Misstaging and misgrading: it’s a problem

Currently available treatment options for the early (localized) stages of prostate cancer are potentially curative. However, patients with locally advanced disease are less likely to be cured by today’s treatments.

The Problem of Misstaging

If your doctor finds that you have prostate cancer after carrying out a biopsy, the next question that he has to try to answer is, “What is the clinical stage of this cancer?” Unfortunately, this can be a hard question to answer in any particular case except that of clearly metastatic disease, where tumors have spread to parts of the body far from the prostate, and can be seen on a bone scan.

Hank had a DRE and a PSA a while ago, and went on to have a biopsy. This is what Hank’s urologist knew after he’d got the biopsy results:

  • He thought he could feel a small, suspicious nodule on the left lobe of Hank’s prostate when he did the DRE.
  • Hank’s PSA was 8.9 ng/mL.
  • The biopsy confirmed prostate cancer only in one small nodule in the left lobe of Hank’s prostate, close to the capsule (or wall) of the prostate.
  • The biopsy report on the tumor gave a Gleason score of 4 + 3 = 7.

On a classical basis, Hank has all the indications of clinical stage T2aN0M0 disease — locally confined prostate cancer in one lobe of the prostate detectable by DRE.

Hank was just 49 years old at the time, and he opted for minimally invasive surgery. Unfortunately, after the procedure, Hank’s doctor had to tell him that his prostate cancer was in fact locally advanced. Despite the fact that there was no good reason to expect this, prostate cancer cells were found in Hank’s seminal vesicles by the pathologist. His pathological stage is actually T3bNxM0. Why the Nx? Because there was no good reason for anyone to think about doing a lymph node dissection at the time of the surgery, so no one knows whether Hank’s regional lymph nodes are positive or negative.

About 18 months later, despite an excellent initial response to surgical treatment, Hank’s PSA starts to rise again. Hank has recurrent prostate cancer.

Of course, Hank’s doctor knew that this outcome was possible, and he had told Hank that this was a possibility when they discussed treatment options together. He also told him that this was a not a strong probability. That doesn’t make anyone any happier. But it happens … and it happens more often than anyone would like.

There is a strong and very natural desire on the part of patients and their physicians to want to believe (and thus to act as though) individual cases of apparently localized prostate cancer are going to curable — particularly those cases of prostate cancer which look as though they have a good chance of being curable — like Hank’s! After all, who wants to throw in the towel on the grounds that the worst case is bound to happen?

However, it is relatively easy to mis-estimate the initial clinical stage of an individual patient’s cancer. Most often, when the stage is wrong, the cancer is subsequently found to be of higher stage than the doctors first thought. In Hank’s case, because he insisted on having a ProstaScint test when his PSA started to rise again, the cancer was actually discovered to be stage T3bNoM1a, with a tiny degree of extension of the cancer into one of Hank’s seminal vesicles and micrometastasis to a non-regional lymph node.

There is, in fact, no reasonable way that anyone could have known Hank’s precise stage at the time of diagnosis. Even if his doctor had given him the ProstaScint test prior to surgery, the degree of accuracy of this test is not sufficient to confirm distant metastasis in one of the non-regional lymph nodes, and (given the position of the apparently small tumor clearly confined in the prostate), there was also no apparent need to biopsy the seminal vesicles.

The Problem of Misgrading

The other thing that happens in somewhere between 20 and 40 percent of cases is the problem of misgrading, where the initial Gleason grades (and therefore the Gleason score) assigned by the pathologist at the time of biopsy are later found to be higher (or lower) than the grade of the tumor when the actual prostate is surgically removed.

Data from over 1,350 patients published by one experienced academic center on the correlation between pre-surgical (biopsy-based) staging and post-surgical staging (based on the entire prostate) clearly demonstrated that the accuracy of pre-surgical staging at that institution improved significantly from  1992-96 (when there was 58 percent correlation) to 2002-06 (when there was 75 percent correlation). However, that still means that there is a lack of correlation among 25 percent of recent patients.

In this situation, of course, the pathologist can only grade what he or she gets to see. If the biopsy needle doesn’t “hit” a piece of tumor with the highest grade at the time of the biopsy, then no one could have known that there actually was higher grade tumor until the pathologist was able to look at the entire prostate after surgery.

As in the case of mis-staging, the published data also clearly show that undergrading at biopsy is far more common than overgrading. Of the 1,363 patients in the study referenced, 361 (26 percent) were undergraded at biopsy and just 65 (5 percent) were overgraded.

The point of this discussion is only, once again, to advise you that there are no certainties in the treatment of prostate cancer. Despite everyone’s best attempts, there will be many occasions when the apparent best is not good enough. Until we are able to develop absolutely definitive tests that can tell any individual patient (a) whether there is any cancer outside his prostate and (b) that we have been able to find and biopsy all relevant tissue prior to a decision about treatment, this situation will continue to be the case.

Content on this page last reviewed and updated March 18, 2010
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