Tuesday, July 27, 2010

The Conundrum of Prostate Cancer

The conundrum of prostate cancer is the problem of dealing aggressively with prostate cancer. In a recent NCI note reporting on a report in the Archives of Internal Medicine they note:

The NCI states:

The researchers found that 77 percent of men with a serum PSA level of 4.0 nanograms per milliliter (ng/mL)—the level at which a prostate biopsy is often recommended—or lower underwent either complete removal of their prostate, known as a radical prostatectomy, or radiation therapy. This treatment occurred even though more than half of these men were considered to be at low risk of disease progression based on commonly used factors, such as the Gleason score and the extent of local tumor spread.

Despite evidence that suggests older men are less likely to have a survival benefit from surgery or radiation compared with more conservative treatments, age was not a barrier to low-risk men receiving aggressive treatment. Nearly 69 percent of men age 65 to 74 and approximately 40 percent of men 75 and older underwent either surgery or radiation.

Let us examine the statements:

1. Clearly as has been demonstrated a PSA of 4.0 is still too high a cutoff, and that 2.5 is more likely a reasonable value but the real problem is velocity, namely change in PSA as well as percent free. A high PSA reflects possibly an enlarged prostate but a low percent free may indicate cancerous cells rather than just benign enlargement via BPH or PIN. Thus one would expect that a biopsy yielding a positive PCa at 4.0 or lower is not unrealistic.

2. There is currently no clinically acceptable means for ascertaining aggressive PCa from indolent forms. Family history may help but it is still guess work. We know the pathways but finding the cell that contains all activated pathways may be akin to finding a needle in a haystack. Low risk is not really a clinically well determined description. It may mean the PCa and family history are representative of low risk. A Gleason of 7 or greater is clearly PCa that one should be concerned about.

3. Old age statistics were based on older data as well and thus saying that anyone with PCa detected at over 65 should not be treated is akin to a death sentence for many. Patients all too often ask what are their chances. Frankly chances only mean something for a large group. There are no chances for an individuals, their result is one or the other, life or death.

4. A positive biopsy means PCa and nothing more. The typical patient wants this problem remedied. The physician is generally clueless as to aggressive behavior. If the first degree relative died of an aggressive form that is a strong indication. However it is not foolproof.

The NCI article goes on:

“It has been documented that men who receive any treatment have increased risk of treatment-related adverse effects,” Dr. Shao and colleagues wrote. “Therefore, it is critical that patients be counseled about treatment-associated adverse effects and benefits when they are deciding about therapy.”

In an accompanying editorial, Drs. Richard Hoffman of the University of New Mexico and Steven Zeliadt of the University of Washington advocated for greater use of so-called active surveillance. This approach “balances the desire to avoid treatment complications against the equally strong desire not to ignore a cancer—while at the same time minimizing the risk of overtreatment,” they explained.

Yes there are adverse effects, and many of them are from less experienced physicians. As to so-called active surveillance, also known as watchful waiting, or whatever euphemism one wants, it assumes the cell doubling is long, when it may very well be short. It is a guess. Nothing more. If it is an aggressive form then by waiting it is most likely going to result in mets, since the cell doubling time is in weeks not months!

An educated patient is important and so too is an educated physician. The problem we are facing here is a clear example of the Comparative Clinical Effectiveness plan under the new Health Care Bill, namely if you are over 65 then no matter what the biopsy says you just wait till it mets to the bones and hope there is enough morphine until the DICs occur and you are gone! So this is what the new health care plan has in store, yes, there is really a "death panel".

The main problem with prostate cancer and this debate is that medicine does not have a test to determine what prostate cancers are virulent and which are indolent. The pathways controlling the growth are somewhat known but the presence of micro RNAs has added additional complexity. Thus the issue is do we wait until we know it is a virulent strain or do we act with an informed patient. Prostatectomy is not a trivial surgical procedure. It has sequellae such impotence and incontinence. Yet death from mets to the bone is much worse. The logic of the NCI piece fails in that on average it works but averages only works for large groups. It should and must be an individual decision. The patient must be the ultimate decision maker, informed of the consequences, but the decision maker.