Studies examine methods to determine whether cancer is indolent or highly aggressive
Posted Sept. 1, 2009
Many of the more than 192,000 cases of prostate cancer expected to be identified in 2009 will involve indolent neoplasms. Nevertheless, the disease also will claim more than 27,000 lives, according to the American Cancer Society, making it the second leading cause of cancer-related death in American men.
In 2008, the AVMA Group Health and Life Insurance Trust paid benefits of more than $792,000 related to the treatment of malignant neoplasm of the prostate.
The Gleason score is a method for evaluating the differentiation of prostate cancer. On the
right side of this histologic slide, the prostate cancer has a Gleason value of 3 out of 5
(moderately differentiated cancer). On the left side, the Gleason value is 4 out of 5 (highly
undifferentiated). The Gleason score is the sum of the two worst areas on the slide.
Regular screening is an important weapon in reducing the number of deaths from prostate cancer. The five-year survival rate for men with early-stage prostate cancer is nearly 100 percent, according to the National Cancer Institute, and the 10-year survival rate is 86 percent. That is why annual tests of serum for prostate-specific antigen are part of the comprehensive wellness benefits available through GHLIT. These include free PSA tests at the GHLIT Wellness Center during the AVMA Annual Convention. At the 2008 convention, 12 of 403 PSA tests were in the high range (> 4 ng/mL). The individuals with these results were referred to their physician for further monitoring.
Modern detection methods result in more prostate cancers being diagnosed earlier; there is no reliable method for distinguishing between indolent and highly aggressive forms of the disease in its earliest stages, however. This can lead to overtreatment, exposing patients unnecessarily to such adverse effects as incontinence, impotence, bowel irritation, and skin irritation. Indeed, a study by researchers at the University of Michigan—which appeared in the Aug. 16, 2006, issue of the Journal of the National Cancer Institute—found that 10 percent of patients with lower-risk prostate cancer were overtreated with prostatectomy and 44 percent were overtreated with radiation therapy.
The findings of several recent studies may provide physicians and patients with critical clues as to whether active surveillance or a more aggressive approach, including surgery and radiation, is the most appropriate course of action. These findings, when considered in conjunction with indicators that currently drive treatment decisions, have the potential to lead to fewer instances of over- and under-treatment.
Currently, treatment decisions are based primarily on three indicators:
- PSA: Concentrations of 4 ng/mL or more indicate a need for biopsy or ultrasonography (some experts advocate further testing for concentrations above 2.5), as does any increase over time. A rapid increase in PSA concentrations during the year prior to diagnosis also may signal a significantly higher risk of death, even after radical prostatectomy, according to a study in the July 8, 2004, issue of the New England Journal of Medicine.
- Gleason score: Determined by examination of biopsy specimens, the Gleason score evaluates the cancer's differentiation and assigns a score of 2 to 10. Well-differentiated neoplasms (Gleason score of 2 to 5) are less likely to be aggressively malignant, while poorly differentiated neoplasms (Gleason score of 8 to 10) are likely to be highly aggressive.
- Staging: Typically determined by a bone scan, computerized tomography, magnetic resonance imaging, or another test, the stage (I to IV) indicates tumor size, involvement of the lymph nodes, and whether the cancer has metastasized.
Unfortunately, these indicators provide little insight as to whether an early-stage prostate cancer is indolent or highly aggressive. Help may be on the horizon. Several new studies provide clues that may drive better-informed treatment decisions.
Researchers with Wake Forest University and the University of Wisconsin confirmed earlier findings that men whose total serum calcium concentration falls in the highest third of the distribution have double the risk of fatal prostate cancer as men in the lowest third. The study, published in the February issue of Cancer Epidemiology, Biomarkers & Prevention, also found that men whose concentrations of ionized serum calcium, the physiologically active component of serum calcium, were in the highest third were three times as likely to die of prostate cancer.
Another study by researchers at the University of Michigan determined that concentrations of sarcosine are substantially higher in men with aggressive prostate cancers. The findings could lead to a simple urine test to differentiate between indolent and aggressive cancers.
Published in the Feb. 12 issue of Nature, the study found that sarcosine concentrations were elevated in 79 percent of samples from patients with metastatic prostate cancer and in 42 percent of samples from patients with clinically localized cancer. None of the cancer-free samples had detectable concentrations of sarcosine. In the study, sarcosine was also a better indicator of advancing disease than was the PSA test.
For men who have already undergone treatment, a third study may help drive decisions regarding secondary treatment. The findings were presented at the annual meeting of the American Society of Clinical Oncology in June. After tracking 774 prostate cancer patients for a median of eight years, researchers from Johns Hopkins determined that a three-way combination of measurements—the length of time it takes for the PSA concentration to double, the Gleason score, and the interval between prostatectomy and the first detectable PSA concentration—has the best chance of predicting metastasis. Thus, the combination of measurements may help determine which patients may benefit from additional therapy when postsurgical PSA concentrations increase.
Ongoing research into methods for differentiating between indolent and aggressive prostate cancer may ultimately serve to reduce the instances of over- and under-treatment. More important, when coupled with continued screening for early detection, results of such research may further increase the long-term survival rates of men in whom this deadly disease has been detected.
Information about GHLIT insurance—including rates, exclusions, limitations, eligibility, and renewal provisions—is available by calling (800) 621-6360.