5)	3 (15.8)	0.526
Side of orchiectomy = Right (%)	27 (55.1)	6 (31.6)	0.107
Pathology = Seminoma (%)	11 (22.4)	8 (42.1)	0.135
Pathologic stage (%)			0.050
I	10 (20.4)	0 (0.0)
II	33 (67.3)	14 (73.7)
III	6 (12.2)	5 (26.3)
Port = Yes (%)	4 (8.2)	3 (15.8)	0.390
Type of chemotherapy (%)
BEP X 3	45 (91.8)	13 (68.4)
BEP X 3 + EP X 1	4 (8.2)	2 (10.5)
EP X 4	0 (0.0)	4 (21.1)
RPLN ≥ 3.0 cm = Yes (%)	10 (20.4)	8 (42.1)	0.123
RPLND = Yes (%)	12 (24.5)	6 (31.6)	0.555
Recurrence after chemotherapy = Yes (%)	3 (6.1)	2 (10.5)	0.614

BMI: Body mass index; BEP: Bleomycin, etoposide, and cisplatin; EP: Etoposide and cisplatin; RPLN: Retroperitoneal lymph node; RPLND: Retroperitoneal lymph node dissection.

Table 4 Patients with testicular germ cell tumors who underwent cisplatin-based chemotherapy and experienced a thromboembolic event in the literature

Ref.	Number of patients	Percentage of patients with TE	Main findings
Piketty et al[9], 2005	100 patients with GCT; 100 controls with various neoplasms	19 (19%)	> All stages of TGCT;
			> TE: 1st day of chemo to 6 mo after;
			> Of 19 TEE, 14 occurred during chemotherapy, 5 after chemo;
			> Risk factors for TEE: High body surface area, elevated serum LDH
Honecker et al[6], 2013	193	22 (11%)	> All stages of TGCT;
			> TEE: Considered therapy-associated if occurred from start of chemotherapy to 6 wk after;
			> 18 (%) TEE occurred before chemotherapy;
			> Risk factors for TEE: Pure seminoma, retroperitoneal or supraclavicular lymph node metastases, elevated LDH, CVC
Bezan et al[18], 2017	657	34 (5.2%)	> All stages of TGCT;
			> TEE: During 1st year of follow-up;
			> Risk factors for TEE: Higher clinical stage and RPLN, increased number of cycles of chemotherapy
Tran et al[19], 2019	1135	150 (10%)	> Metastatic TGCT;
			> TEE: During or within 90 d of chemotherapy;
			> Risk factors for TEE: Large RPLN, CVC
Paffenholz et al[16], 2019	225	49 (19%)	> All stages of TGCT;
			> TEE: Start of chemotherapy to 6 mo after;
			> Risk factors for TEE: Higher clinical stage, elevated serum LDH, febrile neutropenia, CVC;
			> Patients with TEE had significantly reduced overall survival during median follow-up of 8 mo
Current Study, 2020	68	18 (26.5%)	> All stages of TCGT;
			> TEE: Following orchiectomy;
			> Risk factors for TEE: Higher pathologic stage, greater number of chemotherapy cycles

TGCT: Testicular germ cell tumor; TEE: Thromboembolic event; LDH: Lactic acid dehydrogenase; RPLN: Retroperitoneal lymph node; CVC: Central venous catheter.