Prostate cancer may be indolent, justifying a “wait and see” approach, or it may be aggressive, warranting decisive action up to and including prostatectomy. The problem is, it can be hard to tell which, even after prostate-specific antigen (PSA) screening and histological analysis of biopsy tissue. Among the men who are diagnosed with prostate cancer, more than 70% are likely to have less aggressive tumors that follow an indolent course, and about 17% have aggressive, potentially fatal disease.

A different kind of test—one that may better distinguish between indolent and aggressive prostate cancer—has been proposed by scientists based at Massachusetts General Hospital. This test uses magnetic resonance spectroscopy (MRS) to generate metabolomic profiles. MRS, the scientists have reported, can measure disease-related metabolic alterations to determine the grade and stage of a tumor. MRS can also predict a tumor’s risk of recurrence.

Details about the new test appeared March 26 in the journal Scientific Reports, in an article entitled, “Metabolomic Prediction of Human Prostate Cancer Aggressiveness: Magnetic Resonance Spectroscopy of Histologically Benign Tissue.” The article notes that cancer research is increasingly focused on tumor–stroma interactions and tumor microenvironments, as presented in the context of cancer genomics, proteomics, and transcriptomics.

In particular, the article indicates that metabolites localized on cancer lesions are expected to aid cancer detection by their differentiation from histologically benign surroundings: “Using histology of an entire removed prostate as the gold standard, we investigated the assumption that cancer-related metabolic alterations precede morphological changes.”

The scientists conducted a retrospective study of 185 patients (2002–2009) that included prostate tissues from prostatectomies (n = 365), benign prostatic hyperplasia (n = 15), and biopsy cores from cancer-negative patients (n = 14). Since this was a retrospective study of patients diagnosed up to 15 years ago, the researchers had access to both pathological analysis of the entire prostate gland and the eventual outcome for each patient.

“Tissues were measured with high resolution magic angle spinning (HRMAS) MRS, followed by quantitative histology using the Prognostic Grade Group (PGG) system,” wrote the article’s authors. “Metabolic profiles, measured solely from 338 of 365 histologically-benign tissues from cancerous prostates and divided into training-testing cohorts, could identify tumor grade and stage, and predict recurrence.”

Metabolic profiles of what appeared to be benign prostate tissue were able to differentiate more aggressive from less aggressive tumors and tumors found throughout the prostate gland from those confined to a limited area. “Specifically, metabolic profiles: (1) show elevated myo-inositol, an endogenous tumor suppressor and potential mechanistic therapy target, in patients with highly-aggressive cancer, (2) identify a patient sub-group with less aggressive prostate cancer to avoid overtreatment if analysed at biopsy; and (3) subdivide the clinicopathologically indivisible PGG2 group into two distinct Kaplan-Meier recurrence groups, thereby identifying patients more at-risk for recurrence,” the authors detailed.

“Prostate cancer detection through elevated PSA levels followed by prostate tissue biopsies often cannot differentiate between patients with early-stage, patients with indolent disease, and patients with aggressive cancers,” said Leo L. Cheng, Ph.D., associate biophysicist, pathology and radiology, Massachusetts General Hospital, and co-corresponding author of the current study. “The additional metabolic information provided by magnetic resonance spectroscopy can help guide treatment strategy, both to prevent overtreatment of slow-growing tumors—a critical and widely recognized current issue—and to identify the aggressive tumors for which additional treatment should be considered.

“Measurement of a tumor's metabolic activity in the initial biopsy, even in histologically benign tissue, could help to determine whether a patient should have a prostatectomy or, for those with less aggressive disease, could enter active surveillance with peace of mind.”

Dr. Cheng and his colleagues concluded that metabolomics information can help transform a morphology-based diagnostic system by invoking cancer biology to improve evaluation of histologically benign tissues in cancer environments. The team is now analyzing samples from more than 400 additional prostate cancer cases and working to refine the field of metabolites that provide information valuable for treatment planning.








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