National Comprehensive Cancer Network

Genetic Testing Misses Half of Women at Risk for Breast Cancer

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Nearly half of patients with breast cancer who, on multigene panel testing, are found to have a pathogenic or likely pathogenic variant for breast cancer do not meet current National Comprehensive Cancer Network (NCCN) guidelines for genetic testing, new research shows.

In a cohort of 959 women who were either currently undergoing treatment or had previously been treated for breast cancer, 49.9% met established 2017 NCCN germline genetic testing guidelines, and 50% did not, lead author Peter Beitsch, MD, Dallas Surgical Group–TME/Breast Care Network, Texas, and colleagues report.

Of those patients who met NCCN guidelines for germline testing, 9.39% had either a pathogenic or a likely pathogenic variant; 7.9% of those who did not meet the guidelines also had a pathogenic or likely pathogenic variant. The difference between the two groups was not statistically significant, the investigators add.

“Our results indicate that nearly half of patients with breast cancer with a P/LP [pathogenic/likely pathogenic] variant with clinically actionable and/or management guidelines in development are missed by current testing guidelines,” the investigators observe.

“We recommend that all patients with a diagnosis of breast cancer undergo expanded panel testing,” they conclude.

The study was published online December 7 in the Journal of Clinical Oncology.

However, in a related editorial, breast cancer experts argue that widespread testing would detect genetic variants of unknown significance for which there are currently no established clinical courses of action.

Study Details

For their study, Beitsch and colleagues set up a multicenter, prospective registry with the help of 20 community and academic sites, all of which were experienced in cancer genetic testing and counseling.

They focussed on 959 patients who had a history of breast cancer but had not undergone prior single-gene or multigene testing.

“All patients underwent germ line genetic testing with a multicancer panel of 80 genes,” the authors explain.

“Overall, 83 (8.65%) of 959 patients had a P/LP variant,” they write.

The investigators then considered findings from only BRCA1 and BRCA2 genetic testing.

In this subgroup analysis, positive BCRA1/2 rates were fourfold higher among those who met current NCCN germline testing guidelines, at 2.51%, compared to those who did not, at 0.63% (P = .020).

However, the authors point out that patients with a clearly identifiable personal and family history consistent with NCCN testing guidelines were likely to have already undergone genetic testing and therefore would have been excluded from the study.

In contrast, rates of variants of “uncertain significance” were virtually identical between those who met current NCCN guidelines for genetic testing and those who did not.

“Carriers of clinically actionable variants in genes other than BRCA1/2 are likely to fall outside of the current guidelines,” Beitsch and colleagues point out.

“Results of our study suggest that a strategy that simply tests all patients with a personal history of breast cancer would almost double the number of patients identified as having a clinically actionable genetic test result,” they reason.

Variants of Unknown Significance

In a related editorial, Kara Milliron, MS, and Jennifer J. Griggs, MD, MPH, both from the University of Michigan Cancer Center in Ann Arbor, argue that widespread uptake of genetic testing would increase the likelihood of identifying pathogenic variants of genes for which there are no established guidelines for reducing cancer risk.

For example, pathogenic variants in ATM are associated with an increased breast cancer risk, “but there is insufficient evidence to support risk-reducing breast surgery or bilateral salpingo-oophorectomy,” they point out.

Furthermore, more widespread testing is likely to increase detection rates of variants of unknown significance, which were common in the study by Beitsch and colleagues.

“These variants present challenges for both patients and medical providers in the management of ambiguity that arises in a patient with a malignancy and family members,” Milliron and Griggs write. This issue is particularly problematic in certain racial and ethnic groups in which such variants are both more common and more poorly characterized, they add.

Of greater concern are barriers to high-quality counseling following genetic testing.

“The shortage of genetic counselors has been well documented,” the editorialists note, and currently, “many patients receive genetic testing without seeing a genetic counselor,” they state.

Lastly, the cost of widespread testing and counseling cannot be overlooked, especially when considering expanding that testing to all patients with breast cancer.

Medicare does cover BCRA1/2 testing, and some states cover genetic testing.

“Thus, costs to patients may be prohibitive in the most vulnerable populations,” the editorialists write.

NCCN guidelines for genetic testing were published about 20 years ago and were designed to identify patients who were most likely to carry BRCA1/2 variants.

This was done to reduce the number needed to test; at that time, the cost of genetic testing was $2000 to $5000 per test.

Now, it is approximately 10 times less costly to conduct germline testing than it was when the guidelines were originally established.

Still, Milliron and Griggs calculate that the call to have all women with breast cancer undergo genetic testing would amount to about $400 million in total costs to insurance companies. They arrive at this estimate by considering the current cost of $1500 per test multiplied by the number of new breast cancer cases diagnosed each year in the United States.

FDA Update on Rare Breast Implant-Associated Type of Lymphoma

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The US Food and Drug Administration (FDA) has provided an update on breast implant–associated anaplastic large cell lymphoma.

In January 2011, the agency identified a possible associationbetween breast implants and the development of anaplastic large cell lymphoma (ALCL).

 Since then, “we have strengthened our understanding of this condition and concur with the World Health Organization designation of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) as a rare T-cell lymphoma that can develop following breast implants,” the FDA said in a statement March 21.

Over 350 Cases, 9 Deaths

The FDA notes that most data suggest that BIA-ALCL occurs more often after implantation of breast implants with textured surfaces rather than those with smooth surfaces.

As of February 1, 2017, the FDA has received a total of 359 medical device reports (MDRs) of BIA-ALCL, including 9 deaths. Of the 231 reports that included information on the implant surface, 203 concerned textured implants and 28, smooth implants.

Of the 312 reports that included information on implant fill types, 186 described implants filled with silicone gel and 126, implants filled with saline.

“It is important to note that details on breast implant surface and fill type are limited. While the MDR system is a valuable source of information, it may contain incomplete, inaccurate, untimely, unverified, or biased data,” the FDA says.

 During the last 6 years, a “significant body” of literature has been published on BIA-ALCL, including additional case histories and comprehensive reviews of the natural history and long-term outcomes of the disease, the agency notes.  “All of the information to date suggests that women with breast implants have a very low but increased risk of developing ALCL compared to women who do not have breast implants.”

Most cases of BIA-ALCL are treated by removal of the implant and the capsule surrounding the implant, and some cases have been treated by chemotherapy and radiation. However, because BIA-ALCL has “generally only been identified in patients with late onset of symptoms such as pain, lumps, swelling, or asymmetry, prophylactic breast implant removal in patients without symptoms or other abnormality is not recommended,” the FDA said.

The exact number of cases of BIA-ALCL worldwide is unknown.

The FDA is continuing to collect and evaluate information about BIA-ALCL. For now, the agency recommends that clinicians who have patients with breast implants take the following action:

  • Be aware that most confirmed cases of BIA-ALCL have occurred in women with textured breast implants. Provide the manufacturer’s labeling as well as any other educational materials to your patients before surgery and discuss with them the benefits and risks of the different types of implants.
  • Consider the possibility of BIA-ALCL in a patient with late-onset, persistent peri-implant seroma. In some cases, patients presented with capsular contracture or masses adjacent to the breast implant. A patient with suspected BIA-ALCL should be referred to an appropriate specialist for evaluation. When testing for BIA-ALCL, collect fresh seroma fluid and representative portions of the capsule and send for pathology tests to rule out BIA-ALCL. Diagnostic evaluation should include cytologic evaluation of seroma fluid with Wright-Giemsa–stained smears and cell block immunohistochemistry testing for cluster of differentiation and anaplastic lymphoma kinase markers.
  • Develop an individualized treatment plan in coordination with the patient’s multidisciplinary care team. Consider current clinical practice guidelines, such as those from the Plastic Surgery Foundation  or the National Comprehensive Cancer Network (NCCN) when choosing your treatment approach.
  • Report all confirmed cases of ALCL in women with breast implants to the FDA’s MedWatch system.

Source:medscape.com

Does Diagnostic Radiation Increase Breast Cancer Risk in Women with BRCA Mutations?

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European questionnaire-based study leaves the question unanswered.

Because ionizing radiation can damage DNA, diagnostic x-ray exposure in individuals with defects in DNA repair mechanisms (such as those associated with BRCA1 and BRCA2 mutations) could lead to excess risk for cancer. Investigators surveyed women with documented BRCA1/2 mutations in the Netherlands, France, and the U.K. to evaluate any association between radiation exposure and later development of breast cancer. Questionnaires were administered to BRCA1/2 carriers from 2006 to 2009 to elicit their recollections of the type and number of diagnostic procedures they had received in their lifetimes. Estimates of radiation doses to the breast during each type of diagnostic procedure (mammography, fluoroscopy, and computed tomography and conventional radiography of the chest or shoulder) were used to determine total cumulative dose. Cases that were diagnosed >5 years before completion of the study questionnaire were excluded to prevent survival bias.

Of the 1993 participants, 43% (mean age, 49.7) had received diagnoses of breast cancer. Self-reported exposure to any form of diagnostic radiation before age 30 was associated with significantly higher risk for breast cancer (hazard ratio, 1.90; 95% confidence interval, 1.20–3.00), and risk rose with increasing cumulative dose. A history of mammography before age 30 was associated with nonsignificantly increased risk for breast cancer (HR, 1.43; 95% CI, 0.85–2.40). No evidence of excess risk was found for diagnostic radiation exposure between ages 30 and 39.

Comment: As with other epidemiologic studies of diagnostic radiation and risk for breast cancer in BRCA1/2 mutation carriers, the results of this study are inconclusive. The retrospective questionnaire design is subject to recall bias, especially given that women were asked to recollect events occurring up to 30 years earlier. Moreover, no attempt was made to document the date and type of radiologic tests that were reported. Furthermore, estimates of cumulative radiation dose were hypothetical and subject to wide variation based on factors in individuals as well as facilities. Until further data are obtained, the National Comprehensive Cancer Network recommendation of screening with magnetic resonance imaging and mammography in BRCA mutation carriers beginning at age 25 should be followed.

Source: Journal Watch Oncology and Hematology

 

 

 

Clinical Pathways in Cancer Care Catching On.

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For a woman diagnosed with HER2-negative, estrogen-receptor negative breast cancer that has spread to the lymph nodes, guidelines from the National Comprehensive Cancer Network (NCCN) recommend chemotherapy following surgery.

Within this recommendation, however, is a lot of room for variation. In fact, there are 16 possible chemotherapy regimens, explained Dr. Bruce Feinberg, chief medical officer of Cardinal Health Specialty Solutions, based in Dublin, OH. Many of these regimens are similar, “but most of them will never be tested head to head” to determine which are the most effective, least toxic, and least costly, he said.

Clinical pathways can help physicians choose the best treatments for individual patients from several possible regimens.

As a result, even within the same oncology practice, two similar patients may get very different treatments, often because their oncologists prefer or are more comfortable with one particular regimen than another.

Enter “clinical pathways”—programs that are being designed and implemented by large networks and smaller practices to limit such variation. The programs do this by helping doctors select what the available evidence indicates are the best regimens for a particular patient. That evidence is derived from sources that can include clinical trial data and professional guidelines.

In the breast cancer example above, the clinical pathway used by many Michigan oncologists narrows the first-line treatment options from 16 to 4 regimens, explained Dr. Feinberg, who ran a large Atlanta-based oncology practice for 23 years.

Pathways programs that Cardinal Health has helped to establish in Michigan, Maryland, Pennsylvania, and several other states have “reduced variation, and allowed those oncologists to gain more refinement and better knowledge of the treatments,” Dr. Feinberg said. And that, proponents of clinical pathways believe, can improve the quality of care.

Pathways may also save money, by reducing treatment complications and the unnecessary use of some drugs, for example. And with annual direct costs of cancer treatment in the United States estimated to reach $173 billion by 2020, any way of cutting costs—without sacrificing quality—is under serious consideration.

Building a Pathway

The pathways concept appears to be picking up steam. In a small survey conducted at NCCN’s 2012 annual conference, for example, nearly 60 percent of respondents said they had implemented or were considering implementing clinical pathways.

Clinical pathways are just one route the oncology community is pursuing to improve the quality and efficiency of care, explained Dr. Steven Clauser, chief of the Outcomes Research Branch in NCI’s Division of Cancer Control and Population Sciences (DCCPS).

“In the last few years, we’ve begun to see a real emphasis on trying to improve and measure quality,” Dr. Clauser said. That includes efforts to track adherence to clinical guidelines, “and using [the resulting] data to better understand an organization’s clinical environment and how they’re treating their patients,” he continued.

Clinical pathways are similar to clinical guidelines, but they take the concept one step further.

The US Oncology Network, a nationwide network with approximately 1,000 oncologists, develops its clinical pathways following a specific formula, explained Dr. Roy Beveridge, chief medical officer for McKesson Specialty Health. (McKesson acquired US Oncology in 2010.)

“First, we look at randomized controlled trials…which we believe are the most important data,” Dr. Beveridge said. “We want to see the manuscript, and we look for definitive trials.”

When a randomized trial shows that one treatment is significantly better than “anything else out there,” he continued, “then that is the top choice in the pathway. Period.”  In cases where two treatments are equally effective but differ in toxicity, the less-toxic regimen is favored. And in cases where efficacy and toxicity are similar, then cost—in the form of what insurers pay—is taken into account.

The idea that adherence to a guideline or a pathway is a measure of quality is complicated. That’s the part we have to be careful about.

—Dr. Stephen Taplin

Cardinal Health and Via Oncology, a spinoff of a clinical pathways program developed at the University of Pittsburgh Medical Center (UPMC) Cancer Center, follow similar criteria. All three companies rely on physician-led committees to review clinical trial results, published studies, and, with the exception of Via Oncology, professional clinical guidelines to develop each pathway.

In the physician networks that implement pathways, oncologists can review and comment on draft pathways before they’re finalized. These committees convene regularly to review the latest data and determine whether a pathway needs to be updated.

The pathways are not iron clad, nor should they be, explained Dr. Peter Ellis, Via Oncology’s medical director. In all of the major pathway programs, the rule of thumb for adhering to a pathway is 80 percent, a threshold that appears to be based primarily on clinical experience, not firm data.

If an individual oncologist has an adherence rate above 80 percent, “we’re worried about it,” said Dr. Ellis. Adherence above 80 percent “could mean that they’re not thinking through the needs of individual patients. There are going to be circumstances when a patient really should be on something other than the pathway choice.”

UPMC, Dr. Ellis said, has a compliance rate of 77 percent with its available pathways, which now cover approximately 90 percent of cancer treatment decisions, as well as tests, post-treatment surveillance, radiation therapy, and supportive care.

The pathways concept isn’t always welcomed with open arms, though. Practicing oncologists must “deal with reality, where variances [to pathways] go by different names, such as vomiting, fever, drug shortages, pulmonary emboli, frustration, grief,” Dr. Craig Hildreth, an oncologist in St. Louis, wrote last year on his Cheerful Oncologistblog. (Free registration is required to access the blog.)

In some cases, medical practices within a health care network that has implemented a pathways program have refused to use them.

At practices in the US Oncology Network, Dr. Beveridge said, the response has been good. “Our Level I Pathways is an evidence-based medicine initiative,” he said. “The buy-in has been high because these treatment guidelines are physician-led and developed based on proven evidence.”

A practice’s setting will also likely influence the decision to implement clinical pathways, said Dr. George Weiner, director of the University of Iowa Holden Comprehensive Cancer Center. Academic medical centers with tumor boards and “strong in-house multidisciplinary programs,” where there is a significant amount of collaboration and discussion among the different clinicians involved in patient care, may be less likely to go the pathways route, he believes.

Do Pathways Improve Care, Save Money?

The Systems around the Pathways

The US Oncology Network’s clinical pathways are built into the organization’s electronic health record (EHR) system, iKnowMed. The EHR lists the “on-pathway” treatments for a given diagnosis and the documentation to support their inclusion in the pathway.

The documentation of the evidence to support a pathway is particularly helpful for oncologists caring for patients with less common cancers, said Dr. Debra Patt, medical director of the US Oncology Network Pathways Task Force and a breast cancer specialist at Texas Oncology, a network affiliate.

The documentation can also help patients, she continued. “It’s a wonderful experience to show patients…the hyperlinks to the studies, then hyperlinks to the Pathways Task Force committee report,” Dr. Patt said. “It’s a great educational tool, and I can say to them, ‘This is the evidence to support the recommended treatment,’ and it helps them to participate in informed decision making.”

Building a robust IT infrastructure around clinical pathways has been a top priority and a big financial investment for Via Oncology, Dr. Ellis explained. The most recent version of the company’s web-based pathways portal can connect directly into a practice management system, so pathway choices are incorporated into the doctor’s schedule for each patient visit.

The concept of clinical pathways is a strong one, said Dr. Stephen Taplin, chief of the Process of Care Research Branch in DCCPS. But, he cautioned, it’s unclear whether clinical pathways improve quality.

“The idea that adherence to a guideline or a pathway is a measure of quality is complicated,” Dr. Taplin said. “That’s the part we have to be careful about.”

Oncologists must consider factors like patient preference and suitability for treatment when making decisions about care, he stressed.

The best way to develop and use pathways will need to be closely studied, noted Dr. Weiner.  “How rigorous should they be? How much flexibility should they include?”

Dr. Ellis acknowledges that it’s difficult to prove that clinical pathways improve care quality.  Even so, he argued, “If a pathways system can document that evidence-based care is given, then it naturally follows that the quality of care will improve.”

But at this point, Dr. Feinberg noted, the idea that pathways improve care quality is “largely an act of faith…. You have to look for behavior changes that you believe represent better care.”

Some documented behavior changes include less use of combination chemotherapy as third- and fourth-line treatments. Patients treated on a pathway also have fewer emergency room and hospital admissions because of chemotherapy side effects, the US Oncology Network and Cardinal Health have reported.

The US Oncology Network is, thus far, the only group to publish data on potential cost savings. Using electronic medical record data from eight of its affiliated practices, they found that, over 1 year, outpatient treatment costs were 35 percent lower ($18,000 versus $28,000) for patients with non-small cell lung cancer treated on-pathway than off-pathway.

Some insurers have been skeptical about whether pathways can improve care or reduce costs, Dr. Beveridge acknowledged. “That’s why we conducted the study,” he said. “Because of our study results, I believe most payers are now interested in learning more about a pathways approach.”

Insurers are central to the model used by Cardinal Health, which facilitates collaborations with insurers and oncology groups on pathway development. As part of that collaboration, the insurers provide financial incentives to practices that participate in the program and meet compliance benchmarks.

Even with the uncertainty, clinical pathways are proliferating. The US Oncology Network has licensed its pathways to several hospital systems and practices, Dr. Beveridge said. Hospitals and oncology practices in 11 states are using Via Oncology’s pathways. The most recent addition came just last month with Indiana University Health System, which will implement the pathways at the central site and its affiliated oncology practices.

With the advent of accountable care organizations and other efforts to measure quality of care and reduce costs, clinical pathways—or something like them—may very well be part of the future for all hospitals and medical practices, Dr. Ellis believes.

“There’s got to be more accountability and proof of quality of care,” he said. “You’re not going to be able to say to patients and payers, ‘Trust me, I’m a good doctor.’”

Source: NCI

 

 

 

Active Surveillance May Be Preferred Option in Some Men with Prostate Cancer.

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Findings of a recent study, the largest and longest of its kind, provide strong evidence supporting a conservative approach to managing prostate cancer in some men. The study was not a randomized clinical trial; rather, it was a long-term analysis of a cohort of men diagnosed with what is called very-low-risk prostate cancer. Instead of immediately undergoing surgery or radiation therapy, the men had opted to undergo a process known as active surveillance at the Johns Hopkins University School of Medicine.

A diagnosis of very-low-risk prostate cancer means that the disease is highly unlikely to become a clinically significant, life-threatening cancer. These men could be safely monitored by active surveillance, the study found, with only a modest percentage eventually requiring some form of treatment and none dying from prostate cancer. The results were published online April 4 in the Journal of Clinical Oncology (JCO).

As is the case with prostate cancer in general in the United States, most of the men in the study were 65 or older. The results provide very strong evidence that active surveillance is the “preferred option” for most men in this age group with very-low-risk disease, said the study’s senior investigator, Dr. H. Ballentine Carter. In fact, he continued, “The overwhelming evidence says that for men over 65 who are diagnosed with low-risk disease, their first question should be whether any therapy is appropriate for them, not which therapy.”

The clinical relevance of the findings is hard to overstate, Dr. Carter stressed. Among the 217,000 men in the United States diagnosed each year with prostate cancer, a substantial proportion has very-low-risk or low-risk disease. The vast majority of these men immediately undergo some form of treatment, including men aged 75 and over, despite the fact that many would be unlikely to experience significant symptoms, let alone die from prostate cancer.

Defining Very-Low-Risk Prostate Cancer

The Johns Hopkins definition of very-low-risk prostate cancer is similar to the NCCN definition. For the study in JCO, very-low-risk was defined as:

  • Clinical stage T1c (no palpable disease, biopsy recommended based on abnormal PSA)
  • Gleason score of 6 or less
  • PSA density (ratio of PSA level to prostate gland size) of 0.15 ng/mL or less
  • Two or fewer biopsy cores in which cancer is present, and less than 50 percent cancer present in any involved core

Patient Selection, Compliance Are Key

At Hopkins, the active surveillance program involves a semi-annual check-up and an annual biopsy. Patient selection is very important, Dr. Carter explained.

Among the 769 men enrolled in Hopkins’ active surveillance program between 1995 and 2010, approximately 80 percent had very-low-risk disease. Whether a patient has very-low-risk disease is determined based on factors such as the Gleason score (a common measure of tumor aggressiveness) and the extent of cancer in the biopsy samples, or cores, from the prostate gland. (See the sidebar for all of the factors.)

The remaining men had at least one biopsy feature that precluded their disease from being considered very-low-risk, Dr. Carter explained. These men were typically older and had other health problems, he continued, which made active surveillance more attractive than treatment with surgery or radiation, both of which can have significant side effects.

Compliance with the approach has been quite strong, the Hopkins team reported, with nearly 90 percent of participants completing their annual biopsies.

Although no men in the study died of prostate cancer, 255 did undergo some form of treatment, 74 percent of whom did so because their disease was reclassified based on the findings of an annual biopsy.

Overall, 41 percent of men in the study did not require any form of treatment, even after 10 years of follow-up, a “remarkable” finding, said Dr. Bhupinder Mann from NCI’s Division of Cancer Treatment and Diagnosis. “This study adds to the accumulating evidence that, in carefully selected patients, active surveillance is safe.”

The results “strongly support” recent revisions to prostate cancer treatment guidelines from the National Comprehensive Cancer Network (NCCN), said the guidelines’ panel chair, Dr. James Mohler from the Roswell Park Cancer Institute. Updated last year, the guidelines recommend that physicians advise men with very-low-risk disease who have a life expectancy of up to 20 years to pursue active surveillance.

Findings like these on active surveillance, combined with related research on the growing problem of overdiagnosis and overtreatment of prostate cancer linked to PSA screening, appear to be reaching down into the community setting, Dr. Mohler believes.

“I think men and their doctors are becoming more educated about the overtreatment issue,” he said.

As evidence, Dr. Mohler pointed to the START trial, a phase III clinical trial being led by NCI-Canada, in collaboration with the U.S. NCI, in which men diagnosed with very-low-risk or low-risk disease are being randomly assigned to active surveillance or immediate treatment. When the trial opened in 2007, most men who declined to enroll did so because they did not want to take the risk of being assigned to the active surveillance arm. “Now most men are declining to participate because they want active surveillance,” Dr. Mohler said.

Having a strong system in place to ensure that men pursuing active surveillance are followed and receive reminders for their check-ups and biopsies is extremely important, Dr. Carter stressed.

At the moment, the Hopkins surveillance program is managed primarily by an administrator using a manual process. But the program is moving to a Web-based approach for monitoring and following patients, he added.

Approaches Can Vary

Although the evidence in favor of active surveillance continues to accumulate, the optimal approach to managing the process is not yet defined, Dr. Mann noted. This is particularly true with respect to how patients’ disease is tracked.

At Hopkins, men are followed via check-ups and annual biopsies. Any reclassification of their disease is typically based on biopsy findings, such as a change in Gleason score, which might then produce a recommendation for treatment. But many other centers, such as Roswell Park, do not require men who choose active surveillance to undergo regular biopsies. Rather, they use some form of what is commonly called PSA kinetics, which are changes in PSA levels over time (for instance, how long it takes for PSA levels to double).

Results from several studies, however, have raised doubts about the value of PSA kinetics in initially identifying or managing prostate cancer. Based on their experience, PSA kinetics is “not reliable for predicting the presence of high-grade cancer on an individual basis,” the Hopkins team wrote in JCO. “Thus, if the goal of surveillance is to identify and treat higher-risk cancers, we believe that annual biopsies may be necessary to ensure patient safety.”

But regular biopsies are by no means without their own risks. A small percentage of men end up in the hospital with antibiotic resistant infections as a result of a prostate biopsy, Dr. Mohler said, and repeat biopsies can lead to inflammation and scar tissue formation that can preclude nerve-sparing surgery to treat the prostate cancer in some men whose disease progresses.

According to Dr. Carter, Hopkins researchers are now studying whether men who have had two consecutive biopsies that show no evidence of disease progression can safely have the interval between routine biopsies extended. In the meantime, the NCCN guidelines are being revised again, Dr. Mohler said, using data from large active surveillance programs at Hopkins, the University of Toronto, and the University of California, San Francisco, to provide recommendations on managing men who choose this conservative approach.

Further clarity on this matter should be forthcoming, Dr. Mann said. In addition to the START trial, which will follow men using both PSA measures and prostate core biopsies, a similar trial is being conducted in the United Kingdom that is using only PSA levels to monitor patients. Also, in December, NCI and CDC are sponsoring an NIH State-of-the-Science Conference to review the role of active surveillance in managing localized prostate cancer and to help guide future research in this area.

Source: NCI.