A Publication of the James Buchanan Brady Urological Institute Johns Hopkins Medical Institutions

After Radical Prostatectomy
When Surgical Margins are Positive, or Too Close to Call

In an ideal world, after radical prostatectomy, the pathologist would send a triumphant report to the surgeon: "I've looked at the prostate tissue you removed from Mr. Jones, and all of the edges are clear. Congratulations! You've removed all the cancer!"

Most often, it happens that way. Sometimes, however, the pathologist's report is more ambiguous: Either the margins -- the edges of the removed tumor -- are "positive," meaning they show cancer cells, or they're "close," meaning cancer is just a hair's breadth away from the edge of the specimen.

Hopkins pathologist Jonathan I. Epstein, M.D., who has probably looked at more radical prostatectomy specimens than anyone in the world and is an expert at interpreting how prostate cancer cells look, has good news about margins:

Close margins are almost always negative. Epstein recently finished a study of patients whose tumors were particularly close -- less than two tenths of a millimeter -- from the surgical margin, the edge of the removed tissue. Even though there wasn't a comfortable cushion of tissue between the tumor and the edge of the prostate, " those patients do just as well as if there's more separation between the tumor and the margin."

And, even if the surgical margins are positive, this does not necessarily mean that the cancer is left behind. How can this be? "There are several different explanations why, when the margins are positive, the tumor may still be cure," says Epstein. "One is that literally you cut across the last few tumor cells" -- that what appears to be remaining cancer is actually a cross-section of the perimeter of the tumor. "And even though it looks like it's a positive margin, there's really nothing left in the patient."

Another explanation is that the act of surgery itself finishes the job, killing any remaining cells. No cut or injury to tissue happens in a vacuum; the area around the cut is affected, too. (Think of lightning striking a tree; the tree dies, but so does a ring of grass around it). "When the surgeon cuts across tissue the blood supply is cut off, there's dead tissue, and that can kill off the last few tumor cells that might have been left behind," Epstein says.

There's also potential -- "and this probably accounts for a lot of cases" -- that it's an "artificial" (basically, a fake) positive margin. Sometimes, "since there's so little tissue next to the prostate, when the surgeon tries to dissect it from the body, and he hands it to the nurse, and then the nurse hands it to the pathologist, and everyone's kind of touching the gland, and if you're talking about two tenths of a millimeter of tissue, that tissue can get disrupted very easily. It can appear that the tumor is at the margin -- but in fact, there was some additional tissue there that just got disrupted during all the handling of the specimen." In other words, a few good "buffer" cells got rubbed off.

And then there's the "sticky cell" phenomenon. When cancer reaches beyond the prostate to invade nearby tissue, it produces a dense scar tissue that acts, as surgeon Patrick C. Walsh, M.D., describes it, "like Super Glue." As a surgeon removes the prostate, this thick scar tissue sticks to the surrounding cancer cells -- picking them up like a lint brush. So in some cases, although the pathologist may see cancer cells at the margin -- and make a judgment of "positive surgical margins" -- there are no cancer cells left inside the patient. The sticky scar tissue took them all away.

Epstein recently studied such instances, when Walsh removed the prostate, looked at it, suspected that some cancer cells were present, went back and cut out more of the surrounding tissue. "So in pathology, we got two separate specimens," says Epstein. "One was the prostate, one was this extra tissue, the neurovascular bundle that he was thinking of leaving in the patient, but decided to remove." Even when there appeared to be a positive surgical margin at the edge of the prostate, in 40 percent of these patients there turned out to be no cancer left behind in that adjacent tissue.

"So when pathologists call a positive margin, or for that matter, a close margin, it doesn't necessarily mean that these patients need some other form of therapy, like radiation," says Epstein "and also that they need not necessarily be tremendously worried."

But what if a positive margin does mean that there's still cancer in the area? Many of these men may still be cured with radiation to the prostate bed, the area where the prostate used to be. Here is where other factors come into play. For more on these, and who might benefit from radiation, see the next story.


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