"Watchful waiting" may be best approach for prostate cancer

Researchers set out to help older men with an early diagnosis chart a path through the maze of treatment options.

By Susan J. Landers — Posted March 10, 2008

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To treat or not to treat has long been a puzzle in prostate cancer, with studies lending support to both options. Now comes a new, large study of older men with early-stage cancer that points to "watchful waiting" rather than treatment as the better option for this population.

The study, presented Feb. 14 at the 2008 Genitourinary Cancers Symposium in San Francisco, found that a conservative approach that included monitoring for increasing levels of prostate-specific antigen and other signs of the cancer's growth was a successful strategy for the majority of the older men studied who had stage I or stage II prostate cancer.

The symposium was sponsored by the American Society of Clinical Oncology, the American Society for Therapeutic Radiology and Oncology, and the Society of Urologic Oncology.

The researchers concluded that the men's cancers grew so slowly that after 10 years, about 80% of the men were alive with no complications from their cancer or had died of other causes. More than 5,000 of the 9,000 men in the study were older than 75, and all were older than 66. Unlike in some earlier studies, all men in the latest study had been diagnosed in 1992 or 1993, after PSA testing became available.

Although the PSA test is a great boon in that it allows earlier diagnoses of prostate cancer, it has made conversations between physicians and their patients more complex. There is no question the test can help spot many prostate cancers early, but it cannot tell how dangerous the generally slow-growing cancer is, according to the American Cancer Society. Men can live for many years with the disease and without treatment, which involves surgery and radiation and carries its own dangers.

AMA policy recommends that tests for early detection be given to all men with a life expectancy of at least 10 years and include those 50 or older; African-American men 40 and older; and all men age 40 and older who have a first-degree relative affected by the cancer. It also recommends that a PSA test as well as a digital rectal examination be included in the physical examination. The ACS has similar policy.

The disease is a serious problem. In 2007, about 218,000 men were diagnosed with prostate cancer, and 27,050 died from the disease, according to the Agency for Healthcare Research and Quality, which reported last month that a review of treatment options did not reveal a clear winner.

"When it comes to prostate cancer, we have much to learn about which treatments work best, and patients should be informed about the benefits and harms of treatment options," said AHRQ Director Carolyn Clancy, MD, when releasing the report Feb. 4.

Treatment conundrums

The management of older men with early-stage cancer is particularly problematic. Some studies suggest that men who receive therapy fare better than those who do not, while other research has reported that many of these men can safely forgo therapy and eventually will die with prostate cancer, not from it.

The authors of the study presented at the genitourinary cancers symposium set out to determine whether they could provide treatment answers. "Many men feel like they are facing a maze when it's time to make a treatment decision," said lead author Grace Lu-Yao, PhD, a cancer epidemiologist at the Cancer Institute of New Jersey in New Brunswick.

Dr. Lu-Yao described her study as one of the first to chart the natural history of the disease.

Deciding which patients among those with elevated PSA levels should be treated aggressively is still unclear.

"Most prostate cancer doctors believe that many cases of prostate cancer are overtreated," said Howard M. Sandler, MD, moderator of a briefing in which these results were presented. He also is a professor at the University of Michigan in Ann Arbor's radiation oncology department.

"The trick has been to try to identify those patients who are likely not at risk by doing active surveillance. I think this study provides evidence for the idea that it is patients with the lower-grade tumors, the Gleason 6 tumors or perhaps some Gleason 7 tumors, who have a low 10-year risk of dying from prostate cancer," Dr. Sandler said.

But patients with higher-grade tumors might be poor candidates for an active surveillance program, he said, and those patients might benefit from active treatment such as radiation or surgery.

Looking ahead

Meanwhile, researchers are in pursuit of a urine test that can be used with the PSA test to more accurately detect prostate cancer.

Although it is not ready for clinical use, an experimental biomarker test has been developed by researchers at the University of Michigan in Ann Arbor. Results of a study on this "first generation" test are in the Feb. 1 Cancer Research, a journal of the American Assn. for Cancer Research.

The test screens for the presence of four different RNA molecules. "One of the biomarkers in our test is PCA3, which has previously been shown, in urine tests, to outperform serum PSA for predicting which men have prostate cancer," said researcher Scott Tomlins, MD, PhD, a fellow at the University of Michigan's Center for Translational Pathology. "Our test shows that adding additional biomarkers can improve upon PCA3 alone for the prediction of prostate cancer."

Also on the research front, a prostate cancer vaccine has been developed that prevented cancer in 90% of the mice who received it. The research was also in the Feb. 1 Cancer Research. The mice in the study had been genetically predestined to develop the cancer.

"By early vaccination, we have basically given these mice lifelong protection against a disease they were destined to have," said the study's lead investigator, W. Martin Kast, PhD. He is a professor of molecular microbiology and immunology at the University of Southern California's Norris Comprehensive Cancer Center in Los Angeles.

"This has never been done before and, with further research, could represent a paradigm shift in the management of human prostate cancer," Dr. Kast said.

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Limitations of the PSA screen

Although the PSA test is useful in detecting prostate cancer early in many men, it has significant shortcomings.

  • The PSA test can detect small tumors, but these may be slow-growing and unlikely to threaten a man's life.
  • False-positive results can occur, where PSA levels are elevated but no cancer is present. Most men with elevated PSA levels turn out not to have cancer.
  • False-negative results also can occur, where PSA levels are normal but prostate cancer is present.

Coming up

The Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial is under way at 10 sites across the country to help determine whether screening tests for these four common cancers reduce deaths. Results aren't expected for several years.

Source: National Cancer Institute

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External links

"Comparative Effectiveness of Therapies for Clinically Localized Prostate Cancer," Agency for Healthcare Research and Quality, Feb. 5 (link)

"A First-Generation Multiplex Biomarker Analysis of Urine for the Early Detection of Prostate Cancer," abstract, Cancer Research, Feb. 1 (link)

"Prostate Stem Cell Antigen Vaccination Induces a Long-term Protective Immune Response against Prostate Cancer in the Absence of Autoimmunity," abstract, Cancer Research, Feb. 1 (link)

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