Whether you call it "active surveillance", "expectant management", or "watchful waiting", a recent study reported in the New England Journal of Medicine has generated some discussion about the merits of mere observation of localized low risk prostate cancer rather than having the prostate surgically removed.  The article, "Radical Prostatectomy versus Observation for Localized Prostate Cancer" by Wilt and colleagues in the NEJM Volume 367 No. 3 (July 19, 2012) is limited to surgery, and does not compare protons or radiation therapy versus observation. Nonetheless, its implied question "Is this treatment necessary" is worth addressing in an age of increasing health insurance and medical costs.

Along with having read Dr. Wilt's article, I have first-hand experience with watchful waiting, since I tried it myself for five years before showing up at the MD Anderson Proton Center. Back in 2005, before the Proton Center opened, I personally was diagnosed with a single Gleason 6 (3+3) core, out of 19 samples taken during a memorable biopsy. My PSA was about 8 and my stage was T1c. After my urologist gave me a book to read about surgery, I declined his recommendation to have it done, due chiefly to possible side effects, my reluctance to wear diapers, and my fear of sensitive parts of my anatomy being injected with an array of catheters and other equipment. (I might have considered proton treatment, but the only choice back then was Loma Linda, CA, but I could not time off from my law and CPA practice to fly out to Southern California for eight weeks of treatments.)

Instead, I chose watchful waiting, and developed a taste for pomegranate juice and vitamin supplements labeled "good for prostate health". In about a year, my PSA was about 2, and stayed there for a couple of years. I liked that.  But then my PSA started climbing back up. I didn't pay much attention until 2010, when my primary care physician told me to get another biopsy. This biopsy (my first in five years) disclosed a single Gleason 9 (4+5) accompanied by a single Gleason 7 (4+3), while my stage was still T1c and my PSA 9. My prostate cancer had turned from a benign Gleason 6 to a dangerous Gleason 9 during my five years of watchful waiting. Luckily for me, the Proton Center recently had broadened its patient base to include those with high risk Gleasons, and Dr. Lee accepted me as one of his patients. I began my Lupron treatments in August 2010 and underwent 39 proton treatments during November, 2010 - January 2011. 

During my initial appointment with Dr. Lee he asked me about my watchful waiting. I explained that I had one biopsy every five years and a PSA test every nine to 12 months. Dr. Lee listened, frowned and shook his head: "No. Watchful waiting involves an annual biopsy and PSA readings taken every three months."

The watchful waiting criteria in Dr. Wilt's study cited above were different from both Dr. Lee's cautious and careful approach and my unsuccessful "whatever" approach. The patients in the study visited the doctor once every six months for between 8 and 15 years, or until the patient died. Bone scans were taken every five years to test for bone metastases. Urinary incontinence, erectile and bowel dysfunction were assessed after patients entered the study. The study article did not mention biopsies or PSA tests being administered. The study offered palliative care or chemotherapy for patients in the watchful waiting group if their cancer metastasized. However, about 20% of those in the observation group bailed out and opted for either surgery or radiation during their first four to five years of participating in the study. (I'm not surprised --- when they started, 34% of the observation group had PSA's higher than 10; Gleason scores of 8-10 were found in 6% of the observation group; and 44% of the observation group had one or more tumors were T2a or higher and thus could be detected with a digital rectal exam.)

The "take away" in the lay press is been that there is not a significant difference between surgery and the kind of watchful waiting done in the study in low risk patients at the time they entered the study. The reporting of the study does not present the entire picture, however: 

• Metastatic prostate cancer. Once prostate cancer metastasizes to bone, there is no cure, but only control. Although this is an important topic, it was not covered in the lay press. None of the patients had metastatic prostate cancer at the time they entered the study, but 17 of the 364 men in the surgery group, and 39 of the 367 in the watchful waiting group got it later on. The risk of men (regardless of prostate cancer characteristics) in the surgery group getting metastatic prostate cancer was only 44% of the risk of the men in the watchful waiting group getting it. The chance that this result could have been random was only 1 in 1,000 (p-value = 0.001), vastly lower than the usual 1 chance in 20 measure of statistical significance.  The benefits of surgery compared to watchful waiting were even more striking for men over 65, and men with Gleason 7 or higher.   

• Death from prostate cancer itself. The risk of death from prostate cancer for surgery group high risk patients and those with a PSA > 10 was only 40% to 50% of the risk of similar patients in the watchful waiting group. Those results were statistically significant, but were not publicized in the lay press. 

• Death from any cause (whether cancer, another disease, old age, or in an accident.) While almost all of the groupings in the study showed that surgery was preferable to watchful waiting, the benefit of surgery over observation in death from any cause was not statistically significant (i.e., the chance that the study results were merely random was more than the 1 chance in 20 measure that is acceptable as statistical significance.) This was the basis for the publicity of the study. It is worth pointing out that none of the findings showed a statistically significant benefit from watchful waiting compared to surgery. The one statistically significant result benefit from surgery was for men with a PSA greater than 10 (79% of the risk of death from any cause when compared to PSA >10's in the watchful waiting group.) 

The message to me from this article is that if you really want to do watchful waiting, use Dr. Lee's more exacting standard; ignore the standard in Dr. Wilt's study, which is too risky in my humble opinion.  Personally, as one who did watchful waiting for five years, I am not in favor of watchful waiting generally, unless it is done under a radiation oncologist's watchful eye. Here is why:  

    You never know for sure whether that benign little Gleason 6 (like the one I had) will eventually have a cousin that's an angry Gleason 9 like mine did. You need to monitor it carefully. The authorities that Joe Landry's article above make the excellent point that 75% of cancers are the low risk Gleason 6 (3+3) kind, most of which do not need treatment. When you have "most" that do not need treatment, that implies that "some" do need treatment. Because you cannot be certain whether and for how long that Gleason 6 (3+3) will stay slow growing and indolent, you need to stay on top of it. Hopefully, medical research will develop tests to separate the aggressive from the peaceful tumors, and the sooner the better.

• A biopsy reveals only what is contained in the samples taken. If you have a tiny slow-growing cancer, you cannot know for certain that nothing worse is growing inside without removing your entire prostate gland. Since you don't want to do that, you need to have future biopsies.  If you do have an aggressive cancer, it is more likely to turn up in an annual biopsy than when you have one taken every (say) 5 years.
• Just because you have a low PSA does not mean you should stop monitoring your cancer. About six or seven years ago, one of my clients died of prostate cancer even though his PSA never got above 2 or 3.

What if you have a big annual health insurance deductible? Biopsies are expensive; they can cost $2,000 or $3,000 and, besides, they hurt. And having PSA testing four times a year and an annual biopsy is a hassle. What then?

My answer to that is a question: "Does your health insurance cover at least a large portion of the cost of proton therapy? Does your Medicare cover proton therapy?" In that event, you might want to consider skipping watchful waiting. Thinking back on it now, I lived with cancer in my body for 5 years before taking action on it, but it was not due to a poor health insurance policy or a fear of biopsies; instead it was due to my fear of surgery and its side effects. Had the Proton Center been operating in 2005, I probably would have opted for treatment here, since ordinarily proton therapy side effects are far less than those from surgery.

Dave Stevens, Director, ProtonPals and Lupron Legionnaire 

Active Surveillance -   A Recommended Plan