Experimental imaging technique details spread of prostate cancer
MGH-led study could lead to improved treatment, lower costs

BOSTON - June 18, 2003 - A study conducted at Massachusetts General Hospital and University of Nijmegen hospital in the Netherlands finds that an investigational advanced MRI technique may be able precisely to identify the spread of prostate cancer to lymph nodes. Published in the June 19, 2003, New England Journal of Medicine, the report details how high-resolution MR studies using an iron-oxide-containing contrast agent produced very accurate localization of tumor metastases, information that could be key in guiding the treatment of men with prostate cancer. The imaging agent currently is being evaluated for FDA approval.

"These imaging techniques allow us to clearly distinguish between benign and malignant nodes and to construct three-dimensional maps to guide surgical planning," says lead author Mukesh Harisinghani, MD, of the abdominal imaging division of the MGH Department of Radiology.

"This approach relies on advanced high-resolution MR imaging, detailed and computerized image analysis and the novel contrast agent - a lymph-node-seeking magnetic nanoparticle," says Ralph Weissleder, MD, PhD, director of the MGH Center for Molecular Imaging Research, the report's senior author. "The experimental aspects of this technique have been tested and validated at MGH over the last decade, and we believe it has the potential of revolutionizing the way we do cancer staging [determining how advanced a tumor is]." Weissleder is a professor of Radiology at Harvard Medical School (HMS).

Almost 200,000 men in the U.S. are diagnosed with prostate cancer annually, and more than 30,000 die. The course of the disease varies widely, with some men living for years with slow-growing tumors and others needing more aggressive treatment - including surgery, radiation and testosterone-reduction therapy - to control the spread of their cancer. Being able to identify which patients need aggressive treatment could improve the care of many patients, and a key factor in that identification is finding metastases, tumors that have spread beyond the prostate.

Standard practice in treating prostate cancer has been for lymph nodes adjacent to the prostate gland to be removed and analyzed for the presence of cancer, but it is not uncommon for metastases to first appear in nodes beyond the usual area of analysis. Standard MRI and CT scanning cannot detect metastases, so the use of imaging has been limited to identifying enlarged nodes that may contain tumor cells. But some enlarged nodes prove benign, and metastases can occur in very small nodes.

The researchers at MGH and University Medical Center (UMC) in Nijmegen set up a study to examine whether a protocol developed at the MGH could identify prostate cancer metastases in abdominal lymph nodes. Each institution enrolled 40 patients who had been diagnosed with prostate cancer. The patients had preliminary high-resolution abdominal MR studies done before receiving intravenous infusions of the iron-containing contrast agent. A second set of MR studies was taken 24 hours later. A total of 334 lymph nodes were imaged in the 80 study participants.

The study was designed to allow careful comparison of the imaging studies with the surgical findings for all patients. After the MR studies, the participants received standard prostate cancer treatment, which for most was removal of the prostate gland. Patients had the usual lymph nodes removed for pathologic analysis; however, nine patients had additional nodes removed based on results of the MR studies.

The MR studies indicated that 272 of the imaged nodes were benign. Detectable metastases were found in 63 nodes from 33 patients. All of these diagnoses were confirmed by pathological examination of the removed nodes. And of the 63 malignant nodes, more than 70 percent were so small they would not have been identified as malignant by current imaging techniques.

"The high accuracy and less invasive nature of this method will allow us to stage our prostate cancer patients more efficiently," says Shahin Tabatabaei, MD, an MGH urologist who is a coauthor of the current report. "This technique may revolutionize the diagnosis and treatment of prostate cancer and probably other genitourinary malignancies."

The researchers note that a large-scale, controlled clinical trial is needed to assess this technique's impact on patients' outcomes, and they hope to embark on such a study in the near future. But if the study's results hold up, this approach, which uses equipment found at most MR centers, has the potential to significantly improve patient care and to reduce costs by eliminating unnecessary procedures.

"This approach also has the potential to be applied to a wide variety of malignancies," says Harisinghani, who is an instructor in Radiology at HMS. "And eventually we could go beyond staging the disease to offering treatments using lymphotrophic [attracted to lymph-nodes] agents that could attack the metastases without the systemic effects of other chemotherapy drugs."

Other authors of the study are co-first author Jelle Barentsz, MD, PhD, of UMC; Peter Hahn, MD, PhD, of MGH; and Willem Deserno, MD, Christine Hulsbergen van de Kaa, MD, PhD, and Jean de la Rosette, MD, PhD, of UMC. The research was supported by a National Cancer Institute grant and funds from the radiology departments at both hospitals. The experimental contrast agent was supplied at no cost by U.S. and French manufacturers of the agent.

Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $350 million and major research centers in AIDS, cardiovascular research, cancer, cutaneous biology, medical imaging, neurodegenerative disorders, transplantation biology and photomedicine. In 1994, MGH and Brigham and Women's Hospital joined to form Partners HealthCare System, an integrated health care delivery system comprising the two academic medical centers, specialty and community hospitals, a network of physician groups, and nonacute and home health services.

Media Contact: Sue McGreevey, MGH Public Affairs

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