Last fall the U.S. Preventive Services Task Force dropped a bombshell, arguing that healthy men should stop undergoing a routine blood test as a screen for prostate cancer. An analysis of the best available evidence, it argued, had shown little or no long-term benefit from the measure—called the prostate-specific antigen (PSA) test—for most men with no symptoms of the disease. Use of the screening was not saving lives. In fact, it was needlessly exposing hundreds of thousands of men who were tested and found to have prostate cancer to such common complications as impotence and urinary incontinence (from surgical removal of the prostate) and rectal bleeding (from radiation treatment). Indeed, the task force estimated that more than one million men have been treated because of PSA testing who otherwise would not have been since 1985. At least 5,000 of them died soon after treatment, and another 300,000 men suffered impotence or incontinence, or both. Instead of praise for sparing more men from suffering similar fates, however, the task force’s announcement quickly drew outrage and counterarguments from several professional medical groups, including the American Urological Association.
The controversy is not new. Experts have long debated the value of the PSA test, but until now the weight of opinion in the U.S. fell on the side of doing the test. As a medical oncologist specializing in prostate cancer, however, I essentially agree with the task force’s assessment of the evidence. Most people outside the medical community do not realize how flimsy the evidence has been in favor of the screening tests. (Make no mistake, the PSA test still provides valuable information after a prostate cancer has already been diagnosed, however.) Nor does the public realize how common complications can be—even from sophisticated treatment that proponents advertise as the most advanced.
As the debate over PSA testing continues, controversy also swirls over a related question: when and if to treat people who ultimately turn out to have prostate cancer after testing positive on a screening test. Here, too, the evidence favors a significant change in course—away from aggressive early treatment for all and toward taking a more cautious, individualized approach.
At the root of these changing attitudes is the realization that prostate cancer can behave very differently from one patient to another and that “early” treatment is not the panacea that most physicians, including myself, used to think it would be.
The Source of the Controversy The controversies have arisen because the screening test and treatments are both deeply flawed. In a perfect world, a screening test would identify only cancers that would prove lethal if untreated. Then men who had small, curable cancers would be treated, and their lives would be saved. Ideally, the treatments would not only be effective, they would have no serious side effects. Such a scenario would justify massive screening and treatment of everyone with a positive test.
But the reality is far different. The PSA test does not tell you if a man has cancer, just that he might have it. The test measures the amount of a protein called prostate-specific antigen, which is produced by the cells of the prostate and whose levels can rise for a variety of reasons—including benign growth of the prostate gland with age, infection, sexual activity or the proliferation of malignant cells. So a positive test means men have to have a biopsy, which involves some discomfort and risk. And that is not the worst if it. A biopsy can, at least, distinguish men who actually do have cancer from those who probably do not. The real problem, though, is that doctors do not have a reliable way to determine which of these very small cancers that are caught by a biopsy are potentially dangerous and which will never bother a man in his lifetime. (Indeed, autopsy studies show that more than half of men in their 50s and three quarters of men in their 80s in the U.S. had prostate cancer but died of something else.) That uncertainty means doctors do not know who absolutely needs treatment to survive and who would be fine without it.
Such ambiguity would not be so bad if the treatments were virtually risk free. In that case, treating everyone might be worth the extra effort and cost to save the few who actually needed it. Yet the treatments are far from risk free. Unfortunately, the prostate is situated close to the rectum, bladder and penis, making it difficult to remove surgically or to treat with radiation without long-lasting complications.
Each type of treatment comes with its own side effects. Surgery (open radical prostatectomy) often results in urinary leakage because the removal of the prostate requires the lower portion of the bladder to be disconnected from the urinary tube running through the penis. The surgeon later reconnects the bladder and urethra, but damage to the nearby muscle that controls urination may lead to incontinence. Meanwhile the nerves and blood vessels controlling erections may be severed during surgery, causing erectile dysfunction (impotence). Although advertisements typically extol lower complication rates with robot-assisted surgery, large independent studies that rigorously compare the two approaches have not been conducted.
In addition to impotence, radiation therapy of the prostate often ends up damaging the rectum and bladder because it is hard to avoid radiation scatter, which hits the front of the rectum and the base of the bladder. Moreover, rectal bleeding and fecal soiling are frequent but commonly underreported side effects of both radiation therapy (including radioactive seed implants) and surgical approaches. (As an aside, side effects of the medical therapies that are used for advanced cancer that requires treatment—hormonal treatments, immune therapies or chemotherapy—include loss of sexual drive, impotence, weight gain, bone thinning, hot flashes, and heart and liver abnormalities.) Thus, when a decision is made to offer treatment, the true risks must be carefully weighed against potential benefits.
Updating the Guidelines The evidence against PSA screening has been growing for some time. In 2008, which was the last time the Preventive Services Task Force looked at the PSA guidelines, it recommended that physicians stop testing asymptomatic men older than the age of 75. The data showed that most men with prostate cancer at 75 were more likely to die of something else. Just one year later two very large prospective studies were published that seemed to settle the question for younger men as well.
Referred to as the European study and the U.S. study, respectively, the two reports took otherwise healthy men, most of whom were in their 50s and 60s, and randomly divided them into two groups. One group of men was periodically screened for prostate cancer with either the PSA test or a digital rectal exam (in which a physician inserts a finger into the rectum to feel for abnormalities in the prostate), or both. If either test was abnormal, a biopsy was performed, and if the biopsy showed cancer, treatment was generally recommended. The second group of men was not offered routine testing; however, they received standard medical care as needed. For example, if they started showing symptoms of prostate cancer—such as trouble urinating (which is also a sign of benign enlargement of the prostate gland)—then they were tested. At the end of the specified study periods, participants were evaluated for two important outcomes:
Did the tested and treated men live any longer than those not tested?
Did the tested and treated men lessen their chance of dying of prostate cancer, compared with those not tested?
Remarkably, in neither study did the tested and treated men live any longer, and in the European study only those who were tested and treated had about a 20 percent lower likelihood of dying of prostate cancer. Such a decrease in prostate cancer mortality was not found in the U.S. study.
The European study went on to calculate how many men would need to be screened and treated to prevent a single death resulting from prostate cancer. Determining this so-called number needed to screen (NNS) ratio has become increasingly important in trying to figure out which screening tests are most helpful. The European researchers determined that to save one life from prostate cancer, about 1,400 men would have to be screened, leading 48 men to undergo treatment. So 47 men would be treated unnecessarily—many of whom would suffer fairly serious side effects—so that one man’s death from prostate cancer could be prevented. And yet, despite successfully preventing a death from prostate cancer, the value of screening for even that one person is debatable because the overall death rate from all causes was identical in both the screened and unscreened groups. More recent analyses of subgroups in the European study have suggested that the number needed to treat may be as low as 12. The more favorable results all come from one area in Sweden, however, and therefore may not be widely applicable.
As always with medical studies, a few caveats must be keptin mind. Whereas the data strongly suggest that most healthy, asymptomatic men do not have to undergo routine screening, those with a strong family history of prostate cancer—men who, for example, had a father, an uncle or a grandfather die of the disease before the age of 70—may reasonably decide to undergo routine PSA screening. Practically speaking, as a physician, I would find it hard to deny offering them the PSA test, especially if they requested it. They probably have inherited a genetic predisposition to the illness that makes them particularly susceptible and thus unlike the general population. In a few more years we may be able to use specific genetic tests to identify individuals who need to pay closer attention to their risks.
Mr. H. Says No As it happens, one of my patients unknowingly anticipated the position of the Preventive Services Task Force 16 years ago, when he was 54 years old. In 1996, against the advice of every cancer specialist that he consulted (including me), he decided to forgo any therapy after a routine PSA test led to a diagnosis of prostate cancer. Even then, his reading of the available research led him to conclude that his particular cancer was unlikely to kill him, at least for the foreseeable future. Moreover, he reasoned, the delay might prove beneficial if newer, more effective therapies came along in a few years’ time. Therefore, he refused immediate treatment, although he adopted healthier habits and lost weight. Every year after his bold decision, I would advise Mr. H., as I will refer to him, to undergo treatment. Every year he would just as steadfastly refuse my advice.
Sixteen years later Mr. H. is still very much alive, and the tumor remains confined to his prostate gland. He has not received surgery, radiation or medicinal treatments for his cancer. His PSA level has risen from seven to 18 units—a very slow rate of rise, indicating that the cancer is growing very slowly. (Of course, had we known that in 1996 the decision not to treat would have been an easier one.) By demanding to know what proof we had for our recommendations, he was able to make a reasoned decision and avoided trading almost certain harms for uncertain benefits.
Changing Assumptions In fact, when I first met Mr. H., our recommendations were based not on strong clinical trials but on a mistaken idea of how prostate cancer behaves over time. We knew that some prostate tumors were slow-growing and others were very aggressive. Still, we assumed that most tumors eventually progressed from small cancerous growths to bigger ones to metastatic tumors that spread throughout the body and became incurable. Catching a cancer in its early stages and removing or destroying it would, therefore, nearly always mean we had saved someone’s life. That seemingly logical assumption led us to advise our patients to undergo treatment whenever a cancer was caught in its earliest stages—and count themselves lucky that they had. Indeed, this logic is the support for all our screening programs in cancer.
Unfortunately, the mortality data collected over the past 25 years show that the natural history of prostate cancer is not as straightforward as my colleagues and I once believed. True enough, the death rate from prostate cancer has fallen from its peak in the 1990s. While proponents of screening argue that this decline must be related to PSA testing, their conclusion is not, as we have seen, borne out by prospective studies. Furthermore, if our understanding of how prostate cancers grow and progress had been correct, the death rate should have fallen much further and faster. In fact, we now know that many prostate cancers do not progress at all. Their growth is slower than slow. It is stalled.
As researchers discover more examples of cancers that are diagnosed by their cellular abnormalities but nonetheless grow so slowly that they neither spread or turn fatal, there is talk of giving these growths a different name, such as indolent tumor, to underscore the fact that they do not necessarily have to be treated for a very long time or perhaps ever. Of course, we do not know which ones are indolent at first diagnosis, but we can have strong suspicions based on various characteristics of the tumor and can confirm the hunch by monitoring patients over time.
Changing Practice Changing ingrained habits is just as hard in medicine as it is in other areas of life. There are bound to be many men (not to mention their physicians) who simply will not feel comfortable forgoing a PSA test after all the years of advice to the contrary. And some individuals will swear that the PSA test saved their life. Fortunately, I think we can manage their care in ways that protect them from unnecessary treatment. This approach can also offer a way out of the “to treat or not to treat” dilemma. It consists of delaying therapy until a cancer more definitively shows itself to be indolent, slow-growing or potentially lethal.
In my own practice, a substantial percentage of the men I care for with prostate cancer are not receiving any treatment at present. Rather they are enrolled in a program that used to be called “watchful waiting” and is now more sophisticated and known as “active surveillance with delayed intention to treat.” In other words, these men have elected to undergo PSA screening and have learned they have a tumor but have chosen not to be treated right away. Instead they continue to have their PSA levels monitored and undergo periodic biopsies of the prostate gland to keep a watch on the activity of the tumor. Last December a consensus panel of experts convened by the National Institutes of Health examined the evidence and declared that “active surveillance has emerged as a viable option that should be offered to patients with low-risk prostate cancer.”
Treatment is considered if further biopsies show that the growth has gotten bigger, PSA results increase rapidly or the newly biopsied cells look markedly more dangerous under a microscope as measured by the so-called Gleason score. Results of a long-term Canadian study indicate that the death rate from the disease for men who elect active surveillance is 1 percent over 10 years—compared with a 0.5 percent risk of dying from complications in the first month after prostate cancer surgery.
The point is that the initial decision to forgo treatment is not necessarily the final one. Surgery, radiation and other therapies are still available later on, and the data indicate that the outcome will not be negatively affected by the delay. For those who eventually need treatment, newer techniques that destroy just the cancerous part of the prostate (so-called prostate lumpectomy or focal therapy) may be appropriate and result in fewer side effects—although rigorous comparison studies have not yet been completed.
As for the 4 percent of U.S. men with prostate cancer whose disease has spread to the bones or other organs, there is still no cure, but treatments are slowly becoming more effective. Testosterone-blocking medication—which interferes with the cancer’s ability to grow—is the standard of care for advanced cases. Eventually, however, a few tumor cells overcome the effects of this chemical castration and continue to wreak havoc. More recently, the U.S. Food and Drug Administration has approved two new approaches to treating late-stage disease. The first involves a complex biochemical process that boosts the immune system’s ability to destroy malignant cells [see “A New Ally against Cancer,” by Eric von Hofe; Scientific American, October 2011].
The second is a drug called abiraterone, which stops the production of testosterone in prostate cancer cells. Studies of both therapies show that they prolong survival by an average of four months. Other treatments, which target molecules that the cancer cells need to grow and spread, are under investigation.
We have learned a good deal about prostate cancer in the years since Mr. H. first opted against treatment for what turned out to be a very slow growing tumor. That knowledge is improving our ability to tailor treatments for individuals rather than always treating everyone the same. It has also taught doctors that we have to be very clear both with ourselves and with our patients about what we really know, from a scientific point of view, and what we do not know—and have the courage to act on the evidence and not just our beliefs.
The controversy is not new. Experts have long debated the value of the PSA test, but until now the weight of opinion in the U.S. fell on the side of doing the test. As a medical oncologist specializing in prostate cancer, however, I essentially agree with the task force’s assessment of the evidence. Most people outside the medical community do not realize how flimsy the evidence has been in favor of the screening tests. (Make no mistake, the PSA test still provides valuable information after a prostate cancer has already been diagnosed, however.) Nor does the public realize how common complications can be—even from sophisticated treatment that proponents advertise as the most advanced.
As the debate over PSA testing continues, controversy also swirls over a related question: when and if to treat people who ultimately turn out to have prostate cancer after testing positive on a screening test. Here, too, the evidence favors a significant change in course—away from aggressive early treatment for all and toward taking a more cautious, individualized approach.
At the root of these changing attitudes is the realization that prostate cancer can behave very differently from one patient to another and that “early” treatment is not the panacea that most physicians, including myself, used to think it would be.
The Source of the Controversy The controversies have arisen because the screening test and treatments are both deeply flawed. In a perfect world, a screening test would identify only cancers that would prove lethal if untreated. Then men who had small, curable cancers would be treated, and their lives would be saved. Ideally, the treatments would not only be effective, they would have no serious side effects. Such a scenario would justify massive screening and treatment of everyone with a positive test.
But the reality is far different. The PSA test does not tell you if a man has cancer, just that he might have it. The test measures the amount of a protein called prostate-specific antigen, which is produced by the cells of the prostate and whose levels can rise for a variety of reasons—including benign growth of the prostate gland with age, infection, sexual activity or the proliferation of malignant cells. So a positive test means men have to have a biopsy, which involves some discomfort and risk. And that is not the worst if it. A biopsy can, at least, distinguish men who actually do have cancer from those who probably do not. The real problem, though, is that doctors do not have a reliable way to determine which of these very small cancers that are caught by a biopsy are potentially dangerous and which will never bother a man in his lifetime. (Indeed, autopsy studies show that more than half of men in their 50s and three quarters of men in their 80s in the U.S. had prostate cancer but died of something else.) That uncertainty means doctors do not know who absolutely needs treatment to survive and who would be fine without it.
Such ambiguity would not be so bad if the treatments were virtually risk free. In that case, treating everyone might be worth the extra effort and cost to save the few who actually needed it. Yet the treatments are far from risk free. Unfortunately, the prostate is situated close to the rectum, bladder and penis, making it difficult to remove surgically or to treat with radiation without long-lasting complications.
Each type of treatment comes with its own side effects. Surgery (open radical prostatectomy) often results in urinary leakage because the removal of the prostate requires the lower portion of the bladder to be disconnected from the urinary tube running through the penis. The surgeon later reconnects the bladder and urethra, but damage to the nearby muscle that controls urination may lead to incontinence. Meanwhile the nerves and blood vessels controlling erections may be severed during surgery, causing erectile dysfunction (impotence). Although advertisements typically extol lower complication rates with robot-assisted surgery, large independent studies that rigorously compare the two approaches have not been conducted.
In addition to impotence, radiation therapy of the prostate often ends up damaging the rectum and bladder because it is hard to avoid radiation scatter, which hits the front of the rectum and the base of the bladder. Moreover, rectal bleeding and fecal soiling are frequent but commonly underreported side effects of both radiation therapy (including radioactive seed implants) and surgical approaches. (As an aside, side effects of the medical therapies that are used for advanced cancer that requires treatment—hormonal treatments, immune therapies or chemotherapy—include loss of sexual drive, impotence, weight gain, bone thinning, hot flashes, and heart and liver abnormalities.) Thus, when a decision is made to offer treatment, the true risks must be carefully weighed against potential benefits.
Updating the Guidelines The evidence against PSA screening has been growing for some time. In 2008, which was the last time the Preventive Services Task Force looked at the PSA guidelines, it recommended that physicians stop testing asymptomatic men older than the age of 75. The data showed that most men with prostate cancer at 75 were more likely to die of something else. Just one year later two very large prospective studies were published that seemed to settle the question for younger men as well.
Referred to as the European study and the U.S. study, respectively, the two reports took otherwise healthy men, most of whom were in their 50s and 60s, and randomly divided them into two groups. One group of men was periodically screened for prostate cancer with either the PSA test or a digital rectal exam (in which a physician inserts a finger into the rectum to feel for abnormalities in the prostate), or both. If either test was abnormal, a biopsy was performed, and if the biopsy showed cancer, treatment was generally recommended. The second group of men was not offered routine testing; however, they received standard medical care as needed. For example, if they started showing symptoms of prostate cancer—such as trouble urinating (which is also a sign of benign enlargement of the prostate gland)—then they were tested. At the end of the specified study periods, participants were evaluated for two important outcomes:
Did the tested and treated men live any longer than those not tested?
Did the tested and treated men lessen their chance of dying of prostate cancer, compared with those not tested?
Remarkably, in neither study did the tested and treated men live any longer, and in the European study only those who were tested and treated had about a 20 percent lower likelihood of dying of prostate cancer. Such a decrease in prostate cancer mortality was not found in the U.S. study.
The European study went on to calculate how many men would need to be screened and treated to prevent a single death resulting from prostate cancer. Determining this so-called number needed to screen (NNS) ratio has become increasingly important in trying to figure out which screening tests are most helpful. The European researchers determined that to save one life from prostate cancer, about 1,400 men would have to be screened, leading 48 men to undergo treatment. So 47 men would be treated unnecessarily—many of whom would suffer fairly serious side effects—so that one man’s death from prostate cancer could be prevented. And yet, despite successfully preventing a death from prostate cancer, the value of screening for even that one person is debatable because the overall death rate from all causes was identical in both the screened and unscreened groups. More recent analyses of subgroups in the European study have suggested that the number needed to treat may be as low as 12. The more favorable results all come from one area in Sweden, however, and therefore may not be widely applicable.
As always with medical studies, a few caveats must be keptin mind. Whereas the data strongly suggest that most healthy, asymptomatic men do not have to undergo routine screening, those with a strong family history of prostate cancer—men who, for example, had a father, an uncle or a grandfather die of the disease before the age of 70—may reasonably decide to undergo routine PSA screening. Practically speaking, as a physician, I would find it hard to deny offering them the PSA test, especially if they requested it. They probably have inherited a genetic predisposition to the illness that makes them particularly susceptible and thus unlike the general population. In a few more years we may be able to use specific genetic tests to identify individuals who need to pay closer attention to their risks.
Mr. H. Says No As it happens, one of my patients unknowingly anticipated the position of the Preventive Services Task Force 16 years ago, when he was 54 years old. In 1996, against the advice of every cancer specialist that he consulted (including me), he decided to forgo any therapy after a routine PSA test led to a diagnosis of prostate cancer. Even then, his reading of the available research led him to conclude that his particular cancer was unlikely to kill him, at least for the foreseeable future. Moreover, he reasoned, the delay might prove beneficial if newer, more effective therapies came along in a few years’ time. Therefore, he refused immediate treatment, although he adopted healthier habits and lost weight. Every year after his bold decision, I would advise Mr. H., as I will refer to him, to undergo treatment. Every year he would just as steadfastly refuse my advice.
Sixteen years later Mr. H. is still very much alive, and the tumor remains confined to his prostate gland. He has not received surgery, radiation or medicinal treatments for his cancer. His PSA level has risen from seven to 18 units—a very slow rate of rise, indicating that the cancer is growing very slowly. (Of course, had we known that in 1996 the decision not to treat would have been an easier one.) By demanding to know what proof we had for our recommendations, he was able to make a reasoned decision and avoided trading almost certain harms for uncertain benefits.
Changing Assumptions In fact, when I first met Mr. H., our recommendations were based not on strong clinical trials but on a mistaken idea of how prostate cancer behaves over time. We knew that some prostate tumors were slow-growing and others were very aggressive. Still, we assumed that most tumors eventually progressed from small cancerous growths to bigger ones to metastatic tumors that spread throughout the body and became incurable. Catching a cancer in its early stages and removing or destroying it would, therefore, nearly always mean we had saved someone’s life. That seemingly logical assumption led us to advise our patients to undergo treatment whenever a cancer was caught in its earliest stages—and count themselves lucky that they had. Indeed, this logic is the support for all our screening programs in cancer.
Unfortunately, the mortality data collected over the past 25 years show that the natural history of prostate cancer is not as straightforward as my colleagues and I once believed. True enough, the death rate from prostate cancer has fallen from its peak in the 1990s. While proponents of screening argue that this decline must be related to PSA testing, their conclusion is not, as we have seen, borne out by prospective studies. Furthermore, if our understanding of how prostate cancers grow and progress had been correct, the death rate should have fallen much further and faster. In fact, we now know that many prostate cancers do not progress at all. Their growth is slower than slow. It is stalled.
As researchers discover more examples of cancers that are diagnosed by their cellular abnormalities but nonetheless grow so slowly that they neither spread or turn fatal, there is talk of giving these growths a different name, such as indolent tumor, to underscore the fact that they do not necessarily have to be treated for a very long time or perhaps ever. Of course, we do not know which ones are indolent at first diagnosis, but we can have strong suspicions based on various characteristics of the tumor and can confirm the hunch by monitoring patients over time.
Changing Practice Changing ingrained habits is just as hard in medicine as it is in other areas of life. There are bound to be many men (not to mention their physicians) who simply will not feel comfortable forgoing a PSA test after all the years of advice to the contrary. And some individuals will swear that the PSA test saved their life. Fortunately, I think we can manage their care in ways that protect them from unnecessary treatment. This approach can also offer a way out of the “to treat or not to treat” dilemma. It consists of delaying therapy until a cancer more definitively shows itself to be indolent, slow-growing or potentially lethal.
In my own practice, a substantial percentage of the men I care for with prostate cancer are not receiving any treatment at present. Rather they are enrolled in a program that used to be called “watchful waiting” and is now more sophisticated and known as “active surveillance with delayed intention to treat.” In other words, these men have elected to undergo PSA screening and have learned they have a tumor but have chosen not to be treated right away. Instead they continue to have their PSA levels monitored and undergo periodic biopsies of the prostate gland to keep a watch on the activity of the tumor. Last December a consensus panel of experts convened by the National Institutes of Health examined the evidence and declared that “active surveillance has emerged as a viable option that should be offered to patients with low-risk prostate cancer.”
Treatment is considered if further biopsies show that the growth has gotten bigger, PSA results increase rapidly or the newly biopsied cells look markedly more dangerous under a microscope as measured by the so-called Gleason score. Results of a long-term Canadian study indicate that the death rate from the disease for men who elect active surveillance is 1 percent over 10 years—compared with a 0.5 percent risk of dying from complications in the first month after prostate cancer surgery.
The point is that the initial decision to forgo treatment is not necessarily the final one. Surgery, radiation and other therapies are still available later on, and the data indicate that the outcome will not be negatively affected by the delay. For those who eventually need treatment, newer techniques that destroy just the cancerous part of the prostate (so-called prostate lumpectomy or focal therapy) may be appropriate and result in fewer side effects—although rigorous comparison studies have not yet been completed.
As for the 4 percent of U.S. men with prostate cancer whose disease has spread to the bones or other organs, there is still no cure, but treatments are slowly becoming more effective. Testosterone-blocking medication—which interferes with the cancer’s ability to grow—is the standard of care for advanced cases. Eventually, however, a few tumor cells overcome the effects of this chemical castration and continue to wreak havoc. More recently, the U.S. Food and Drug Administration has approved two new approaches to treating late-stage disease. The first involves a complex biochemical process that boosts the immune system’s ability to destroy malignant cells [see “A New Ally against Cancer,” by Eric von Hofe; Scientific American, October 2011].
The second is a drug called abiraterone, which stops the production of testosterone in prostate cancer cells. Studies of both therapies show that they prolong survival by an average of four months. Other treatments, which target molecules that the cancer cells need to grow and spread, are under investigation.
We have learned a good deal about prostate cancer in the years since Mr. H. first opted against treatment for what turned out to be a very slow growing tumor. That knowledge is improving our ability to tailor treatments for individuals rather than always treating everyone the same. It has also taught doctors that we have to be very clear both with ourselves and with our patients about what we really know, from a scientific point of view, and what we do not know—and have the courage to act on the evidence and not just our beliefs.
