title: Solid tumors after chemotherapy or surgery for testicular nonseminoma: a population-based study.
abstract: OBJECTIVE
  Increased risks of solid tumors after older radiotherapy strategies for testicular cancer (TC) are well established. Few population-based studies, however, focus on solid cancer risk among survivors of TC managed with nonradiotherapy approaches. We quantified the site-specific risk of solid cancers among testicular nonseminoma patients treated in the modern era of cisplatin-based chemotherapy, without radiotherapy.
  
  
  METHODS
  Standardized incidence ratios (SIRs) for solid tumors were calculated for 12,691 patients with testicular nonseminoma reported to the population-based Surveillance, Epidemiology, and End Results program (1980 to 2008) and treated initially with either chemotherapy (n = 6,013) or surgery (n = 6,678) without radiotherapy. Patients accrued 116,073 person-years of follow-up.
  
  
  RESULTS
  Two hundred ten second solid cancers were observed. No increased risk followed surgery alone (SIR, 0.93; 95% CI, 0.76 to 1.14; n = 99 solid cancers), whereas significantly increased 40% excesses (SIR, 1.43; 95% CI, 1.18 to 1.73; n = 111 solid cancers) occurred after chemotherapy. Increased risks of solid cancers after chemotherapy were observed in most follow-up periods (median latency, 12.5 years), including more than 20 years after treatment (SIR, 1.54; 95% CI, 0.96 to 2.33); significantly increased three- to seven-fold risks occurred for cancers of the kidney (SIR, 3.37; 95% CI, 1.79 to 5.77), thyroid (SIR, 4.40; 95% CI, 2.19 to 7.88), and soft tissue (SIR, 7.49; 95% CI, 3.59 to 13.78).
  
  
  CONCLUSIONS
  To our knowledge, this is the first large population-based series reporting significantly increased risks of solid cancers among patients with testicular nonseminoma treated in the modern era of cisplatin-based chemotherapy. Subsequent analytic studies should focus on the evaluation of dose-response relationships, types of solid cancers, latency patterns, and interactions with other possible factors, including genetic susceptibility.
authors.affiliation: Chunkit Fung, Michael T. Milano, and Lois B. Travis, University of Rochester Medical Center, Rochester, NY; and Sophie D. Fossa and Jan Oldenburg, Norwegian Radium Hospital, Oslo, Norway.
authors.forename: Chunkit
authors.initials: C
authors.lastname: Fung
authors.forename: Sophie D
authors.initials: SD
authors.lastname: Fossa
authors.forename: Michael T
authors.initials: MT
authors.lastname: Milano
authors.forename: Jan
authors.initials: J
authors.lastname: Oldenburg
authors.forename: Lois B
authors.initials: LB
authors.lastname: Travis
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D015994:Incidence; D007680:Kidney Neoplasms / Q000453:epidemiology; D008297:Male; D009373:Neoplasms, Germ Cell and Embryonal / Q000188:drug therapy* / Q000601:surgery*; D016609:Neoplasms, Second Primary / Q000175:diagnosis / Q000453:epidemiology* / Q000401:mortality; D018570:Risk Assessment; D012307:Risk Factors; D018426:SEER Program; D012983:Soft Tissue Neoplasms / Q000453:epidemiology; D013736:Testicular Neoplasms / Q000188:drug therapy* / Q000601:surgery*; D013964:Thyroid Neoplasms / Q000453:epidemiology; D014481:United States / Q000453:epidemiology
chemical_list: D002945:Cisplatin
references.citation: Hematol Oncol Clin North Am. 2011 Jun;25(3):605-13, ix
references.pmid: 21570612
references.citation: IARC Sci Publ. 1987;(82):1-406
references.pmid: 3329634
references.citation: J Clin Oncol. 2006 Dec 10;24(35):5503-11
references.pmid: 17158535
references.citation: Eur J Cancer. 1997 Feb;33(2):253-62
references.pmid: 9135497
references.citation: Urology. 1998 Feb;51(2):203-5
references.pmid: 9495698
references.citation: CA Cancer J Clin. 2012 Jul-Aug;62(4):220-41
references.pmid: 22700443
references.citation: J Clin Oncol. 1993 Mar;11(3):415-24
references.pmid: 8445415
references.citation: Ann Oncol. 2010 Jul;21(7):1546-1551
references.pmid: 20019089
references.citation: Br J Cancer. 1990 Apr;61(4):639-43
references.pmid: 2109999
references.citation: J Clin Oncol. 1993 Sep;11(9):1703-9
references.pmid: 8394879
references.citation: Int J Cancer. 2007 Feb 1;120(3):623-31
references.pmid: 17096341
references.citation: J Clin Oncol. 2005 Sep 20;23(27):6549-55
references.pmid: 16170162
references.citation: J Natl Cancer Inst. 2013 Apr 3;105(7):504-8
references.pmid: 23515901
references.citation: APMIS. 2003 Jan;111(1):76-83; discussion 83-5
references.pmid: 12752240
references.citation: Arch Intern Med. 2009 Dec 14;169(22):2071-7
references.pmid: 20008689
references.citation: Br J Cancer. 2007 Sep 3;97(5):695-9
references.pmid: 17653071
references.citation: Urol Oncol. 2009 Nov-Dec;27(6):604-10
references.pmid: 18799329
references.citation: J Clin Endocrinol Metab. 2001 Nov;86(11):5307-12
references.pmid: 11701697
references.citation: J Clin Oncol. 1992 Nov;10(11):1762-8
references.pmid: 1403057
references.citation: MMWR Morb Mortal Wkly Rep. 2011 Sep 30;60(38):1305-9
references.pmid: 21956406
references.citation: J Clin Oncol. 2010 May 1;28(13):2274-9
references.pmid: 20368572
references.citation: J Natl Cancer Inst. 2005 Sep 21;97(18):1354-65
references.pmid: 16174857
references.citation: Cancer Res. 1992 Jan 1;52(1):149-53
references.pmid: 1727376
references.citation: CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90
references.pmid: 21296855
references.citation: Eur Urol. 2004 Aug;46(2):209-14; discussion 214-5
references.pmid: 15245815
references.citation: Cancer Epidemiol Biomarkers Prev. 2012 Jan;21(1):92-101
references.pmid: 22028399
references.citation: N Engl J Med. 1987 Sep 3;317(10):588-93
references.pmid: 3475572
references.citation: BMC Clin Pharmacol. 2008 Sep 17;8:7
references.pmid: 18796166
references.citation: J Urol. 1998 Jan;159(1):133-8
references.pmid: 9400455
references.citation: N Engl J Med. 1997 Jul 24;337(4):242-53
references.pmid: 9227931
references.citation: J Clin Oncol. 1998 Apr;16(4):1287-93
references.pmid: 9552027
references.citation: J Natl Cancer Inst. 2010 Aug 4;102(15):1114-30
references.pmid: 20585105
references.citation: J Natl Cancer Inst. 1992 Mar 4;84(5):306-12
references.pmid: 1738180
references.citation: J Natl Cancer Inst. 1997 Oct 1;89(19):1429-39
references.pmid: 9326912
references.citation: N Engl J Med. 1987 Jun 4;316(23):1435-40
references.pmid: 2437455
references.citation: J Natl Cancer Inst. 2006 Jan 4;98(1):15-25
references.pmid: 16391368
references.citation: J Natl Cancer Inst. 2012 Mar 7;104(5):357-70
references.pmid: 22312134
references.citation: J Clin Oncol. 2007 Oct 1;25(28):4370-8
references.pmid: 17906202
references.citation: Cancer. 2011 Sep 15;117(18):4108-11
references.pmid: 21387279
references.citation: Radiol Clin North Am. 2011 Mar;49(2):369-83
references.pmid: 21333783
references.citation: Acta Oncol. 2002;41(4):323-33
references.pmid: 12234023
references.citation: J Natl Cancer Inst. 1996 Mar 6;88(5):270-8
references.pmid: 8614005
references.citation: Acta Oncol. 2000;39(4):519-22
references.pmid: 11041115
references.citation: J Natl Cancer Inst. 2002 Feb 6;94(3):182-92
references.pmid: 11830608
references.citation: J Urol. 2003 Jul;170(1):5-11
references.pmid: 12796635
references.citation: J Clin Oncol. 2002 Aug 15;20(16):3484-94
references.pmid: 12177110
references.citation: J Clin Oncol. 2005 Dec 20;23(36):9290-4
references.pmid: 16361627
references.citation: Eur J Cancer. 1992;28A(8-9):1358-61
references.pmid: 1515251
references.citation: J Natl Cancer Inst. 1995 Apr 5;87(7):524-30
references.pmid: 7707439
references.citation: Radiother Oncol. 1999 Feb;50(2):191-7
references.pmid: 10368043
references.citation: J Clin Oncol. 2012 Oct 20;30(30):3734-45
references.pmid: 23008293
references.citation: N Engl J Med. 1999 Feb 4;340(5):351-7
references.pmid: 9929525
references.citation: J Clin Oncol. 2001 Mar 15;19(6):1610-8
references.pmid: 11250989
references.citation: Ann Oncol. 2007 Feb;18(2):241-8
references.pmid: 17060482
references.citation: Clin Endocrinol (Oxf). 2013 Jan;78(1):134-40
references.pmid: 22812676
references.citation: Cancer. 2003 Apr 15;97(8):1869-75
references.pmid: 12673712
references.citation: Lancet Oncol. 2007 Sep;8(9):784-96
references.pmid: 17714993
references.citation: Ann Intern Med. 1977 Sep;87(3):293-8
references.pmid: 71004
references.citation: Int J Radiat Oncol Biol Phys. 2009 Dec 1;75(5):1420-9
references.pmid: 19931732
references.citation: J Natl Cancer Inst. 2000 Jul 19;92(14):1165-71
references.pmid: 10904090