Lack of national diagnosis, care plan spurs call for action

January 10, 2008

Prostate cancer imaging experts sent out a clear message in 2007: Prostate cancer in the U.S. has become an unrecognized patient care crisis that needs tackling. The good news is these experts agree that advanced imaging technologies could help in early detection and minimally invasive treatment. The lack of a cohesive national strategy is worrisome, however, and they want to see the adoption of a broad initiative for diagnosing and treating prostate cancer similar to that for breast cancer.

Prostate cancer imaging experts sent out a clear message in 2007: Prostate cancer in the U.S. has become an unrecognized patient care crisis that needs tackling. The good news is these experts agree that advanced imaging technologies could help in early detection and minimally invasive treatment. The lack of a cohesive national strategy is worrisome, however, and they want to see the adoption of a broad initiative for diagnosing and treating prostate cancer similar to that for breast cancer.

Leading the effort is the Advancement of Medical Technologies Foundation, or AdMeTech, which held its fourth meeting on the topic last fall. Setting the context almost from the get-go, speakers compared prostate cancer with breast cancer. The number one cancer killer of women worldwide affects one in seven women in the U.S. annually. Nearly one in six men past the age of 40 will be stricken by prostate cancer this year in the U.S., and about 10% of those new diagnoses will be fatal, according to figures released at the meeting.

Prostate-specific antigen blood tests and biopsy, the current diagnostic standards, can aid in early detection of prostate cancer. But both are entangled in a hit-and-miss conundrum. PSA's false-negative rates approach 15% or more, while only 12% of men with abnormal tests actually have cancer. Biopsies miss at least one-fifth of all malignancies and underestimate disease aggressiveness in up to 30% of men. The diagnostic information that either test yields is insufficient to distinguish indolent disease, which requires careful monitoring instead of immediate therapy, from more virulent types that need prompt treatment.

Too many men undergo unnecessary and traumatic biopsies that cost more than $2 billion a year. At least 10% of men undergo unwarranted surgeries, and about 40% get unnecessary radiation treatment. Over 70,000 patients fail treatments that will render half of them impotent or incontinent. The current treatment paradigm costs about $8 billion a year.

Advanced imaging can address all these problems and reduce costs by more than $5 billion annually, said Dr. Faina Shtern, AdMeTech president and CEO.

"Prostate cancer is an epidemic causing profound socioeconomic impact. Our faculty characterized current blind prostate cancer care as medieval. Yet [the AdMeTech meeting] created a message of hope," she said.

Albeit preliminary, scientific evidence is growing that advanced imaging technologies will improve early detection, eliminate unnecessary procedures, and enable minimally invasive treatment of prostate cancer, according to Shtern.

A substantial national investment combined with strategic partnerships that include industry, academia, philanthropy and advocacy groups, however, is required to facilitate R&D, testing, and implementation of prostate diagnostics. Such a strategic partnership-comprising congressional leadership, public and private investment, and advocacy support-was responsible for the success of breast cancer imaging initiatives. The same model has been replicated to advance R&D programs in prostate cancer imaging technologies.

IMAGING APPLICATIONS

AdMeTech luminaries discussed the roles that several imaging modalities and image-guided interventional techniques will play for screening, diagnosis, staging, and management of prostate cancer. Ultrasound, MRI, and nuclear medicine imaging stood out.

"Ultrasound is probably the most cost-effective way to do diagnosis, therapy guidance, and follow-up of prostate cancer," said Dr. Ethan J. Halpern, a professor of radiology and urology at Thomas Jefferson University.

Real-time imaging capability, portability, availability, patient tolerance, and low cost relative to other imaging modalities are sonography's better known assets. An often-unrecognized strength, however, is its ability to detect clinically significant disease, Halpern said. The combination of several techniques, such as Doppler and contrast-enhanced harmonic imaging for detection of tumor-specific blood flow, or elastography, can enhance tumor detection.

Elastography, for instance, mimics the digital rectal examination but is a more objective way of quantifying lesion stiffness. Contrast sonography with harmonics can confirm areas of enhancement highlighted by Doppler. The clinical literature has validated the incorporation of sonography in the development of nomograms, which are multifactorial algorithms that help predict tumor aggressiveness. Ultrasound's major role in prostate cancer imaging will be in screening, guiding biopsies and therapies, and monitoring treatment. The lack of FDA approval for contrast-enhanced ultrasound, however, has damped the development of this technique and its application, Halpern said.

MRI and MR spectroscopy will play an important role in detection, staging, assessment of disease aggressiveness, treatment planning, guidance, and patient follow-up. MRI's superior anatomic detail can help tumor localization, according to investigators from the National Cancer Institute, Harvard University, the University of California, San Francisco, and other institutions. Though they admit that MR findings can be nonspecific in certain cases, the use of MRS, coregistration with PET imaging, and the introduction of powerful 3T systems into routine clinical practice can enhance detection and staging of disease. Researchers point also at MRI's ability to provide accurate imaging guidance for biopsies. Therapy applications range from MR-guided brachytherapy to MR-guided focused ultrasound ablation. The latter technique has already been used successfully for treatment of uterine fibroids.

"Three-T MRI and multiparametric approaches with image registration and segmentation as part of postprocessing and CAD analysis are the current favorites," said Dr. Clare Tempany, a professor of radiology at Harvard Medical School.

Nuclear medicine techniques have a limited role in the diagnosis of focal prostate cancer. It is in the later stages of the disease, particularly after the appearance of metastases affecting soft tissues and bone, that FDG-PET becomes valuable, said Dr. Steven Larson, chief of nuclear medicine at Memorial Sloan-Kettering Cancer Center in New York City. Fluorocholine and fluoroacetate PET are being investigated for their application in the earlier stages of the disease, where they may help us understand its spreading mechanism. Other future applications include quantitative assessments with F-18 fluoride to assess the extent of bone involvement, a task currently done with technetium-99m scintigraphy, and targeted therapy using radiolabeled drugs. For now, the main role of PET and PET/CT will remain the assessment of treatment response, especially when prostate cancer becomes hormone-refractory, Larson said.

"Agents like fluorocholine and the acetate derivatives should be available in two or three years in the community, but it will be up to the regulators to provide us with the path to get approval for these agents," he said.

UPCOMING CHALLENGES

Many imaging technologies discussed at the AdMeTech meeting need further R&D and testing. With appropriate funding, they could become available for clinical practice in five to seven years, considering the additional time needed to get them through the regulatory and reimbursement process. That process is why partnerships between academia, industry, advocacy groups, and government are critical to expedite all stages of technology innovation, testing, and transfer to patients, Shtern said.

"Philanthropic organizations like AdMeTech stimulate and provide funding for the development of new ideas within the academic community. Industry creates instruments that can be tested and made available to patients on a large scale. And advocacy groups are critical for patient participation in clinical trials, as well as funding, reimbursement, and regulatory issues," she said.

AdMeTech officials and other prostate imaging advocates seek to establish an International Prostate MRI Working Group (IP-MRIWG) to be styled after the breast MRI working group that facilitated the development, implementation, and acceptance of MRI as a routine tool for breast cancer screening in high-risk populations. The IP-MRIWG leadership will aim at several goals, according to Shtern: framing clinical needs in prostate cancer care, developing a research strategy and technical specifications to meet these needs, creating pilot priority projects for R&D, and designing a quality assurance program for multicenter clinical trials and clinical applications.

CONGRESSIONAL PLEDGE

Last year, a bipartisan group of legislators announced support for legislation that would authorize $650 million for prostate cancer imaging research and education. The Prostate Research Imaging and Men's Education Act was introduced in the Senate in June by Sen. Barbara Boxer (D-CA) as S 1734. Sens. Frank Lautenberg (D-NJ) and John Kerry (D-MA) are cosponsors. Reps. Elijah Cummings and Albert Wynn, both Democrats from Maryland, crafted the House version.

The PRIME Act will cover the basic $500 million needed to fund advanced prostate imaging research and $100 million for in vitro diagnostics over five years, according to Shtern. Although there is no word yet on the passing of this legislation, Congress has announced the appropriation of $1.6 million to support the prostate imaging research program led by AdMeTech.

"It is our hope that with appropriate public education, the PRIME Act will be passed in about a year. However, we also recognize that 2008 will be devoted to the presidential election, and its impact on the current legislative initiatives may not be easy to predict," Shtern said.

Though far from achieving the expected funding goals, prostate imaging advocates expressed satisfaction. The announcement of the $1.6 million appropriation should boost prostate imaging, galvanize the community to come together around joint aims, and allow a good multicenter trial of the best available imaging to be put together, Tempany said.

Mr. Abella is Associate Editor of Diagnostic Imaging.

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