The Science Behind Active Surveillance

BY MARK SCHOLZ, MD

Active Surveillance versus the “Gold Standard”         
Ten years ago surgery was called the “Gold Standard,” the treatment to which every other kind of treatment should be compared.  Now you rarely encounter the Gold Standard argument to bolster surgery as the preferred treatment approach.  What scientific studies led to this change in perspective and why has it taken so long for this change to come about?
 
Finally, a Clear Answer
The final nail in the “Gold Standard” argument occurred in 2012, when the New England Journal of Medicine published a study by Dr. Timothy Wilt comparing the long-term outcome of surgery versus observation.¹ Between 1994 and 2002, seven hundred and thirty-one men volunteered to undergo either surgery or observation based on a coin flip. 

No Benefit for “Good” Cancer, Modest Benefits for “Bad” Cancer

The average age for the whole group of men was 67. The median PSA was 7.8. The study ultimately concluded that here was no difference in prostate cancer mortality with either approach. Mortality was within the expected range of statistical variation (5.8% died in the surgery group and 8.4% died in the observation group).  A small survival benefit for surgery was seen in men with a PSA over 10.  (Mortality was 12.8% in the observation group and 5.5% in the surgery group.) Dr. Wilt also reported the side effects of surgery.
     
Even before Dr. Wilt’s report was published, Active Surveillance had been gaining mainstream acceptance in the medical community. Multiple, independently-published studies consistently reach the same conclusion that Active Surveillance is safe.  Some of these studies are briefly summarized in the next few paragraphs. The full abstracts are posted on our website at www.keepmyprostate.com. 

Do All Men Have Prostate Cancer?

One of the most compelling arguments for forgoing radical treatment is based on the fact that prostate cancer is simply too common in the general population to represent an imminent threat to life. Studies of prostate glands removed from men dying of unrelated causes show that by the time they die, most men harbor prostate cancer.¹ That prostate cancer is incredibly common in the normal male population is also supported in another report from the New England Journal of Medicine where 4,692 healthy men over age 50 with a normal PSA (average 2.7) volunteered to undergo a simple six-core prostate biopsy.  The resulting biopsies showed that one-fourth of the men had cancer.²

Many Studies, Same Conclusion

Additional research has looked into comparing Active Surveillance with surgery. For example, a study from Johns Hopkins reported that life expectancy is only extended an average of 1.8 months by having immediate surgery.³  Another study in the Journal of Urology confirms that the grade of the tumor is an excellent method for determining which type of cancer is safe to monitor because prostate cancer mortality was almost nonexistent in 12,000 men with Gleason score of six or less  who were monitored for 12 years after surgery.⁴

Additional studies reporting the long-term outcome of Active Surveillance have been published: In a ten-year study of 1,000 men undergoing observation at Johns Hopkins Hospital, not a single man has died of prostate cancer or developed metastases.⁵ In another study of 450 men undergoing observation in Toronto that included some men with grade 7 disease, five out of 450 men died of prostate cancer.⁶

The Dark Side of Treatment

The idea of living with cancer may not seem at all attractive, but once the side effects of surgery are factored in, Active Surveillance starts to look really good. Unfortunately, the side effects of radical treatments like surgery are universally underemphasized by doctors and patients alike. Doctors downplay the effects of surgery because their years of working in the field accustom them to impotence and incontinence in their patients. The patients who have had treatment and are lucky enough to have had a good outcome, sing the praises of treatment because they took a radical step to remove their cancer and were fortunate to avoid bad consequences. The patients with bad outcomes are frequently too embarrassed to talk about their diapers and sexual incapacity.  They minimize the bad effects of the treatment and emphasize their gratefulness about “having been saved from cancer.”

The fact is that surgery and radiation cause permanent side effects with astounding frequency.  In a study of 475 men, four years after having surgery or radiation, less than 20% of men described their sexual function as returning to normal.⁷ In another study of 785 men, three years after surgery or seed implantation, less than 20% of men who had surgery and less than 50% of the men who had seeds described their sexual function as returning to normal.⁸ Unfortunately, to many people, all these statistics are an abstraction. Nevertheless, the tragedy of unnecessarily destroying even one man’s sexual identity cannot be calculated.

At First, New Thinking Always Seems Radical  

Let me close with an acknowledgement that Active Surveillance involves a totally new way of thinking. The very first conference to review the science of Active Surveillance was convened in San Francisco in 2007. At that time two hundred prostate cancer experts laid down the basic guidelines for Active Surveillance.  Doctors around the world are still being introduced to the idea of Active Surveillance. Believe it or not, some doctors have not even heard about it.  Inevitably, it takes time for people to change. Even so, that’s no reason for you to be trapped by outdated thinking.

A Breakthrough Study in Prostate Cancer

BY MARK SCHOLZ, MD

Ten years ago everyone agreed that surgery was the “Gold Standard” to which every other kind of treatment should be compared.  Now as we approach 2013, you rarely encounter the Gold Standard argument to bolster surgery as the preferred treatment approach.  What has led to the change in perspective and why has it taken so long for this change to come about?

Good Science Finally Leads to a Clear Answer

The primary cause for the changed perspective about surgery is the result of a well-performed scientific study published this year by Dr. Timothy Wilt in the New England Journal of Medicine.  The study has been a long time coming.  It was first conceived way back in the early 1990s when Dr. Wilt and others designed a definitive trial to test whether or not radical prostate surgery improves survival compared to observation. Even back then, researchers knew that prostate cancer can often behave benignly and were questioning the benefits of radical surgery.  Therefore, between 1994 and 2002 over five-thousand men were invited to participate in a study comparing immediate surgery with no treatment.  To make the comparison totally fair, individuals volunteering for the study had to be willing to have either surgery or observation based on the flip of a coin.  Most of the more than five thousand men who were invited to participate in the study refused. Ultimately, however, 731 men agreed to participate.

Modest Benefits for “Bad” Cancer, No Benefit for “Good” Cancer

At the start of the study the average age of the men participating was 67 and the median PSA was 7.8. After ten years the difference in prostate cancer mortality was essentially the same in both groups, i.e., within the expected range of statistical variation: 5.8% died in the surgery group and 8.4% died in the observation group.  However, subgroup analysis of the 251 men in the study who started off with PSA levels above 10 showed a modest improvement in survival for the men undergoing surgery: 5.5% died in the surgery group and 12.8% died in the observation group.

Validation of the Right Way to Look at Prostate Cancer

This picture of how different types of prostate cancer behave over long periods of time (having a high PSA for example versus having a low PSA) has been slowly forming in the minds of the prostate cancer experts over the years.  Dr. Anthony V. D’Amico, MD, PhD, Professor of Radiation Oncology at Harvard Medical School, is credited with developing the modern staging system that divides men into Low, Intermediate and High-Risk categories (At the PCRI we call them Shades of Blue, i.e., Sky, Teal and Azure).  Dr. Wilt’s study conclusively validates the fact that favorable prostate cancer—termed Low-Risk—can be safely monitored without immediate treatment, whereas men with High-Risk disease derive a modest benefit from immediate treatment.  His study also reported an intermediate outcome for the men with Intermediate-Risk disease: After 10 years, men in the Intermediate category showed no improvement in cancer survival with surgery.  However, there was a 10% lower incidence of metastases in the men with Intermediate-Risk who had surgery.   

Conclusion

Dr. Wilt’s study is an important breakthrough because it is the first modern, large, long-term, prospective, randomized study comparing treatment versus no treatment in men with relatively early-stage disease, i.e. diagnosed via PSA screening.  This study provides critically important scientific confirmation validating the policy of withholding radical treatment in men with Low-Risk disease.  The study also validates the predictive accuracy of the D’Amico staging system which functions by dividing men into Low, Intermediate and High-Risk categories.  Lastly, Dr. Wilt’s study provides a quantifiable measure of the degree of benefit associated with immediate surgery in men with Intermediate-Risk and High-Risk disease.  Using this information, individuals with High-Risk disease can better understand the rather modest survival advantages of surgery, and weigh them against the probable deleterious side effects, enabling them to determine for themselves whether or not they want to proceed with radical treatment.

The Un-Cancer

BY MARK SCHOLZ, MD

It’s easier to teach a proper golf swing to a true beginner than to someone who has previously developed bad habits that are now ingrained.  The young mind of a child learns a new language much more easily than the cluttered mind of the adult.  Good first impressions are valued so highly because we all know how hard it is to undo a bad first impression.  The biggest challenge of educating people about prostate cancer is overcoming their preconceived notions—what they already think they know about cancer.

What is prostate cancer?  Many say it’s harmless, that “you die with it, not from it.”  But how does that jibe with 28,000 deaths annually?  One reasonable conclusion is that prostate cancer occurs and acts in a variety of different ways. The Prostate Cancer Research Institute (pcri.org) recommends dividing prostate cancer up into five categories or Shades of Blue. This is helpful both for understanding the varieties of prostate cancer and for guiding the choice of treatment.

However, even though there are many forms of prostate cancer, this fact fails to convey how differently prostate cancer as a whole acts, compared to other cancers.  Why is it so important to understand this difference?  First of all, surgery—which is everyone’s first thought when they hear the word “cancer”—can have dire consequences.  For example, surgery almost always causes partial or complete impotence. Second, new research published by Dr. Timothy Wilt in the July issue of this year’s New England Journal of Medicine, shows that forgoing immediate treatment and embarking on a program of close monitoring known as “active surveillance,” has exactly the same survival rate as immediate surgery.  Bottom line: For far too many men, immediate treatment for prostate cancer is not only damaging, it is often unnecessary.

Forgoing treatment with something called cancer is certainly counterintuitive.  In order to support the case for monitoring, let’s compare the statistics for prostate cancer with those of colon cancer.

	Prostate Cancer:  The “Un-Cancer”	Colon Cancer: A “Typical” Cancer	Difference Factor
Deaths Annually	28,000	26,000	1 : 1
New Cases Diagnosed	241,000	73,000	3.5 : 1
Mortality Rate	8.5%	35.5%	4.2 : 1
Average Survival if Relapse Occurs	13 Years	13 Months	12 : 1

As the table shows, men diagnosed with colon cancer are not only three and a half times more likely to die from the disease, they die twelve times more quickly.  Unfortunately, almost all cancers—lung, pancreas, stomach, gallbladder, kidney, brain, bone, etcetera—approximate the behavior of colon cancer rather than prostate cancer.

The fact remains that it is logical for the general population to be terrified by the very idea of cancer.  When you consider all the different types combined, cancer is the second most common cause of death, just below heart disease. The risk of death from most cancers is high and if a cure is not obtained, death follows all too quickly. The unfortunate men who die from prostate cancer make the “news,” even though it may not be generally understood that it took 13 years for those men to succumb. However, the fact remains that there are 2.8 million prostate cancer survivors presently living in the U.S. That should be news too.

Ninety-one and a half percent of men diagnosed with prostate cancer will have a normal life expectancy, and will die of natural causes. The eight and a half percent who die from prostate cancer will live an average of 13 years, with this number expected to increase dramatically over the next ten years, thanks to continuing improvements in medical technology.  Treatment can definitely improve survival in selected cases.  However, it would seem that only men in the high-grade category are likely to benefit consistently.

The encouraging facts about prostate cancer outlined in this blog have been compiled to help men realize that survival rates with prostate cancer are extremely favorable compared to other types of cancer.  Now that studies show that survival with active surveillance matches that of immediate surgery, a great many men should take heart, and resist all efforts to rush into a treatment with such uncertain rewards but such predictable and devastating side effects.