Positive Margins

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English Roger
Regular Member


Date Joined Oct 2011
Total Posts : 180
   Posted 1/24/2013 1:33 AM (GMT -6)   
One element of a pathology report that every urologist looks for after performing a prostatectomy is the status of the surgical margins. The term “margins” refers to the cut surfaces of the prostate and, specifically, whether prostate cancer can be found at these cut surfaces. When pathologists receive a prostate specimen after a prostatectomy they usually cover the surfaces of the prostate with ink. They then look to see if prostate cancer cells can be found within these inked margins. The presence of prostate cancer at one of these inked surfaces is termed a “positive margin”. Found in approximately 30% of prostatectomy specimens, positive margins can impact the prognosis of men with prostate cancer as well as result in the need for adjuvant therapy after surgery. However, as I will explain, not all positive margins are the same. In this post, I will describe the different types of positive margins as well as the significance of these findings.

Types of Positive Margins

You would imagine that a positive margin is a pretty straightforward thing. After all, cancer cells are either present at the margins or not, right? While this is true, prostate margins are, in reality, a little more complicated. Different types of positive margins occur for different reasons and, in turn, have different consequences.

1) Positive Margin in Organ Confined Disease (T2): The prostate is covered by a lining called the capsule. Prostate cancer that is organ confined is located entirely within the limits of the prostate and, in turn, within the capsule. During prostatectomy, the surgeon may accidentally cut into the prostate, stripping some of the prostate capsule away and possible exposing an area of prostate that contains prostate cancer. In this situation, prostate cancer can be seen extending to the margin while no capsule is seen in the area. In this situation, the pathology report may state that the capsule in the area of the positive margin is “stripped” or “not seen.” This type of positive margin is usually due to technical error during surgery rather than to aggressive disease. Positive margins have been reported in 5-27% of men undergoing prostatectomy for organ confined disease.


2) Positive Margin in Non Organ Confined Disease (T3-T4): Occasionally aggressive prostate cancer can extend through the capsule and out of the prostate. This is called extracapsular extension (ECE) or extraprostatic extension(EPE). Either way, it means that the cancer went outside of the prostate before the prostatectomy was performed. Occasionally, the surgeon can cut around the prostate widely enough to still remove the cancer completely despite the ECE. Sometimes, however, the cancer extends beyond where the surgeon can safely cut and, so, some cancer is left behind, creating a positive margin. The pathology report in this situation usually reports that cancer cells are seen “extending through the capsule and are noted at the margin.” This positive margin is caused by the aggressiveness of the cancer rather than by surgical technique. Positive margins have been reported in 17-65% of men undergoing prostatectomy for non organ confined disease.

3) Artifactual Positive Margin: Sometimes what appears to be a positive margin is not one at all. Occasionally, the way a prostate specimen is manipulated during surgery or during pathology processing creates an appearance of a positive margin. This is, of course, often difficult to distinguish from the real thing. Given the anatomy of the apex of the prostate (the tip of the prostate that connects to the urethra) what appears to be a positive margin at that location is often thought to be an artifact.


Risk Factors for Positive Margins

Many studies have determined specific preoperative factors that make positive margins more likely. As you might imagine, the different types of positive margins have different risk factors. Positive margins in non organ confined disease are usually more likely to be found in men with high risk prostate cancer at biopsy. These men usually have higher PSA, higher Gleason score, and/or prostate nodules that can be felt on rectal exam. In contrast, risk factors for positive margins in organ confined disease are more technical in nature. A prostatectomy performed on an obese man or someone with a narrow pelvis is usually more challenging to perform, making an inadvertent cut into the prostate and subsequent positive margin more likely. Obese men, for example, have twice the likelihood of having a positive margin as compared to men of normal weight. Similarly, surgeons with less experience are less likely to be able to identify and preserve the important surgical landmarks of the prostate, also making positive margins more likely.

Impact of Positive Margins

So why do we care about positive margins? Aside from serving as a surgical benchmark for urologists, positive margins also have a significant impact on cancer outcomes after prostatectomy. For example, studies have shown that men with a positive surgical margin have double the risk of a PSA recurrence (cancer recurrence) as compared to men with negative margins, even after taking into account other risk factors. Of course, positive margins in men with non organ confined disease (positive ECE) have a worse prognosis than those with positive margins and organ confined disease. For example, in one study, while 18% of men with positive margins and ECE developed metastases, no men with a positive margin and organ confined disease developed metastatic spread after 7 years of follow up. Nonetheless, positive margins in organ confined disease also often yield a worse prognosis. One study, for example, demonstrated that men with organ confined disease and a positive margin have as high a likelihood of having progression of their prostate cancer as men with ECE but negative margins (25%). Hence, positive margins in organ confined disease have the effect of “up staging” the prostate cancer from T2 to T3 when seen from the standpoint of prognosis. While demonstrating such a significant impact on prostate cancer outcomes, however, positive margins do not always result in a prostate cancer recurrence. In fact, studies have demonstrated that 40-50% of men with a positive margin never demonstrate a PSA recurrence. This statistic is often attributed to the existence of the artifactual positive margins described above as well as to small positive margins in cases of non-aggressive prostate cancer.

Dissecting Positive Margins Further

As if positive margins and their consequences were not confusing enough, pathologists are now looking at margins in even more detail to create further risk categories. Some elements of positive margins that have been studied include the length of the positive margin, its location within the prostate, and whether there is a single versus multiple positive margins. Studies have demonstrated significant impacts of the margin sub-characteristics on the chance of PSA recurrence (and, in turn, prostate cancer recurrence) after surgery. Multiple positive margins, for example, have been demonstrated to yield a 40% higher chance of PSA recurrence as compared to a single positive margin. Also, an extensive or long positive margin (the critical length has ranged from less than 1 to over 3 millimeters) has been shown to result in a PSA recurrence 30% more often than small or “focal” positive margins. The location of positive margins has, also, been demonstrated to predict the potential for recurrent prostate cancer. Historically, for example, a positive margin at the apex (or tip) of the prostate has been considered to be much less worrisome than positive margins at other areas of the prostate, particularly those at the back of the prostate near its lateral edge. Unfortunately, there is a great deal of contradictory data emerging about these sub-characteristics of positive margins. In addition, a recent large study of over 5000 patients demonstrated that while these sub-characteristics do help to predict the risk of cancer recurrence, they do not appear to add any further predictive power above and beyond that derived from the simple presence or absence of positive margins. As a result, while these sub-characteristics of positive margins are somewhat useful in helping to sort out the significance of a positive margin, they are not powerful enough to substantially change the approach to dealing with a given positive margin.

Managing Positive Margins

While understanding positive margins can be helpful in predicting the risk of cancer recurrence after prostatectomy, this knowledge also creates a dilemma of how to proceed. As mentioned previously, while positive margins can double the risk of prostate cancer recurrence, nearly half of men with positive margins never have a recurrence of their prostate cancer. As a result, immediately treating ALL men with positive margins to prevent a recurrence would mean that 50% of these men would be undergoing treatment unnecessarily. Given the fact that the treatment of choice in this situation would be radiation the added, unnecessary, risks of this radiation to 50% of the men in question would be unacceptable. As a result, a great deal of controversy exists as to who should get radiation treatment for a positive margin right away (adjuvant radiation) and who should wait for a PSA recurrence first (salvage radiation). I have discussed this controversy in my previous post entitled, “High Risk Prostate Cancer After Prostatectomy: Radiate or Wait?” :
Rodger. 

 

Age 59 at diagnosis
PSA 9
Biopsy positive 4+3=7
15 May 2010
Gleason 4+3=7
Stage T2B
Perineum invasion
PSA at 3 months=undetectable
6 month PSA still 0.03
12 Mth PSA 0.04
18 Mth 0.03
2 Yr 0.03
33 mth 0.04
Incontinance no problem
ED came good now back to where i started ED a problem Viagra no help.

HighlanderCFH
Veteran Member


Date Joined Dec 2012
Total Posts : 674
   Posted 1/24/2013 3:27 AM (GMT -6)   
Thanks for the information. A great post!

I did have a small positive margin following my DaVinci procedure at Mayo Clinic in 2011. But my surgeon said that their data shows any positive margin of 0.5 cm or less is almost never any problem. He then told me he believes I should consider myself to be cured. The final pathology report shows that my positive margin was only 0.2 cm and that the tumor was "confined to the prostate."

No follow up treatment was needed and, after post-op PSAs of zero after 3 and 9 months, the doctor said I only need to return once a year for an annual PSA test.

So, hopefully he is correct that I am cured. Naturally I am a bit apprehensive about the future, but he said that ALL the "numbers" are in my favor. I sure hope so!! LOL

Thanks again,
Chuck

July 2011 local PSA lab reading 6.41 (from 4.1 in 2009). Mayo Clinic PSA Sept. 2011 was 5.7.
Local urologist DRE revealed significant BPH, but no lumps.
PCa Dx Aug. 2011 at age of 61.
Biopsy revealed adenocarcinoma in 3 of 20 cores (one 5%, two 20%). T2C.
Gleason score 3+3=6.
CT of abdomen, bone scan both negative.
DaVinci prostatectomy 11/1/11 at Mayo Clinic (Rochester, MN), nerve sparing, age 62.
My surgeon was Dr. Matthew Tollefson, who I highly recommend.
Final pathology shows tumor confined to prostate.
5 lymph nodes, seminal vesicles, extraprostatic soft tissue all negative.
1.0 x 0.6 x 0.6 cm mass involving right posterior inferior,
right posterior apex & left mid posterior prostate.
Right posterior apex margin involved by tumor over a 0.2 cm length, doctor says this is insignificant.
Prostate 98.3 grams, tumor 2 grams. Prostate size 5.0 x 4.7 x 4.5 cm.
Catheter out in 7 days. No incontinence, occasional minor dripping.
Post-op exams 2/13/12, 9/10/12, PSA <0.1.
Semi-erections now happening 14 months post-op & getting stronger.

Post Edited (HighlanderCFH) : 1/24/2013 1:30:43 AM (GMT-7)


English Roger
Regular Member


Date Joined Oct 2011
Total Posts : 180
   Posted 1/24/2013 3:45 AM (GMT -6)   
HighlanderCFH.
Why I posted it was yesterday had my 6 Mth visit with my urologist.
I asked him why my PSA after nearly 3 yrs is always 0.3 or 0.04 and
not lower.He drew a circle and right on the edge he put a dot and said
that is where the tumor was right on the margin and there is no way
of telling if it came out of the circle.I was a bit confused as after 3 yrs
of low PSA I thought I was doing great.I also remember a another urologist
say it was on the margin but he took extra tissue and it was clear.So i'm
still confused as the uro yesterday said I might need radiation in the future
it is the first I had heard this in nearly 3 years.I now wish I had not asked.
Rodger.
Age 59 at diagnosis
PSA 9
Biopsy positive 4+3=7
15 May 2010
Gleason 4+3=7
Stage T2B
Perineum invasion
PSA at 3 months=undetectable
6 month PSA still 0.03
12 Mth PSA 0.04
18 Mth 0.03
2 Yr 0.03
33 mth 0.04
Incontinance no problem
ED came good now back to where i started ED a problem Viagra no help.

HD_Rider
Regular Member


Date Joined Apr 2011
Total Posts : 380
   Posted 1/24/2013 9:27 AM (GMT -6)   
I had my follow-up with my Uro yesterday.  It has now been 18 months since my robotic surgury.

As you can see from my signature, the only time my PSA truly went "undetectable" was 6 weeks after surgery.  Since that time, I've been watching a slow and consistent rise in my PSA.  My doc believes this is due to the EPE and focal positive margin identified from the post-op pathology. 
 
I have a referral to a radiation oncologist in late April to discuss radiation therapy.  I think it's pretty much a given that I'll be undergoing SRT just as the summer kicks off.
 
Just goes to show you, even with a relatively non-aggressive cancer (gleason 6), recurrence is a true possibility and we must always remain vigilant in this war.

 

· John
· Age at diagnosis: 49
· PSA: 04/2007, 3.5; 03/2011, 4.5
· Biopsy, 12 cores: 04/13/11
· Dx: Gleason 3+4=7, 04/19/11
· DaVinci: 06/09/11; cath removed: 06/17/11
· Post-Op Report: pT2cpN0, Gleason downgraded to 3+3=6, Margins+, PNI+, SVI-, LNI-
· PSA: 07/2011 - <.01 | 10/2011 - .01 | 01/2012 - .01 | 04/2012 - .03 | 07/2012 - .03 | 10/2012 - .05 | 01/2013 - .07

HighlanderCFH
Veteran Member


Date Joined Dec 2012
Total Posts : 674
   Posted 1/24/2013 1:40 PM (GMT -6)   
Scary stuff for sure. All we can do is hope for the best.

Here's hoping & praying that both of you, myself, and everyone else with positive margins does okay in the future.

Chuck

July 2011 local PSA lab reading 6.41 (from 4.1 in 2009). Mayo Clinic PSA Sept. 2011 was 5.7.
Local urologist DRE revealed significant BPH, but no lumps.
PCa Dx Aug. 2011 at age of 61.
Biopsy revealed adenocarcinoma in 3 of 20 cores (one 5%, two 20%). T2C.
Gleason score 3+3=6.
CT of abdomen, bone scan both negative.
DaVinci prostatectomy 11/1/11 at Mayo Clinic (Rochester, MN), nerve sparing, age 62.
My surgeon was Dr. Matthew Tollefson, who I highly recommend.
Final pathology shows tumor confined to prostate.
5 lymph nodes, seminal vesicles, extraprostatic soft tissue all negative.
1.0 x 0.6 x 0.6 cm mass involving right posterior inferior,
right posterior apex & left mid posterior prostate.
Right posterior apex margin involved by tumor over a 0.2 cm length, doctor says this is insignificant.
Prostate 98.3 grams, tumor 2 grams. Prostate size 5.0 x 4.7 x 4.5 cm.
Catheter out in 7 days. No incontinence, occasional minor dripping.
Post-op exams 2/13/12, 9/10/12, PSA <0.1.
Semi-erections now happening 14 months post-op & getting stronger.

SpecialLady
Veteran Member


Date Joined Nov 2011
Total Posts : 858
   Posted 1/24/2013 1:50 PM (GMT -6)   
It is a great post, although it gets a bit contradictory (postive margin in organ confined disease has both, better and worse prognosis).

For anyone experiencing BCR (and that does not include English Roger), this video is very informative, imho:

askdrmyers.wordpress.com/2012/12/19/when-recurrent-pca-isnt-cancer/
Father diagnosed in Jan 2011 (at age 68):
DRE positive, PSA 7.5, biopsy Gleason 7 and 8.
two inconclusive bone-scintigraphies, MR scan showed 2 bone mets
Feb 2011: Started hormonal therapy (Trelstar+Casodex)
18-Jan-12: 0.055
2-Feb-12: last Trelstar injection
9-Apr-12: 0.078
4-Jul-12: 0.138
4-Oct-12: 1.08
23-Jan-13: 1.15

Buddy Blank
Veteran Member


Date Joined Jan 2013
Total Posts : 988
   Posted 1/24/2013 2:09 PM (GMT -6)   
Great info - thanks.
PSAs: 4.76 (May 2012), 4.23/PSAF 12.29% (August 2012), 3.98/PSAF 13.32% (October 2012)
Biopsy right prostate: Benign tissue
Biopsy left prostate: Prostatic adencarcinoma, Gleason score 7 (4+3), Tumor involves 2 of 10 cores and 5% of total tissue sampled, Positive for perineural invasion
TRUS measured prostate volume 19.36 cc
Stage T1c
Having a mental fight re: DaVinci surgery vs. HDR brachytherapy

Ricky2
Regular Member


Date Joined Dec 2009
Total Posts : 96
   Posted 1/24/2013 7:49 PM (GMT -6)   
This was an excellent post and hits on the thing that has me concerned and curious. I had slight positive margins and when I met with my surgeon after surgery, he said not to worry about them because they were so small. (.1mm to.25mm) small as a tip of a pen. This December I had a 3 year follow up with my surgeon and I asked him about the positive margin. He told me that my margins are what they call "false positives". They were caused by the small claws on the robot when it took the prostrate out. He told me that I now have less then a 10% chance or reoccurrence.
Age 70
PSA 7/09- 6.1, retested 9/09-5.1.
Biopsy 9/09 4 of 12 positive.G3+4
RALP 10/09
Path Rep.G3+4 Margins slightly involved <.1mm to .25mm. Perineural invasion present, stage pT2c. Tumor 18%. Seminal Vesicle & nodes - clear. ED: use VED for therapy Trimex and quadmix don't give usable erection, diagnosed with venous leak, Implant of LGX on 11/16/2011
9 PSAs through 05/08/12, all <.1

Ed C. (Old67)
Veteran Member


Date Joined Jan 2009
Total Posts : 2335
   Posted 1/24/2013 10:52 PM (GMT -6)   
Roger, thanks for the post. I'm one of those with high Gleason 8 and EPE but with negative margins. ISo far I have been blessed almost 4 years of <.01 PSA.
Age: 67 at Dx on 12/30/08 PSA 3.8
2 cores out of 12 were positive Gleason (4+4)
DaVinci surgery 2/9/09 Gleason 4+4 EPE,
Margins, SV, clear, nerve bundles removed
Prostate weighed 57 grams 10-20% involved
PSA tests every 3 months undetectable
PSA at 32 months: .005
PSA on 1/25/12 .094 (ouch) lab error
retested2/21/2012 <.01
PSA on 4/3/12 <.01 (38 months)
PSA on 10/1/2012 <.01 (44 months)
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