Thursday, December 8, 2011

PSA Testing, Combined With Other Relevant Patient Data Can Reduce Unnecessary Prostate Biopsies


Separate study suggests combining urine test with PSA can aid cancer diagnosis

Prostate cancer screening that combines an adjusted blood test with other factors including the size of the gland, the patient’s overall weight and family history, can help up to one-quarter of men avoid biopsies and the risks associated with them, a Beth Israel Deaconess Medical Center-led research team says.
Writing in a study published online by the journal Cancer, the team led by Martin G. Sanda, MD, Director of the Prostate Center at Beth Israel Deaconess Medical Center and Professor of Urology at Harvard Medical School, suggests that instead of using “one-size-fits-all” levels of PSA to determine who should have a biopsy, considering other factors such as prostate size can substantially improve the ability of PSA testing to identify aggressive prostate cancers for which treatment is warranted, while avoiding detection of indolent cancers that are better undiagnosed because they do not require treatment.

A second study led by Sanda, and published online in the journal Urologic Oncology, suggests the presence or absence of genes commonly found in the urine of men, when combined with a PSA test, can also be used to determine whether a biopsy is necessary.
The new suggested approaches come as the United States Preventive Services Task Force expert panel concluded that current PSA-based prostate cancer screening saves few or no lives, but causes harm through treatment or further invasive testing such as biopsies. That’s because prostate cancers can vary in aggressiveness and more men die of other causes aside from that cancer – and because the PSA test alone cannot determine how dangerous any particular cancer may be.

“The US Preventative Services Task Force threw the baby out with the bathwater by their blanket recommendation against prostate cancer screening,” says Sanda, noting that PSA screening can instead be refined to more selectively identify only aggressive cancer for which treatment is indicated by adjusting PSA results for other considerations such as family history, obesity, and prostate size.

Results from the multi-center study that suggest that PSAD levels of less than 0.1 – in contrast to the unadjusted level of between 2.5 and 4 – can be a better benchmark of a potential cancer. The density, determined by a digital rectal exam, enables physicians to take into account other factors like benign prostatic hyperplasia, an enlargement of the gland that affects all men as they age.

Combining the PSAD with the digital exam, a look at the patient’s family history and a body mass index of 25 of less – the calculation used to define obesity – would avoid biopsy in approximately one-quarter of biopsy-eligible men, the researchers found.
“Urological practice, patient outcome and cost-effectiveness of health care would each benefit from new targeted strategies, such as nomograms (a predictive tool) that improve prediction of aggressive cancers, to enable selective identification of candidate for prostate biopsy that would improve the yield of clinically significant, histologically aggressive cancers warranting subsequent definitive treatment,” researchers wrote.

In a separate multicenter study published in Urologic Oncology, researchers said a test looking for two specific genetic biomarkers – TMPRSS2:ERG and PCA3 – taken after a digital rectal exam, could help limit biopsies to men who possess both genes and whose PSA readings range between 2 and 10, potentially sparing one-third of men from biopsies.

“Urine testing for prostate cancer is in its infancy,” says Sanda, noting next steps are underway as a result of study funded by a $3.1 million grant from the National Institutes of Health , that is evaluating new urine and blood test for prostate cancer in more 2,400 men over the next five years with a goal of improving upon the problems of over-diagnosis and over-treatment.

A focal point of the proposed work involves a community outreach effort led by BIDMC primary care physician J. Jacques Carter, MD, MPH, Medical Director of the Dana Farber Cancer Institute Prostate Cancer Screening and Education Program and an Assistant Professor of Medicine at Harvard Medical School. A key component of this study will be African-American men, who appear to develop prostate cancer more frequently, and who are at increased risk of dying from prostate cancer.

Panel endorses active monitoring and delay of treatment for low-risk prostate cancer


An independent panel convened this week by the National Institutes of Health has concluded that many men with localized, low-risk prostate cancer should be closely monitored, permitting treatment to be delayed until warranted by disease progression. However, monitoring strategies—such as active surveillance—have not been uniformly studied and available data do not yet point to clear follow-up protocols. The panel recommended standardizing definitions and conducting additional studies to clarify which monitoring strategies are most likely to optimize patient outcomes.

“It’s clear that many men would benefit from delaying treatment, but there is no consensus on what constitutes observational strategies and what criteria should be used to determine when treatment might ultimately be needed among closely-monitored men,” said Dr. Patricia A. Ganz, conference panel chairperson and director of the Division of Cancer Prevention and Control Research at the Jonsson Comprehensive Cancer Center at the University of California in Los Angeles.

Prostate cancer is the most common non-skin cancer in men in the United States. It is estimated that in 2011, approximately 240,000 men will be newly diagnosed with prostate cancer and 33,000 will die of the disease. More than half of these cancers are localized (confined to the prostate), not aggressive at diagnosis, and unlikely to become life-threatening. However, approximately 90 percent of patients receive immediate treatment, such as surgery or radiation therapy. For many of these patients, treatment has substantial short- and long-term side effects, such as diminished sexual function and loss of urinary control, without clear benefits, such as improved survival. Identifying appropriate management strategies for different subgroups of patients is critical to improving survival and reducing the burden of adverse effects.

Currently, clinicians often describe two alternatives to immediate treatment of low-risk prostate cancer: observation with and without the intent to cure. Observation without intent to cure, sometimes referred to as watchful waiting, is a passive approach, with treatment provided to alleviate symptoms if they develop. Observation with intent to cure, often referred to as active surveillance, involves proactive patient follow-up in which blood samples, digital rectal exams, and repeat prostate biopsies are conducted on a regular schedule, and curative treatment is initiated if the cancer progresses.

The panel identified emerging consensus in the medical community on a definition for low-risk prostate cancer: a prostate-specific antigen (PSA) level less than 10 ng/mL and a Gleason score of 6 or less. Using this definition, the panel estimated that more than 100,000 men diagnosed with prostate cancer each year would be candidates for active monitoring rather than immediate treatment. Importantly, however, the panel found that protocols to manage active monitoring still vary widely, hampering the evaluation and comparison of research findings.

Prostate cancer affects some 30-40 percent of men over the age of 50. Some of these men will benefit from immediate treatment, others will benefit from observation. We need to standardize definitions, group patients by their risks, and conduct additional research to determine the best protocols for managing low-risk disease,” stated Dr. Ganz.

The panel further recommended that disease terminology should be refined as a result of changes in the patient population with prostate cancer due to prostate-specific antigen (PSA) testing. Because of the very favorable prognosis of PSA-detected, low-risk prostate cancer, the panel recommended that strong consideration be given to removing the anxiety-provoking term “cancer” for this condition.

The panel also found that clinicians’ framing of disease management options is an important factor in patient decision-making. Other influential factors include views of family members, cancer experiences of family and friends, lifestyle priorities, and personal philosophy. Findings from studies in communication sciences and behavioral economics could be applied in clinical settings to promote informed, shared decision-making. While research continues to fill knowledge gaps and develop consensus, the decisions faced by men and their providers following a diagnosis of localized, low-risk prostate cancer should be highly individualized, and include the consideration of biological, psychological, social, and cultural factors.

With regard to future research, the panel recommended against future federal funding for single-institutional site studies, and emphasized instead the importance of supporting multisite clinical research studies. The panel also supports the establishment of registry-based cohort studies that collect longitudinal data on active monitoring participants, including clinical and patient-reported outcomes.

An updated version of the panel's draft statement, which incorporates public comments received in an open conference session this morning, will be posted later today at

The panel will hold a press telebriefing to discuss their findings today at 2 p.m. eastern time. To participate, call 888-428-7458(inside the United States) or 201-604-5177 (International) and reference the NIH State-of-the-Science Conference. Audio playback will be available shortly after conclusion of the telebriefing and can be accessed by calling 888-632-8973 (US) or 201-499-0429(International) and entering replay code 11996437.

The state-of-the-science conference was sponsored by the NIH Office of Medical Applications of Research, the National Cancer Institute, and the Centers for Disease Control and Prevention, along with other NIH and U.S. Department of Health and Human Services components. This conference was conducted under the NIH Consensus Development Program, which convenes conferences to assess the available scientific evidence and develop objective statements on controversial medical issues.

The 14-member state-of-the-science panel included experts in the fields of cancer prevention and control, urology, pathology, epidemiology, genetics, transplantation, bioethics, economics, health services research, shared decision-making, health communication, and community engagement. A complete listing of the panel members and their institutional affiliations is included in the draft conference statement. Additional materials, including panel biographies, photos, and other related resources, are available at Interviews with panel members can be arranged by contacting Elizabeth Neilson at 301-496-4999 or

The conference was webcast live and will be archived shortly. Links to the archived webcast will be available at