What does a positive surgical margin actually predict after surgery?


Maybe 20-30 percent of all prostate cancer patients will be told, today, after a radical prostatectomy, that they a have a positive surgical margin. But exactly what impact a positive surgical margin has on a patient’s risk for disease recurrence has never been very clear.

So that we are very clear, a positive surgical margin is an area on the edge of the prostate specimen, after surgical removal, that stains positive for prostate cancer cells when it is tested in the pathology laboratory. The implication being that the surgeon may have cut too little tissue out at that particular point, and left some (or even many) prostate cancer cells behind in the prostate bed.

Boorjian et al. have recently published data based on a series of 11,729 patients who underwent open radical retropublic prostatectomy at the Mayo Clinic in Rochester, Minnesota, between 1990 and 2006. Their goal was to better establish the impact of surgical margin status on clinical progression and mortality. The basic results of this careful analysis were as follows:

  • Overall 3,651/11,729 patients (31.1 percent) had a positive margin.
  • The frequency of positive surgical margins in this series dropped over time — from 41.1 percent in 1990-95 to 32.0 percent in 1996-2000 and to 19.6 percent in 2001-2005.
  • Median postoperative follow-up was 8.2 years.
  • Risk for a positive surgical margin was significantly associated with the following preoperative data:
    • A higher preoperative PSA level
    • A higher body mass index (BMI)
    • A higher Gleason score
    • A higher clinical stage
  • The 10-year rate of freedom from biochemical recurrence was 56 percent for patients who did have a positive surgical margin and 77 percent for those who did not.
  • The 10-year rate of local recurrence-free survival was 89 percent  for patients who had a positive surgical margin and 95 percent for those who did not.
  • Surgical margin status also had a smaller, but statistically significant impact on
    • Systemic progression-free survival (93% vs 97%, p < 0.001)
    • Cancer-specific survival (96% vs 99%, p < 0.001)
    • Overall survival (83% vs 88%, p < 0.001).

However, when multivariate analysis was carried out, it was apparent that:

  • The presence of a positive surgical margin was associated with an increased risk for
    • Biochemical recurrence (hazard ratio, 1.63)
    • Local recurrence (hazard ratio, 1.78)
    • Receipt of salvage therapy (hazard ratio 1.79)
  • The presence of a positive surgical margin was not a significant predictor of
    • Systemic progression
    • Cancer-specific death
    • Overall mortality

The authors note that their data show a distinct reduction in the frequency of positive surgical margins (at least in  their series) over the past 20 years. They conclude that the presence of a positive margin after radical prostatectomy does increase the probability of biochemical recurrence, local recurrence, and the delivery of salvage therapy. However, it does not reliably predict risk for systemic progression, cancer-specific death, or overall mortality.

A critical question does remain unresolved, however. What is the standard of care for a man with a positive surgical margin after radical prostatectomy? At present it seems to us that the precise care needs to take account not only of the size and number of the positive margins but also other risk factors, most particularly including the preoperative and postoperative PSA level, the pathological Gleason score, and the pathological stage of the patient’s disease. A 55-year-old patient with a PSA level > 10 ng/ml, a Gleason score of 8, and a positive surgical margin is presumably at greater risk for clinically significant (as opposed to just biochemical) recurrence than a 55-year-old with a PSA of < 10 ng/ml, a Gleason score of 6, and a positive surgical margin.

17 Responses

  1. As a patient who had low pre-op numbers — T1c, Gleason 6, PSA 5.2, but who, after nerve-sparing prostatectomy, had a pathology showing a positive margin on the right (Gleason 6, cancer in 30% of gland, T2, gland in small category, organ-confined apart from PSM) I am keenly interested in this topic.

    Much of the literature highlights a relatively poor prognosis when PSMs are found, but I notice some recent studies which indicate that in low-risk disease PSMs are less relevant. After my op in September ’08 I became increasingly anxious and depressed about my PSM and have since been on citalopram. My urologist has tried to reassure me, but I think he and perhaps many others fail to appreciate the devasting mental impact of a PSM on the patient, especially if they are not well counselled. Other outcomes — erections and continence are excellent, PSA continues to be undetectable, but anxiety overshadows these positives and I hope for more encouraging literature as this topic is studied in the context of the PSA era.

  2. Dear Mr. Savill:

    Thank you for your comment. You have hit the nail on the head. It is absolutely critical that the patient is “well counseled” under the circumstances you describe. Anxiety is inevitable when one hears news that is worrisome, but the well-counseled patient should be able to learn from the counsel he receives — especially over time as the outcome appears to correrspond with the counsel.

    It would be utterly inappropriate (in our opinion) for the surgeon not to tell a patient about the presence of a positive surgical margin. So the wise physician needs to be able to explain the options available in a way that the patient can understand and accept. And we suspect that the wise physician will also realize that this may take more than one 5-minute conversation.

    On an entirely personal level, we hope that this article will have added to your knowledge — and perhaps your acceptance of the idea that a PSM is quite commonly just that, a PSM, and there may never be any further need for treatment, especially for those who started out with low-risk disease.

  3. I had positive surgical margins also (Gleason 3 + 4, T3a, PSA doubling in less than 8 months … 3.4 to 7.8) so I opted for radiotherapy (IMRT) to the prostate bed. Did I have to do this? No, but given the numbers and, as mentioned, the anxiety, I’m glad that I did. PSA still undetectable after 2 years.

    I wonder what the stats would be for those with positive margins in the prostate bed (but not in the lymph nodes or vesicles) who, after RP, also opted for radiotherapy?

    Harvey

  4. Dear Harvey:

    For patients like you, who have a positive surgical margin, a PSA doubling time of < 9 months, and pathological stage T3 disease, there would seem to be no question but that immediate additional treatment is essential — and IMRT would certainly be an appropriate option.

    The more difficult question appears to be around patients who have (say) T2b disease, a small positive surgical margin, and a relatively long PSA doubling time (say 15 months or more). Data reported by Walsh's group at Johns Hopkins suggest that these men are unlikely ever to have metastatic disease or to die of their prostate cancer at 15 years of follow up. And it is patients like this who form the majority of men who have a positive surgical margin after surgery in America today.

  5. I just had radical prostatectomy with the da Vinci on 7/13/2010. I went in with a pre-op PSA that had fluctuated between 3.7 and 4.0 ng/ml over the past 2 years. My pre-op biopsy done in Jan 2010 showed cancer in 7/12 cores with 5/6 cores with cancer on the right lobe; Gleason score 3 + 4 = 7; clinical stage T2a (via Dr. Epstein of Johns Hopkins with a notation that the Gleason 7 was only in one core and the rest were Gleason 6). Post-op pathology revealed a PSM at one spot due to surgeon cutting too close. Seminal vesicles were negative and no other signs of extracapsular invasion. My urologist said that I should get 6 weeks of adjuvant radiation therapy (ART) once my urinary control is “dry”. According to him studies have revealed that patients who opt for ART have a better survival rate than those that opt for salvage radiation therapy (SRT). SRT is done with patients who opt to wait to see if their post-op PSA rises above non-detectable levels of 0.10.

    I have been trying to find data that would cover this area of debate. I t seems that I fall closer to the group with Gleason 6 with pre-op PSA of less than or equal to 10 and a clinical stage T2 and thus I would most likely have a higher chance of not having a recurrence and metastasis. So am I taking a big risk if I decide to hold off on the ART and monitor my PSA on a monthly basis? If my PSA stays nondetectable wouldn’t I be okay? If it were to start rising then I could do SRT, right? Last thought here … it seems that the medical community is on the verge of a drug or a vaccine that could eliminate prostate cancer and so if I can kick the can down the road and buy time where if in the future I needed something more than SRT, then it would be available. Comments would be welcome.

  6. Dear Steve:

    The question of who needs adjuvant radiation therapy after certain specific findings in the surgical pathology report is among the most hotly debated issues within the specialist prostate cancer community. My suggestion would be that you join the social network and post the above story there for discussion — where I have little doubt that you would get lots of points of view.

    If I was you, my immediate questions for my urologist (and the pathologist) would be: (a) Was the Gleason pattern of the tissue at the site of the PSM a 3 or a 4? (b) How extensive was the surgical margin (length or better still area)? Until you have that information, I don’t see how you could make a sensible decision.

  7. Sitemaster:

    That is an excellent way for me to frame the question to my urologist when I have my followup appointment on August 24th.

    Thanks

  8. In January 2012 I had a non-nerve-sparing radical prostatectomy with the da Vinci robot. Pre-surgery my PSA was 12.8, Gleason 7 (3 + 4), and clinical stage T2c. After a biopsy the cancer was found on only the right side of the prostate. The lymph nodes were removed during surgery. I was informed a “wide path/margin” had been cut to make sure that all the cancer cells had been removed; however, the post-surgery pathology report showed a positive surgical margin and a spot on one of the lymph nodes which was unidentifiable under the microscope. Also, cancer cells were found on the left side of the prostate as well. It is now time to decide the next course of treatment (if any). Are there alternative forms of treatment such as Burzynski or other natural methods instead of hormone or radiation treatments?

  9. Dear Chuck:

    First and foremost, before you make any decisions about whether further treatment is necessary or advisable, you might want to see just what your PSA is about 8-12 weeks after your surgery. If it is < 0.1 ng/ml and stable, there may be no need to do anything (despite the positive surgical margin and the spot on one lymph node). Having said that, the younger you are (i.e., if you are under 50 years of age) the more sensible it might be to consider immediate adjuvant therapy, but this is something you will need to discuss with your doctors.

    Second, there is increasingly good evidence that a healthy diet and a regular exercise regimen can help to delay any recurrence in patients weith relatively lower risk disease after first-line treatment. So … Look hard at your diet and make sure you are (at least) taking some serious exerise in the form of regular walks of a couple of miles at 3 miles/h or better.

    Third, there is no published, peer-reviewed evidence that we are aware of that treatments offered at the Burzynski Clinic have ever had any significant clinical impact on the progression of prostate cancer (or any other form of cancer) in patients. Dr. Burzynski and his colleagues have consistently failed to enroll patients into trials that they have promised to conduct.

  10. My husband had a Gleason score of 9 pre- and post-surgery, a pre-op PSA of 5, is identified as pathological stage T3b and has more than one positive surgical margin. Radiation is starting soon. He is also on hormone therapy. The anxiety is devouring me. What is his prognosis and what quality of life can he expect? We had a 5-minute chat with the surgeon 4 weeks after surgery. He rambled off the pathology report and explained very little.

  11. Dear Christel:

    Well, first and foremost, I hope that the radiation oncologist is a better communicator than the surgeon.

    Second, let us be very clear that your husband has high-risk prostate cancer. However, the proposed treatment (androgen deprivation therapy [ADT] + external beam radiation) is the correct one (to the extent that I can tell). If you were to join our social network, it would be a lot easier to offer you and your husband some detailed guidance, because to try to answer your other questions about prognosis and quality of life we do need answers to questions of our own.

  12. Hi.

    I had my prostatectomy 4 months ago. Post-operation pathology report shows positive margins, Gleason 7 (3 + 4), pT2a. My PSA level at 6 weeks post-surgery was not undetectable. Please advise if I have to have other treatment such us radiotherapy sooner than later.

  13. Dear Andy:

    If you join our social network we can walk you though all the relevant issues in detail.

  14. I had robot-assisted surgery recently. Gleason score 7 (4 + 3 and 3 + 4); PSA 11.5 ng/ml; stage pT2. Now I am waiting for the first post-operation blood test and to see the surgeon. What do you think I should expect?

  15. Dear Augustin:

    A great deal depends on: (a) whether the cancer was truly confined to the prostate (which is what the pathgolopgical stage pT2 suggests); (b) whether there were any positive surgical margins; and (c) whether your PSA level drops to < 0.1 ng/ml. Without that information, it is impossible to be able to tell you what to expect. You are going to need to make sure that you get all this information from your surgeon before we could help you further.

  16. Hi there. My father had surgery 5 weeks ago; pathology report came back with Gleason 9 (4 + 5); only one positive lymph node no others positive; waiting for PSA results to come back, but how do we know that it has not affected any other lymph nodes? Is the report correct stating that only one lymph node is positive? Doctor said that he fears the cancer will get the better of him. I’m hoping radiation and hormone will help. Can radiation get rid of cancer in the lymph node?

  17. Dear Heather:

    First, regardless of any issue related to the pelvic lymph nodes, the fact that your father had Gleason 9 disease places him at high risk for prostate cancer progression on its own.

    Second, it is impossible to tell the level of risk related to your father’s single positive lymph node without a lot more information, specifically including the total number of lymph nodes sampled by the surgeon in testing to see whether your father did, in fact, have positive lymph nodes. All I can tell you at this time is that having even the original, single positive lymph node is a second indicator for high risk of progressive prostate cancer.

    It would be relatively normal in a man like your father to give him adjuvant treatment with radiation therapy to both the original area of the prostate and to the wider pelvic region in order to maximize his chances of a complete remission of the cancer. The use of androgen deprivation therapy (ADT, also known as “hormone” therapy) along with the radiation therapy is usually dependent on (a) his PSA level prior to his surgery and (b) his PSA level after his surgery (which you don’t know yet, as I understand it).

    If you haven’t already done this, you may want to join our social network, where it is easier to discuss the details of your father’s case individually. We would be able to offer you more detailed guidance there, but we are going to need some more detailed information from you too.

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