High pretreatment PSA velocity predicts worse outcome

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The most significant single predictor of aggressive prostate cancer is an elevated rate of increase in prostate specific antigen (PSA) levels, according to a new study. Published in the July 1, 2007 issue of CANCER, a peer-reviewed journal of the American Cancer Society, the study found that a pre-treatment rate of PSA increase, called PSA velocity, of more than 2 ng/ml/year was strongly associated with a high risk of death from prostate cancer. Elevated PSA velocity was a stronger poor prognostic factor than any other single high-risk indicator, such as a biopsy Gleason score greater than 7, a PSA level of 10 ng/ml or an advanced disease category.

Prostate cancer is expected to be diagnosed in more than 200,000 American men in the U.S. this year and cause more than 27,000 deaths, the leading cause of cancer death after lung cancer in U.S. men. Most tumors are slow growing and asymptomatic, and the disease affects primarily men over 50 years old. As a result, most men diagnosed with prostate cancer die of other age-related causes.

However, in a significant subset of prostate cancer patients, the cancer will be aggressive and quick enough to cause morbidity and death. Identifying these men is critical to reducing deaths from prostate cancer. Researchers have identified several indicators with the potential to identify high-risk patients and developed various algorithms, using such factors as the microscopic features of the tumor (i.e., Gleason score), size, spread of the disease, and location of disease, to determine prognosis. However, recent trends suggest that these factors are not effective and that better indicators are needed. Calculating PSA velocity has shown promise as a prognostic indicator. Studies suggest that PSA velocity more than 2 ng/ml/year strongly suggests aggressive disease. Understanding its significance after treatment, particularly relative to other risk factors, is critical to identifying high-risk patients.

Dr. Anthony D'Amico of Boston's Brigham and Women's Hospital and co-investigators characterized PSA velocity significant in prostate cancer-specific mortality (PCSM) rates following treatment with radical prostatectomy (RP) or radiation therapy (RT). Dr. D'Amico reviewed data from 948 men with localized prostate cancer who had one or more high-risk factors.

Dr. D'Amico and his co-authors found that the most important single prognostic factor was PSA velocity. As expected, men who had multiple risk factors died from their disease significantly earlier than those with one factor. Of the men who underwent treatment with RP or RT, 44 percent and 28 percent, respectively, had pre-treatment PSA velocities of > 2 ng/ml/year as their only identified high-risk factor. Of those men who died with only one identified high-risk factor, 88 percent of RP-treated patients and 80 percent of RT-treated patients had pre-treatment PSA velocities of > 2 ng/ml/year.

In identifying this association, the authors also point out that other studies have found that time to death shortens as PSA velocity increases. This suggests that further research should examine using stratified PSA velocities to assess risk in men with localized disease.

"These findings," conclude the authors, "highlight the ability of a pre-treatment PSA velocity > 2 ng/ml/year alone to identify men with aggressive prostate cancer and in whom effective systemic treatment in addition to mono-therapy with RP or RT is needed to decrease PCSM rates."

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A commentary in the British Journal of Urology International (BJUI) asked, “Should we really consider Gleason 6 prostate cancer?”

The National Cancer Institute defines the Gleason score as:

A system of grading prostate cancer tissue based on how it looks under a microscope. Gleason scores range from 2 to 10 and indicate how likely it is that a tumor will spread. A low Gleason score means the cancer tissue is similar to normal prostate tissue and the tumor is less likely to spread; a high Gleason score means the cancer tissue is very different from normal and the tumor is more likely to spread.

But on that spectrum of 2 to 10, different doctors draw different cut-off points for decision-making. The BJUI commentary stated:

“There is no doubt that prostate cancer kills, but only a minority of men who are given this diagnosis, die from prostate cancer. In the developed world we are now overdiagnosing and, more importantly, overtreating prostate cancer, a fact for which we will be criticized in generations to come. As well-intentioned urologists, we should have no trouble in justifying our radical therapy for pathologically moderate to high grade, Gleason 7 – 10 cancers. Despite the opinions of some urological luddites, careful active surveillance is slowly becoming the standard for Gleason 6, particularly for those with low volume disease associated with low serum PSA values, however, many patients with Gleason 6 still receive radical treatment. We (and others) would like to hypothesize, at least for the sake of discussion, that Gleason 6 pattern prostate pathology is not in itself a lethal prostate cancer, but rather can be associated with a higher risk of potentially lethal prostate cancer (e.g. Gleason 7 or higher) or, alternatively, is a precursor to such prostate cancer. This change in thinking would mean that patients with Gleason 6 scores would not be labelled with a ‘ lethal ’ cancer diagnosis and would be less anxious about the appropriate treatment plan of active surveillance. Many patients drop out of active surveillance and pursue radical treatment, not because of rising PSA levels, biopsy results or other forms of disease progression, but because of anxiety. There may be less morbidity (and cost) if patients were not given the ‘cancer-label ’ until they had Gleason 7 disease.

Whether Gleason 6 is really a cancer or not is a mute point, one that can only be debated, at this time. We continue to over-diagnose and subsequently over-treat unfortunate men who are labelled with a ‘lethal’ cancer, when in fact they will probably never die from it. It is a fact, however, that some men continue to die from prostate cancer, so we must try and direct our therapies to those men, a task that will only be possible through enlightened discussion coupled with basic and clinical research. We need to change our paradigm when dealing with Gleason 6 pattern diagnosis, whether it is a low-risk cancer, a benign disease associated with a high risk of developing real potentially lethal cancer, or a true prostate cancer precursor. Let ’s find a way to treat only those men who are destined to die from this serious cancer and relieve some of the psychological burden and significant morbidity from those men who should never have been labelled ashaving a lethal cancer in the first place. Let us make the case and put in the effort to develop improved prostate cancer screening for the higher grade prostate cancers,while at the same time relegating low volume Gleason 6 to the status of no more than a significant risk factor. Let us decide as a profession to stop the push for inappropriate, expensive, inopportune and perhaps even unethical radical therapies for a condition that by itself does not kill our patients.”

What to call certain abnormal cellular findings is increasingly becoming an issue for doctors.

In breast cancer, there’s been some discussion of re-naming ductal carcinoma in situ and removing the “carcinoma” from the diagnosis.

In cervical cancer, there are ASCUS cells – or “atypical squamous cells of unknown significance.”

Gleason 6 cells in the prostate cancer field have been called “adenosis.” They’ve been called IDLE – indolent lesions of epithelial origin.

Whatever these cells are called, one practical goal for now is to educate men about the harms of overdiagnosis and overtreatment and offer active surveillance as a treatment option.

[url]http://onlinelibrary.wiley.com/doi/10.1111/j.1464-410X.2011.10854.x/abstract

HealthNewsReview.org

Note: According to Dr. Matt Cooperberg, assistant professor at UCSF, active surveillance for prostate cancer means that based on the information available, the likelihood of cancer progressing in the short-term, while not zero, appears to be very low. Active surveillance does not mean the cancer will never need to be treated, but rather that it does not need treatment now. The "window of opportunity" for curing low risk prostate cancer is measurable in years in most cases, if not decades. In the meantime, men can avoid the risks and costs of surgery, radiation therapy and other interventions.