What does a positive surgical margin actually imply?

In an editorial commentary on the UroToday web site, Evans has discussed a recent paper from researchers at the University of Nijmegen on the length of positive surgical margins and the risk for prostate cancer recurrence.

According to the original article by van Oort et al., published back in March this year in Histopathology, the total length of any positive surgical margins in a patient’s surgical specimen is an independent predictor of risk for prostate cancer recurrence in patients with an undetectable PSA after surgery.

Specifically they report data from a series of 267 consecutive patients who had a radical prostatectomy between 1995 and 2005 and who were shown to have one or more positive surgical margins post-surgery, as follows:

  • The length of the positive surgical margins ranged from 0.4 to 174.5 mm, with a median of 11.2 mm.
  • The length of the positive surgical margins correlated with all of the following factors: the preoperative PSA level, the post-surgical, pathological stage, the  tumor volume, the number of positive surgical margins, the Gleason grade of the prostate cancer tissue at the positive surgical margin, and the patient’s Gleason score.
  • 174/267 patients had an undetectable PSA after surgery and were eligible for analysis to assess the potential for an association between length of positive surgical margins and biochemical recurrence of prostate cancer (34 patients with detectable postoperative PSA levels and 59 who received adjuvant therapy of some type were not eligible).
  • In these 174 patients the overall 5-year risk of biochemical recurrence was 29 percent
  • In patients with a positive surgical margin of ≤ 10 mm and > 10 mm, the 5-year risk of biochemical recurrence was 21 percent and 39 percent, respectively.
  • On multivariable analysis, biochemical recurrence was associated with an increasing length of positive surgical margins (hazard ratio [HR] = 2.15).

It should be noted that, in this study, if there was more than one positive surgical margin, the pathologists summed the total length of all the positive surgical margins.

As Evans points out, most urologists do not currently send a patient for adjuvant radiation therapy (with or without androgen deprivation) if they have a single, small, positive surgical margin. This appears to be justifiable if only 29 percent of all patients with a positive surgical margin and an undetectable PSA after surgery actually go on to have biochemical recurrence.

What The “New” Prostate Cancer InfoLink finds a little puzzling about this paper, however, is that a positive surgical margin encompasses an area of tissue at the surgical margin. While the length of the surgical margin may be interesting, surely it is the total area of that margin that would drive risk for disease progression? A positive surgical margin that is 10 mm long and 3 mm wide has only half the area of a margin that is 100 mm long and 6 mm wide. Doesn’t that affect the risk?

In this paper, the compete prostate specimens were available and were sectioned at 4-mm intervals, so it should have been relatively simple to estimate the total area of a surgical margin with some degree of accuracy.

According to Evans, the authors also showed that  pre-operative PSA level, pathological stage, Gleason score, tumor volume, location of the positive surgical margin, and Gleason pattern at the site of the positive surgical margin were not independently predictive of risk for biochemical recurrence. This seems a little odd when you consider that several of these factors are key components of prognostic nomograms such as the Kattan post-surgical nomogram predicting risk for biochemical recurrence after surgery. However, it also suggests to us that the question of whether it is area or length of the positive surgical margin that is important may be of some crucial relevance.

4 Responses

  1. Is it possible that the researchers’ hypothesis was that the length the tumor adjacent to the margin of the prostate is related to the probability of cancerous cells escaping from the prostate to the prostate bed?

  2. We have to assume that that is indeed the hypothesis from which they are working, but I have not been able to read the complete paper.

  3. On the length vs. area ambiguity:

    My first thought was the same as NPC Infolink, shouldn’t the measure be area rather than length?

    Contemplating the practice of measurement of “positive surgical margins,” perhaps “length” is more reproducible a measurement, rather than area? Area would require some sort of image of the positive margin. If there were an easy way of imaging positive margins, there probably wouldn’t be any positive margins, because the surgeon would excise the malignant tissue if it were visible during the procedure. Obviously this isn’t current surgical practice.

    My understanding is that positive margins are determined by biopsies of discrete points. Perhaps the reported “length” is the distance between the farthest two positive biopsy points? This does raise the question of the technique getting a one-dimensional measurement from three-dimensional reality (inside of an irregular three-dimensional void), but if the authors had some consistent measurement technique, perhaps the details are less important.

  4. Dear Dave:

    The positive margins are determined by staining the outsides of the post-surgical specimen provided to the pathology laboratory (the entire prostate with the attached seminal vesicles). They have nothing to do with biopsies. It would actually be extremely easy to determine the area of the positive margin — even though it may be an irregular area — by using a microscopic grid to calculate the number of square millimeters of the area of the positive margin.

    That’s why I find the whole thing puzzling.

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