Second Malignant Neoplasms in Testicular Cancer Survivors

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Second malignant neoplasms (SMNs) are a potentially life-threatening late effect of testicular cancer (TC) and its therapy. Although the increased risk for developing solid tumors among TC survivors is largely attributed to radiotherapy, chemotherapy may also be associated with excess risks. However, the baseline risks of developing site-specific SMNs in TC survivors have not yet been quantified, nor have interactions between treatments and other risk factors been elucidated. Studies to date report overall relative risks ranging from 1.4- to 2.8-fold for SMN in TC survivors, with significantly elevated risks apparent for more than 35 years. Analytic investigations show relationships between increasing radiation dose and/or field size and solid tumor risk. Small excess risks of leukemia follow treatment with either chemotherapy or radiotherapy. Recently, concern has been expressed about the increased risk of SMN from radiation exposure during imaging surveillance for recurrence. A small number of studies have examined this issue, generating inconclusive results. Given the current changes in TC treatment that result in lower radiation doses, in the future solid tumors will likely have a considerably lower impact on the lives of TC survivors, although diligent follow-up will be required to accurately quantify long-term risks and to ascertain risks associated with chemotherapy.

Correspondence: Lois B. Travis, MD, ScD, Rubin Center for Cancer Survivorship and Department of Radiation Oncology, James P. Wilmot Cancer Center, University of Rochester Medical Center, 265 Crittenden Boulevard, Box CU420318, Rochester, NY 14642. E-mail: lois_travis@urmc.rochester.edu
  • 1

    HowladerNNooneAMKrapchoM. eds. SEER Cancer Statistics Review1975–2008. Surveillance Epidemiology and End Results Web site. Available at: http://seer.cancer.gov/csr/1975_2008/. Accessed October 12 2011.

    • Search Google Scholar
    • Export Citation
  • 2

    TravisLBBeardCAllanJM. Testicular cancer survivorship: research strategies and recommendations. J Natl Cancer Inst2010;102:11141130.

    • Search Google Scholar
    • Export Citation
  • 3

    RichiardiLSceloGBoffettaP. Second malignancies among survivors of germ-cell testicular cancer: a pooled analysis between 13 cancer registries. Int J Cancer2007;120:623631.

    • Search Google Scholar
    • Export Citation
  • 4

    LiCEkwuemeDURimSHTangkaFK. Years of potential life lost and productivity losses from male urogenital cancer deaths—United States, 2004. Urology2010;76:528535.

    • Search Google Scholar
    • Export Citation
  • 5

    BachaudJMBerthierFSoulieM. Second non-germ cell malignancies in patients treated for stage I-II testicular seminoma. Radiother Oncol1999;50:191197.

    • Search Google Scholar
    • Export Citation
  • 6

    FossaSDLangmarkFAassN. Second non-germ cell malignancies after radiotherapy of testicular cancer with or without chemotherapy. Br J Cancer1990;61:639643.

    • Search Google Scholar
    • Export Citation
  • 7

    HemminkiKLiuHSundquistJ. Second cancers after testicular cancer diagnosed after 1980 in Sweden. Ann Oncol2010;21:15461551.

  • 8

    TravisLBAnderssonMGospodarowiczM. Treatment-associated leukemia following testicular cancer. J Natl Cancer Inst2000;92:11651171.

  • 9

    TravisLBCurtisREStormH. Risk of second malignant neoplasms among long-term survivors of testicular cancer. J Natl Cancer Inst1997;89:14291439.

    • Search Google Scholar
    • Export Citation
  • 10

    TravisLBFossaSDSchonfeldSJ. Second cancers among 40,576 testicular cancer patients: focus on long-term survivors. J Natl Cancer Inst2005;97:13541365.

    • Search Google Scholar
    • Export Citation
  • 11

    van den Belt-DuseboutAWde WitRGietemaJA. Treatment-specific risks of second malignancies and cardiovascular disease in 5-year survivors of testicular cancer. J Clin Oncol2007;25:43704378.

    • Search Google Scholar
    • Export Citation
  • 12

    van LeeuwenFEStiggelboutAMvan den Belt-Dusebout. Second cancer risk following testicular cancer: a follow-up study of 1,909 patients. J Clin Oncol1993;11:415424.

    • Search Google Scholar
    • Export Citation
  • 13

    WanderasEHFossaSDTretliS. Risk of subsequent non-germ cell cancer after treatment of germ cell cancer in 2006 Norwegian male patients. Eur J Cancer1997;33:253262.

    • Search Google Scholar
    • Export Citation
  • 14

    JonesWGFossaSDMeadGM. Randomized trial of 30 versus 20 Gy in the adjuvant treatment of stage I testicular seminoma: a report on Medical Research Council Trial TE18, European Organisation for the Research and Treatment of Cancer trial 30942 (ISRCTN18525328). J Clin Oncol2005;23:12001208.

    • Search Google Scholar
    • Export Citation
  • 15

    OliverRTMeadGMRustinGJ. Randomized trial of carboplatin versus radiotherapy for stage I seminoma: mature results on relapse and contralateral testis cancer rates in MRC TE19/EORTC 30982 study (ISRCTN27163214). J Clin Oncol2011;29:957962.

    • Search Google Scholar
    • Export Citation
  • 16

    GrollRJWardePJewettMA. A comprehensive systematic review of testicular germ cell tumor surveillance. Crit Rev Oncol Hematol2007;64:182197.

    • Search Google Scholar
    • Export Citation
  • 17

    AlbersPAlbrechtWAlgabaF. EAU guidelines on testicular cancer: 2011 update. Eur Urol2011;60:304319.

  • 18

    ClassenJSchmidbergerHMeisnerC. Radiotherapy for stages IIA/B testicular seminoma: final report of a prospective multicenter clinical trial. J Clin Oncol2003;21:11011106.

    • Search Google Scholar
    • Export Citation
  • 19

    PattersonHNormanARMitraSS. Combination carboplatin and radiotherapy in the management of stage II testicular seminoma: comparison with radiotherapy treatment alone. Radiother Oncol2001;59:511.

    • Search Google Scholar
    • Export Citation
  • 20

    SchmidbergerHBambergMMeisnerC. Radiotherapy in stage IIA and IIB testicular seminoma with reduced portals: a prospective multicenter study. Int J Radiat Oncol Biol Phys1997;39:321326.

    • Search Google Scholar
    • Export Citation
  • 21

    Garcia-del-MuroXMarotoPGumaJ. Chemotherapy as an alternative to radiotherapy in the treatment of stage IIA and IIB testicular seminoma: a Spanish Germ Cell Cancer Group study. J Clin Oncol2008;26:54165421.

    • Search Google Scholar
    • Export Citation
  • 22

    EinhornLHDonohueJ. Cis-diamminedichloroplatinum, vinblastine, and bleomycin combination chemotherapy in disseminated testicular cancer. Ann Intern Med1977;87:293298.

    • Search Google Scholar
    • Export Citation
  • 23

    DonohueJPThornhillJAFosterRS. The role of retroperitoneal lymphadenectomy in clinical stage B testis cancer: the Indiana University experience (1965 to 1989). J Urol1995;153:8589.

    • Search Google Scholar
    • Export Citation
  • 24

    FosterRBihrleR. Current status of retroperitoneal lymph node dissection and testicular cancer: when to operate. Cancer Control2002;9:277283.

    • Search Google Scholar
    • Export Citation
  • 25

    StephensonAJBoslGJMotzerRJ. Retroperitoneal lymph node dissection for nonseminomatous germ cell testicular cancer: impact of patient selection factors on outcome. J Clin Oncol2005;23:27812788.

    • Search Google Scholar
    • Export Citation
  • 26

    OechsleKBokemeyerC. Treatment of brain metastases from germ cell tumors. Hematol Oncol Clin North Am2011;25:605613ix.

  • 27

    DaugaardGPetersenPMRorthM. Surveillance in stage I testicular cancer. APMIS2003;111:7683; discussion 83–85.

  • 28

    ReadGStenningSPCullenMH. Medical Research Council prospective study of surveillance for stage I testicular teratoma. Medical Research Council Testicular Tumors Working Party. J Clin Oncol1992;10:17621768.

    • Search Google Scholar
    • Export Citation
  • 29

    WardePHuddartRBoltonD. Management of localized seminoma, stage I-II: SIU/ICUD Consensus Meeting on Germ Cell Tumors (GCT), Shanghai 2009. Urology2011;78(4 Suppl):S435443.

    • Search Google Scholar
    • Export Citation
  • 30

    ChamieKKurzrockEAEvansCP. Secondary malignancies among nonseminomatous germ cell tumor cancer survivors. Cancer2011;117:42194230.

  • 31

    TarinTVSonnGShinghalR. Estimating the risk of cancer associated with imaging related radiation during surveillance for stage I testicular cancer using computerized tomography. J Urol2009;181:627632; discussion 632–633.

    • Search Google Scholar
    • Export Citation
  • 32

    van WalravenCFergussonDEarleC. Association of diagnostic radiation exposure and second abdominal-pelvic malignancies after testicular cancer. J Clin Oncol2011;29:28832888.

    • Search Google Scholar
    • Export Citation
  • 33

    International Germ Cell Consensus Classification: a prognostic factor-based staging system for metastatic germ cell cancers. International Germ Cell Cancer Collaborative Group. J Clin Oncol1997;15:594603.

    • Search Google Scholar
    • Export Citation
  • 34

    BajorinDFSarosdyMFPfisterDG. Randomized trial of etoposide and cisplatin versus etoposide and carboplatin in patients with good-risk germ cell tumors: a multiinstitutional study. J Clin Oncol1993;11:598606.

    • Search Google Scholar
    • Export Citation
  • 35

    KondaguntaGVBacikJBajorinD. Etoposide and cisplatin chemotherapy for metastatic good-risk germ cell tumors. J Clin Oncol2005;23:92909294.

    • Search Google Scholar
    • Export Citation
  • 36

    KondaguntaGVBacikJDonadioA. Combination of paclitaxel, ifosfamide, and cisplatin is an effective second-line therapy for patients with relapsed testicular germ cell tumors. J Clin Oncol2005;23:65496555.

    • Search Google Scholar
    • Export Citation
  • 37

    LoehrerPJSrGoninRNicholsCR. Vinblastine plus ifosfamide plus cisplatin as initial salvage therapy in recurrent germ cell tumor. J Clin Oncol1998;16:25002504.

    • Search Google Scholar
    • Export Citation
  • 38

    NicholsCRCatalanoPJCrawfordED. Randomized comparison of cisplatin and etoposide and either bleomycin or ifosfamide in treatment of advanced disseminated germ cell tumors: an Eastern Cooperative Oncology Group, Southwest Oncology Group, and Cancer and Leukemia Group B study. J Clin Oncol1998;16:12871293.

    • Search Google Scholar
    • Export Citation
  • 39

    WilliamsSDBirchREinhornLH. Treatment of disseminated germ-cell tumors with cisplatin, bleomycin, and either vinblastine or etoposide. N Engl J Med1987;316:14351440.

    • Search Google Scholar
    • Export Citation
  • 40

    TravisLBBhatiaSAllanJM. Second primary cancers. In: DeVitaVTJrLawrenceTSRosenbergSA eds. Cancer: Principles and Practice of Oncology. Philadelphia, PA: Lippincott Williams & Wilkins; 2011:23932410.

    • Search Google Scholar
    • Export Citation
  • 41

    van den Belt-DuseboutAWAlemanBMBesselingG. Roles of radiation dose and chemotherapy in the etiology of stomach cancer as a second malignancy. Int J Radiat Oncol Biol Phys2009;75:14201429.

    • Search Google Scholar
    • Export Citation
  • 42

    ZwahlenDRMartinJMMillarJLSchneiderU. Effect of radiotherapy volume and dose on secondary cancer risk in stage I testicular seminoma. Int J Radiat Oncol Biol Phys2008;70:853858.

    • Search Google Scholar
    • Export Citation
  • 43

    FossaSDHorwichARussellJM. Optimal planning target volume for stage I testicular seminoma: a Medical Research Council randomized trial. Medical Research Council Testicular Tumor Working Group. J Clin Oncol1999;17:1146.

    • Search Google Scholar
    • Export Citation
  • 44

    KollmannsbergerCBeyerJDrozJP. Secondary leukemia following high cumulative doses of etoposide in patients treated for advanced germ cell tumors. J Clin Oncol1998;16:33863391.

    • Search Google Scholar
    • Export Citation
  • 45

    KollmannsbergerCHartmannJTKanzLBokemeyerC. Therapy-related malignancies following treatment of germ cell cancer. Int J Cancer1999;83:860863.

    • Search Google Scholar
    • Export Citation
  • 46

    TravisLBHolowatyEJBergfeldtK. Risk of leukemia after platinum-based chemotherapy for ovarian cancer. N Engl J Med1999;340:351357.

  • 47

    BokemeyerCSchmollHJ. Secondary neoplasms following treatment of malignant germ cell tumors. J Clin Oncol1993;11:17031709.

  • 48

    HartmannJTKollmannsbergerCKanzLBokemeyerC. Platinum organ toxicity and possible prevention in patients with testicular cancer. Int J Cancer1999;83:866869.

    • Search Google Scholar
    • Export Citation
  • 49

    StewartDJMikhaelNZNanjiAA. Renal and hepatic concentrations of platinum: relationship to cisplatin time, dose, and nephrotoxicity. J Clin Oncol1985;3:12511256.

    • Search Google Scholar
    • Export Citation
  • 50

    TothillPKlysHSMathesonLM. The long-term retention of platinum in human tissues following the administration of cisplatin or carboplatin for cancer chemotherapy. Eur J Cancer1992;28A:13581361.

    • Search Google Scholar
    • Export Citation
  • 51

    UozumiJUedaTYasumasuT. Platinum accumulation in the kidney and liver following chemotherapy with cisplatin in humans. Int Urol Nephrol1993;25:215220.

    • Search Google Scholar
    • Export Citation
  • 52

    AllanJMTravisLB. Mechanisms of therapy-related carcinogenesis. Nat Rev Cancer2005;5:943955.

  • 53

    ClaijNte RieleH. Microsatellite instability in human cancer: a prognostic marker for chemotherapy?Exp Cell Res1999;246:110.

  • 54

    RobinsonENeugutAI. Clinical aspects of multiple primary neoplasms. Cancer Detect Prev1989;13:287292.

  • 55

    FajardoLF. The pathology of ionizing radiation as defined by morphologic patterns. Acta Oncol2005;44:1322.

  • 56

    NiederCMilasLAngKK. Tissue tolerance to reirradiation. Semin Radiat Oncol2000;10:200209.

  • 57

    TibbsMK. Wound healing following radiation therapy: a review. Radiother Oncol1997;42:99106.

  • 58

    SchairerCHisadaMChenBE. Comparative mortality for 621 second cancers in 29356 testicular cancer survivors and 12420 matched first cancers. J Natl Cancer Inst2007;99:12481256.

    • Search Google Scholar
    • Export Citation
  • 59

    BrennerDJHallEJ. Computed tomography—an increasing source of radiation exposure. N Engl J Med2007;357:22772284.

  • 60

    Smith-BindmanRLipsonJMarcusR. Radiation dose associated with common computed tomography examinations and the associated lifetime attributable risk of cancer. Arch Intern Med2009;169:20782086.

    • Search Google Scholar
    • Export Citation
  • 61

    Health risks from exposure to low levels of ionizing radiation: BEIR VII phase 2. Washington, DC: The National Academies Press; 2005.

  • 62

    O’MalleyMEChungPHaiderM. Comparison of low dose with standard dose abdominal/pelvic multidetector CT in patients with stage 1 testicular cancer under surveillance. Eur Radiol2010;20:16241630.

    • Search Google Scholar
    • Export Citation
  • 63

    FungCVaughnDJ. Complications associated with chemotherapy in testicular cancer management. Nat Rev Urol2011;8:213222.

  • 64

    FeldmanDR. The approach to the patient with synchronous bilateral germ cell tumors: a lesson in oncologic prioritization. Oncology (Williston Park)2010;24:761763.

    • Search Google Scholar
    • Export Citation
  • 65

    BuchlerTKubankovaPBoublikovaL. Detection of second malignancies during long-term follow-up of testicular cancer survivors. Cancer2011;117:42124218.

    • Search Google Scholar
    • Export Citation
  • 66

    TravisLBNgAKAllanJM. Second malignant neoplasms and cardiovascular disease after radiotherapy. J Natl Cancer Inst2012;104:357370.

  • 67

    BestTLiDSkolAD. Variants at 6q21 implicate PRDM1 in the etiology of therapy-induced second malignancies after Hodgkin’s lymphoma. Nat Med2011;17:941943.

    • Search Google Scholar
    • Export Citation
  • 68

    KnightJASkolADShindeA. Genome-wide association study to identify novel loci associated with therapy-related myeloid leukemia susceptibility. Blood2009;113:55755582.

    • Search Google Scholar
    • Export Citation
  • 69

    TravisLBRabkinCSBrownLM. Cancer survivorship— genetic susceptibility and second primary cancers: research strategies and recommendations. J Natl Cancer Inst2006;98:1525.

    • Search Google Scholar
    • Export Citation
  • 70

    Berrington de GonzalezAMaheshMKimKP. Projected cancer risks from computed tomographic scans performed in the United States in 2007. Arch Intern Med2009;169:20712077.

    • Search Google Scholar
    • Export Citation
  • 71

    KushiLHDoyleCMcCulloughM. American Cancer Society Guidelines on Nutrition and Physical Activity for Cancer Prevention: reducing the risk of cancer with healthy food choices and physical activity. CA Cancer J Clin2012;32:3067.

    • Search Google Scholar
    • Export Citation
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