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Medical Forum / Diseases and Disorders / Prostate Cancer / January 2006Margins
One of the margins showed up positive on the pathology report after my RRP. My uro said that it is not uncommon to get a false reading. Anyone's thoughts about this would be appreciated. > One of the margins showed up positive on the pathology report after my RRP. > My uro said that it is not uncommon to get a false reading. Anyone's > thoughts about this would be appreciated. Tom...Not sure what the uro meant by "false reading." When a pathologist examines the removed prostate, he pays particular attention to see if there are any cancerous cells present right where the knife detached the prostate from surrounding tissue (the margin). Cancerous cells are either present or not present at the margin. As Walsh points out, cancerous cells, even if present at the margin, may not extend into the healthy remaining tissue. Or if they do extend into remaining tissue, the surgical procedure could have killed (disrupted) those remaining cells, if only small numbers were involved. I think that "on average" positive margins occur around 15% of the time, give or take. Obviously some surgeons encounter them more often than others. Typically, positive margins increase in frequency as patient staging advances. Much has been written about the effect of positive margins upon recurrence. While authors have argued both ways (positive margins mean nothing / mean something in terms of recurrence), recent articles seem to lean in the direction that there is some correlation between margins and recurrence, see the abstracts below...Best wishes and good health, Ron J Urol. 2005 Sep;174(3):903-907 DO MARGINS MATTER? THE PROGNOSTIC SIGNIFICANCE OF POSITIVE SURGICAL MARGINS IN RADICAL PROSTATECTOMY SPECIMENS. Swindle P, Eastham JA, Ohori M, Kattan MW, Wheeler T, Maru N, Slawin K, Scardino PT. >From the Department of Urology, Memorial Sloan-Kettering Cancer Center, Sidney Kimmel Center for Prostate and Urologic Cancer, New York, New York (PS, JAE, MO, MWK, PTS), and the Departments of Urology and Pathology, Baylor College of Medicine, Houston, Texas (TW, NM, KS). PURPOSE: The prognostic significance of positive surgical margins (PSM) in radical prostatectomy (RP) specimens remains unclear. While most studies have concluded that a PSM is an independent adverse prognostic factor, others report that surgical margin status has no effect on prognosis. One reason for these discordant conclusions is the variable number of patients with a PSM who receive adjuvant therapy and the differing statistical methods used to account for the effects of the time course of adjuvant treatment on recurrence. We evaluated the prognostic significance of PSMs using multiple methods of analysis accounting for patients who received adjuvant therapy. MATERIALS AND METHODS: We analyzed 1,389 consecutive patients with clinical stage T1-3 prostate cancer treated with RP by 2 surgeons from 1983 to 2000. Of 179 patients with a PSM, 37 received adjuvant therapy (AT), 29 radiation therapy and 8 received hormonal therapy. Because the method used to account for men receiving AT can affect the outcome of the analysis, data were analyzed by the Cox proportional hazards technique accounting for patients receiving AT using 5 methods: 1) exclusion, 2) inclusion (AT ignored), 3) censoring at time of AT, 4) failing at time of AT and 5) considering AT as a time dependent covariate. RESULTS: Overall 179 patients (12.9%) had a PSM, including 6.8% of 847 patients with pT2 and 23% of 522 patients with pT3 disease. A PSM was a significant predictor of cancer recurrence when analyzed using methods 1, 3, 4 and 5 (p=0.005, p=0.014, p=0.0005, p=0.002, respectively). However, it was not a predictor of recurrence using method 2 in which AT was ignored (p=0.283). Using method 5 multivariate analysis demonstrated that a PSM (p=0.002) was an independent predictor of 10-year progression-free probability (PFP) along with Gleason score (p=0.0005), extracapsular extension (p=0.0005), seminal vesicle invasion (p <0.0005), positive lymph nodes (p <0.0005) and preoperative serum prostate specific antigen (p <0.0001). Using method 5 the 10-year PFP was 58% +/- 12% and 81% +/- 3% for patients with and without a PSM, respectively (p <0.00005). The relative risk of recurrence in men with a PSM using method 5 was 1.52 (95% confidence interval 1.06-2.16). CONCLUSIONS: We confirm that a PSM has a significant adverse impact on PFP after RP in multivariate analysis using multiple statistical methods to account for patients who received AT. While prostate cancer screening strategies have resulted in a majority of men having organ confined disease at RP, surgeons should continue to strive to reduce the rate of positive surgical margins to improve cancer control outcomes. PMID: 16093984 J Clin Pathol. 2005 Oct;58(10):1028-32 The influence of extent of surgical margin positivity on prostate specific antigen recurrence. Emerson RE, Koch MO, Jones TD, Daggy JK, Juliar BE, Cheng L. Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, Indiana, IN 46202, USA. BACKGROUND: Positive surgical margins are an adverse prognostic factor in patients undergoing prostatectomy for prostate cancer. The extent of margin positivity varies and its influence on clinical outcome is uncertain.AIMS: To evaluate the linear extent of margin positivity and the number and location of positive sites as prognostic indicators in a series of prostatectomy specimens evaluated with the whole mount technique. METHODS: Eighty six consecutive margin positive prostatectomy specimens were evaluated, and all pathology data were collected prospectively. The linear extent of margin positivity was measured with an ocular micrometer and the total extent of all positive sites was summed. The total number of sites with positive margins and anatomical sites of the positive margins were analysed. RESULTS: The linear extent of margin positivity ranged from 0.01 to 68 mm (mean, 6.8; median, 3.0) and was associated with prostate specific antigen (PSA) recurrence in univariate logistic regression (p = 0.031). In addition, the extent of margin positivity weakly correlated with preoperative PSA (p = 0.017) and tumour volume (p = 0.013), but not with age, prostate weight, Gleason score, pathological stage, or perineural invasion. The total number of positive sites was significantly higher in patients with PSA recurrence (p = 0.037). The location of the positive margin site was not associated with PSA recurrence. The extent of margin positivity correlated with PSA recurrence in univariate analysis, although it had only marginal predictive value when adjusted for Gleason score (p = 0.076). CONCLUSIONS: The extent of margin positivity correlates with PSA recurrence in univariate analysis, although it has no predictive value independent of Gleason score. PMID: 16189146 Sounds like a bunch of bovine feces to me. You had an RRP. That means your doc took it out whole and they sliced it and diced it in a lab. If it's positive, they go back and look at it -- probably twice. If it's negative, they probably go back an dlook at it. It's not like a pregnancy tester where the sample is gone... or like a PSA that has a spike. Biopsies do not show false positives. If your uro doesn't know, then he or the lab screwed something up. Of course, I am not a doc or a lab technician, so take it for what it's worth.  SignaturePSA 16 10/17/2000 @ 46 Biopsy 11/01/2000 G7 (3+4), T2c RRP 12/15/2000 G7 (3+4), T3cN0M0 Neg margins PSA .1 .1 .1 .27 .37 .75 EBRT 05-07/2002 @ 47 PSA .34 .22 .15 .21 .32 Lupron 07/03 (1 mo) 8/03 (4 mo), 12/03, 4/04, 09/04, 01/05, 5/05, 10/05 PSA .07 .05 .06 .05 .08 Non Illegitimi Carborundum > One of the margins showed up positive on the pathology report after my > RRP. My uro said that it is not uncommon to get a false reading. Anyone's > thoughts about this would be appreciated. > One of the margins showed up positive on the pathology report after my RRP. > My uro said that it is not uncommon to get a false reading. Anyone's > thoughts about this would be appreciated. Note that the article posted by ron, in his response, says that margin status did correlate with the likelihood of recurrence, but that it has no predictive value independent of pathological gleason score. That means for example that if you had a Gleason 7=3+4 and a positive margin and I had a Gleason 7=3+4 with negative margins, then we are both equally likely to have a recurrence. Remember also, that any single study is not definitive. Perhaps what the doctor meant (they tend to oversimplify because they assume we are stupid and know nothing) was that a positive margin does not necessarily mean that PCa has "escaped the capsule," that PCa cells are loose in your body, or that you should be overly concerned about it at this point. The silver lining, well silver plate, is that recurrence w/ positive margins is more likely to local only and still curative. Bill Denton RP 2/12/02 PSA >.6 Memphis If I am going to need radiation, I'm sure they will have a good idea where to aim it. At least the main bad actor (the prostate) is gone and can't cause any more trouble. > Perhaps what the doctor meant (they tend to oversimplify because they > assume we are stupid and know nothing) was that a positive margin does [quoted text clipped - 7 lines] > PSA >.6 > Memphis Traditionally, they aim it at the prostate bed. Thanks to PSA, they know it's there before it can be seen, so they take the chance that the most likely place for it is the prostate bed. SignaturePSA 16 10/17/2000 @ 46 Biopsy 11/01/2000 G7 (3+4), T2c RRP 12/15/2000 G7 (3+4), T3cN0M0 Neg margins PSA .1 .1 .1 .27 .37 .75 EBRT 05-07/2002 @ 47 PSA .34 .22 .15 .21 .32 Lupron 07/03 (1 mo) 8/03 (4 mo), 12/03, 4/04, 09/04, 01/05, 5/05, 10/05 PSA .07 .05 .06 .05 .08 Non Illegitimi Carborundum > If I am going to need radiation, I'm sure they will have a good idea where > to aim it. At least the main bad actor (the prostate) is gone and can't [quoted text clipped - 11 lines] >> PSA >.6 >> Memphis > ... > Note that the article posted by ron, in his response, says that margin status did [quoted text clipped - 3 lines] > then we are both equally likely to have a recurrence. Remember also, that any single > study is not definitive. Leonard, What's the right way to read this sentence: "... Using method 5 multivariate analysis demonstrated that a PSM (p=0.002) was an independent predictor of 10-year progression-free probability (PFP) along with Gleason score (p=0.0005), extracapsular extension (p=0.0005), seminal vesicle invasion (p <0.0005), positive lymph nodes (p <0.0005) and preoperative serum prostate specific antigen (p <0.0001). " Does that mean that if you hold all of these variables constant except one, variations in that one predict different progression free probabilities? The next reference to Gleason says: "The linear extent of margin positivity ranged from 0.01 to 68 mm (mean, 6.8; median, 3.0) and was associated with prostate specific antigen (PSA) recurrence in univariate logistic regression (p = 0.031). In addition, the extent of margin positivity weakly correlated with preoperative PSA (p = 0.017) and tumour volume (p = 0.013), but not with age, prostate weight, Gleason score, pathological stage, or perineural invasion." I presume that means that the extent of positive margins is somewhat associated with pre-op PSA and tumor volume, but not with Gleason score or the other named factors. In other words, having a high or low Gleason would not, by itself, predict whether you are likely to have positive margins. Finally: "The extent of margin positivity correlated with PSA recurrence in univariate analysis, although it had only marginal predictive value when adjusted for Gleason score (p = 0.076)." I interpret this to mean that Gleason is as good a predictor of pregression free probability as positive margins, and adding the two together gives us only a marginal improvement in our ability to predict long term outcome. Have I got all that right? If I do, then maybe the way to resolve the apparent contradiction between the first and last quotes is that Gleason and PSM independently predict progression free probability, but they still tend to vary together, i.e., people with PSM are likely to have high Gleason scores and vice versa. Does that make statistical sense? Maybe not :( Thanks. Alan >>... >>Note that the article posted by ron, in his response, says that margin status did [quoted text clipped - 19 lines] > one, variations in that one predict different progression free > probabilities? Roughly that is what it means. But to be sure, I would have to look at the particular multivariate analysis scheme they are using. > The next reference to Gleason says: > [quoted text clipped - 12 lines] > having a high or low Gleason would not, by itself, predict > whether you are likely to have positive margins. Yes. But note that they were using a different statistical method to draw that conclusion. It is possible for different methods to come up with apparently contradictory results. The contradictions arise because the statistics says something very precise in a mathematical sense about the study population, but that drawing conclusions beyond that requires some assumptions and often one doesn't have a good idea of whether those assumptions are valid. > Finally: > [quoted text clipped - 7 lines] > two together gives us only a marginal improvement in our ability > to predict long term outcome. That is right. Note that this appears to contradict the earlier statement. One would have to look in detail at how the statistics was done to explain why it isn't a contradiction. > Have I got all that right? If I do, then maybe the way to resolve > the apparent contradiction between the first and last quotes is > that Gleason and PSM independently predict progression free > probability, but they still tend to vary together, i.e., people with > PSM are likely to have high Gleason scores and vice versa. I think the point is that two variables can appear to be more "independent" when part of a larger set of variables pulled out of one kind of analysis but still somewhat correlated when compared one to the other in another kind of analysis. I've seen this sort of thing happen before, and I tried to understand it all in the distant past. Multivariate analysis is an area fraught with difficulties and controversies. Biomedical researchers use statistical packages, but they seldom understand the theory underlying the tests they use. I haven't thought about any of this for quite a while, but my impression back when I did is that the only way to get a sensible result from a dataset is to go back to basics, pose a specific meaningful question which makes sense in the context and then choose a statistical method which is tailored to question you want to ask. In addition, one should be very careful not claim anything beyond what one has actually shown. For example, Suppose you have shown that if you find that in a study population of pateints who died of prostate cancer within a 10 year period who were diagnosed in the first five years of the period, that compared to a cancer free population, there was no greater use of PSA testing. You should not conclude from this that PSA testing has no value in reducing mortality from prostate cancer. The reason is that you don't know what the results would have been if you used a 20 year period with diagnosi in the first 15 years or some other time schedule. Results tend to apply just to the specific question asked and just to the population studied. One can go easily astray by generalizing to other questions and the population at large. The questions may seem to be the same intutitively, but in fact they may be very different when you look at the details. I remember when one of my psychology colleagues tried to determine whether quality of instruction as perceived by students in questionnaires was a factor in performance on a common final. The first year he did the study, using one of the standard multivariate analysis packages he concluded it was a significant factor. The next year he did the study again on the next year's crop of calculus students and discovered in was not a significant factor. My conclusion was that one should take all such studies with more than a grain of salt. I think one needs repeated studies and a good understanding at a phenomenological level of what is being studied before drawing firm conclusions. > Does that make statistical sense? Maybe not :( > > Thanks. > > Alan Thanks Leonard. That was very helpful. Alan |
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