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Benefits exceed risks for PSA in prostate cancer screening

MedWire - ASCO Prostate Cancer Symposium (San Francisco, CA, USA) - February 24, 2006: The pros and cons of widespread PSA screening are constantly debated at medical meetings, and clinicians are still divided on whether or not it can reduced overall mortality. At this session, a leading expert put forward the argument that the benefits of universal PSA screening outweigh the risks.

“PSA helps identify men with potentially lethal prostate cancer.”

Dr. William J Catalona, Robert H Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL, USA

Prostate cancer screening with prostate specific antigen (PSA) has benefits that exceed its risks, according to Dr. Catalona. He referred to longitudinal studies that showed a decrease in prostate cancer mortality since the advent of the so-called “PSA era,” and the fact that few tumors that are diagnosed subsequent to PSA screening are clinically insignificant.

However, physicians are divided on the ultimate role for PSA screening, Dr. Catalona commented during an interview. “The medical community is polarized with regard to prostate cancer screening.” For example, he explained that epidemiologists and primary care physicians can be skeptical about the value of universal PSA screening, while urologists and radiation and medical oncologists tend to see its benefits.

“Too often patients have presented with incurable disease, and we only wished they had come in earlier when we could have done more for them,” he said. The PSA, with its ability to detect prostate cancer early, has proven its value over time, he said.

“We have three major cancers where screening has proven to be effective: cervical cancer, breast cancer, and colorectal cancer.

“For cervical cancer the issue of screening was settled without a prospective trial, based on the registry of tumor statistics.[1] With mammography and colorectal cancer, trials have shown that screening saves lives, and the difference is reflected in the national database.”

In his presentation at the congress, Dr. Catalona noted that at the start of the PSA screening era in 1991, metastases were present in 20% of cases of newly diagnosed prostate cancer.[1] By 2002, that rate had decreased to 5%, giving a 75% reduction overall. “Down-staging is an essential ingredient for screening to be effective,” he said.

Accompanying this has been a decrease in prostate cancer-related death. The prostate cancer mortality rate peaked in 1995 at 40 deaths per 100,000 men, and has fallen 4% per year since then. In 2002, the mortality rate less than 30 cases per 100,000 men, or a 25% reduction.[2]

“Prostate cancer used to be the second leading cause of cancer death, after lung cancer,” Dr. Catalona said. “This year, it fell below colorectal and lung to third place.” He noted that prostate cancer mortality rates recorded by the World Health Organization have fallen since 1992 in parts of the world where PSA screening is widely used, and that mortality rates have increased in places where it is seldom used.

In the PCPT investigators found that they could detect prostate cancer using needle biopsy in 15% of men with PSA levels below 4 ng/ml, even with a benign digital rectal examination (DRE). [3] Dr. Catalona said that critics of universal PSA screening use this finding, and the fact that autopsies show microscopic prostate cancer in 35% of men over 50 years old, as arguments that PSA identifies clinically insignificant prostate cancer.

However, he stressed that, “the great majority of PSA-detected cancers have the features of clinically significant cancers.” He also pointed out that longitudinal studies throughout the PSA era do not show high levels of over-diagnosis, with clinically insignificant tumors constituting less than 10% of those found as the result of PSA screening.[4]

The criticisms of universal PSA screening have concentrated on the possible over-treatment of presumably low-risk tumors and the adverse effects associated with radical prostatectomy, such as erectile dysfunction and incontinence.

“What do we want to do, stop screening so that 20% of men have metastases at the time they’re diagnosed? Live with a higher mortality rate? I don’t think anyone wants to go there,” Dr. Catalona said.

“What we have to work on is improving the treatments so that patients don’t have as many adverse effects. For example, radiotherapy has improved so that it’s more targeted, with fewer side effects.

“We can also do nerve-sparing surgery and preserve potency and continence in patients.” He added that both erectile dysfunction and incontinence are treatable, and that investigators are looking for other ways to use PSA data, such as PSA density and PSA velocity. [5]

“With screening, we can identify prostate cancer earlier,” Dr. Catalona said. “If we treat patients effectively, we can have a major reduction of the mortality rates.

“Further, in order for a patient to be a candidate for active monitoring, clinicians have to know the tumor characteristics. If you don’t diagnose the cancer, you won’t have that information available. If you diagnose it, you will enable the patient to be an informed partner in this decision.”

In his presentation, Dr. Catalona quoted a prostate cancer patient, who said: “Most patients are aware that life is uncertain and that all of these things like Gleason grade have uncertainty with them.

“Therefore, most patients would rather be treated early to be on the safe side than to delay treatment and to face possible death and suffering from prostate cancer.”

References:

Boring CC Squires TS, Tong T. Cancer statistics, 1991. CA Cancer J Clin 1991; 41 :19-36. Ries LAG, Eisner MP, Kosary CL et al (eds). SEER Cancer Statistics Review, 1975-2002. Betheseda, MD: National Cancer Institute. http://seer.cancer.gov/csr/1975_2002/, based on November 2004 SEER data submission, posted to the SEER web site 2005. Thompson IM, Pauler DK, Goodman PJ et al . Prevalence of prostate cancer among men with a prostate-specific antigen level < or = 4.0 ng per millilitre. N Engl J Med 2004; 350 :2239-46. Krumholtz JS, Carvalhal GF, Ramos CG et al . Prostate-specific antigen cutoff of 2.6 ng/mL for prostate cancer screening is associated with favorable pathologic tumor features. Urology 2004; 60 :469-73; discussion 473-74. D’Amico AV, Chen MH, Roehl KA, Catalona WJ. Preoperative PSA velocity and the risk of death from prostate cancer after radical prostatectomy. N Engl J Med 2004; 351 :125-35.

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