Heart disease may be a risk factor for prostate cancer

Published: Wednesday, February 8, 2012 - 15:36 in Health & Medicine
In a large analysis of men participating in a prostate drug trial, researchers at the Duke Cancer Institute found a significant correlation between coronary artery disease and prostate cancer, suggesting the two conditions may have shared causes. If confirmed that heart disease is a risk factor for prostate cancer, the malignancy might be combated in part by lifestyle changes such as weight loss, exercise and a healthy diet, which are known to prevent heart disease.

"What's good for the heart may be good for the prostate," said Jean-Alfred Thomas II, MD, a post-doctoral fellow in the Division of Urology at Duke and lead author of the study, which appears online this month in the journal Cancer Epidemiology, Biomarkers & Prevention.

Coronary artery disease kills more adults in the United States than any other cause, accounting for one in four deaths. Risk factors include inactivity, obesity, high blood pressure and cholesterol, cigarette smoking, and diabetes.

Similarly, prostate cancer is a common killer. It's the second-most lethal cancer for U.S. men, behind lung cancer, with about 240,000 new cases diagnosed a year, and 34,000 deaths. Previous studies exploring the relationship between coronary artery disease and prostate cancer risk have found conflicting results, making it difficult to determine whether the malignancy is fueled by poor lifestyle choices.

In the current study, the Duke team used data from 6,390 men enrolled in a large study called REDUCE, a four-year, randomized trial to test the prostate cancer risk reduction benefits of a drug called dutasteride. All the study participants had a prostate biopsy at the two- and four-year marks, regardless of their PSA levels. They also provided a detailed medical history that included their weight, incidence of heart disease, alcohol intake, medication use, and other factors.

Among the men in the study, 547 reported a pre-enrollment history of coronary artery disease. This group of men tended to be older, heavier and less healthy, with higher baseline PSA levels, plus more diabetes, hypertension, and high cholesterol. The men were also much more likely to develop prostate cancer, even after accounting for all the baseline differences.

Having coronary artery disease increased the men's risk of prostate cancer by 35 percent, with the risk rising over time. The group was 24 percent more likely to be diagnosed with prostate cancer within the first two years of the study than men who reported no heart disease, and by four years into the study, this group's prostate cancer risk was 74 percent higher.

"We controlled for a number of risk factors, including hypertension, taking statins, or aspirin," Thomas said. "We don't have a good grasp on what's causing the link, but we are observing this association."

Stephen Freedland, MD, associate professor of surgery and pathology in the Division of Urology at Duke and senior author of the paper, said the study had some shortcomings. Notably, it relied on data from a previous trial that didn't account for factors such as diet, physical activity and severity of heart disease that may have influenced the results.

But Freedland said the study eliminated a screening bias common in previous findings that correlated prostate cancer and heart disease using men with high PSA levels.

"This is giving us a lot of good ideas for what to look at next," Freedland said, noting that the overlap between prostate cancer and other diseases associated with poor health habits is a focus of his research group.

In addition to Thomas and Freedland, study authors from Duke include Leah Gerber; Lionel L. Bañez; and Daniel M. Moreira. The Duke authors also hold positions in the surgery section of the Durham VA Medical Center. Study author Roger S. Rittmaster is from GlaxoSmithKline; Gerald L. Andriole is from Washington University School of Medicine in St. Louis.

Source: Duke University Medical Center

he genomic complexity of primary human prostate cancer

Prostate cancer is the second most common cause of male cancer deaths in the United States. However, the full range of prostate cancer genomic alterations is incompletely characterized. Here we present the complete sequence of seven primary human prostate cancers and their paired normal counterparts. Several tumours contained complex chains of balanced (that is, ‘copy-neutral’) rearrangements that occurred within or adjacent to known cancer genes. Rearrangement breakpoints were enriched near open chromatin, androgen receptor and ERG DNA binding sites in the setting of the ETS gene fusion TMPRSS2–ERG, but inversely correlated with these regions in tumours lacking ETS fusions. This observation suggests a link between chromatin or transcriptional regulation and the genesis of genomic aberrations. Three tumours contained rearrangements that disrupted CADM2, and four harboured events disrupting either PTEN (unbalanced events), a prostate tumour suppressor, or MAGI2 (balanced events), a PTEN interacting protein not previously implicated in prostate tumorigenesis. Thus, genomic rearrangements may arise from transcriptional or chromatin aberrancies and engage prostate tumorigenic mechanisms.
Nature
Volume:
470,
Pages:
214–220
Date published:

Prostate Specific Antigen Mass Ratio Potential as a Prostate Cancer Screening Tool

Purpose
Studies suggest lowering the threshold of the prostate specific antigen test in obese men due to the hemodilution effect but prostate specific antigen may be affected by prostate volume and insulin resistance, which also increase with obesity. Thus, we examined the combined effect of these factors on prostate specific antigen.

Materials and Methods
We analyzed 3,461 Korean men 30 to 80 years old with prostate volume data available who underwent routine evaluation. We examined the effect of plasma volume, homeostatic model assessment index, prostate volume and body mass index on prostate specific antigen, and prostate specific antigen mass and mass ratio (total circulating prostate specific antigen protein per prostate volume) by the trend test and/or ANOVA after adjusting for age and/or prostate volume.

Results
Body mass index had positive associations with plasma volume, the homeostatic model assessment index and prostate volume (p for trend <0.01). Prostate specific antigen had a positive association with prostate volume and a negative association with plasma volume (p for trend <0.01) but not with homeostatic model assessment index. The adjusted R2 of prostate volume vs prostate specific antigen was greater than for plasma volume vs prostate specific antigen while for body mass index vs prostate volume it was less than for body mass index vs plasma volume (0.0892, 0.0235, 0.1346 and 0.3360, respectively). Prostate specific antigen mass was not associated with plasma volume or body mass index but it was still associated with prostate volume after adjusting for plasma volume or body mass index (p for trend <0.01). Mean prostate specific antigen mass ratio did not change significantly across body mass index, plasma volume or prostate volume quartiles in men older than 55 years.

Conclusions
It is not logical to lower the prostate specific antigen threshold based on only the hemodilution effect since body mass index related prostate volume enlargement can increase prostate specific antigen in obese men. Another tool is needed and prostate specific antigen mass ratio may be an option.

Volume 184, Issue 2, Pages 488-493 (August 2010)

prostate Specific Antigen Mass Ratio Potential as a Prostate Cancer Screening Tool

Ho-Chun Choi, Jin-Ho Park, Be-Long Cho, Ki-Young Son, Hyuk-Tae Kwon

Bone-marker levels in patients with prostate cancer: Potential correlations with outcomes

Centre Hospitalier de l'Université de Montréal, Montreal, Quebec, Canada.

Milton S. Hershey Medical Center, Pennsylvania State University Cancer Institute, Hershey, Pennsylvania, USA.

The skeleton is typically the first site of metastasis in patients with prostate cancer, and bone metastases can result in severe bone pain and potentially debilitating fractures. Although bone scans are a reliable means of assessing osteoblastic lesions, tools for monitoring early changes in bone health are lacking. Biochemical markers of bone turnover might fulfill this unmet need.

Correlative studies have suggested that bone-marker levels may have utility in assessing disease progression and response to bone-directed therapy. Elevated levels of the markers, N-telopeptide of type I collagen and bone-specific alkaline phosphatase, are associated with higher rates of death and skeletal-related events in the bone metastasis setting. Marker levels also correlate with response to zoledronic acid treatment, and similar data with the investigational agent, denosumab, are emerging.

Changes in bone-marker levels reflect alterations in skeletal homeostasis and can provide important insights into bone disease progression and response to bone-directed therapy in patients with prostate cancer. More mature data from currently ongoing clinical trials will provide further insight on the utility of marker assessments as an adjunct to established monitoring methods in prostate cancer.

Written by:
Saad F, Lipton A

Prostate Cancer Treatments

Different types of treatment are available for prostate cancer. You and your doctor will decide which treatment is right for you. Some common treatments are—

•Active surveillance (watchful waiting): This consists of closely monitoring the patient's prostate cancer by performing the PSA and DRE tests regularly, and treating it only if and when the prostate cancer causes symptoms or shows signs of growing.
•Surgery (radical prostatectomy): Prostatectomy is surgery to remove the prostate completely. Radical prostatectomy removes the prostate as well as the surrounding tissue.
•Radiation therapy: Radiation destroys cancer cells, or prevents them from growing, by directing high-energy X-rays (radiation) at the prostate. There are two types of radiation therapy—
◦External radiation therapy: A machine outside the body directs radiation at the cancer cells.
◦Internal radiation therapy (brachytherapy): Radioactive seeds or pellets are surgically placed into or near the cancer to destroy the cancer cells.
•Hormone therapy: This treatment uses drugs, surgery, or other hormones to remove male sex hormones or block them from working, which prevents cancer cells from growing.
Other therapies used in the treatment of prostate cancer that are still under investigation include—

•Cryotherapy: Placing a special probe inside or near the prostate cancer to freeze and kill the cancer cells.
•Chemotherapy: Using special drugs to shrink or kill the cancer. The drugs can be pills you take or medicines given through an intravenous (IV) tube, or, sometimes, both.
•Biological therapy: This treatment works with your body's immune system to help it fight cancer or to control side effects from other cancer treatments. Side effects are how your body reacts to drugs or other treatments. Biological therapy is different from chemotherapy, which attacks cancer cells directly.
•High-intensity focused ultrasound: This therapy directs high-energy sound waves (ultrasound) at the cancer to kill cancer cells.
For more information, visit the National Cancer Institute's (NCI) Prostate Cancer Treatment Option Overview. This site can also help you find a doctor or treatment facility that works in cancer care. Visit Facing Forward: Life After Cancer Treatment for more information about treatment and links that can help with treatment choices.

Clinical Trials
If you have prostate cancer, you may want to take part in a clinical trial. Clinical trials are research studies that help find new treatment options. Visit the NCI and National Institutes of Health (NIH) sites listed below for more information about finding clinical trials.

•Introduction to Clinical Trials (NCI)
•Search for Clinical Trials (NCI)
•ClinicalTrials.gov (NIH)
Complementary and Alternative Medicine
Complementary medicine is a group of medicines and practices that may be used in addition to the standard treatments for cancer. Alternative medicine means practices or medicines that are used instead of the usual, or standard, ways of treating cancer. Examples of complementary and alternative medicine are meditation, yoga, and dietary supplements like vitamins and herbs.

Complementary and alternative medicine does not treat prostate cancer, but may help lessen the side effects of the cancer treatments or of the cancer symptoms. It is important to note that many forms of complementary and alternative medicines have not been scientifically tested and may not be safe. Talk to your doctor before you start any kind of complementary or alternative medicine.

For more information about complementary and alternative medicine, visit NCI's Complementary and Alternative Medicine.

Which Treatment Is Right for Me?
Choosing which kind of treatment is right for you may be hard. If you have prostate cancer, be sure to talk to your doctor about the treatment options available for your type and stage of cancer. Doctors can explain the risks and benefits of each treatment and their side effects.

Sometimes people get an opinion from more than one doctor. This is called a "second opinion." Getting a second opinion may help you choose the treatment option that is right for you.

The natural history of metastatic progression in men with PSA-recurrent prostate cancer after radical prostatectomy: 25-year follow-up

Journal of Clinical Oncology, 2009 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 27, No 15S (May 20 Supplement), 2009: 5008

Background: In men with prostate specific antigen (PSA) recurrence following radical prostatectomy (RP) and no other therapy, the natural history of metastatic progression was previously described in 1999.

We now report data reflecting up to 25 years of follow-up. Methods: We performed a retrospective analysis of 774 men treated with RP between 4/1982 and 7/2008 who developed PSA recurrence (>0.2 ng/ml) and never received adjuvant or salvage therapy.

We investigated factors influencing the development of metastases. Results: Mean follow-up after RP was 8.5 y (median 8 y). Of 774 men with PSA recurrence, 295 (38%) developed metastases, and 433 had data on PSA doubling time (PSADT), forming our cohort. The mean time from RP to PSA recurrence in the entire cohort was 4.2 y (median 3 y). In those who developed metastases, the mean time from PSA recurrence to metastasis was 3.1 y (median 2 y). The mean PSA at the time of metastasis was 90.3 ng/ml (median 31.4 ng/ml). In Cox regression analysis: PSADT, Gleason score, and time to PSA progression were predictive of the development of metastases (Table).

In Kaplan-Meier survival analysis, the median actuarial time from PSA recurrence to metastasis was 10 y (95% CI 9 - 15 y). Median actuarial metastasis-free survival from PSA recurrence for men with PSADT <3 mo, 3 - 8.9 mo, 9 - 14.9 mo, and >15 mo was 1 y (95% CI 0 - 1 y), 4 y (95% CI 2 - 6 y), 9 y (95% CI 7 - 13 y), and 15 y (95% CI 12 - 20 y), respectively.

Conclusions: PSADT, Gleason score, and time to PSA progression are strong independent predictors of metastasis-free survival in men with PSA-recurrent prostate cancer. These data facilitate patient counseling and logical risk-based treatment planning. They also provide the background for appropriate selection of patients, treatments, and endpoints for clinical trials

Time Between Treatment And PSA Recurrence Predicts Death From Prostate Cancer

Time Between Treatment And PSA Recurrence Predicts Death From Prostate Cancer

ScienceDaily (Nov. 9, 2009) — Men whose prostate specific antigen (PSA) rise within 18 months of radiotherapy are more likely to develop spread and die of their disease, according to an international study led by Fox Chase Cancer Center radiation oncologist Mark K. Buyyounouski, M.D., M.S. and presented today at the annual meeting of the American Society for Radiation Oncology (ASTRO).

"PSA is the gold standard for following prostate cancer patients after they receive radiation or surgery. But we haven't know if having prostate specific antigen (PSA) rise sooner means a patient has a greater danger of dying of prostate cancer, though it seems logical," Buyyounouski says.

Using a single institution database, Buyyounouski and colleagues showed previously that men who suffered an early biochemical failure, which is defined as their lowest PSA level plus 2 ng/mL, were at greater risk of dying of prostate cancer. The new study confirms those results using a multinational database and shows that the measure is ready for use in the clinic.

"Now we can use the simple criteria from this study, which is widely available for anyone who has PSA testing, to identify men who have a greater than 25% chance of dying from prostate cancer in the next five years. That is huge. There is nothing else that can do that," says Buyyounouski.

A total of 2,132 men with clinically localized prostate cancer who suffered biochemical failure after treatment were studied. The median interval between treatment and biochemical failure was 35.2 months for the entire study group. However, 19% of patients developed biochemical failure at 18 months or less. The five-year cancer-specific survival for these men was 69.5% compared with 89.8% for men who developed biochemical failure after 18 months.

A multivariate analysis showed that the interval to biochemical failure correlated with cancer specific survival, as did Gleason score, tumor stage, age, and PSA doubling time. However, the interval to biochemical failure had the best predictive value for cancer-specific mortality, compared with the other variables.

Currently, most physicians do not start treatment based on biochemical failure alone, but rather wait until the PSA reaches a high level or there is some other evidence tumor spread. "The potential impact of this finding is that patients can initiate treatment far sooner without waiting for other signs or symptoms of prostate cancer," Buyyounouski says. "If a patient has biochemical failure at 16 months, rather than wait and learn later that the PSA is rising sharply and risk the development of distant metastasis, therapy can be started sooner based on the increased risk of death."