Prostate cancer remains the most common cancer overall and the second leading cause of cancer related death in men. In comparison to other cancers, prostate cancer has a long natural history and is frequently indolent (i.e., it does not progress to clinically significant disease before the patient dies of natural causes. In contrast, recurrence is seen in as many as 30% of treated patients. The findings highlight the need to develop prognostic markers beyond PSA and tumor grade in order to better distinguish patients who will most likely benefit from treatment from those for whom treatment should be deferred. We have shown that MRI and MRSI combined with clinical findings of PSA and Gleason score significantly improve the accuracy for predicting tumor stage and aggressiveness. In this competitive renewal, we will build on these findings with the objective of optimizing the use of MRI/MRSI for accurately identifying indolent prostate cancers. Our approach will be to correlate MR findings preoperatively both with patient outcomes and with the expression of key molecular markers known to be important in prostate cancer biology: Ki-67, PTEN, Akt, p27/Kip1, Bax, and Bcl-2. We also intend to use high resolution magic angle spinning spectroscopy on the operative specimen to obtain idealized spectra for non-destructive tumor analysis. The proposed work will test the hypothesis that a low risk localized PCa cohort identified by both clinical parameters and optimized MRI/MRSI will have better long-term outcome than a similar cohort identified by clinical parameters alone.
The specific aims of the study are:
Specific Aim 1 : Evaluate measures of accuracy of MRI/MRSI in the prediction of indolent cancer, using step section pathology as a standard of reference.
Specific Aim 2 : Correlate the MRI/MRSI features of low-risk localized PCa with the molecular features of the disease assessed in radical prostatectomy specimens and determine whether noninvasive MRI/MRSI can further differentiate between less aggressive variants of Gleason score 6 (pattern 3+3) cancer that are appropriate for a deferred therapy protocol and more aggressive variants of Gleason score 6 cancer that are more appropriate for definitive therapy.
Specific Aim 3 A: Compare patient outcome (disease progression-rate) between definitive treatment and deferred therapy in low-risk localized PCa patients identified by combined NCCN guidelines and MRI/MRSI Specific Aim 3B: Determine the incremental value of combined NCCN guidelines and MRI/MRSI to a historical literature data set in the selection of patients for deferred therapy.
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