Historical thinking has been that in the face of metastatic CaP, removal of the primary tumor is of no benefit. This study selected patients with advanced or lymph node positive CaP for one year of androgen deprivation therapy (ADT) and docetaxel followed by radical prostatectomy (RP) or cystoprostatectomy. Pathologic and molecular features of the primary tumor were analyzed and compared with archived patients with high-risk CaP that did not undergo systemic treatment.
The study was a prospective phase II trial for 40 men with high-risk CaP with probability of lymph-node metastasis but not bone metastasis. Patients received 3 cycles of docetaxel chemotherapy plus ADT followed by surgery. Immunohistochemistry (IHC) and tissue microarrays (TMAs) were assessed by IHC for markers of epithelial function and intracellular signaling, stromal-epithelial interaction and angiogenesis. At the end of treatment, 30 men underwent RP and 2 cystoprostatectomy. They did not find correlation between the expression of the biomarkers and the pathologic T stage or tumor volume. There was no difference between treated and control patients with regard to markers of proliferation, apoptosis, or neuroendocrine differentiation. Also, there was no difference of activated androgen receptor (AR) between treated and control specimens. However, biosynthetic enzymes CYP17 and SRD5A1 had enhanced expression in epithelial and stromal compartments of the treated specimens compared to controls. Hedgehog signaling was increased in the epithelia and stroma of treated patients. IGF-I was increased only in epithelial cells after treatment. All three pathways (intracrine androgen biosynthesis, hedgehog and IGF) were increased in 20 of 29 treated tumors and 8 upregulated two of the three.
These data suggest that several pathway targets persist after one year’s treatment with ADT and docetaxel chemotherapy that drive tumor progression.
Tzelepi V, Efstathiou E, Wen S, Troncoso P, Karlou M, Pettaway CA, Pisters LL, Hoang A, Logothetis CJ, Pagliaro LC
J Clin Oncol. 2011 Jun 20;29(18):2574-81
10.1200/JCO.2010.33.2999
PubMed Abstract
PMID: 21606419
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