Factors associated with improved biochemical response to neoadjuvant androgen deprivation therapy before definitive radiation therapy in prostate cancer patients.
BACKGROUND
In prostate cancer patients treated with androgen deprivation therapy (ADT) and radiation therapy (RT), a pre-RT PSA level 0.5 ng ml(-1), determined after neoadjuvant ADT and before RT, predicts for worse survival measures. The present study sought to identify patient, tumor and treatment characteristics associated with the pre-RT PSA in prostate cancer patients.


METHODS
We reviewed the charts of all patients diagnosed with intermediate- and high-risk prostate cancer and treated with a combination of neoadjuvant (median, 2.2 and 2.5 months, respectively), concurrent, and adjuvant ADT and RT between 1990 and 2011.


RESULTS
A total of 170 intermediate- and 283 high-risk patients met inclusion criteria. On multivariate analysis, both intermediate- and high-risk patients with higher pre-treatment PSA (iPSA) were significantly less likely to achieve a pre-RT PSA <0.5 ng ml(-1) (iPSA 10.1-20 ng ml(-1): P=0.005 for intermediate risk; iPSA 10.1-20 ng ml(-1): P=0.005, iPSA >20 ng ml(-1): P<0.001 for high risk). High-risk patients undergoing total androgen blockade were more likely to achieve a pre-RT PSA <0.5 ng ml(-1) (P=0.031). We observed an interaction between race and type of neoadjuvant ADT (P=0.074); whereas African-American men on total androgen blockade reached pre-RT PSA <0.5 ng ml(-1) as frequently as other men on total androgen blockade (P=0.999), African-American men on luteinizing hormone-releasing hormone (LH-RH) agonist monotherapy/orchiectomy were significantly less likely to reach pre-RT PSA <0.5 ng ml(-1) compared with other men on LH-RH monotherapy/orchiectomy (P=0.001).


CONCLUSIONS
Our findings suggest that total androgen blockade in the neoadjuvant period may be beneficial compared with LH-RH monotherapy for achieving a pre-RT PSA <0.5 ng ml(-1) in African-American men with high-risk prostate cancer. In addition, men with higher iPSA are more likely to have a pre-RT PSA greater than 0.5 ng ml(-1) in response to neoadjuvant ADT and are therefore candidates for clinical trials testing newer, more aggressive hormone-ablative therapies.
1] Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA [2] Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
J Z
JZ
Cerne
S E
SE
McGuire
S R
SR
Grant
M F
MF
Munsell
A K
AK
Lee
R J
RJ
Kudchadker
S L
SL
Choi
U
U
Mahmood
K E
KE
Hoffman
T J
TJ
Pugh
S J
SJ
Frank
D A
DA
Kuban
D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D017430:Prostate-Specific Antigen / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D012307:Risk Factors; D016896:Treatment Outcome
D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D017430:Prostate-Specific Antigen