title: Neoadjuvant androgen deprivation and prostate gland shrinkage during conformal radiotherapy.
abstract: OBJECTIVE
  The shrinking effect of 3-month neoadjuvant androgen deprivation (NAD) on preradiotherapy prostate gland volume is well documented. However, recently, it has been shown that the cancerous prostate gland keeps shrinking up to 12 months after NAD start. Thus, if such a reduction is not taken into account, a larger than planned portion of the surrounding normal tissues might shift in the high-dose region during conformal radiotherapy (3DCRT) course. The present study was undertaken to quantify this issue.
  
  
  METHODS
  Prostate gland volume reduction between planning CT (plCT) and the last week of 3DCRT (tmtCT) was prospectively assessed in 33 consecutive patients with localized prostate carcinoma. The median time interval between plCT and tmtCT was 2.5 months (2.1-2.7 months). A single observer was asked to draw on each slice prostate gland volume as appropriate. The observer was 'blind' to the timing of CT (plCT vs. tmtCT). In order to estimate intra-observer variability, prostate gland delineation was repeated twice for each data set. Mean prostate gland change, plCT and tmtCT cumulative dose volume histogram (DVH) calculations for the rectum were analyzed for each patient. Results were correlated to AD status and its duration before plCT. Means were compared by non-parametric rank tests.
  
  
  RESULTS
  Based on an internal protocol, 14 patients (42%) did not receive AD, while 19 patients (58%) had undergone neoadjuvant and concomitant AD. The median duration of AD before plCT ranged from 0.2 to 6 months (median: 2.9 months). Although individual data were highly variable, compared to plCT volume, mean prostate gland volume change at the end of 3DCRT was similar for patients receiving (-7.3%) or not (-7%) androgen deprivation (P=0.77). However, within the group of patients treated with hormones, patients starting AD within 3 months from plCT had a significantly larger reduction in prostate volume (-14.2%) than patients with longer NAD duration (-1.1%, P=0.03). At tmtCT, on average, patients undergoing 3DCRT within 3 months from AD start showed an increase of the amount of rectum receiving 40-75 Gy compared to plCT values. At 40 Gy (V40) the mean difference between tmtCT and plCT was +7.5%. In the other two groups, average variations of V40-70 were within +/-2% of plCT values. However, these differences are not significant.
  
  
  CONCLUSIONS
  For patients who undergo plCT and 3DCRT shortly after AD start, prostate gland shrinkage may be substantial. In some of these patients, this might lead to an unexpected increase of the percentage of rectal wall exposed to intermediate doses.
authors.affiliation: Department of Radiation Oncology, National Institute for Cancer Research, Genoa, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Sanguineti
authors.forename: Michela
authors.initials: M
authors.lastname: Marcenaro
authors.forename: Paola
authors.initials: P
authors.lastname: Franzone
authors.forename: Franca
authors.initials: F
authors.lastname: Foppiano
authors.forename: Vito
authors.initials: V
authors.lastname: Vitale
mesh_terms: D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004307:Dose-Response Relationship, Radiation; D005485:Flutamide / Q000627:therapeutic use*; D006801:Humans; D016729:Leuprolide / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D015588:Observer Variation; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000032:analysis; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D020266:Radiotherapy, Conformal / Q000009:adverse effects; D012007:Rectum / Q000528:radiation effects*; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D005485:Flutamide; D017430:Prostate-Specific Antigen; D016729:Leuprolide