National Cancer Institute NCI Cancer Bulletin: A Trusted Source for Cancer Research News
January 10, 2012 • Volume 9 / Number 1

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Cancer Research Highlights

Use of Robotics May Not Reduce Side Effects of Prostate Cancer Surgery

Older men who have their prostates removed to treat cancer have a high risk of developing incontinence and sexual problems within a year, regardless of whether their surgeons use robotic technology in the operating room, a new survey suggests. The results appeared online January 3 in the Journal of Clinical Oncology.

More than four out of five prostatectomies are done with the use of robotic technology to remove the organ laparoscopically. Some researchers have noted that the widespread adoption of this technology has occurred in the absence of evidence demonstrating that the robotic approach has clear benefits for patients over traditional surgery.

To explore this question further, Dr. Michael Barry of Massachusetts General Hospital and his colleagues sent surveys to a random sample of 800 men, drawn from Medicare claims files, who had undergone radical prostatectomy for prostate cancer. They received responses from 685 men; nearly twice as many respondents reported having robotic-assisted surgery as having a traditional open radical prostatectomy.

Both groups of patients reported high rates of incontinence and sexual dysfunction, indicating that the robotic technology did not appear to reduce these complications.

“The very rapid dissemination of robotic surgeries for radical prostatectomy seems to have come with an assumption that there may be fewer side effects because of the increased precision offered by the technology,” said Dr. Barry. But the new results, which are consistent with those of an earlier study, challenge that assumption. In fact, the study showed a slight increase in incontinence among men who had robotic surgery, although the difference was not statistically significant.

One limitation of the study was that the authors did not have baseline information about continence and sexual function for the men prior to the prostatectomy. Prospective studies and studies of younger men will be needed to assess the risks and benefits, as well as the cost effectiveness, of robotic surgery for prostate cancer compared with traditional surgery, the authors noted.

Despite the study’s limitations, the results are “sobering,” given the high rates of problems associated with both procedures, the authors of an accompanying editorial concluded. They noted that the outcomes for any type of procedure “are based not only on the technology but also on the skill and experience of the provider and the hospital system.”

Dr. Barry agreed. “Each man should know that the type of surgery he chooses is not as important as the experience that his surgeon has with that particular procedure,” he said. “And just because the surgery is robotic does not mean that it is safer or better than another technique.”

Chemotherapy Associated with Microscopic Changes in the Brain

A new study adds to an emerging body of evidence suggesting that subtle physical changes in the brain may underlie the constellation of symptoms dubbed “chemobrain”—cognitive changes associated with cancer or cancer treatment that are most often experienced as difficulties with concentration, memory, multitasking, and planning.

Using an advanced imaging technique, European researchers found evidence that changes in cognitive functioning in women with breast cancer who were treated with chemotherapy are associated with physical alterations in the fibers that connect neurons in the brain. The study appeared online December 19 in the Journal of Clinical Oncology.

The researchers used a type of magnetic resonance imaging (MRI) known as diffusion tensor MRI (DT-MRI) to detect changes in the brain’s white matter, which regulates communication among different brain regions. Previous studies have shown that damage to white matter can lead to changes in cognitive performance.   

Three groups of premenopausal women, whose median age was 43, participated in the study: 34 women with early-stage breast cancer who were scheduled to receive chemotherapy; 16 women with early-stage breast cancer who were not scheduled to receive chemotherapy; and 19 healthy, cancer-free control subjects.

Before receiving any chemotherapy, and again 3 to 5 months after completing their treatment, the chemotherapy-treated patients underwent whole-brain DT-MRI imaging and a series of neuropsychological and cognitive tests to measure abilities such as concentration, memory, and capacity to plan. The patients who were not exposed to chemotherapy and the healthy control subjects underwent the same assessment at matched intervals. The three groups showed no difference in performance on the pretreatment tests.

In the follow-up tests, however, women in the chemotherapy-treated group performed worse on the neuropsychological tests and reported more cognitive problems than women in both control groups. This poorer performance correlated with findings on the DT-MRI imaging tests that indicated microscopic alterations to the white matter in the brains of the chemotherapy-treated women.

“These results suggest that microstructural [white matter] changes in patients exposed to chemotherapy may underlie their cognitive dysfunction,” wrote the study authors, who were led by Dr. Stefan Sunaert of University Hospital in Leuven, Belgium.

“Patient complaints of persistent cognitive difficulties after cancer treatment ends must not be dismissed,” wrote Dr. Patricia Ganz of the University of California, Los Angeles, in an accompanying editorial. But “fears of developing cognitive difficulties should not deter the use of potentially beneficial chemotherapy,” she cautioned.

Dr. Ganz added: “We can no longer deny the existence of this long-term effect of cancer treatment; we must work to tailor future treatments to minimize this adverse outcome.”

Further reading: “Delving Into Possible Mechanisms for Chemobrain” and “Brain Scans Show Structural Effects of Chemotherapy

Drug Shows Promise against Hard-to-Treat Chronic Lymphocytic Leukemia

Navitoclax, an experimental drug that inhibits a group of proteins that promote cell survival, has shown encouraging results in a phase I trial in patients with difficult-to-treat chronic lymphocytic leukemia (CLL). The drug targets several related proteins in the BCL2 family, which are present in many types of tumor cells and which block the natural tendency of abnormal cells to undergo programmed cell death, or apoptosis.

Among 26 patients who received navitoclax after their cancer had relapsed or stopped responding to other treatments, nine experienced a partial response and seven maintained stable disease for more than 6 months, an international research team reported December 19 in the Journal of Clinical Oncology. And of 21 patients with lymphocytosis (an increase in the number of lymphocytes in the blood) at the start of the trial, 19 had a reduction in lymphocyte count of at least 50 percent. The main dose-limiting toxicity was thrombocytopenia.

This study “provides the first convincing clinical validation of BCL2 as a useful therapeutic target in CLL,” wrote the authors, Dr. Andrew W. Roberts of the Royal Melbourne Hospital in Australia and his colleagues.

The response to navitoclax was “impressive” considering that the drug was given as a single agent to patients who had received multiple prior therapies, Dr. Peter Hillmen of St. James’s Institute of Oncology in the United Kingdom commented in an accompanying editorial.

The strategy of inhibiting anti-apoptotic BCL2 family members “seems likely to herald the beginning of a revolution in the treatment of CLL,” Dr. Hillmen continued. He added that navitoclax is one of several investigational agents now in clinical development that target different aspects of CLL biology. The next steps, he went on, are to determine how to combine these new agents most effectively. “The logical combination of these agents promises to dramatically alter the treatment of CLL and may eventually lead to therapy that is both more effective and less toxic,” he wrote. 

Previous phase I studies have demonstrated the safety and preliminary efficacy of navitoclax in patients with difficult-to-treat lymphomas and small-cell lung cancer, wrote Dr. Loren D. Walensky of the Dana-Farber Cancer Institute in an accompanying article describing the biological pathway of navitoclax in CLL. The drug now “advances to phase II testing as a single agent and in combination to combat cancer chemoresistance, he noted.

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