The number of high-risk factors and the risk of prostate cancer-specific mortality after brachytherapy: implications for treatment selection.
OBJECTIVE
To determine whether an increasing number of high-risk factors is associated with higher prostate cancer-specific mortality (PCSM) among men treated with brachytherapy (BT)-based treatment, and whether supplemental therapy has an impact on this risk.


METHODS
We analyzed the cases of 2234 men with localized prostate cancer treated between 1991 and 2007 with low-dose rate BT monotherapy (n = 457) or BT with supplemental external-beam radiotherapy (EBRT, n = 229), androgen suppression therapy (AST, n = 424), or both (n = 1124). All men had at least one high-risk factor (prostate-specific antigen >20 ng/mL, biopsy Gleason score 8-10, or clinical stage ≥T2c). Competing-risks multivariable regressions were performed to determine whether the presence of at least two high-risk factors was associated with an increased risk of PCSM, with adjustment for age, comorbidity, and the type of supplemental treatment.


RESULTS
The median follow-up time was 4.3 years. The number of men with at least two high-risk factors was highest in the group treated with BT, EBRT, and AST (21%), followed by BT plus EBRT or AST (13%), and BT alone (8%) (p(trend) < 0.001). The adjusted hazard ratio (AHR) for PCSM for those with at least two high-risk factors (as compared with one) was 4.8 (95% confidence interval [CI], 2.8-8.0; p < 0.001). The use of both supplemental EBRT and AST was associated with a decreased risk of PCSM (AHR 0.5; 95% CI, 0.2-0.9; p = 0.03) compared with BT alone. When the high-risk factors were analyzed separately, Gleason score 8-10 was most significantly associated with increased PCSM (AHR 6.2; 95% CI, 3.5-11.2; p < 0.001).


CONCLUSIONS
Men with high-risk prostate adenocarcinoma treated with BT have decreased PCSM if they receive trimodailty therapy that includes EBRT and AST. This benefit is likely most important in men with multiple determinants of high risk.
Harvard Radiation Oncology Program, Department of Radiation Oncology, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02115, USA. dwattson@partners.org
Daniel A
DA
Wattson
Ming-Hui
MH
Chen
Judd W
JW
Moul
Brian J
BJ
Moran
Daniel E
DE
Dosoretz
Cary N
CN
Robertson
Thomas J
TJ
Polascik
Michelle H
MH
Braccioforte
Sharon A
SA
Salenius
Anthony V
AV
D'Amico
D000230:Adenocarcinoma / Q000188:drug therapy / Q000401:mortality* / Q000473:pathology / Q000532:radiotherapy*; D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use; D001918:Brachytherapy / Q000379:methods / Q000401:mortality*; D002423:Cause of Death; D003131:Combined Modality Therapy / Q000379:methods / Q000401:mortality; D016001:Confidence Intervals; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D012189:Retrospective Studies; D012307:Risk Factors
D000726:Androgen Antagonists; D017430:Prostate-Specific Antigen