Jewish World Review Sept. 20, 2004 / 5 Tishrei, 5765

Prostatectomy vs. radiation therapy for prostate cancer; optimal screening of patients with breast cancer gene mutations; health outcomes following surgery for morbid obesity; statins & acute coronary syndrome; maternal teaching & the incidence of childhood sunburns

By Robert A. Wascher, M.D., F.A.C.S. | Journal of the National Cancer Institute: While the optimal treatment of prostate cancer continues to be debated among cancer experts, several very different types of treatment options are currently available to patients with this disease. These include surgical removal of the prostate gland (prostatectomy), external beam irradiation, brachytherapy (the implantation of numerous tiny radioactive "seeds" into the prostate gland), and the use of hormone blocking drugs. Depending upon how advanced their disease is, patients with prostate cancer may be able to choose any of these approaches. Each treatment option is, of course, associated with a unique set of risks and benefits when compared to alternative options. Common side effects of prostate cancer treatment include impotence (seen following surgery and radiation), bowel urgency and hemorrhoids (seen primarily after radiation therapy), and decreased urinary continence (seen after both surgery and radiation therapy).

A new study adds some important information regarding the long-term side effects of prostatectomy versus external beam radiotherapy. In this study, 901 men were treated with radical prostatectomy, and 286 men were treated with external beam irradiation. All of the men were between 55 and 74 years of age, and all had early stage prostate cancer, with cancer confined to the prostate gland alone. All of the men were evaluated 2 years after completing their prostate cancer therapy, and then again 5 years after completion of their treatment. At the 5-year mark, sexual potency had significantly declined in both treatment groups, although this was more prevalent in the prostatectomy group: 79 percent of the men in the prostatectomy group reported erectile dysfunction (ED), while 64 percent of the men who were treated with radiotherapy experienced ED. Urinary incontinence was reported by approximately 15 percent of men in the prostatectomy group, and by 4 percent of the men in the radiation therapy group. Bowel urgency and hemorrhoidal complaints were much more common in the radiation group than in the prostatectomy group, as expected. These findings in both groups of men were consistent at both 2 years and 5 years following the completion of treatment for prostate cancer.

While the debate about the optimal treatment for prostate cancer is far from settled, this new study does provide additional useful information, for both patients and their physicians, about quality-of-life differences in the outcomes of prostatectomy versus radiation therapy for early stage prostate cancer.

Annals of Surgery: The causes of morbid obesity are not completely clear at this time. Doubtless, various combinations of genetic, physiological, and psychological factors are involved in each individual case. However, the health effects associated with being morbidly obese, or at least 100 pounds (about 45 kg) overweight, are very clear, indeed. Obesity, in general, has been clearly linked to an increased risk of high blood pressure, diabetes, heart disease, stroke, lung disease, arthritis, blood clots, cancer, and early death. Here in the United States, we are currently facing an unprecedented epidemic of obesity among our generally sedentary population. Recently, the US Government has concluded that the public health and economic impact of obesity-related diseases have become serious enough to reconsider a previous ban on Medicare coverage for obesity surgery. Indeed, premature deaths related to obesity reached an estimated 400,000 in 2002, making obesity the second most common cause of preventable death in the United States (just behind smoking, the number one cause of preventable death).

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It has been estimated that more than 7 million Medicare beneficiaries are obese. The surgery for morbid obesity is expensive, and there is a significant risk of complications associated with this surgery. However, as the social and economic costs of obesity continue to skyrocket in the United States, alternatives to the generally ineffective nonsurgical obesity treatments currently available are being sought. There is no question but that obesity surgery is effective in helping morbidly obese people lose excess weight. Whether or not this surgically-induced weight loss translates into significant improvements in health, however, has not been clear so far. A new study now appears to show that obesity surgery does indeed significantly reduce the incidence of obesity-associated diseases and premature death, as well as the demand for health care by morbidly obese patients.

The study evaluated 1,035 morbidly obese patients for up to 5 years following obesity surgery. An age- and gender-matched group of 5,746 morbidly obese patients who did not undergo obesity surgery were observed as a control group. The group that underwent obesity surgery lost an average of 67 percent of their excess weight after surgery. These patients, when compared to the control group, also experienced statistically significant reductions in the incidences of heart disease, cancer, infectious diseases and psychiatric diseases. As would be expected, however, from an operation that bypasses a significant portion of the gastrointestinal tract, the obesity surgery patients experienced an increased incidence of gastrointestinal problems when compared to the control group patients. Most importantly, the incidence of death among the patients who had undergone obesity surgery was 0.68% during the course of this 5-year study. In contrast, the incidence of death in the control group, during the same period, was more than 6 percent. This translates into an 89 percent reduction in the relative risk of death in the patients who underwent obesity surgery.

Data from studies such as this will play an important role in determining who should undergo obesity surgery, and whether or not the health insurance industry will decide to universally cover obesity surgery as a hedge against the spiraling healthcare costs associated with the our increasingly more obese society.

Journal of the American Medical Association: Acute coronary syndrome (ACS), which is defined as cardiac chest pain associated with unstable angina or heart attack, is associated with a very high risk of future heart attacks and death. Statin drugs, along with other medications that reduce the heart's consumption of oxygen, and increase blood flow to the heart muscle, are now a mainstay of treatment for ACS. The timing and dosage of statin therapy for ACS continues to be controversial, however.

A new study looked at the early initiation of intensive statin therapy in patients diagnosed with ACS, and compared this approach to the delayed initiation of lower dose statin therapy. This was an international, randomized, doubled-blind trial. A total of 2,265 patients received 40 mg of simvastatin per day for 1 month, followed by 80 mg per day thereafter. Another 2,232 patients took placebo (sugar) pills for 4 months, followed by 20 mg of simvastatin per day thereafter. All patients were then followed for at least 6 months, and for up to 24 months. The incidence of the following events was considered to be the primary end-point of the study: death due to cardiovascular causes, nonfatal heart attack, readmission to the hospital for worsening ACS, and stroke.

A total of 17 percent of patients taking the lower dose of simvastatin experienced one or more of the study's end-point complications, while 14 percent of the patients in the group with early initiation of high-dose simvastatin experienced one or more of the index complications. Death due to cardiovascular causes occurred in 5.4% of the low simvastatin dose group patients, as compared to 4.1% of the high-dose patients. After at least 4 months of simvastatin therapy, the high-dose simvastatin group was noted to experience a 25 percent reduction in the incidence of the study's end-point complications. Laboratory evidence of muscle injury, a complication known to occur with statin drug therapy, was identified in 0.4% of the patients receiving the 80 mg per day dose of simvastatin, while none of the patients who received the 20 mg per day dose experienced this complication. Interestingly, 1 patient developed laboratory evidence of muscle injury during the portion of the study when they were taking the placebo pill each day.

Although the benefits of the early initiation of high-dose statin therapy were relatively modest in this study, there did appear to be a statistically significant trend towards more favorable cardiovascular outcomes when compared to the more conventional regimen of delayed initiation of moderate-dose statin therapy.

Archives of Dermatology: It has been well established that the risk of developing melanoma, the deadliest form of skin cancer, is markedly increased following repeated sunburns during childhood. A new study provided hospital-based training about sun protective measures to randomly selected new mothers, while other randomly selected new mothers received the hospital-based training and printed educational materials, plus ongoing telephone counseling. The study's researchers then assessed the mothers' sun protection practices, and the degree of sun-induced skin damage present in their babies, when their babies were 6 months and 18 months of age.

First, this study determined that there were no significant differences in the sun protective behaviors of the mothers, or in the degree of sun exposure among their babies, between either of the study's two groups. However, significant differences in these study parameters were observed among all babies between 6 months of age and 18 months of age. During the first summer of their lives, 93 percent of the 6 month-old babies' mothers routinely used hats, shirts and shade to protect their infants from the sun when outdoors. The continuation of these sun-protective practices dropped, on average, to a rather dismal 34 percent during the babies' second summer. Conversely, sunscreen use actually increased from 22 percent of the time spent outdoors during the first summer of the babies' lives, to 54 percent of outdoor encounters during the babies' second summer of life. Unfortunately, dermatological examinations revealed that 22 percent of the babies received sunburns during their first summer of life, while a whopping 54 percent experienced sunburns during their second summer of life.

This study strongly suggests that sun-protective measures are more rigorously practiced by parents during their babies' first summer of life than during their second summer. The observation that more than half of babies experienced sunburns during their second summer of life in a coastal Massachusetts town is worrisome, indeed. Despite intensive training, including printed educational materials and telephone counseling, this surprisingly high incidence of sunburns during early childhood suggests that alternative methods of educating parents about sun protection strategies, and the importance of such strategies, should be urgently explored.

Journal of the American Medical Association: It is estimated that 10 to 15 percent of breast cancer cases have a genetic basis. So far, two specific breast cancer-associated gene mutations have been identified, BRCA1 and BRCA2. These gene mutations are variably associated with a 60 to 85 percent lifetime risk of developing breast cancer in affected women, as well as an increased risk of ovarian cancer in affected women, and an increased risk of both breast and prostate cancer in affected men. These mutations are, relatively speaking, far more common in the Ashkenazi Jewish population than in other populations. While only 0.2 percent of the general population studied so far carries one or both of these gene mutations, almost 3 percent of the Ahskenazi Jewish population is affected. Not only are women with BRCA1 or BRCA2 mutations at increased risk of developing breast cancer but, they also tend to develop breast cancer at a younger age than other women in the general population.

In view of the need to begin earlier breast cancer screening in women with BRCA1 or BRCA2 gene mutations (usually at about 25 years of age), various algorithms have been proposed. Unfortunately, the breasts of premenopausal women tend to be quite dense, and this lowers the sensitivity of mammograms, which rely upon very low-dose x-rays to identify breast abnormalities. Ultrasound penetrates the dense breasts of young women better than mammograms, but do not identify all breast cancers. MRI scans have been used to screen the breasts of young women who are at high risk of developing breast cancer, and in whom mammograms and ultrasounds have previously proven to be unreliable, but the role of MRI in breast cancer screening is unclear at this time. MRI scans appear to be more sensitive at detecting small or subtle breast cancers. However, MRI scans are also less specific than mammograms and ultrasounds, in that they tend to reveal more "suspicious" lesions that later, following biopsy, turn out to be benign in nature.

Currently, women with BRCA1 or BRCA2 gene mutations are advised to be screened every 6 months, starting at age 25, with mammography, and with ultrasound examinations when increased breast density limits the usefulness of mammography. In addition to these radiological screening studies, clinical breast examinations by an experienced clinician should also be performed every 6 months. A new study has compared the accuracy of combining 4 different screening modalities in diagnosing early stage breast cancer in women with either of the two known breast cancer mutations: clinical breast exam, mammography, ultrasound and MRI. The use of these 4 combined screening modalities was then compared to the current "gold standard" of mammography plus clinical breast examination. This Canadian study evaluated 236 women, ages 25 to 65 years, with either BRCA1 or BRCA2 gene mutations. All of the women underwent 1 to 3 annual screening examinations that included clinical breast exams, mammography, ultrasound and MRI. A total of 22 cancers were diagnosed during the course of this study, of which 77 percent were detected by MRI, 36 percent by mammography, and 33 percent by ultrasound, while only 9 percent were evident by clinical breast examination alone. This study revealed that 95 percent of all cancers that were diagnosed in this group of high-risk women could be detected using a combination of these 4 screening modalities. While it will likely increase the number of unnecessary biopsies performed, this combination of MRI, mammography, ultrasound and clinical breast examination should be considered the new "gold standard' for following women with BRCA1 or BRCA2 gene mutations. Whether or not this intensive (and very expensive) screening regimen will yield improvements in survival among women with these gene mutations is unclear, and additional studies will be necessary to answer this very important question.

JWR contributor Dr. Robert Wascher is an oncologic surgeon, professor of surgery, oncology research scientist, and author. He lives in Honolulu with his wife and two daughters. Comment by clicking here.



© 2004, Dr. Robert A. Wascher