Magnetic Resonance Imaging of the Prostate

The high incidence of prostate cancer, combined with downstaging at diagnosis and the slow natural progression of the disease, has made its management a complex and controversial issue. Endorectal MRI is emerging as the most accurate imaging modality for the local anatomic assessment of prostate cancer. This dissertation assesses the value of current State-of-the-Art endorectal MRI in clinical practice and discusses the promise of the modality for improving prostate cancer management. MR images allow noninvasive assessment of the local extent of prostate cancer (including organ-confinement, extracapsular extension, seminal vesicle invasion and lymph node metastasis) and can provide an indication of tumor aggressiveness based on signal intensity; thus MRI can assist in local staging and assessment of recurrence-free probabilities while providing surgeons with a visual road-map for optimal treatment planning. MRSI of the prostate depicts the altered metabolism associated with prostate cancer. The addition of 1H MRSI to MRI has further improved the accuracy of MR imaging in prostate cancer staging. It may become possible to use MRI/1H MRSI to achieve more precise stratification of patients in clinical trials, to monitor the progress of patients who select watchful waiting or minimally aggressive cancer therapies, and to guide and assess emerging local prostate cancer therapies. The second part of this dissertation illustrates the potential clinical applicat! ion of color-coded parameter imaging derived from postprocessing of dynamic multiphasic gadolinium-enhanced MRI (DMGE-MRI) of abdominal tumors. With more refined techniques, such as high-field imaging, and with more experienced readers and more uniform image interpretation, the MR imaging–MR spectroscopy approach will have a tremendous capacity to improve patient care. Chapter 2 shows that MR findings (from endorectal MRI or combined endorectal MRI/MRSI) contribute significant incremental value to clinical staging nomograms in the prediction of organ-confined prostate cancer (OCPC) in all risk groups (low, intermediate, and high). The incorporation of endorectal MR imaging into future staging nomograms for the prediction of OCPC may therefore be warranted, particularly since clinical staging in the current staging nomograms is based only on digital rectal examination. Moreover, unlike MRI, the staging nomograms cannot assist in the localization of ECE, which is critical for optimal treatment planning. It is worth noting that in the study, the accuracy of radiologists' predictions of OCPC was higher in the combined MR group (MRI+MRSI) than in the endorectal MR imaging. Chapter 3 indicates that endorectal MR imaging findings are significant presurgical predictors of extracapsular extension (ECE) in patients with prostate cancer and add incremental value to clinical variables. At univariate analysis, all variables were associated with ECE. At ROC univariate analysis, endorectal MR imaging findings had the largest area under the ROC curve. At multivariate analysis, serum PSA level, greatest percentage of cancer in all core biopsy specimens, and endorectal MR imaging findings were predictors of ECE. A model containing endorectal MR imaging findings had a significantly larger area under the ROC curve than a model containing only clinical variables. In addition, endorectal MR imaging findings are spatially localized, and therefore, unlike clinical variables, they have the potential to allow tailored treatment modifications. Chapter 4 demonstrates that endorectal MR imaging findings can be significant predictors for ECE in patients with prostate cancer, after controlling for PSA level, Gleason score, greatest percentage of cancer in all core biopsy specimens, percentage of cancer-positive core specimens in all core biopsy specimens, PNI, and clinical stage of tumor. A comparison of the ROC curves drawn from the results of readings performed by genitourinary MR imaging radiologists and general body MR imaging radiologists showed that endorectal MR imaging findings added value to all other predictor variables only when MR images were interpreted by genitourinary MR imaging radiologists. In the genitourinary radiologist group endorectal MR imaging findings displayed a combination of sensitivity and specificity that was superior to that of all other predictors tested. In the general body radiologist group, however, the combination of sensitivity and specificity of endorectal MR imaging findings was! similar to that of the clinical predictors. Advances in technology and in the expertise of radiologists dedicated to the genitourinary field suggest that endorectal MR imaging could play an increasingly useful role in the treatment of patients with prostate cancer. Chapter 5 shows that endorectal MRI findings can contribute significant incremental value to the Kattan nomogram for predicting SVI. On both univariate and multivariate analysis, endorectal MRI findings were a significant presurgical predictor of seminal vesicle invasion. Chapter 6 shows that a PACS cross-referencing tool allows radiologists to more accurately interpret prostate MR imaging, improving prostate cancer tumor staging by MRI. In the detection of ECE and SVI, radiologists performed substantially better when using MRI with PACS cross-referencing rather than MRI alone. PACS cross- referencing is particularly helpful in displaying the junction of the seminal vesicles and the central zone of the prostate. Chapter 7 describes a study showing that incorporation of the Partin nomogram results with MRI findings regarding both extracapsular extension and seminal vesicle invasion improves the MR prediction of LNM in patients with prostate cancer. The study confirmed that MRI has a high negative predictive value and an exceptionally high specificity in the prediction of LNM compared with clinical and histological variables. As MRI also provides anatomical information that is useful in treatment planning, it could potentially be used along with the Partin nomogram to determine whether additional imaging with lymphotropic superparamagnetic nanoparticles is indicated. Chapter 8 shows that review of preoperative MRI findings significantly improves the surgeon's decision to preserve or resect the NVB(s) during radical prostatectomy. Preoperative MRI improved surgical planning in high-risk patients and provided appropriate reassurance for preserving the NVB(s) in other patients. The strength of MRI for low-risk and intermediate-risk patients lies in a high negative predictive value (i.e., demonstration of the absence of tumor in the region of interest). Chapter 9 shows that the addition of MRI findings significantly improves the accuracy of the Kattan pre- operative nomogram in predicting postoperatively determined recurrence-free probabilities in the total study cohort and in a subset of patients (PSA³10, Gleason score ³7 on biopsy or clinical stage T2) at high risk for biochemical recurrence. Chapter 10 discusses a study demonstrating that MRI has potential in the noninvasive assessment of prostate cancer biological aggressiveness. First, there is a significant correlation between prostate cancer Gleason grade and tumor-to-muscle signal intensity ratio on T2-weighted MR images; a higher Gleason grade is associated with a lower tumor-to-muscle signal intensity ratio. Second, on T2- weighted MR images, Gleason grade 3 cancer in the transition zone has a significantly lower tumor-to-muscle signal intensity ratio than Gleason grade 3 cancer in the peripheral zone of the prostate. Chapter 11 is restricted to current reviews of major topics in radiology and brief case reports on postprocessing of dynamic multiphasic gadolinium-enhanced MRI (DMGE-MRI) of the abdominal tumors. Post-processing of dynamic multiphasic gadolinium-enhanced MRI (DMGE-MRI) of the abdomen allows the generation of color-coded parameter images and time-intensity curves that provide new opportunities for research and for improving the detection, staging and therapeutic monitoring of disease and the development of anti- tumor drugs. First, on the basis of pharmacokinetic modeling, the color-coded parameter images and time-intensity curves contribute to a better understanding of tumor enhancement patterns and angiogenesis, and hence may result in improved quantitative characterization of tumors. Second, the mechanisms behind the differential signal enhancement of dynamic multiphasic gadolinium- enhanced MRI (DMGE-MRI) are thought to include differences in tumor perfusion and the level! s of tumor capillary wall permeability and hydrostatic pressure. Third, the time-intensity curves and only a small number of parameters need to be displayed as color-coded parameter images on a workstation. These robust parameters include: 1) relative enhancement; 2) wash-in rate; 3) wash-out rate; 4) brevity of enhancement. In Chapter 12, the results of all the studies mentioned above are discussed in relation to one another and to the current literature. Recommendations for clinical practice are made. CONCLUSIONS The following overall conclusions can be made: 1. In patients with prostate cancer, endorectal MR imaging non- invasively improves pretreatment staging and treatment planning and the evaluation of recurrence-free probabilities; it can also provide an indication of cancer aggressiveness. 2. The incorporation of endorectal MR findings into future nomograms for the prediction of prostate cancer stage and freedom from biochemical recurrence is warranted. 3. Advances in technology, such as a PACS cross-referencing tool, and in the expertise of radiologists dedicated to the genitourinary field suggest that endorectal MR imaging can play an increasingly useful role in prostate cancer management. 4. Information from preoperative MR imaging allows the surgeon to significantly refine the surgical plan, maximizing the preservation of periprostatic tissues (important for recovery of urinary and sexual function) 5. Inclusion of time-intensity curves and color-coded images as part of the routine abdominal MR imaging work-up protocol facilitates the diagnostic work-up of disease for detection, staging, and monitoring of anti-tumor therapy.

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