Positive surgical margins and prostate cancer-specific mortality

An article in the June issue of the Journal of Urology has suggested a definitive link between positive surgical margins (PSMs) post-surgery and prostate cancer-specific mortality (PCSM).

Over the years there have been extensive data suggesting an association between PSMs after radical prostatectomy and biochemical recurrence of prostate cancer. However, there has also been a great deal of case-specific evidence that surgical margins are not necessarily associated with prostate cancer recurrence or progression. As far as we are aware, the newly published paper by Wright et al. is the first to clearly suggest that PSMs are associated with an increased risk for PCSM.

Wright and his colleagues reviewed data from 13 regional data sets in the SEER cancer registry for patients diagnosed with prostate cancer between 1998 and 2006 and who subsequently received radical prostatectomy as their primary treatment. Patients were excluded from their analysis if there was no data on their clinical stage of their tumor grade (Gleason score), if they had a clinical stage of T3b or T4, if they had positive lymph nodes, or if they had received external beam radiation prior to their surgery.

The results of their data analysis showed the following:

  • 65,633 patients met the study criteria for data analysis.
  • PSMs were recorded in 13,905 patients (21.2 percent).
  • Median post-surgical follow-up was just over 4 years (40 months) with a range from 1 to 107 months.
  • 2,927 patients (4.5 percent) died of non-prostate cancer-related causes.
  • 291 patients (0.44 percent) died of prostate cancer.
  • The cumulative PCSM was nearly three times higher in patients with PSMs (0.86 percent) than it was in patients with negative surgical margins (0.33 percent).
  • The cumulative non-PCSM was similar in patients with PSMs (4.5 percent) and patients wit negative surgical margins (4.3 percent).

The bottom line to this study appears to be clear: positive surgical margins are associated with a threefold increase in risk for prostate cancer-specific mortality at a median follow-up of 4 years post-surgery. However, it is also worth noting something else. At the same median follow-up of 4 years, less than 0.5 percent of surgical patients (less than 1 in 200) died of their prostate cancer.

The authors themselves point out that there are significant limitations to this study, most notably including the following:

  • The absence of PSA data on each patient over time.
  • The absence of detailed pathological data post-surgery (most particularly including the lack of data on the number and location of PSMs).
  • The lack of consistent, centralized pathological review of surgical specimens.

The “New” Prostate Cancer InfoLink would also point out that a 4-year median follow-up is relatively short when considering issues related to prostate cancer-specific mortality in patients treated surgically for localized prostate cancer. It would be interesting to see a re-analysis of these data at (say) 8 or 10 years of follow-up to get confirmation of the association suggested in these data.

The conclusion that the authors draw from this study is that, “These data demonstrate the importance of optimizing surgical technique to achieve a negative surgical margin in [prostate cancer] and underscore the need for pathological standardizations of tissue processing to accurately define surgical margin status.” The “New” Prostate Cancer InfoLink would agree with this conclusion, which correlates with the growing appreciation that the skill, focus, and experience of the surgeon are critical factors in projection of surgical outcomes after radical prostatectomy.

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