title: Risk of Acute Testicular Failure After Preoperative Radiotherapy for Rectal Cancer: A Prospective Cohort Study.
abstract: The aim of this study was to assess the acute effect of preoperative RT for rectal cancer on endocrine testicular function.
  
  
  
  Preoperative radiotherapy (RT) enhances local control and cancer-specific survival in patients treated for rectal cancer. In case series, a negative acute effect on Leydig cell function has been reported.
  
  
  
  This prospective cohort study included 168 males with rectal or prostate cancer stage I-III. Males treated with preoperative RT and surgery for rectal cancer formed the exposed group (n = 93). Males treated with surgery alone were assigned to the unexposed group (n = 75). The androgen levels were assessed at baseline and after preoperative RT. The exposure was quantified with the treatment planning system to estimate the cumulative testicular dose (TD). The risk of low T (serum T < below 8 nmol/L) was the primary endpoint. Secondary endpoints were serum testosterone (T), bioavailable T, luteinizing hormone (LH), and the LH-T ratio.
  
  
  
  The baseline levels of androgens were not related to exposure status or type of cancer. The proportion of low T increased from 14.6% at baseline to 35.4% after RT, relative risk 2.41 (95% CI 1.57 to 3.71, P < 0.001). Preoperative RT resulted in a significant decrease of serum and bioavailable T and a significant increase of LH and LH-T ratio. The decline in serum and bioavailable T was related to the TD.
  
  
  
  Preoperative RT for rectal cancer results in dose-dependent primary testicular failure increasing the risk of hypogonadism at the time of surgery by 2.4 times (number needed to harm = 5).
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Christian
authors.initials: C
authors.lastname: Buchli
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Anna
authors.initials: A
authors.lastname: Martling
authors.affiliation: Department of Medical Physics, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Massoud Al
authors.initials: MA
authors.lastname: Abani
authors.affiliation: Department of Oncology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Jan-Erik
authors.initials: JE
authors.lastname: Frödin
authors.affiliation: Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Matteo
authors.initials: M
authors.lastname: Bottai
authors.affiliation: Department of Medical Physics, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Ingmar
authors.initials: I
authors.lastname: Lax
authors.affiliation: Center for Andrology and Sexual Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Stefan
authors.initials: S
authors.lastname: Arver
authors.affiliation: Department of Molecular Medicine and Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Holm
mesh_terms: D000230:Adenocarcinoma / Q000532:radiotherapy* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000009:adverse effects*; D000078542:Proctectomy; D011446:Prospective Studies; D011471:Prostatic Neoplasms / Q000532:radiotherapy* / Q000601:surgery; D011832:Radiation Injuries / Q000175:diagnosis / Q000209:etiology*; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000532:radiotherapy* / Q000601:surgery; D012307:Risk Factors; D013733:Testicular Diseases / Q000175:diagnosis / Q000209:etiology*; D016896:Treatment Outcome