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Other highlights in the Sept. 25 JNCI

Journal of the National Cancer Institute

Accurate Prostate Cancer Diagnosis Depends on Biopsy Location

The part of the prostate that is biopsied may matter more than the number of biopsy samples taken for accurately diagnosing prostate cancer.

It is difficult to know whether prostate biopsies are correctly identifying prostate cancer because men with prostate biopsies do not usually undergo surgery to have their prostates removed.

To determine the accuracy of prostate biopsies, Gabriel Haas, M.D., of the State University of New York Upstate Medical Center in Syracuse and colleagues performed biopsies on prostates from 164 deceased men who had no history of prostate cancer. Biopsies were taken from various areas of the prostate in an attempt to mirror the way biopsies are performed on live patients.

Almost 30% of the prostates had cancer cells, and 43% of those were clinically significant cancers as defined by tissue characteristics. Cancer detection depended more on the part of the prostate that was biopsied than on the number of samples that were taken.

"This information ... can assist the clinician to design the appropriate biopsy regimen to detect clinically significant cancers that pose biologic risk and avoid the overdiagnosis of clinically insignificant cancers that would be unlikely to have an adverse effect on the patient," the authors write.

Contact: Gabriel Haas, haasg@upstate.edu, (315) 464-4473


"Destemming" Stem Cells

In a commentary, Richard Hill, Ph.D., of the University of Toronto and Roberto Perris, Ph.D., of the University of Parma in Italy discuss the need for a more accurate definition of cancer stem cells. Currently, cancer stem cells are defined as cancer cells that have the ability to self-renew and differentiate into the various types of cancer cells in the tumor.

Targeting the small number of cancer stem cells holds promise for treating cancer, and interest in this area has been great among cancer researchers. But it is still unclear whether cancer cells act like other adult stem cells, and the authors suggest that they be called "cancer-initiating cells" instead. They caution that developing new drugs to kill these cells may prove less effective than expected if the drugs are based on erroneous assumptions about how cancer stem cells work.

"The many unresolved issues concerning the nature of cancer-initiating cells hamper the full understanding of their unique identity and their potential as specific therapeutic targets," the authors write.

Contact: Jane Finlayson, senior public affairs advisor, Princess Margaret Hospital, jane.finlayson@uhn.on.ca, (416) 946-2846


Microenvironment of Tumors Plays Role in Drug Resistance

The difficulty in penetrating tumors and reaching all of the cancer cells is an important but under-appreciated cause of drug resistance in solid tumors, according to a review article. Olivier Trédan, M.D., of the University of Toronto and colleagues describe how the tumor microenvironment may be involved in drug resistance and propose possible strategies for improving drug treatments by altering the microenvironment.

"Agents that improve drug delivery or activity by targeting the tumor microenvironment ... represent an important direction for cancer therapy," the authors write.

Contact: Jane Finlayson, senior public affairs advisor, Princess Margaret Hospital, jane.finlayson@uhn.on.ca, (416) 946-2846


Alternative Phase II Trial Design Could Reduce Phase III Failures

An alternative design for phase II cancer clinical trials may improve success rates for new cancer drugs in phase III trials.

Phase II cancer trials are conducted in order to determine whether a new drug is effective enough to warrant further study. Usually, this is demonstrated by treating all patients in the study with the new drug and showing that a certain proportion of these patients has a substantial reduction in the size of their tumors. However, phase II tests are often not good predictors of a drug's later success. Cancer drug development has been hindered by high rates of failure in phase III trials where the new drug is compared head-to-head with standard therapy to see whether it improves survival time or slows disease progression. To improve phase III success rates, it may be useful to consider alternative ways to evaluate drugs in phase II.

Theodore Karrison, Ph.D., of the University of Chicago and colleagues describe a phase II trial design that uses tumor size--measured on a continuous scale--as the measure of the drug's success. In the study, two groups of patients receive different doses of the drug and a control group receives the standard therapy.

The authors argue that this design has the advantage of including a control group and making more efficient use of the data on tumor size changes. The design does require studying more patients, and its success at predicting phase III outcome has not been demonstrated. Nonetheless, the authors write, "With growing numbers of agents and agent classes available for evaluation, it is crucial to develop phase II clinical trial strategies that utilize patient resources efficiently and provide data more predictive of phase III results than current phase II approaches."

In an accompanying editorial, Larry Rubinstein, Ph.D., of the National Cancer Institute in Bethesda, Md., and colleagues discuss the potential problems with using tumor size as an endpoint, though they say it is worth further study. "If validated and used properly, this endpoint could provide an efficient early indication of potential benefit in situations in which neither objective tumor response nor progression-free survival is a feasible endpoint, and its use could facilitate randomized comparisons for subpopulations that are difficult to accrue," the editorialists write.

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Also in the September 25 JNCI:

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