Toxicities Associated with Cisplatin-Based Chemotherapy and Radiotherapy in Long-Term Testicular Cancer Survivors

Table 2

Relative risks of second malignant neoplasms (SMN) in testicular cancer survivors.

	No. of patients	Calendar years of testicular cancer diagnosis	Duration of follow-up (years)	Treatment	Obs.	RR	(95% CI)
Study populations^a
All SMNs
Norwegian radium hospital [66]	2006	1952–1990	Mean = 12.5	Any	153^b	1.7	1.4–1.9
				RT	130	1.6	1.3–1.9
				CT	4	1.3	0.4–3.4
				RT + CT	15	3.5	2.0–5.8
Fourteen population-based tumor registries in Europe and North America [55]	40,576	1943–2001	Mean = 11.3	Any	1694	1.9	1.8–2.1
				RT	892	2.0	1.9–2.2
				CT	35	1.8	1.3–2.5
				RT + CT	25	2.9	1.9–4.2
Thirteen International Cancer Registries [164]	29,511	1943–2000	Median = 8.3	Any	1811^c	1.7	1.6–1.7
Netherlands testicular cancer survivor cohort [46]	2707	1965–1995	Median = 17.6	Any	270^d	1.7	1.5–1.9
				RT	199	1.7	1.5–2.0
				CT	23	1.4	0.9–2.1
				RT + CT	29	3.0	2.0–4.4
				SDRT	N/A	2.6^g	1.7–4.0
				SDRT + MRT	N/A	3.6^g	2.1–6.0
				PVB/BEP	N/A	2.1^g	1.4–3.1
				SDRT (26–35 Gy)	N/A	2.3^g	1.5–3.6
				SDRT (40–50 Gy)	N/A	3.2^g	2.1–5.1
Swedish family cancer database [165]	5533	1980–2006	N/A	Any	274^e	2.0	1.8–2.2
Second solid cancers	12,691	1980–2008	Median = 7.0	Initial surgery only	99	0.9	0.8–1.1
Sixteen population-based registries within the SEER program [67]				Initial CT (no RT)	111^f	1.4	1.2–1.7
Therapy-associated leukemia
Nested case-control study of leukemia in 8 population-based tumor registries in Europe and North America [56]	18,567	1970–1993	N/A	No RT/CT	4	1.0	—
				RT	22	3.1	0.7–2.2
				CT	8	5.0	1.1–40
				RT + CT	2	5.1	0.5–28

Adapted with permission from Fung et al. J Natl Compr Canc Netw 2012; 10:545-56 (Table 2). RR: relative risk; CI: confidence interval; Obs.: observed number of cases; RT: any radiation treatment; CT: chemotherapy; IDRT: infradiaphragmatic radiation; SDRT: supradiaphragmatic radiation; MRT: mediastinal radiation; PVB: cisplatin, vinblastine, bleomycin; BEP: bleomycin, etoposide, cisplatin; N/A: not available (data not provided). (a) There was overlap in the cancer registries included in the cohort studies by Richiardi et al. [164] and Travis et al. [55], with the following countries contributing patients to both studies: Denmark, Finland, Norway, and Sweden; (b) six cases of leukemia were observed with a RR of 1.9 (95% CI: 0.7–4.1); (c) thirty-eight cases of myeloid leukemia were observed with a RR of 3.6 (95% CI: 2.6–5.0); thirteen cases of lymphoid leukemia were observed with a RR of 1.0 (95% CI: 0.5–1.7); twenty-three cases of other types of leukemia were observed with a RR of 3.5 (95% CI: 2.2–5.2); (d) six cases of leukemia were observed with a RR of 1.6 (95% CI: 0.6–3.5); (e) hazard ratios are shown, with the referent group consisting of patients treated with surgery alone (HR = 1.0). Twelve cases of leukemia were observed with a RR of 3.8 (95% CI: 2.0–6.7); (f) significantly increased risks occurred for cancers of the kidney (SIR = 3.4; 95% CI 1.8–5.7; n = 13); thyroid (SIR = 4.4; 95% CI: 2.2–7.9; n = 11); and soft tissue (SIR = 7.5; 95% CI: 3.6–13.8; n = 10).