PSA failure risk elevated in cancer patients within two cells of the surgical margin.


DENVER—Close surgical margins in radical prostatectomy specimens could place patients at increased risk of PSA failure, according to a study that may challenge conventional wisdom.

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In a retrospective, 904-patient study, a team of pathologists and urologists found that 15% of patients whose cancer was within two cells of the surgical margin—conventionally described as negative—experienced an increase in PSA after surgery, as did 9% of those whose cancer was two to six cells from the margin—also convention-ally grouped with negative margins. By comparison, the rate was 14% in patients with completely negative margins and 18% in those with unequivocally positive margins.


However, the patients with such ‘abutting’ or ‘close’ margins did not experience a rise in PSA levels any more rapidly than did those with positive or even negative margins.


Furthermore, the multivariate regression analysis performed by the team, which was led by Lawrence True, MD, professor of pathology at the University of Washington Medical Center in Seattle, did not show a significant effect of abutting or close margins on the rate of such PSA failure. The data were presented here at the United States and Canada Academy of Pathology’s 2008 annual meeting.


The study involved consecutive patients undergoing radical prostatectomy for clinically localized prostate cancer at his institution between 1998 and 2007. Patients were excluded from the retrospective analysis if they had neoadjuvant hormonal, radiation or chemotherapy, or cancer that was staged greater than pT2, N0, or M0. Ninety-four percent of the patients had Gleason grade 6 or 7 and the median follow-up was two years.


A total of 35 patients had tumor abutting the surgical margin, 94 had tumor close to the margin, 154 had positive margins and 621 had negative margins. The median time to PSA failure was 295 days in those with abutting margins, 422 among the close-margin patients, 278 days among those with positive margins and 244 days in those with negative margins.


“If it is a nerve-sparing prostatectomy, the surgeon is going to trim very close to the edge of the prostate… and in some cases they might miss a few layers of cancerous cells,” Dr. True said. “My concern is that in that minority of patients whose tumor abuts the margin, it is significant for managing those patients. [At our center] we’ve been consistently reporting abutting margins for about eight years.”


The previous ‘gold standard’ study in the field, led by Jonathan Epstein, MD, indicated that close or abutting margins were of no clinical significance (J Urol. 1997;157:241-243).


Commenting on the new findings, Peter Scardino, MD, Florence and Theodore Baumritter/Enid Ancell Chair of Urologic Oncology at Memorial Sloan-Kettering Cancer Center in New York, observed that Dr. Epstein’s study may have been too small to distinguish the negative impact of close compared with negative margins.


The new finding, he added, “rings true. If we can confirm this in larger studies, it could mean that a close margin is a risk factor [for disease progression], but it might not be as serious a risk factor as a positive margin.”