Prostate Cancer-To screen or not to screen, that is the question!

First, let me be crystal clear on this issue of screening for prostate cancer. There have been a lot of advances in the field of Urology since I entered the field 56 years ago. None, however, were as important as the development of the PSA test for the early detection of prostate cancer. This simple blood test greatly increased the chances that we could detect the cancer while it was still confined to the prostate gland and remove it before it had metastasized and become incurable. A recent article in the New England Journal Of Medicine, the PIVIT study, suggests that males treated by surgery for the prostate cancer fair no better than those who forgo treatment. The authors of this 16 year study also stress the complications that result from radical prostatectomy. There are several aspects of this study that raise serious questions as to its validity. I expect the first thing to emphasize is that the lead author, Timothy J. Wilt, is an internist. Internists have a very superficial understanding of prostate cancer and the vast majority of them have never treated a patient with the malignancy. Urologists treat patients with prostate cancer, not internists, family physicians or nurse practitioners. Look at it this way. Would you believe anything I, an urologist, wrote about the survival rates of people who had surgery for brain tumors. I certainly hope not! Even if you would, please keep this in mind. This study was performed by physicians who have no firsthand experience with the disease they are writing about. If they did have experience treating men with prostate cancer they would not have made so many glairing errors in their article, a few of which I will point out below. Also remember that this VA study was funded by the federal government which is doing everything it can to reduce the cost of health care. Just think of the monies that can be saved if the Feds can convince males that they have nothing to gain by being treated for early prostate cancer. This goes way beyond death panels since it suggests that we, as a society, ignore from the get-go a malignancy that kills over 28,000 American males every single year, more than any malignancy other than lung cancer. How is it possible that we should ignore a disease that kills so many people! Doesn't pass the smell test does it? The authors claim that this was a study of males with early prostate cancer yet the PSAs in the group who were randomized for surgery had a mean PSA value of 10.1. Thus, for every male in the treatment arm of the study who had a PSA around 5 or 6, which would have made him an ideal candidate for surgery, there was someone with a PSA of 15 to 16 which would make him a questionable candidate for curative surgery. In fact, men were entered into the study as long as their PSAs were less than 50. I have never heard of a man with prostate cancer being a candidate for surgery with a PSA approaching 50 or, for that matter, even in the 15 to 20 range! Such men invariably have metastatic disease and can't be cured by surgery, or anything else for that matter. Although the title of the article, Radical Prostatectomy versus Observation for Localized Prostate Cancer, implies that this is a study designed to compare the results of surgery with watchful waiting (doing nothing) in men with prostate cancer, it is not! In fact, of the 364 men randomized to have surgery, only 281 actually had surgery and of the 367 males who were assigned to the observation wing of the study, only 292 were, in fact, observed! When all was said and done, 53 of the males who were assigned to have surgery ended up being observed and 36 of those who were initially assigned to be observed underwent radical prostatectomy. The authors of the paper completely ignore this important fly in the ointment and apparently so did the journal's reviewers. Why were these men allowed to change horses in mid stream? Well, most likely because they became aware of the bill of goods they had been sold when they agreed to enter the study and changed their minds as they watched their PSAs climb to higher and higher levels during the observation period. The question is how long did they wait before insisting on surgery and how high were their PSAs when they finally had surgery. We have no idea because the internists that wrote this paper do not understand the importance of early detection and rapid intervention in this deadly malignancy, as such, they simply ignored the issue. What should have been obvious to them, however, was the fact that they had muddied the waters in a significant way when they allowed men who had been observed for a period of time to be added to the radical prostatectomy arm of the study. This is so because the chances of curing these men decreased significantly with each passing day as their PSAs continued to climb to higher and higher levels. This gave the study a strong bias against radical prostatectomy. Obviously, these patients should have been dropped from the study. So why weren't they? Well, there are several possibilities. It seems clear that the authors had a pre-study bias towards watchful waiting and did not buy into the concept that, with respect to prostate cancer, treatment delayed is often treatment denied. To them it made no difference when a man had surgery. After all, with a few very limited exceptions, surgery wasn't going to accomplish anything anyway, except, of course, to make their lives more miserable as a result of the complications of the prostatectomy. Second, and equally likely, is the fact that they were obviously having difficulty recruiting men who were foolish enough to enter the study. The authors originally had set a goal of 2000 men for their study. After 8 years of trying they could only recruit 731 individuals who were willing to put their lives at risk for the sake of humanity. This study was based on statistics, it was a numbers game. As such, the authors could not afford to lose a single person from the study, let alone 12.3% from the observation arm and 18.8% of the radical prostatectomy side of the study. In any case, the paper should have been rejected because of the large number of switchovers between the two components of the study and it was not! Shame on you New England Journal of Medicine. But the tangled web the authors weave doesn't end there. No not by a long shot! Although the authors of the PIVIT study do not address the issue in the text of their paper, Figure 1 ( Study Enrollment and Treatment) reveals that the males in this study were not treated solely with radical prostatectomy. Nor were the men in the observation arm simply observed! To the contrary, men in both arms of the study were treated with everything but the kitchen sink! In fact, in addition to the 36 men in the observation group who ended up having radical prostatectomies; 29 received external beam radiation; 8 were treated with radioactive seeds; and one even underwent the barbaric cryotherapy (freezing). The statistics from the radical prostatectomy arm of the study were equally messed up as, 76 of the 281 males in this group were either observed or treated with some form of irradiation. The authors do not tell us who got what or for what reason. Apparently, they relied on their statistical analysis to sort out the mess that resulted from their poorly randomized study which got progressively more convoluted as time went on. The newspaper reports of the PIVIOT study have been baffling to say the least. It seemed impossible, as the reports claimed, that 12.2% of the men who had radical prostatectomy had some form of bowel dysfunction or, for that matter, that 11.3 of those that were selected for observation complained of the same. I also had difficulty swallowing the claim that 17.1% of those treated by surgery had significant urinary incontinence. The incontinence rate following radical prostatectomy should be around 1 to 2%, not 17%. If the true incontinence rate after radical prostatectomy was a whopping 17% no man in his right mind would agree to have the procedure and no surgeon worth his salt would perform the operation, except maybe on his worst enemy. Certainly, I thought, Rosie Mestel of the Los Angeles Times and the other columnists writing articles on the PIVIT study had got this wrong. But that was not the case, the journalists had reported exactly what was written in the article. Under the section titled Surgical morbidity the reader is referred to table 2 which lists the complications for males treated by surgery or observation. No mention is made of the fact that large numbers of men in both arms of the study had also received various forms of irradiation, all if which are associated with significant side effects including urinary incontinence and bowel dysfunction. The author's base their claim that men with early prostate cancer do not benefit from surgery on statistics assuming a median survival of 10 years. Well, the men with prostate cancer were entered into the study between 1994 and 2002 and the study ended in 2010. Thus, men who entered the study in 2001 and 2002 could not have been followed for 10 years! The authors admit this discrepancy but dismiss it as unimportant, stating that their use of Kaplan-Meir survival plots overcome this discrepancy. And to some extent they due. However, the data used to calculate the Kaplin-Meier plots was so flawed that the survival pots are meaningless. This statistical methodology was not designed to be used in a study such as this where men were switched willy-nilly from one arm of the study to another and received a multitude of different treatment modalities other than radical prostatectomy, any one of which could have affected the Kaplin-Meier survival plots. There is an old saying in medical statistics, shit in shit out, and that's what we have here! Finally, not a word is said about the local complications associated with the do nothing approach to prostate cancer. I expect this is so because Dr Wilt and most of his co-authors do not have a clue as to the quality of life issues that a man faces when he has an uncontrolled cancer in his prostate gland. Many of these men's lives are a living hell because of the urinary obstruction and bleeding caused by their cancerous prostates. Men with locally advance prostate cancer commonly require repeated transurethral resections of the prostate to relieve their urethral obstruction and when the cancer invades the external urethral sphincter, as it often does, these operations commonly result in total urinary incontinence. More troublesome, and difficult for the patient and his urologist to manage, is the bleeding associated with a rapidly growing cancerous prostate gland. The bleeding prostate gland not only causes clot retention but the blood clots also invariably obstruct the catheters that are used bypass the obstructing and bleeding prostates. Some of these unfortunate men end up spending more time in the emergency rooms than they do at home. It is extremely important to address the morbidity associated with watchful waiting for prostate cancer because these local complications of prostatic cancer do not occur in men who are treated by radical prostatectomy. Men who have the gland surgically removed may die from metastatic disease if the malignancy has already spread before surgery, but they do not suffer the ravages of a bleeding obstructing prostate during the last years of their lives. Thus, there are significant quality of life benefits to the procedure, even if it does not cure them. It is well known in academic medicine that statistics can be made to show almost anything and there is a great deal wrong with the way the authors employ statistics in this study. The PIVIT study is so flawed that it never should have been accepted for publication, certainly not it the prestigious New England Journal of Medicine. Is this esteemed medical journal going the way of the New York Times? I write this blog in the hopes that any male, of appropriate age, who reads it will think twice before forgoing their PSA tests. I also hope that the reader will consider his options very carefully before letting himself be talked into some silly none-treatment plan involving watchful waiting, if he is unfortunate enough to be one of the 17% of American males who will develop the cancer during their lifetime. It's really quite simple. If your prostate cancer can be detected while it is still confined to the prostate gland, you can be cured by surgery 100% of the time. No if ands or buts about it! If, on the other hand, you chose to ignore the cancer it will ultimately kill you if you live long enough, of that there can be no doubt! I can't cover all important aspects pertaining to the diagnosis and treatment of prostate cancer in this blog. If you would like to learn more including when to start being screened for prostate cancer; when to stop being screened for the disease; and what to do if you are unfortunate enough to be diagnosed with the malignancy, read my e-book What You Should Know About Prostate Cancer- Get it before it gets you!