TY - JOUR
T1 - Docetaxel and mitoxantrone before radical prostatectomy in men with high-risk prostate cancer
T2 - 10-year follow-up and immune correlates
AU - Bergstrom, Colin P.
AU - Ruffell, Brian
AU - Ho, Christine M.T.
AU - Higano, Celestia S.
AU - Ellis, William J.
AU - Garzotto, Mark
AU - Beer, Tomasz M.
AU - Graff, Julie N.
N1 - Publisher Copyright:
© Copyright 2016 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2017/1
Y1 - 2017/1
N2 - The aims of this study were to report the clinical outcomes in a cohort of men with high-risk prostate cancer treated with neoadjuvant docetaxel and mitoxantrone 10 years after treatment, identify pretreatment clinical parameters that may be predictors of recurrence, and describe tumor-infiltrating leukocytes present in radical prostatectomy specimens. We conducted a phase I/II study of neoadjuvant docetaxel and mitoxantrone before radical prostatectomy in high-risk localized prostate cancer to determine the feasibility of this combination and predictors of prostate cancer recurrence after cytotoxic chemotherapy. After 10 years of follow-up, 34 (63%) of 54 participants experience a recurrence. In univariate analysis, prostate-specific antigen (PSA) density (P= 0.01), pathological stage (P=0.03), lymph node status (P< 0.0001), seminal vesicle invasion (P=0.003), and tissue vascular endothelial growth factor (VEGF) expression (P=0.016) were significantly associated with recurrence. In multivariate analysis, only lymph node status, PSA density, and VEGF expression were significant predictors of disease recurrence. We used a tissue microarray for the first 50 participants to characterize the tumor-infiltrating lymphocytes and evaluate them for association with recurrence. We measured CD3, CD4, CD8, FoxP3, CD20, CD15, CD68, and CD163 by immunohistochemistry in both tumor and normal prostate specimens, but did not find an association between immunophenotype and recurrence. There was a significantly different density of CD68+ and CD163+ cells between normal and tumor tissue. Lymph node status, PSA density, and tissue VEGF expression predict recurrence after chemotherapy for high-risk prostate cancer. Additional studies are needed to determine the potential benefit of chemotherapy in the neoadjuvant setting.
AB - The aims of this study were to report the clinical outcomes in a cohort of men with high-risk prostate cancer treated with neoadjuvant docetaxel and mitoxantrone 10 years after treatment, identify pretreatment clinical parameters that may be predictors of recurrence, and describe tumor-infiltrating leukocytes present in radical prostatectomy specimens. We conducted a phase I/II study of neoadjuvant docetaxel and mitoxantrone before radical prostatectomy in high-risk localized prostate cancer to determine the feasibility of this combination and predictors of prostate cancer recurrence after cytotoxic chemotherapy. After 10 years of follow-up, 34 (63%) of 54 participants experience a recurrence. In univariate analysis, prostate-specific antigen (PSA) density (P= 0.01), pathological stage (P=0.03), lymph node status (P< 0.0001), seminal vesicle invasion (P=0.003), and tissue vascular endothelial growth factor (VEGF) expression (P=0.016) were significantly associated with recurrence. In multivariate analysis, only lymph node status, PSA density, and VEGF expression were significant predictors of disease recurrence. We used a tissue microarray for the first 50 participants to characterize the tumor-infiltrating lymphocytes and evaluate them for association with recurrence. We measured CD3, CD4, CD8, FoxP3, CD20, CD15, CD68, and CD163 by immunohistochemistry in both tumor and normal prostate specimens, but did not find an association between immunophenotype and recurrence. There was a significantly different density of CD68+ and CD163+ cells between normal and tumor tissue. Lymph node status, PSA density, and tissue VEGF expression predict recurrence after chemotherapy for high-risk prostate cancer. Additional studies are needed to determine the potential benefit of chemotherapy in the neoadjuvant setting.
KW - Immunohistochemistry
KW - Neoadjuvant therapy
KW - Prostate cancer
KW - Prostate-specific antigen
KW - Prostatic neoplasms
KW - Vascular endothelial growth factor A
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U2 - 10.1097/CAD.0000000000000438
DO - 10.1097/CAD.0000000000000438
M3 - Article
C2 - 27669423
AN - SCOPUS:84988734922
SN - 0959-4973
VL - 28
SP - 120
EP - 126
JO - Anti-Cancer Drugs
JF - Anti-Cancer Drugs
IS - 1
ER -