In This Article
- The clinical utility of current prostate specific antigen cancer screenings is limited due to its poor specificity for aggressive cancer. Diagnostic inaccuracies remain
- Ex vivo magnetic resonance spectroscopy of prostate biopsy cores before their histology evaluations overcomes inaccuracy by identifying metabolic differences between histologically-benign tissue and prostate cancer-confirmed tissue
- Early studies at Massachusetts General Hospital indicate high resolution magic angle spinning magnetic resonance spectroscopy is a productive technology for identifying potentially malignant areas, characterizing tissues and predicting aggressiveness
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Prostate cancer screening is specific to the origin tissue within the prostate, not to cancer cells, and current medical imaging detects 44%–87% of clinically significant prostate cancers. As a result, prostate cancer patients may lack confidence in the results of these evaluations.
Adam S. Feldman, MD, MPH, director of the Combined Harvard Urologic Oncology Fellowship and director of Urologic Research at Massachusetts General Hospital, and his colleagues, are working to change this.
Mass General is a research leader in refining rapidly evolving advanced imaging technology to analyze the biochemistry of tissues. The search for metabolic signatures of cancer is performed by high-resolution magic angle spinning (HRMAS) magnetic resonance spectroscopy (MRS).
Collaborating with Mass General's Martinos Center for Biomedical Imaging, Dr. Feldman and his team of investigators developed expertise in HRMAS-MRS that enables them to capture metabolic information and decode it to profile a prostate tumor even before it develops, as well as to predict its aggressiveness.
"Because our metabolomics approach can predict disease aggressiveness," Dr. Feldman says, "it offers clinically translatable prognostic information that has significant potential to improve patient outcomes."
The Metabolomics Advantage
Metabolomics is an emerging field that analyzes cellular energy flows to decipher healthy and pathological states through studying the metabolome. The metabolome is the dynamic biochemical suite found in all cells, tissues and fluids of the body.
Dr. Feldman's colleague, Leo L. Cheng, PhD, is a biophysicist specializing in pathology and radiology. He and his colleagues developed much of the pioneering HRMAS-MRS technology on prostate tissue samples ex vivo—an innovative means of evaluating the cancer metabolome. According to Dr. Cheng, the inventor of HRMAS-MRS for intact tissue analysis, "HRMAS-MRS has proven useful as a means to improve cancer diagnosis and prognosis. In fact, it is one of the major techniques now used in cancer metabolomic research. Through HRMAS-MRS, we can preserve tissue architecture, enabling us to conduct both histological and molecular pathology analysis without the need of collecting additional biopsy cores from, and presenting additional risks to, patients."
Mass General pathologist Chin-Lee Wu, MD, a collaborating researcher adds: "The technique allows us to quantify everything from individual metabolites through metabolite ratios and even entire metabolomic profiles. The technology shows promise for the future of prostate cancer diagnosis and may change how we offer diagnostic information to the patients and doctors."
The HRMAS-MRS technology reveals the dynamic world of cells in a new way, with finer detail at the molecular level.
Under the conventional diagnostic paradigm, prostate cancers have been typically identified with the prostate specific antigen (PSA) test. However, because the PSA test conveys information about the prostate, and less specifically to cancers, its results are vulnerable to inaccuracy.
Given the potential complications associated with false-positive tests, patients may be dissuaded from seeking prostate cancer screening. The resulting gap in treatment allows potentially aggressive cancers to go undetected.
Investigating Metabolic Markers
To identify metabolic markers of prostate cancer, investigators conducted a study using ex vivo MRS paired with multiparametric (mp)MRI/ultrasound fusion targeted biopsies. Their findings were presented and awarded Best Poster at the American Urological Association and received the Summa Cum Laude Award at the Annual Meeting of the International Society for Magnetic Resonance in Medicine.
Of the 54 patients studied, all received mpMRI targets re-read by a single radiologist for quality control.
- ≥3 cores of each target were taken, followed by a standard 12-core template biopsy
- All patient-matched target and non-target cores underwent HRMRS on a Bruker 600MHz spectrometer, with spectra processed identically
- Principal component (PC) analysis was performed with all 33 identified metabolic spectral regions
- After MRS, all biopsy cores underwent standard histopathology for patient pathology records
Results demonstrated differences in tissue obtained from mpMRI lesions as compared with mpMRI normal regions. In particular, they showed:
- Metabolic differences between mpMRI lesions having biopsy-confirmed cancer and lesions having benign biopsies
- Metabolomic changes in core biopsies with no identifiable cancer, but which were adjacent to core biopsies with identifiable cancer
- Support for the concept of metabolomic field effect that signals earliest metabolic changes in cancers not currently detected
The continued investigation of metabolic differences in mpMRI lesions is important because it may help translate ex vivo MRS into novel in vivo MRS biomarkers—thus improving the discrimination of prostate cancer through noninvasive imaging.
Though results need further validation, they seem poised for improving diagnosis, according to Dr. Feldman, as well as to transforming the current morphology-based histology paradigm.
"A metabolomics-informed evaluation system that is sensitive to cancer biology in individuals will advance the realization of personalized medicine and enable more informed clinical decision-making," says Dr. Cheng.
Learn more about the Prostate Cancer Treatment Program
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