Senate Hearing on Prostate Cancer: The Silent Killer

E. David Crawford, MD
Professor of Surgery and Radiation Oncology
University of Colorado Health Sciences Center
Denver, Colorado

• In the fight against prostate cancer, early detection, treatment and cure is the strategy with the most immediate benefit.



• The establishment of Prostate Cancer Awareness Week has resulted in a phenomenal increase in the number of menwho seek screening for the disease.



• Research and funding in prostate cancer still lag far behind other major American healthcare concerns.
  
  

This is an edited transcript of a September 23, 1997 hearing before the Special Committee on Aging of the Unites States Senate. (Congressional Record 105-12, 1997)

Prostate cancer is a male epidemic.  During 1997, it is projected that over 300,000 men will be diagnosed with prostate cancer and 41,000 will die as a direct result of the disease.  In the past 15 years, the number of new cases of prostate cancer diagnosed has increased by three-fold.  Less than 7 years ago, more than 80% of the cases of prostate cancer diagnosed were advanced, and therefore incurable.  This article explains why testing for prostate cancer is important and discusses the urgent need for research support.

Faced with the grim statistics just mentioned, there are a number of possible strategies to pursue.  Some bury their heads in the sand and ignore the problem, citing the fact that prostate cancer is usually a disease of older men, and “you have to die of something.”  Others rationalize that our healthcare system cannot afford to deal with this disease because there are so many other pressing issues such as AIDS, childhood immunizations, smoking cessation, etc. 

Another strategy is to try to prevent the disease.  Ideally, this is the optimal solution.  We have learned a lot about what causes prostate cancer, leading to the development of ways to alter its initiation.  If we look at the worldwide incidence of the disease, we see that it is extremely low in Japan, China, and other Asian cultures.  Yet it is dramatically increased in the United States—especially in black males (Table 1).

Table 1.

A Western diet that is high in fat plays a major role in the development of prostate cancer.  Recently, there have been reports of a reduced incidence of prostate cancer in men consuming foods such as tomato products, soy products, vitamin E and selenium, to name a few.  These findings suggest that adding one or more of these substances to our natural diet may have an impact on decreasing the risk of prostate cancer.  However, even if we knew how to prevent prostate cancer today, it would be many years before a positive impact on either the incidence or mortality rate would occur. 

Another disturbing issue is the alarmingly high rate of prostate cancer and increased mortality among black men.  In some cases this is due to the lack the of access to healthcare, but many other factors are emerging through research in this  area that need to be understood if we are to change the high incidence and death rate from prostate cancer experienced in this population.

A third strategy is to develop a cure for advanced prostate cancer.  Progress has been made in this area during the last decade, but the “magic bullet” has yet to be discovered.  We conducted a large, randomized clinical trial in which the simple addition of a well-tolerated oral antiandrogen (eulexin) improved survival in this fatal disease by 26%.  Recently it has also been reported that mitozantrone, a well-tolerated chemotherapy drug, can improve the quality of life in men dying of prostate cancer.  Neither one of these treatments represents a cure; however, significant potential exists.  Progress is being made that will either cure many patients with advanced prostate cancer or at least slow its growth. 

The fourth strategy, and one with the most immediate benefit, is early diagnosis, treatment and cure.  In a 1988 survey of several hundred men over the age of 40, <50% had a physical exam within the last 2 years, and—of greater concern—of those who did, less than half of their physicians had performed a rectal exam to attempt to detect prostate cancer. 

In 1989, prostate cancer became the most common cancer diagnosed in American males, surpassing lung cancer in incidence.  That same year, the Prostate Cancer Education Council was created to inform men about how common prostate cancer is and to encourage early diagnosis.  During Prostate Cancer Awareness Week in September 1989, nearly 10,000 men visited sites around the country to find out about prostate cancer, as well as to undergo early screening with a rectal examination.  The event attracted a lot of media attention, and it appeared that men were starving for information.

The growth of Prostate Cancer Awareness Week has been phenomenal.  In the past 7 years, over 3 million men have been screened during Prostate Cancer Awareness Week, and millions of others have requested examination because of the publicity generated (Table 2). 

Vital information has been accumulated since the initial Prostate Cancer Awareness Week in 1989. We found that a simple blood test known as PSA (prostate specific antigen) was capable of detecting cancers at an early, curable stage.  We discovered that the combination of an abnormal PSA blood test and abnormal rectal exam (DRE) has a 50% predictive value for the presence of prostate cancer (Table 3).

This compares very favorably with an accepted screening modality, mammography for breast cancer detection, the predictive value of which is only 20%.  Through careful data analysis, the sensitivity of testing to detect the disease while reducing false-negative results has been improved.  Over the years our testing has vastly improved.  Recently, different forms of the PSA blood test have been discovered that have further refined our diagnostic accuracy.  We have learned to screen for prostate cancer earlier in higher-risk groups such as blacks and those individuals with a family history of the disease.  Finally, advanced incurable prostate cancer has been virtually eliminated in men who participate in annual screening.  Screening for prostate cancer has been shown to be cost-effective compared with the financial outlays to detect breast cancer among others (Table 4).

In spite of all this good news, controversy surrounding the value of screening remains.  A number of prestigious organizations do not endorse screening, yet they do not deny that it might be beneficial.  

In order to comprehend their position, it is necessary to separate the components of the concern.  No one can deny that screening detects early and potentially curable cases of prostate cancer.  Screening costs money, but it is not prohibitive, and it falls within cost parameters to detect other cancers, including breast cancer.   Through screening we have reduced or even eliminated the presence of advanced, incurable prostate cancer.  The real area of controversy is the value and side effects of treatment.  If an early prostate cancer in a man with a 10-year life expectancy is found and treated, his life can be extended.  Unfortunately, there are no randomized clinical trials to prove this conviction.  This situation is unlike breast cancer, where research support existed in the early 1960s for studies that ultimately showed a survival benefit.  At the University of Colorado, we are participating in a large and important National Institutes of Health-sponsored trial called the PLCO (prostate, lung, colorectal, ovarian) Cancer Screening Trial.  The purpose of this study is to establish the value of early detection.  It will be many years (perhaps 10 to 15) before we know the results of this pivotal study.  In the meantime, we have established a motto for Prostate Cancer Awareness Week stating that “men should be able to choose to know in order to know to choose their treatment.”  Options from simple watchful waiting to surgery or radiation can be considered.  It is discouraging to still see many men who are refused the opportunity to have a PSA test and rectal exam.  Just 3-1/2 years ago, legislation was passed in the state of Colorado mandating that the PSA test be covered by health insurance carriers.  We need this coverage on a nationwide basis.

Significant research support is needed to evaluate and improve the results, as well as the side effects from treatment.

In summary, there is good and bad news about prostate cancer.  The good news is that there has been an intense public focus concerning the disease.  At least for those men who undergo screening, we have revised the grim statistics regarding their chance of developing an incurable cancer.  Because prostate cancer is so common, more researchers are interested in finding a cure, prolonging survival and eliminating the pain and suffering that accompanies the disease. 

The bad news is that men are still reluctant to declare war on prostate cancer.  The number of black men participating in early detection is still low.  We do not have enough research dollars to effectively combat this disease.  These moneys are necessary in the arena of prevention, early detection and cure of advanced disease.  In 1989, when we first began to talk about this lack of research support, <$10 million was allocated for prostate cancer research.  During 1990 to 1997, $376 million was directed toward prostate cancer research, well below the amount allocated for breast cancer (Tables 5 and 6).

Programs like Prostate Cancer Awareness Week need to be supported.  Researchers become frustrated when great ideas in science exist, when months are spent writing grant applications, and then learn there is <20% chance of receiving any funding.  A great deal of what occurs with this disease in the next decade is dependent on the research dollars that are available for education, detection and treatment.  

Questions and Answers
Senator Reid:  Do you think that the large increase in newly diagnosed cases is due to improved screening techniques rather than to an actual increase in incidence?

Dr. Crawford:  It is true that because of early detection we have found more prostate cancers.  However, the interesting thing that has happened this year is that while 343,000 new cases of prostate cancer were originally projected, the actual number has gone down to about 215,000 to 220,000.  Thus, we have eliminated the prevalence of the disease by screening over the first couple of years.  What we are now finding is the annual incidence, and we think that is important.  Also, for the first time, the mortality rate is going down.

Senator Shelby:  If the average American male lives to be 80 years of age, what is his chance of developing prostate cancer?

Dr. Babaian:  This disease is directly related to aging.  At age 80, the chance of having prostate cancer approaches about 70%.

Dr. McLeod:  That is correct.  The older we get the more apt we are to get it at that age.  But obviously if prostate cancer is diagnosed at age 90, in general, one can live with the disease.

Senator Shelby:  How important is diet?  I know a lot of studies have been done on the subject.

Dr. Babaian:  We do not have the answer yet, however, I would argue that diet is a very important factor in the development of prostate cancer.  There is obviously a need, as Dr. Crawford, mentioned, for a tremendous amount of research and funding for research regarding diet.

Dr. Crawford:  Family history is another important factor.  If a man has a family history—multiple family members with prostate cancer—he has almost a 50% risk of developing the disease.

Dr. Babaian:  As the number of afflicted family members increases, his relative risk also increases.

Senator Shelby:  How old is the PSA test?

Dr. McLeod:  We started using PSA to screen for prostate cancer around 1990.  Some testing was done in 1989, but around 1990, 1991 is when it really took off.  It was developed at Roswell Park with a team of scientists led by Dr. Murphy and Dr. Chu.

Dr. Babaian:  The PSA test was developed in 1979, but it took us urologists quite a long time to figure out how important that discovery was.  Consequently there was a 10-year hiatus before it went into active use.

Senator Shelby:  As specialists in the field of prostate cancer treatment, what is your greatest hope in terms of a scientific breakthrough?

Dr. Babaian:  The greatest hope that I have is to prevent this disease from occurring so men do not need to be treated.

Dr. McLeod:  And for those who do get the disease, to be able to successfully treat them.

Dr. Crawford:  We know prostate cancer is a very common, slow-growing disease.  Perhaps it is not necessary to cure each case, but we should slow it down so that men will die of something else before they die of prostate cancer, particularly older men.  I am very encouraged with the fact that through screening we have virtually eliminated advanced prostate cancer.  In 1989 it usually presented an incurable disease.

Senator Shelby:  But we have made progress in the last 10 years, have we not?

Dr. Babaian:  We certainly have.  And because of the differences in the biology of this tumor, it is very important to explore different avenues of treatment.  There is not one treatment that treats all patients with this disease.

Responses to Committee Questions from Dr. Crawford

1.  Why are detection statistics so low for physicians performing the DRE in screening for prostate cancer?

Most patients with prostate cancer will eventually have an abnormal DRE.  The challenge of relying on DRE alone is that in many cases when the exam is abnormal, the prostate cancer has already locally advanced or spread.  PSA has offered the opportunity to detect cancers before they are palpable by DRE.  However, approximately 20% of cancers do not produce enough PSA to escalate the level to abnormal.  Therefore, DRE is still an integral part of early detection efforts.

2.  In your testimony, you state that “the combination of an abnormal PSA blood test and abnormal DRE had a 50% predictive value for the presence of prostate cancer.”  If we know so much, why are the numbers so minimal?

In actuality, a 50% positive predictive value is very good for screening tests.  An abnormal mammogram, which we accept as a good way to detect breast cancer, has only a 20% positive predictive value.  Nevertheless, we are striving to improve the accuracy of our testing.  The recent discovery of the various forms of PSA have further improved the accuracy of the tests.

3.  Could you talk about relationship between diet and prostate cancer in more detail?

There appears to be a relationship between diet and prostate cancer.  Men living in Asian countries such as Japan and China have a low incidence of prostate cancer—yet when they move to the United States, their incidence of prostate cancer rapidly increases.  Diet appears to be the main factor in this rise in incidence of the disease.  Research is currently focused on whether it is the fat and high carbohydrate content of the American diet which leads to this increased risk, or the lack of protective factors such as soy products and other substances in the typical Asian diet.  Recent research has established that soy products can actually inhibit the growth of prostate cancer.

4.  What do you believe the impact in the growth of managed care will be to prostate cancer screening?

We have already begun to experience the impact of managed care on prostate cancer screening.  In the attempt to control healthcare dollars, screening programs are trimmed.  However, I believe that when the definitive evidence exists to support the value of early detection, the impact will be minimal.

Responses to Committee Questions

from Walter Reed Army Medical Center

1.  How prevalent is surgeon training in the prostate treatment arena?  How are surgeons trained in the new and developing treatment options that are available?

All urologic surgeons are exposed to, and trained in, the diagnosis and treatment of all diseases of the prostate.  As far as prostate cancer is concerned, radical prostatectomy is in the armamentarium of most urologists.  Certainly during residency and fellowships in this area the procedures are well taught.  Only a few training procedures include cryotherapy (freezing of a cancerous prostate), but the efficacy of this treatment is debatable.  In the area of brachytherapy (placement of radioactive seed within a cancerous prostate), only a few training programs have urologists as co-managers.  Certainly, a close relationship is essential among urologists, radiologists and medical oncologists if our patients are to receive optimal benefit from their treatment.

2.  Along with “government-imposed” barriers to treatment advances for prostate cancer, what other barriers are identified at this time?

There are several barriers to treatment advances that are under the government’s control.  There is a lack of Medicare coverage for some medications (eg, anti-androgens, which are increasingly used in neoadjuvant therapy), a delay in implementing Medicare coverage for PSA tests, and a lack of adequate spending on prostate cancer research.

Another significant barrier is the confusion around the diagnosis and treatment of prostate cancer.  Although PSA screening/detection has not been subjected to clinical trials, and medical groups that seek to discourage men from screening/detection or treatment are well intentioned, these groups are causing some men who might benefit from subsequent treatment to refrain from being treated.  This approach is turning the clock back on the progress made in PSA detection.  It would be appropriate to continue to refine the precision of our diagnostic techniques.  Rather than discourage men from finding out if they have prostate cancer, we should be expending this energy on responding to those who are diagnosed with the disease, improving our capacity to predict the course of the disease and educating patients on their treatment options.

In addition, private insurance coverage needs to become as complete as we would like medicare coverage to become.  New disease management approaches that can improve patient care for prostate cancer in managed care plans can benefit patients only if a full range of treatment options are available under the plan.  This combination of more comprehensive coverage,  improved management of treatment and greater adaptability of treatment to the needs of patients can go a long way to resolve the concerns regarding the potential for inappropriate patient care.  As medicare shifts from being a payer for care to a purchaser of managed care plans, the quality of care for Medicare patients will rest increasingly on the breadth of coverage and the sophistication of management tools employed by the managed care plans.

Reimbursement by the government for procedures also tends to be a barrier to care.  Currently, each individual Medicare area handles some of these situations differently.  It would be more appropriate if a uniform federal policy were established by HCFA, as far as Medicare payments are concerned.  This certainly would be to the advantage of most physicians and could help avoid the many controversies that arise when decisions are made by an inexperienced administrator in a local area. 

Lastly, increased research funding is imperative.  Prostate cancer in many instances is a slow and insidious disease; however, it will affect more and more men, especially as life expectancy increases.  Also, it will take years to realize the effects of diagnosis and treatment regimens.  Research into dietary regimens and preventive measures must be funded as many private companies cannot afford to spend scarce research funding in those two areas.