Colonoscopy Prevents Colorectal Cancer Deaths
March 12, 2012 Colorectal cancer is the third most common cancer and the fifth leading cause of cancer death in men worldwide. The majority of colorectal cancers arise from adenomatous polyps, which can be detected with screening colonoscopy. Previously, the investigators of the National Polyp Study (NPS), found that colorectal cancer can be prevented by colonoscopic removal of adenomatous polyps. However, it has been unclear if the cancers prevented were those that had the potential to cause death. Recently, Zauber and colleagues reported* the effect of colonoscopic polypectomy on mortality from colorectal cancer. The researchers conducted a long-term prospective study of the NPS cohort of patients to determine the mortality among patients with adenomas removed compared with the expected mortality from colorectal cancer in the general population. The death rate of patients with adenomas was also compared with an internal control group of patients with nonadenomatous polyps. Among 2,602 patients who had adenomas removed, 12 died from colorectal cancer over a median period 15.8 years, compared with 25 expected deaths in the general population, suggesting a 53% reduction in mortality. Mortality from colorectal cancer among patients with adenomatous polyps was similar to those with nonadenomatous during the first 10 years after polypectomy. Thereafter, mortality increased for patients with adenomas, when strict surveillance was not organized by the study’s investigators. The researchers concede several limitations of the study. A small number of skilled endoscopists performed the colonoscopies, thus the observations may not be applicable to a community practice, for which the reported rates of colorectal cancer after polypectomy are higher than those reported in the NPS. The results of the study may not be representative of the general population, since the study was not a randomized, controlled trial. In conclusion, the study’s findings further support the belief that colonoscopic removal of adenomatous polyps prevents colorectal cancer death. The results also underscore the importance of longterm-term surveillance for patients after the initial removal of adenomatous polyps. More randomized, population-based trials are necessary to determine the effectiveness of screening colonoscopy on colorectal cancer mortality.
Zauber AG, et al. Colonoscopic Polypectomy and Long-Term Prevention of Colorectal-Cancer Deaths. N Engl J Med 2012;366:687-96.
Bretthauer M, Kalager M. Colonoscopy as a triage screening test. N Engl J Med 2012;366:759-60.
Models predicting erectile function after treatment for localized prostate cancer
February 7, 2012 Management of localized prostate cancer aims at achieving the trifecta of cancer control, urinary continence, and preservation of erectile function. With optimal cancer control being achieved through most interventions, the focus is currently on the other two outcomes that form a major quality of life issue in these men who are expected to be cured of their primary disease.
Pre-treatment prediction of post-intervention erectile function would be useful in patient counseling. The Prostate Cancer Outcomes and Satisfaction with Treatment Quality Assessment (PROSTQA) is a prospective, multicenter study that in 2003, began enrolling men with localized prostate cancer scheduled for definitive therapy with radical prostatectomy, external beam radiotherapy or brachytherapy. Apart from baseline patient data, the investigators recorded details of the treatment planned including nerve sparing surgery, hormonal therapy and radiation protocols. Post-intervention patient reported outcomes were recorded by third-party interviews using validated questionnaires.
In a recent trial by Alemozaffar and colleagues published in JAMA, the study investigators reported patient assessed erectile function in 1027 men who had completed 24 months after intervention. A significant increase in erectile dysfunction was reported in all 3 intervention groups: 63% vs 28% in radical prostatectomy, 63% vs 47% in the external radiotherapy group and 57% vs 33% in the brachytherapy group. Among men who were potent prior to intervention, 52% had ED after intervention; 60% in the prostatectomy group, 42% in the external radiotherapy group and 37% in the brachytherapy group. The authors were able to generate models that accurately predicted the occurrence of erectile dysfunction in the three treatment strategies. Models such as this one suggest that stratification by pretreatment patient characteristics and treatment details enables prediction of erectile function 2 years after prostatectomy, external radiotherapy, or brachytherapy for prostate cancer. While such a model cannot be used to judge superiority of one treatment strategy over another, it does aid in counseling patients about their individual outcome probabilities.
Alemozaffar M, Regan MM, Cooperberg MR, Wei JT, et al. Prediction of erectile function following treatment for prostate cancer. JAMA 2011;306:1205-14.
Prostate Cancer Screening Guidelines – DEBATE !!!
October 25, 2011 Last week, the United States Preventive Services Task Force (USPSTF) released a statement that it will downgrade its recommendation for prostate cancer screening. The previous recommendation from August 2008 states “the current evidence is insufficient to assess the balance of benefits and harms of prostate cancer screening in men younger than age 75 years”. The USPSTF now recommends prostate cancer screening via the serum prostate-specific antigen (PSA) test, in asymptomatic men because evidence indicates that the harms of the test outweigh its benefits.
This statement has received significant media attention in the United States and in Europe, and is felt to be very controversial. The American Urological Association (AUA) responded immediately to the USPSTF’s statement, citing “the task force’s recommendations will ultimately do more harm than good to the many men at risk for prostate cancer, both here in the US and around the world. Until there is a better widespread test for this potentially devastating disease, the USPSTF — by disparaging the test — is doing a great disservice to the men worldwide who may benefit from the PSA test” (AUA Daily Scope, October 13, 2011)./
Vitamin E and the Risk of Prostate Cancer
October 25, 2011 The 2009 SELECT (Selenium and Vitamin E Cancer Prevention Trial) study prospectively randomized over 35,000 men into 4 groups: selenium (200 μg/day) with matching placebo; vitamin E (400 IU/day) with matching placebo; both agents; or placebo. This study was halted due to lack of efficacy for risk reduction with no potential for benefit. While preliminary evaluation revealed essentially non-significant data, the safety monitoring committee expressed concern regarding an increased risk of prostate cancer in the group receiving vitamin E close to statistical significance, and a non-significant increased risk of type 2 diabetes mellitus in the selenium plus placebo group.
Following the initial trial, observation continued, with each group having greater than 13,000 person-years of follow-up. There were 521 additional cases of prostate cancer detected since the original study was published. The hazard ratio in the group of men given vitamin E who developed prostate cancer was 1.17; that for the selenium group was 1.09; that for the group who received vitamin E plus selenium was 1.05. The authors concluded absolute increased risks of prostate cancer per 1000 person-years of 1.6 for the vitamin E group; 0.8 for the selenium group; and 0.4 for the group who received both vitamin E and selenium.
Detection and prevention of prostate cancer remains an important public health goal on the worldwide level. The authors noted that these results differ from previous studies on the relationship between vitamin E supplementation and prostate cancer risk. The ATBC (Alpha-Tocopherol, Beta Carotene) trial reported a 35% risk reduction in men who took 50mg/day of vitamin E over an average period of 6.1 years. The reported 17% increased risk of prostate cancer in the SELECT trial follow-up suggests not only the potential for harm through vitamin E supplementation, but as the authors also claim, there is a great need for consumers to be surveillant of the potential health benefit claims of unregulated over-the-counter products that may claim to be beneficial to overall health and cancer prevention.
Klein EA, Thompson IM, Tangen CM, et al. Vitamin E and the risk of prostate cancer. JAMA 2011;306(14):1549-56.
Cigarette Smoking and Prostate Cancer Risk
July 7, 2011 Numerous trials have linked cigarette smoking to increased risk of prostate cancer mortality. Smoking is associated with a 30% increase in fatal prostate cancer due to more aggressive disease. The aim of this study was to assess the relationship between smoking and smoking cessation with overall, prostate cancer-specific, and cardiovascular mortality, as well as biochemical recurrence in men with prostate cancer.
The Health Professionals Follow-Up Study enrolled over 51,000 male health professionals, and smoking status was asked every 2 years since 1986. Men included in the study were free of prostate cancer during recruitment. This study evaluated 5366 men who had been diagnosed with prostate cancer between 1986 and 2006.
Outcomes of this study revealed that 32% of men died from prostate cancer, and 26% due to cardiovascular disease. Smokers had an increased risk of prostate cancer (hazard ratio [HR] = 1.61) as well as biochemical recurrence (HR = 1.61), cardiovascular mortality (HR = 2.13) and total mortality (HR = 2.28). Greater numbers of pack-years of smoking were directly associated with increased risk of prostate cancer but not biochemical recurrence.
In conclusion, smoking at the time of prostate cancer diagnosis was associated with increased mortality due all of the aforementioned causes. Men who quit smoking for at least 10 years were found to have mortality specifically due to prostate cancer at similar rates compared to men who had never smoked.
References: Kenfield SA, Stampfer MJ, Chan JM, Giovannucci E. Smoking and prostate cancer survival and recurrence. JAMA 2011;305(24):2548-2555.
Risk of Serum Phospholipids and Prostate Cancer
May 30, 2011 The risk between inflammation and the pathogenesis of prostate cancer is well understood, yet proliferative inflammatory atrophy, non-steroidal anti-inflammatory drugs, and dietary compounds have also demonstrated an associative relationship.
The authors in this study hypothesized that omega-6 and trans fatty acids (TFAs) would be positively associated with increased prostate cancer risk, while omega-3 fatty acids would be inversely associated with such risk. Subjects were identified as a case-control study nested within the Prostate Cancer Prevention Trial (PCPT).
All men in this study group were aged 55-84 years with no history of prostate cancer or severe benign prostatic hyperplasia, and with a prostate specific antigen (PSA) level of <= 3.0ng/mL. Throughout the 7 years of the PCPT, men who developed an abnormal digital rectal examination or a finasteride-adjusted PSA level of >=4.0ng/mL were referred for a prostate biopsy to rule out cancer. Non-fasting serum lipid analyses were sampled 3 months prior to randomization of this arm of the study, specifically assaying levels of various components of omega-3 fatty acids (eg, alpha-linolenic acid, eicosapentaenoic acid [EPA], docosahexaenoic acid [DHA]), omega-6 fatty acids (eg, linolenic acid, arachidonic acid), and trans fatty acids.
The authors concluded that no fatty acid components were associated with low-grade prostate cancer risk. DHA was associated with high-grade prostate cancer (Gleason 8 or higher) with and odds ratio of 2.5. However, various TFAs were inversely associated with prostate cancer risk (OR 0.55 and 0.48).
These results are the opposite of what might be expected in that the anti-inflammatory omega-3 fatty acids yielded an increased risk of prostate cancer while higher serum concentrations of the pro-inflammatory omega-6 and TFAs suggested a decreased prostate cancer risk, exactly the contrary to what was hypothesized.
By comparison, The Physicians’ Health Study recently discovered inverse associations between serum EPA and DHA with risk of both aggressive and non-aggressive prostate cancers. The European Prospective Investigation into Cancer and Nutrition study revealed that DHA was associated with elevated risks of both low-grade and high-grade prostate cancer.
In conclusion, the authors admit that the pathway(s) of prostate cancer are not completely understood in detail, and that a proposed mechanism for EPA and DHA as carcinogenic agents is not known. Nonetheless, a link between these fatty acids and prostate cancer cannot be claimed, as the complexity of the role of these nutrients across many forms of disease still needs to be elucidated.
Reference: Brasky TM, Till C, White E, et al. Serum phospholipid fatty acids and prostate cancer risk: results from the Prostate Cancer Prevention Trial. Am J Epidemiol 2011; published ahead of print April 24, 2011.
Male Pattern Baldness and Prostate Cancer Risk
March 17, 2011 A novel study conducted in France recently evaluated the potential link between androgenic alopecia and prostate cancer risk. Current estimates posit that over 50% of men will experience androgenic alopecia during their lifetime. Until now, evidence has been conflicting regarding this potential association. A case-control study of 669 subjects (388 with a history of prostate cancer and 281 without) found that patients with prostate cancer were twice as likely to have androgenic alopecia at age 20 [odds ratio (OR) 2.01], yet the specific pattern of hair loss was not determined to be a predictor of hair loss. Moreover, there was no association found between early-onset alopecia and an earlier diagnosis of prostate cancer, or with the development of more aggressive prostate cancer tumors.
The authors admit the possibility of selective recall bias in this study, yet retrospective self-reporting of male balding patterns has been validated across previous studies. As androgenic alopecia can impact self-perception, it was felt that since most men remember developing baldness at an early age. Similarly, the authors did not control for increased risk factors of prostate cancer including African heritage, yet family history was stratified in both case subjects and controls.
Data is abundant with regard to aging men and androgenic alopecia as well as the development of prostate cancer. To date, there is no statistical evidence to support a direct cause-and-effect relationship between alopecia and the development of prostate cancer at any age. As with previous studies, this is retrospective study cannot prove a direct causal relationship. Future research will focus on the identification of specific genetic markers to prove such a relationship.
To read more go to: http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)62342-2/abstract
Reference: Yassa M, Saliou M, De Rycke Y, et al. Male pattern baldness and the risk of prostate cancer. Annals of Oncology, February 2011.
Management of Chronic Prostatitis and Chronic Pelvic Pain in Men
January 20, 2011 A recent meta-analysis published in the January 5, 2011 edition of JAMA (The Journal of the American Medical Association) is the first study to rigorously examine the current literature on chronic prostatitis and pelvic pain syndromes in men. The authors reviewed 23 studies that compared pharmacologic treatments in men with these disorders to symptom scores (based upon the National Institutes of Health Chronic Prostatitis Symptom Index [NIH-CPSI] and International Prostate Symptom Score [IPSS], quality of life measures, and responses to various pharmacologic treatments versus control groups.
Compared to placebo, all 4 alpha-blockers were all found to offer statistically significant improvements in overall quality of life, decreased pain, and improved voiding symptoms. Those patients who received alpha-blocker therapy or steroidal/non-steroidal anti-inflammatory drugs (NSAIDs) had higher favorable responses with relative risk ratios of 1.6 and 1.8, respectively. Patients who received the 5-alpha reductase inhibitor finasteride or phytotherapies were found to have a mild effect on treatment response rates, pain, and voiding symptoms. Notably, statistical analysis revealed publication bias with alpha-blocker therapies in some of the smaller trials, suggesting an over-reporting of successful results relative to symptomatic improvement. The combination of both alpha-blockers and fluoroquinolone antibiotics yielded the greatest improvement over placebo relative to quality of life and pain scores.
The authors of this meta-analysis concluded that while there are statistically significant benefits to these pharmacologic treatments, they admitted that the sample sizes of most studies were quite small, and effect sizes were modest. Thus, this may have yielded over-estimations in power of reported statistical significance. Risk/benefit ratios of these therapies still need to be evaluated, and additional robust research is needed to further evaluate potential therapies for chronic prostatitis and pelvic pain syndromes in men.
Reference: Anothaisintawee T, Attia J, Nickel JC, et al. Management of chronic prostatitis/chronic pelvic pain syndrome. JAMA 2011;305(1)78-86.