The Swedish Prostate Cancer Team: Which Cancers Need Surgery and When

If war is about understanding your opponent, we are only just beginning to understand the genetic changes that truly define the behavior and malignant potential of a cancerous cell. But we've done enough work to realize that a cancerous cell has more than one mutation.
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The "Swedish Bikini Team" concept somehow managed to bring notoriety to Swedish bust lines, but finally, Swedish (and Finnish, and Icelandic) prostate glands are in the headlines. The medical headlines at least.

The most recent New England Journal of Medicine includes updated results of a long-running prostate cancer study headquartered out of Uppsala, Sweden.

From 1989 to 1999, the Scandinavian Prostate Cancer Study Group enrolled about 700 men with localized prostate cancer; half of the group had their prostates surgically removed, and half were simply watched. (That's not a crazy idea -- prostate cancer is common in older men, and typically grows slowly. Many men will die of something else years down the line, so the question is still hotly debated: Who will benefit from surgery, and who will only be hobbled by it?)

Because the study pre-dated the use of prostate-specific antigen (P.S.A.), a blood test now commonly used to screen for cancer, 88 percent of the Scandinavian men in this study had tumors large enough to be felt with a physician's finger, in the way that Chevy Chase immortalized in the movie "Fletch." Only 5.2 percent had their cancer detected by screening, whereas in the U.S., less than 50 percent of men with newly-diagnosed prostate cancer have palpable tumors, and screening with PSA identifies most cancers. And so the direct applicability of this Scandinavian study to current practice has never been clear.

The results look like this: 18 years later, 200 of the roughly 350 men in the surgery group had died, 63 of them from prostate cancer. In the watchful waiting group, 247 men had died, 99 of them due to prostate cancer.

Surgery reduced the risk of dying from any cause from 69 percent to 56 percent, an almost 30 percent reduction. The benefit was strongest in those who underwent surgery at less than 65 years of age.

If dying from prostate cancer, rather than any other particular cause, is somehow your foremost concern, the numbers look like this: 18 years later, 18 percent of those who underwent prostate surgery still died of prostate cancer. (Not surprisingly, the more aggressive the cancer appeared under the microscope, the more likely it was to return, even with surgery. In other words, it had already moved out of the prostate on some microscopic level at the time of surgery.) This compares to prostate cancer death rates of 29 percent in those who did not get surgery. Again, the benefit seemed to come mostly from treating men under age 65 with surgery.

Interestingly, of the men found to have low-risk, seemingly unaggressive prostate cancer, 10 percent still eventually died of it even with surgery, even when we removed the entire prostate gland (compared with 14 percent with low-risk cancer who didn't get surgery). The difference between the two numbers was not statistically significant, i.e., surgery didn't seem to offer any benefit to these men.

This finding demonstrates a couple of important points:

We're not as good as we'd like to be at detecting whether some of the cancer has, on a microscopic level at least, exited the prostate gland. Patients are screened with blood work and CT scans prior to surgery, and if there is any evidence of spread, the surgery is cancelled. But we still can't see on a cellular level. Sometimes when we think we got it all, we didn't.

And we're not as good as we'd like to be at predicting how cancerous prostate cells will behave in the future. Our current system, where we look at the tissue under a microscope and grade it for "warped-ness," for how twisted or malignant it appears, is still one moment in time -- the present.

But we're interested in the future, and the longer a cancerous prostate gland sits around, the longer it has to develop new genetic mutations that might make it more aggressive.

In his Pulitzer Prize-winning book "The Emperor of All Maladies," oncologist Dr. Siddhartha Mukherjee chronicles the long history of our so-called "War on Cancer." Mukherjee points out that for all our sophistication, our current view of tumors in terms of size, microscopic appearance, and anatomical spread misses where the real action is: at the genetic level.

If war is about understanding your opponent, we are only just beginning to understand the genetic changes that truly define the behavior and malignant potential of a cancerous cell. But we've done enough work to realize that a cancerous cell has more than one mutation. For example, an individual breast or colon cancer can have as many as 50 to 80 gene mutations, but a smaller number of those, perhaps 10, directly contribute to the cancerous behavior of the cells. And we don't understand which of those mutations are the freak cards, the ones that will allow the tumor to pick up and exit the prostate, or to replicate more rapidly.

Let's hope that when these Scandinavian researchers take a look at how the study participants are doing in another three years, we'll have more precise and sophisticated ways of understanding which cancerous prostates need to go, and when.