The role of metabolic imaging in radiation therapy of prostate cancer.
The goal of this study was to correlate prostatic metabolite concentrations from snap-frozen patient biopsies of recurrent cancer after failed radiation therapy with histopathological findings, including Ki-67 immunohistochemistry and pathologic grade, in order to identify quantitative metabolic biomarkers that predict for residual aggressive versus indolent cancer. A total of 124 snap-frozen transrectal ultrasound (TRUS)-guided biopsies were acquired from 47 men with untreated prostate cancer and from 39 men with a rising prostate-specific antigen and recurrent prostate cancer following radiation therapy. Biopsy tissues with Ki-67 labeling index ≤ 5% were classified as indolent cancer, while biopsy tissues with Ki-67 labeling index > 5% were classified as aggressive cancer. The majority (15 out of 17) of cancers classified as aggressive had a primary Gleason 4 pattern (Gleason score ≥ 4 + 3). The concentrations of choline-containing phospholipid metabolites (PC, GPC, and free Cho) and lactate were significantly elevated in recurrent cancer relative to surrounding benign tissues. There was also a significant increase in [PC] and reduction in [GPC] between untreated and irradiated prostate cancer biopsies. The concentration of the choline-containing phospholipid metabolites was significantly higher in recurrent aggressive (≈ twofold) than in recurrent indolent cancer biopsies, and the receiver operating characteristic (ROC) curve analysis of total choline to creatine ratio (tCho/Cr) demonstrated an accuracy of 95% (confidence interval = 0.88-1.00) for predicting aggressive recurrent disease. The tCho/Cr was significantly higher for identifying recurrent aggressive versus indolent cancer (tCho/Cr = 2.4 ± 0.4 versus 1.5 ± 0.2), suggesting that use of a higher threshold tCho/Cr ratio in future in vivo (1)H MRSI studies could improve the selection and therapeutic planning for patients who would benefit most from salvage focal therapy after failed radiation therapy.
Department of Radiology and Biomedical Imaging, University of California San Francisco (UCSF), CA, USA.
V Y
VY
Zhang
A
A
Westphalen
L
L
Delos Santos
Z L
ZL
Tabatabai
K
K
Shinohara
D B
DB
Vigneron
J
J
Kurhanewicz
D000368:Aged; D001706:Biopsy; D003401:Creatine / Q000378:metabolism; D003952:Diagnostic Imaging / Q000379:methods*; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D055432:Metabolomics / Q000379:methods*; D010767:Phosphorylcholine / Q000378:metabolism; D011467:Prostate / Q000378:metabolism / Q000473:pathology; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D011859:Radiography
D019394:Ki-67 Antigen; D010767:Phosphorylcholine; D003401:Creatine
Gleason score; HR-MAS; Ki-67; MR spectroscopy; pathologic grade; phospholipid metabolism; prostate cancer; radiation therapy