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Baby-Boomer Increase in Prostate Cancer Magnifies Need for Risk Stratification

Carlson, Robert H.

doi: 10.1097/01.COT.0000292604.81471.f9

ORLANDO, FL—The growing population of aging males in the US and other countries means that more men are being diagnosed with prostate cancer, and more will have recurrent disease. And since not all men with rising prostate-specific antigen (PSA) levels after definitive local treatment will die of the disease, more precise methods are needed to identify those who are at risk for biochemical failure. Several presentations during a Poster Discussion session here at the ASCO Annual Meeting pointed to more precise risk stratification as a means to select men for aggressive therapy as well as those appropriate for active observation.

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Early Hormonal Treatment

The presentations discussed by Judd W. Moul, MD, Professor and Chief of the Division of Urologic Surgery at Duke University Medical Center, included a study describing a novel preoperative nomogram to predict metastatic progression among men with clinically localized prostate cancer treatment by radical prostatectomy.

First author Andrew J. Stephenson, MD, a fellow in the Department of Urology at Memorial Sloan-Kettering Cancer Center, said the tool would be useful to identify high-risk patients for investigational neoadjuvant therapy.

In an intriguing development, the nomogram showed that neoadjuvant androgen-deprivation therapy was an adverse predictor of metastatic progression. “Potentially, neoadjuvant androgen deprivation may diminish the response of prostate cancer to androgen deprivation when it is administered for progressive disease,” the Memorial researchers speculated.

In his discussion, Dr. Moul said the take-home message from this study was that oncologists and urologists must risk-stratify patients considered for adjuvant hormonal therapy.

While hormonal therapy is probably beneficial to men with high-risk localized, locally advanced, and metastatic disease, early hormonal therapy, both neoadjuvant and adjuvant, may be harmful for patients at lower risk and those with localized disease, he said. “We may be seeing the tip of the iceberg with this study. I hope we see more data on this in the future.”

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Another abstract reviewed by Dr. Moul also offered a nomogram to aid in risk stratification. From Johns Hopkins School of Medicine, Stephen J. Freedland, MD, an instructor in the Department of Urology, reported that the clinical parameters of PSA-doubling time, pathological Gleason sum, and the time from radical prostatectomy to biochemical relapse can be used to risk-stratify patients for prostate cancer-specific death following biochemical relapse after prostatectomy.

The study included 5,096 men retrospectively studied after prostatectomy, 379 of whom had biochemical recurrence, for a median follow-up of 10.3 years. The cancer-specific survival rate was 55% at 10 years.

Dr. Freedland and his colleagues reported that it was possible, using those three variables, to estimate the five-, 10- and 15-year risk of cancer-specific survival.

“This clearly suggests that we can risk-stratify these biochemical recurrence patients,” Dr. Moul said.

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Not All PSA Recurrence Is Bad

A study from Dana-Farber Cancer Institute suggested that a rising PSA after definitive treatment does not necessarily portend the worst for prostate cancer patients.



Ping Zhou, MD, PhD, of the Department of Radiation Oncology, reported the study, in which 1,159 patients at high risk for prostate cancer-specific mortality following PSA failure were analyzed by post-prostatectomy or post-radiotherapy doubling time, and Gleason score.

A post-treatment doubling time of less than three months after prostatectomy or radiation, and a Gleason score of 8 or higher in men treated with radiotherapy, were significantly associated with time to prostate cancer- specific mortality following PSA failure.

These parameters helped identify the optimal patient selection for a randomized trial evaluating hormonal therapy with or without docetaxel, Dr. Zhou and his colleagues said.

Dr. Moul, one of the investigators on this study, noted that here the time to biochemical recurrence was not a predictor of cancer-specific mortality.

A more general point, however, was that biochemical failure after initial treatment is not necessarily a prelude to prostate cancer-related death.

“Unfortunately, especially among urologists, we had been taught that all PSA recurrences had been bad,” Dr. Moul said. “The take-home messages here are that physicians must risk-stratify biochemical recurrence, and that not all PSA recurrence is bad.

“We should not ‘pull the trigger’ for hormonal therapy too soon for patients with relatively benign PSA recurrences. We must take a risk-stratified approach to biochemical occurrence and use of hormones.”

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Screening & Follow-up

Another Discussant in the session, Celestia S. Higano, MD, Associate Professor of Urology at the University of Washington, suggested that stricter criteria in screening parameters might result from a study by Fox Chase Cancer Center researchers.

Andre Konski, MD, Clinical Research Director of Radiation Oncology and Clinical Director of the Prostate Cancer Risk Assessment Program there, reported that 45% of 75 men biopsied in a high-risk prostate cancer screening program were diagnosed with prostate cancer.

The criteria for being at high risk included having an abnormal digital rectal exam or having a PSA level above 4.0 ng/mL, or at least 2.0 but below 4.0 ng/mL with the amount of free PSA lower than 22%.

Importantly, the biopsy resulted in a diagnosis of prostate cancer in 25% of those men who had PSA levels of 2.5 ng/mL, Dr. Konski said.

“Twenty-five percent of men diagnosed with prostate cancer would have had a PSA below the newly recommended NCCN screening guideline,” which calls for aggressive screening parameters for men at high risk.

Dr. Higano echoed the Fox Chase researchers in recommending that NCCN guidelines be reconsidered.

“The Fox Chase group is suggesting that for high-risk patients, a free PSA test be done in any patients with PSA values between 1.5 and 10.0, and if the PSA level is 2.5 or greater and the free PSA is less than 27%, biopsy should be performed,” she said. “This should be considered for the next set of NCCN guidelines.”

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Non-Mechanical Experiences

Another trial, from the Southwest Oncology Group, compared the impact of radical prostatectomy alone versus radical prostatectomy plus adjuvant radiation on clinical outcomes and quality of life.

Early results from the trial showed that radiation plus prostatectomy was associated with more tenderness/urgency with bowel movements, more frequent urination, and overall unpleasant global quality of life.



This new study, though, led by Katherine A. Hayden, RN, OCN, found that by five years all significant treatment-arm differences had disappeared.

“This points to the importance of long-term follow-up on these studies, and not just publishing results early and going on to the next thing,” Dr. Higano said.

Still, she said she did not believe that follow-up longer than two years should be required: “We are at the point where we have a good handle on a lot of these relatively short- and also long-term toxicities. It is time we start looking at other ‘non-mechanical’ survivorship issues, such as emotional and other aspects that prostate cancer survivors experience.”

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Many Americans Believe Cancer Myths, Survey Finds

Most US adults believe at least one misconception about cancer, and belief in these misconceptions may result in failure to adhere to treatment, increasing the risk of cancer morbidity and mortality, according to a survey published in the August 1 issue of Cancer, led by Ted Gansler, MD, MBA, of the American Cancer Society.

In all, only one fourth of respondents did not express belief in any of the five cancer treatment misconceptions included in the survey. Almost 41% of those surveyed reported that they believed the study's most prevalent misconception—that treating cancer with surgery can cause cancer to spread throughout the body—and an additional 13% responded that they did not know whether or not that statement was true.

In addition, 27% of participants said they believed the second most common misconception noted in the survey—“there is already a cure for cancer but the medical industry won't tell the public because they make too much money treating cancer”—and 14% indicated that they were not sure whether or not that statement was true.

“I would say we were mildly surprised by the results,” another of the authors, Kevin D. Stein, PhD, the ACS's Director of Quality of Life Research, said in an interview. “We know people have misconceptions about cancer, but we really didn't anticipate the prevalence to which people hold these myths.”

The study, conducted by the ACS along with Prevention magazine and the Discovery health channel, used a random digit dialing telephone survey to interview 957 adults who reported that they had never been diagnosed with cancer. Princeton Research Associates devised the questionnaire, in collaboration with Rodale Press, Prevention's publisher and the ACS, and the interviews were conducted in November 2002 by trained interviewers over an approximately two-week period.

The sample was weighted to match the general US population in terms of gender, age, education, race, Hispanic origin, and US census region.

The initial reason for conducting the survey was to gather information to focus on for the Society's public education programs as well as areas for additional research, Dr. Stein said.

Of the adults surveyed, 68% correctly rejected the statement, “Pain medications are not effective in reducing the amount of pain people have from cancer,” and 89% accurately disagreed with, “All you need to beat cancer is a positive attitude, not treatment.”

In addition, 87% of respondents correctly said that the statement “Cancer is something that cannot be effectively treated” was false.

Participants who were older, nonwhite, Southern, or self-reported that they were ill informed about cancer held the most misperceptions.

“We need to do a better job of educating the public,” Dr. Stein said. “We need to do a targeted, tailored intervention for people who are most at risk for holding these misconceptions.”

Cancer knowledge and literacy may affect patients' decisions on preventive measures, seeking care, and participating in treatment decisions, the authors wrote. For example, a patient who believes that surgery can spread cancer may be reluctant to agree to surgery or to see a physician, Dr. Stein said. “That's really what we're worried about—people acting on these beliefs or rather failing to act because of these beliefs.”

Almost half of those surveyed believed that treating cancer with surgery can cause cancer to spread throughout the body, and an additional 13% said they did not know if that was true. In addition, 27% believed the misconception that “there is already a cure for cancer but the medical industry won't tell the public because they make too much money treating cancer,” and 14% said they were not sure whether or not that statement was true.

© 2005 Lippincott Williams & Wilkins, Inc.
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