title: Incidence of secondary cancer development after high-dose intensity-modulated radiotherapy and image-guided brachytherapy for the treatment of localized prostate cancer.
abstract: OBJECTIVE
  To report the incidence and excess risk of second malignancy (SM) development compared with the general population after external beam radiotherapy (EBRT) and brachytherapy to treat prostate cancer.
  
  
  METHODS
  Between 1998 and 2001, 1,310 patients with localized prostate cancer were treated with EBRT (n = 897) or brachytherapy (n = 413). We compared the incidence of SMs in our patients with that of the general population extracted from the National Cancer Institute's Surveillance, Epidemiology, and End Results data set combined with the 2000 census data.
  
  
  RESULTS
  The 10-year likelihood of SM development was 25% after EBRT and 15% after brachytherapy (p = .02). The corresponding 10-year likelihood for in-field SM development in these groups was 4.9% and 1.6% (p = .24). Multivariate analysis showed that EBRT vs. brachytherapy and older age were the only significant predictors for the development of all SMs (p = .037 and p = .030), with a trend for older patients to develop a SM. The increased incidence of SM for EBRT patients was explained by the greater incidence of skin cancer outside the radiation field compared with that after brachytherapy (10.6% and 3.3%, respectively, p = .004). For the EBRT group, the 5- and 10-year mortality rate was 1.96% and 5.1% from out-of field cancer, respectively; for in-field SM, the corresponding mortality rates were 0.1% and 0.7%. Among the brachytherapy group, the 5- and 10-year mortality rate related to out-of field SM was 0.8% and 2.7%, respectively. Our observed SM rates after prostate RT were not significantly different from the cancer incidence rates in the general population.
  
  
  CONCLUSIONS
  Using modern sophisticated treatment techniques, we report low rates of in-field bladder and rectal SM risks after prostate cancer RT. Furthermore, the likelihood of mortality secondary to a SM was unusual. The greater rate of SM observed with EBRT vs. brachytherapy was related to a small, but significantly increased, number of skin cancers in the EBRT patients compared with that of the general population.
authors.affiliation: Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. Zelefskm@mskcc.org
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Zelefsky
authors.forename: Douglas M
authors.initials: DM
authors.lastname: Housman
authors.forename: Xin
authors.initials: X
authors.lastname: Pei
authors.forename: Zumre
authors.initials: Z
authors.lastname: Alicikus
authors.forename: Juan Martin
authors.initials: JM
authors.lastname: Magsanoc
authors.forename: Lawrence T
authors.initials: LT
authors.lastname: Dauer
authors.forename: Jean
authors.initials: J
authors.lastname: St Germain
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Yamada
authors.forename: Marisa
authors.initials: M
authors.lastname: Kollmeier
authors.forename: Brett
authors.initials: B
authors.lastname: Cox
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000368:Aged; D001918:Brachytherapy / Q000009:adverse effects*; D006801:Humans; D015994:Incidence; D008297:Male; D015999:Multivariate Analysis; D009381:Neoplasms, Radiation-Induced / Q000453:epidemiology* / Q000401:mortality; D016609:Neoplasms, Second Primary / Q000453:epidemiology* / Q000401:mortality; D011471:Prostatic Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D061089:Radiotherapy, Image-Guided / Q000009:adverse effects*; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects*; D012004:Rectal Neoplasms / Q000453:epidemiology / Q000401:mortality; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000453:epidemiology; D001749:Urinary Bladder Neoplasms / Q000453:epidemiology / Q000401:mortality