National Cancer Institute NCI Cancer Bulletin: A Trusted Source for Cancer Research News
July 27, 2010 • Volume 7 / Number 15

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Cancer Research Highlights

PSA Screening Leads to Aggressive Treatment, Even in Older Men at Low Risk

A new study confirms previous research showing that screening for prostate cancer with the prostate-specific antigen (PSA) test has led to overtreatment of many prostate cancers, including aggressive treatments in older men considered to be at low risk for progression of the disease. The results appeared in the July 26 Archives of Internal Medicine.

The researchers found that 77 percent of men with a serum PSA level of 4.0 nanograms per milliliter (ng/mL)—the level at which a prostate biopsy is often recommended—or lower underwent either complete removal of their prostate, known as a radical prostatectomy, or radiation therapy. This treatment occurred even though more than half of these men were considered to be at low risk of disease progression based on commonly used factors, such as the Gleason score and the extent of local tumor spread.

Despite evidence that suggests older men are less likely to have a survival benefit from surgery or radiation compared with more conservative treatments, age was not a barrier to low-risk men receiving aggressive treatment. Nearly 69 percent of men age 65 to 74 and approximately 40 percent of men 75 and older underwent either surgery or radiation.

“Our study demonstrates that Gleason score, PSA level, and risk stratification does not appear to substantially influence the decision to have attempted curative therapy,” wrote lead investigator Dr. Yu-Hsuan Shao of the Cancer Institute of New Jersey and colleagues.

To conduct the study, the researchers used data from NCI’s SEER registry to identify nearly 124,000 men who were newly diagnosed with prostate cancer between 2004 and 2006. Of these men, 14 percent had PSA levels of 4.0 ng/mL or lower. Rates of radical prostatectomy and radiation were actually higher among men whose PSA levels were at or below 4.0 ng/mL than among men whose PSA levels were between 10.1 and 20.0 ng/mL.

“It has been documented that men who receive any treatment have increased risk of treatment-related adverse effects,” Dr. Shao and colleagues wrote. “Therefore, it is critical that patients be counseled about treatment-associated adverse effects and benefits when they are deciding about therapy.”

In an accompanying editorial, Drs. Richard Hoffman of the University of New Mexico and Steven Zeliadt of the University of Washington advocated for greater use of so-called active surveillance. This approach “balances the desire to avoid treatment complications against the equally strong desire not to ignore a cancer—while at the same time minimizing the risk of overtreatment,” they explained.

See also: “PSA Screening and Cancer Mortality: Swedish Study Adds to the Debate

Chemotherapy Regimen Benefits Men with Metastatic Penile Cancer

Men with cancer of the penis that had spread to nearby lymph nodes have benefited from three chemotherapy drugs given prior to surgery, known as neoadjuvant therapy, according to results published online July 19 in the Journal of Clinical Oncology. The nonrandomized phase II study, one of the first such prospective trials of its kind, included 30 men with stage III or stage IV penile squamous cell carcinoma and affected regional lymph nodes, but without distant metastases.

Half of the patients had either a partial or complete response, and 36.7 percent remained free of recurrence at the last clinical assessment. The vast majority of patients were able to tolerate the chemotherapy at full doses and on schedule, and 76.7 percent received all four planned courses. Based on these results, the researchers are recommending that the chemotherapy regimen, which included paclitaxel, ifosfamide, and cisplatin, becomes the new standard treatment for this disease.

The chemotherapy regimen was selected because it has helped some patients with squamous cell carcinoma of the head and neck. Men with penile cancer have a low probability of surviving with lymphadenectomy alone, and a multimodal approach to treatment is desirable for such patients, the researchers said.

“This is a rare disease for which there is no standard of care in stages III and IV,” said lead investigator Dr. Lance Pagliaro of the University of Texas M. D. Anderson Cancer Center. “There has been an urgent need in the field for a well-designed prospective trial to establish a standard chemotherapy regimen. We view this study as a starting point for moving forward in this disease.”

Other chemotherapy drugs currently being tested in this disease can now be evaluated against this regimen, he noted. As a next step, his group and others have been developing trials that will include targeted therapies, such as epidermal growth factor receptor inhibitors.

Hormone Therapy Increases Breast Cancer Risk for Women with Dense Breasts

Women who have dense breasts according to a system radiologists use to score mammograms, the Breast Imaging Reporting and Data System (BIRADS), are at an increased risk of developing breast cancer compared with women whose breasts are of average density. And hormone therapy (HT) after menopause, in particular estrogen plus progestin, also increases the risk of breast cancer. Now a report from the NCI-funded Breast Cancer Surveillance Consortium (BCSC) shows that the combination of these two factors increases breast cancer risk by up to twofold. The study appeared online July 19 in the Journal of Clinical Oncology.

The BCSC team, led by Dr. Karla Kerlikowske of the University of California, San Francisco, examined data from seven registries that represent more than 580,000 women and nearly 1,350,000 screening mammograms. The women were age 30 or older, had normal body-mass indices, and completed questionnaires to report menopausal status, surgical histories, and their use of HT.

The association between breast density and cancer risk was strongest for premenopausal women and women using HT after menopause. In the study, premenopausal women with low or average breast density had a 5-year cancer risk ranging from 0.3 to 1.5 percent, compared with a range of 0.9 to 3.1 percent for women with dense or very-dense breasts. The researchers found that postmenopausal women with low or average breast density who used HT had 5-year risks ranging from 0.3 to 2.5 percent, whereas women with dense or very-dense breasts had a risk ranging from 1.1 to 4.4 percent. (Risk was slightly higher for those who used estrogen plus progestin versus estrogen alone.) However, whether they used HT or not, the risk of breast cancer was low for postmenopausal women who had low breast density.

How HT and breast density act together to increase cancer risk—whether the hormones slow the natural changes in the breast that occur with aging, for example, or whether they spur cell growth in cancer-prone cell types—remains unknown, noted the authors. But, in the meantime, “Postmenopausal women with high breast density may want to consider the added risk of breast cancer when deciding on whether to start or stop [HT], especially estrogen plus progestin,” they wrote.

Brain Cancer Incidence Trends Do Not Support Link to Cell Phones

A new analysis by NCI researchers has turned up no evidence to support a link between cell phone use and brain cancer in the United States. The analysis was carried out in view of concerns about a possible link between widespread use of cell phones and brain cancer risk. With more than 279 million U.S. wireless subscribers today, the researchers reasoned that it should be possible to detect an increase in brain cancer rates over time if, in fact, cell phone use does contribute to risk of this particular cancer. The caveat would be that no effect would be expected if the induction period for brain tumors is very long or increased risk is limited to long-term users.

Dr. Peter Inskip and his colleagues in NCI’s Division of Cancer Epidemiology and Genetics used NCI’s SEER database to examine brain cancer incidence trends between 1992 and 2006. In almost all age groups and in both men and women, the trends for brain cancer during these years were, if anything, slightly downward.

The one exception was a statistically significant increasing trend among females in their twenties, but not males. This increase, however, was driven by cancers in the frontal lobe of the brain, which is not where the researchers would have expected to see an effect from cell phones. Studies have shown that other parts of the brain are more highly exposed to the radiofrequency radiation from cell phones.

The U.S. findings are consistent with a recent study of brain cancer incidence trends in four European countries. That study found no change in rates from 1998 to 2003, the period when possible associations between mobile phone use and cancer risk would likely be apparent assuming an induction period of 5 to 10 years.

See also: Study Finds No Overall Increased Brain Tumor Risk from Cell Phones

For more information, see: NCI’s Cell Phones and Cancer Risk Fact Sheet

Expert Panel Reports on Knowledge Gaps for 20 Suspected Carcinogens

In a monograph released July 15, a coalition of leading health organizations called for more research into the possible cancer-causing effects of exposure to 20 chemical agents. Some of the named agents are commonly found in the environment, whereas others are more often limited to occupational exposures. A summary paper in Environmental Health Perspectives provides an overview of the technical report.

The monograph, titled Identification of research needs to resolve the carcinogenicity of high-priority IARC carcinogens, summarizes available evidence and provides specific guidance on the appropriate studies needed to definitively classify these agents. Several overarching issues were identified that pertain to multiple agents, including recognizing that carcinogenic agents can act through multiple pathways and mechanisms of toxicity.

“This report highlights the importance of conducting research in occupational settings to identify human carcinogens,” said Dr. Debra Silverman, a co-author of the report and chief of the Occupational and Environmental Epidemiology Branch in NCI’s Division of Cancer Epidemiology and Genetics. “Findings from such occupational studies often allow experts to extrapolate the possible effects of low-level exposure to these agents in the general environment.”

“There is significant concern among the public about substances or exposures in the environment that may cause cancer, and there are some common occupational agents and exposure circumstances where evidence of carcinogenicity is substantial but not yet conclusive for humans,” added the report’s lead author, Dr. Elizabeth Ward, from the American Cancer Society (ACS).

The project originated as part of the National Institute for Occupational Safety and Health’s National Occupational Research Agenda to enhance occupational cancer research, and it involves collaboration with NCI, the International Agency for Research on Cancer (IARC), the ACS, and the National Institute of Environmental Health Sciences.

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