RADIATION TREATMENT OF PROSTATE CANCER & RISK OF SECOND CANCERS

Exposure to high doses of ionizing radiation, whether from a nuclear explosion or from radiation therapy for cancer, has long been known to increase the risk of cancer formation.  A growing body of clinical data is helping to further develop our understanding of secondary radiation-induced cancers. 

Much of our current understanding about radiation-induced cancer is based upon long-term observation of the Japanese survivors of the World War II atomic bombings in Hiroshima and Nagasaki.  In particular, an increased incidence of leukemia, myeloma, and cancers of the thyroid, breast, lung, stomach, esophagus, ovary and bladder has been identified in atomic bomb survivors who were close to ground zero.

Following the catastrophic failure of the Chernobyl nuclear reactor in Ukraine, in 1986, an excess of leukemia and thyroid cancer among workers who were involved in the clean-up of the reactor’s contaminated debris has already been documented.

More recently, several studies have reported upon the incidence of secondary cancers in adults who were treated with radiation therapy for lymphoma during childhood and adolescence.  An increased incidence of cancers of the lung and the female breast has been confirmed among patients who previously underwent extended-field chest irradiation (also known as mantle radiation therapy) for Hodgkin’s Lymphoma, and these secondary cancers typically occur 15 to 20 years following treatment.  Rare cancers of the bone and cartilage, called sarcomas, have also been associated with prior radiation therapy treatments.  Now, a new research study suggests that certain forms of prostate cancer radiation therapy may also be linked to an increased risk of subsequent radiation-induced secondary cancers.

Currently, there are several different treatment approaches available for prostate cancer therapy.  Surgery can be performed to completely remove the prostate gland (prostatectomy) when the tumor is still confined to the prostate.  Implants of radioactive seeds, placed within the prostate gland (brachytherapy), can also be used to destroy cancer within the prostate.  External beam irradiation is another form of radiation therapy, but unlike brachytherapy, external beam irradiation is delivered by a machine that concentrates radiation onto the prostate gland from a source external to the body.  Although great progress has been made in fine-tuning the delivery of radiation to the prostate gland with both brachytherapy and external beam irradiation, there is, inevitably, some “collateral damage” that occurs to the organs and tissues that surround the prostate, as it is impossible to confine 100 percent of the delivered radiation dose to the prostate gland alone.

A new study, in the Journal of Urology, evaluated the cancer treatment records of more than 240,000 men who had previously been treated for prostate cancer with prostatectomy, brachytherapy, external beam radiotherapy or a combination of brachytherapy and external beam radiotherapy between 1988 and 2003.  The data for this study was collected from the massive Surveillance, Epidemiology and End Results (SEER) national cancer database, which is maintained by the National Cancer Institute.  This study was conducted by researchers from Columbia University and the Mount Sinai Medical Center. 

In this study, the authors compared the incidence of subsequent cases of cancers of the bladder and rectum occurring in these 243,082 men.  The men who underwent prostatectomy alone, and who did not receive any radiation therapy, essentially served as the “control group” for this study.

An almost insignificant increase in the risk of bladder cancer was seen in the men who underwent brachytherapy alone.  However, there was a more pronounced and statistically significant increase in the risk of both bladder cancer and rectal cancer observed among the men who received either external beam radiotherapy alone or combined brachytherapy and external beam radiotherapy.  Compared to the men who underwent prostatectomy alone, external beam irradiation was associated with an 88 percent increase in the relative risk of developing bladder cancer, and a 26 percent increase in the relative risk of developing rectal cancer.  Among those men who received both brachytherapy and external beam radiotherapy, the relative risk of developing bladder cancer was 85 percent higher than what was observed in the men who underwent prostatectomy alone, while the relative risk of developing rectal cancer was 21 percent higher.  (It should be noted that “relative risk” is a measure of the difference in risk between two patient treatment populations, and is not the same as the “absolute risk” of developing a particular disease.)

In this retrospective study, which involves a relatively short duration of clinical follow-up, external beam irradiation for prostate cancer (either administered alone or in combination with brachytherapy) was associated with a significant increase in the risk of developing subsequent cancers of the bladder and rectum. 

Since most studies of radiation-induced secondary cancers have shown an average biological lag time of 15 to 20 years between radiation therapy and the diagnosis of secondary malignancies, the findings of this study may actually underestimate the long-term risks of secondary bladder and rectal cancers in men who have previously received external beam radiotherapy as treatment for their prostate cancers.  At the same time, however, recent and continuing improvements in the accuracy of radiation therapy delivery have significantly reduced the “innocent bystander” effect, whereby clinically significant doses of radiation are absorbed by the organs that surround the prostate gland (namely, the bladder and the rectum).  As a final note, all retrospective studies that are based upon prospectively collected data, such as this study, are subject to potential biases, including the “completeness” of the clinical data that is present within large databases such as the SEER database.  However, based upon a large body of clinical literature on this topic, the findings of this particular study are not at all surprising, or unexpected.

All patients who are planning to undergo therapy for prostate cancer should first talk with their oncologists about the unique risks and benefits associated with each potential treatment option before choosing the best and most appropriate form of therapy.

 

SEXUAL CONTENT ON TV & TEEN PREGNANCY RISK

Although the effects of violent and sexual content on television, or on video games, on adolescents and young adults is the subject of considerable debate, there are multiple recent studies that appear to substantiate the concerns of many parents who wrestle with these issues.  For example, several clinical research studies have recently found that children who frequently play video games with violent themes are more likely to engage in aggressive or antisocial behavior at school and at home. 

In view of the enormous impact of teen pregnancy on individuals, families and society, many parents and family advocates have viewed with alarm the increasingly unfiltered sexual content present in both movies and television shows.  A new Rand Corporation study, just published in the journal Pediatrics, has concluded that there may well be a significant link between exposure to television shows with sexual content or themes, on the one hand, and the likelihood of pregnancy prior to age 20.  This study was funded by the National Institute of Child Health and Human Development, which is part of the National Institute of Health (NIH).

In this study, data from prospective surveys of teens were analyzed over a 3-year period.  A total of 1,762 adolescents between the ages of 12 and 17 anonymously completed surveys regarding their sexual experiences and their television viewing habits, and the same group of teens then completed the same survey one year later.  The incidence of teen pregnancy in this group of adolescents was monitored for a period of 3 years.

Sexual content in television shows measured by the surveys included: (1) sexually-oriented behaviors such as kissing, intimate touching, and implied or depicted intercourse; and (2) discussions about sexual plans or desires, or about sexual behavior that had already occurred, or “expert advice” about sexually-related topics.

The results of this study demonstrated a linear association between heavy exposure to sexual content on television and the initiation of intercourse and other sexual behaviors during adolescence.  The teens who anonymously admitted to watching the greatest number of sexually-themed television shows were 2 times as likely to initiate sexual intercourse within the following year as were the teens who watched the least amount of sexual content on TV.  In terms of age-related sexual behavior, 12 year-olds who watched the greatest number of television shows with sexual themes engaged in sexual activities at a level comparable to 14- and 15-year-old teens who watched the least number of shows with sexual content.  An especially interesting finding of this study was that television shows that featured only discussions about sexual activities were still associated with an increased likelihood of engaging in intercourse, and in teenage pregnancies, among adolescents viewing such shows. 

Other adolescent behaviors linked with the early initiation of intercourse included: older age, hanging out with older friends, achieving lower grades at school, sensation-seeking behaviors, and rule-breaking behaviors (e.g., skipping classes). 

On the other hand, behaviors most associated with a lower likelihood of intercourse during adolescence included: having parents who monitored their teens’ behavior, having more educated parents, having parents who disapproved of teenage sexual activity, and living with both parents (please note that the greatest deterrents to adolescents engaging in intercourse, based upon the results of this prospective clinical study, involved parent-related factors…).

In this study, an early age at initiation of sexual activity (including intercourse), and the incidence of teen pregnancy, were found to strongly correlate with the extent to which television shows with sexual content (including mere discussions about sexual activities and behaviors) were viewed by teens.  Conversely, minimizing viewing exposures to such television programming, and being supervised by two parents who disapproved of adolescent sexual behavior, was associated with the lowest rates of teen sexual activity and teen pregnancy.

Many parents will respond to the findings of this research study with something along the lines of, “No, duh….”  However, this is the first prospectively conducted research study to confirm what many of us parents have long believed.  My advice is to stay connected with your teens, and stay involved with their lives, even when they demand that you do otherwise.

 

Dr. Wascher is an oncologic surgeon, professor of surgery, a widely published author, and the Director of the Division of Surgical Oncology at Newark Beth Israel Medical Center:

http://www.sbhcs.com/hospitals/newark_beth_israel/mservices/oncology/surgical.html

Send your feedback to Dr. Wascher at:  rwascher@doctorwascher.net
 

To read more of Dr. Wascher’s Health Report columns, please visit his

website at:  http://www.doctorwascher.com

Copyright 2008.  Robert A. Wascher, MD, FACS.  

All rights reserved.

 

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  BENEFITS OF FULL DRUG COVERAGE FOR MEDICARE RECIPIENTS AFTER HEART ATTACK? 

Patient compliance with medications following a heart attack has been shown to improve survival.  However, recent studies (please see my column for 3-2-08) have pointedly confirmed that many patients stop having their heart medications refilled within a year or two of their heart attack.  With an estimated 47 million uninsured people in the United States, and many millions more with inadequate healthcare insurance, it is not surprising that many patients decide to stop taking costly medications.  A new study in the journal Circulation has examined the potential benefits (in terms of additional years of quality life added and costs associated with the treatment of cardiovascular disease) of eliminating out-of-pocket medication costs for Medicare beneficiaries.   

Using complex statistical modeling, the researchers considered the potential benefits of providing 100% drug coverage for the following types of  cardiac medications:  aspirin, beta-blockers, ACE inhibitors and blockers, and statins.  When considering the current Medicare Part D medication coverage plan, patients enrolled in this plan at the time of their heart attack were projected to live, on average, an additional 8.21 quality-adjusted life-years, while incurring an average of $114,000 in medical treatment-related costs.  However, based upon a hypothetical 100% drug coverage model, which assumes that all patients will take their medications as prescribed (i.e., because out-of-pocket costs for drugs are eliminated), additional quality-adjusted life-years following heart attack was estimated to rise to 8.56, while total costs associated with medical treatment was estimated to be $111,600 per patient.  Thus, based upon this statistical model, switching to a 100% drug coverage benefit for Medicare patients, following a heart attack, might be expected to both extend lives and decrease the cost of medical care for individual patients (although the anticipated increase in lifespan, with the addition of 100% medication coverage, would actually nullify any significant overall cost savings, according to the results of this study). 

Of course, it is one thing to try and hypothetically estimate the costs and benefits that might arise from a change in existing drug benefits coverage, but the reality would almost certainly be a bit more complicated.  First, and foremost, the high cost of medications is not the only factor that has been linked to poor patient compliance with medications.  Medication side effects and the inconvenience associated with taking multiple medications are also well-known significant impediments to patient compliance.  It is unlikely that compliance with medications will ever reach 100% in any substantial population of patients, even with a 100% drug benefit.  Additionally, the administrative costs associated with transitioning to this enhanced drug benefit plan, were it ever to be enacted, might further siphon off some of the individual patient savings projected by this study.  Finally, as a physician who treats a large volume of patients from socioeconomically depressed communities, I have to wonder if physician prescribing patterns might also change if patient co-pays were no longer required for medications.  In my own case, when presented with the option of several equally effective drugs for patients, I try to select older, generic medications for my patients, in order to reduce their out-of-pocket expenses.  If co-pays were completely eliminated, I wonder how many physicians would then adopt a “sky is the limit” approach to prescribing medications. 

Despite my reservations regarding this study’s projected benefits from implementation of a full drug coverage plan for Medicare patients, there is no doubt but that the skyrocketing costs of medications, and mandatory patient co-pays for these medications, cause many patients to stop refilling their prescriptions.  Undoubtedly, the elimination of patient co-pays would indeed significantly improve patient compliance with their prescribed medications.  On the other hand, the Medicare entitlement plan is projected to become insolvent if current and predicted expenditures are not radically reduced.  Unfortunately, there is no easy answer for the inherent conflict between limited healthcare budgetary resources and spiraling healthcare costs.  From a purely clinical perspective, however, I would strongly favor 100% medication coverage for the poor and elderly, as these are the patients who would benefit the most from such coverage.

PARENT-TEEN CONVERSATIONS ABOUT SEX 

Every parent I have ever known has dreaded having “The Talk” with their teenage son or daughter about the birds and the bees.  It is no secret that many parents find the topic embarrassing and uncomfortable to discuss with their progeny.  At the same, the pressure on teens to engage in sexual activity has never been greater than it is in our current sex- and body-obsessed culture.  Recent studies have suggested that as many as 1 in 4 teenage girls have already become infected with sexually transmitted diseases in the United States, and in certain inner city and minority populations, the incidence of sexually transmitted diseases in teenage girls may actually be as high as 50%.   

A great deal has already been written about the best approach to having this critically important discussion with your son or daughter, although most of us parents already understand that there is simply no perfect way to actually go about it.  However, a new study in the journal Pediatrics does provide some helpful clinically-based evidence about how to talk to your teenager about sexual topics. 

In this study, 312 adolescents, and their parents, participated in a randomized, controlled clinical research trial involving structured interventions in parent-teen communication about sexual topics.  The teens completed surveys at the beginning of the study, and then at additional specified intervals after the interventions were completed.  At each survey, teen respondents had to report the extent (if any) of parent-teen discussion of each of 22 specific sex-related topics.  The study’s two primary endpoints were the number of times that parents and teens engaged in discussion of sexual topics, and the number of times that each specific topic was discussed.   

Based upon the surveys completed by the teens, repeated discussions of sexual topics with their parents were associated with a closer relationship between parents and their teens, and a higher level of communication between them (both in general and in terms of discussing sexual topics).  Teens who reported that they did not have repeated discussions with their parents about sexual topics reported a much lower level of feeling close to their parents, and a lower level of openness between them and their parents in discussing sex-related themes.  Those adolescents who reported discussing the greatest number of specific sex-related topics with their parents also reported a significantly greater sense of openness of communication with their parents than did the teens who reported that fewer specific topics were discussed.   

While the results of this study appear rather intuitive, they nonetheless reinforce the importance of repetitive discussions, between teens and their parents, about sex-related topics.  In this clinical study, both repetition and increased breadth of discussion appeared to be associated with an enhanced teen-parent level and openness of communication, both with respect to discussing sex-related topics and in general communication as well.  While these sensitive but very important discussions can leave both parents and teens feeling a bit uncomfortable initially, an open, honest, and repetitive approach to such discussions appears to work the best.  

SOY (GENISTEIN) & PROSTATE CANCER 

The effects of so-called “natural products” on disease prevention is an area of great interest to me, and to millions of other health-conscious people.  An area of particular interest to me is the prevention of cancer through lifestyle modification, including dietary habits and natural supplements.  (Estimates by public health experts have suggested that up to 80% of all cases of cancer might be prevented by lifestyle changes alone.)  At the same time, the dietary and “nutritional” supplements industry, with its multi-billion dollar annual sales, continues to promote its products as having significant disease preventing properties, even though the scientific evidence for such claims is often weak, or altogether absent.  With these facts in mind, one must be very careful to maintain a healthy level of skepticism about the myriad claims made by the manufacturers of many of these supplements, or by enthusiastic supporters of such products.  With these cautionary statements in mind, an interesting new prostate cancer research study appears in the current issue of the highly respected journal Cancer Research.   

Genistein, which is found in soy-derived foods and products, has been the subject of intense cancer-related research.  A member of a class of plant-derived substances known as isoflavones, genistein has been found to have antioxidant properties, as well as weakly “estrogenic” effects, which mimic the effects of the dominant female hormone estrogen.  Additional research has also shown multiple other biological effects for genistein, as well.   

A great deal of genistein research has been directed at the two human cancers that are most closely linked with exposure to female and male sex hormones: breast cancer and prostate cancer, respectively.  Unfortunately, as is very common in clinical research, the findings of many of these studies have often provided contradictory results.  In this new study, human prostate cancer cells were implanted into immune-deficient mice, and the effects of dietary genistein supplementation in these mice was then studied. 

The mice were divided into two groups: one group received genistein supplements and the other group was fed only standard “mice chow.”  Blood levels of genistein were measured, and the mice receiving genistein were confirmed to have circulating blood levels of genistein comparable to those seen in men taking genistein supplements.   

The findings in this animal model were rather dramatic.  Although the implanted tumors in the mice receiving genistein supplementation continued to grow just as much as they did in the mice not receiving genistein, the spread of tumors to other organs in the mice receiving genistein was reduced by an astounding 96% when compare to the mice that did not receive this isoflavone supplement.   

These results are very intriguing as prostate cancer, as with most other types of cancer, causes death primarily as a consequence of tumor spreading throughout the body (also known as metastasis).  Although genistein supplementation did not appear to reduce the growth of the implanted primary prostate tumors in these mice, a nearly 100% reduction in tumor metastasis was observed.  Whether this effect is long-lasting or not cannot be determined from this clinical study.  Just as importantly, this study cannot tell us whether or not similar beneficial genistein-associated effects will also occur in humans with prostate cancer.  However, ongoing and recently completed human clinical research trials will, hopefully, provide important answers to these and other important clinical questions.  

Dr. Wascher is an oncologic surgeon, professor of surgery, a widely published author, and the Director of the Division of Surgical Oncology at Newark Beth Israel Medical Center

http://www.sbhcs.com/hospitals/newark_beth_israel/mservices/oncology/surgical.html 

Doctor Wascher’s Home Page:   http://doctorwascher.com 

Send your feedback to Dr. Wascher at rwascher@doctorwascher.net
 

Copyright 2008.  Robert A. Wascher, MD, FACS.  

All rights reserved.

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