Importance of lymph node dissection even in patients with with very low risk of spread to nodes

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proscapt
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   Posted 4/7/2011 6:30 PM (GMT -6)   
Most of us know that some surgeons don't remove lymph nodes in every prostatectomy. The guidelines say that if the probability of LN+ (positive nodes) is less than 2% (some say 1%) under the nomograms then no LN dissection is needed. Not all docs agree.

Now there's more evidence.

article: EAU 2011 - More extensive pelvic lymph node dissection is associated with reduced risk of cancer progression in node negative organ confined prostate cancer patients

url: www.urotoday.com/prostate-cancer-1014/eau-2011-more-extensive-pelvic-lymph-node-dissection-is-associated-with-reduced-risk-of-cancer-progression-in-node-negative-organ-confined-prostate-cancer-patients-session-highlights.html Password is required but it's free to set up an account.

This found that even in patients where the lymph nodes were found to be cancer free, removing them still improved the rates of freedom from biochemical recurrence. Moreover, the more nodes removed, the better the outcome. One plausible explanation is that there can be micro-metastases in the lymph nodes which are not seen, but are nonetheless there, and you're better off if they're removed. In this particular study with relatively early stage cancers 10% of the patients had biochemical recurrence after ten years who had MORE than 20 nodes removed; 25% of the patients had recurrence who had LESS than 20 nodes removed.

So ask your surgeon what his plans are for node removal. This is particularly an issue with robotic surgery, where in general doctors are about half as likely to remove and examine the lymph nodes, other things being equal.

ChrisR
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   Posted 4/7/2011 6:37 PM (GMT -6)   
I was surprised to read this to.  I thought you really don't want them removing lymph nodes unless it is necessary.  You want to keep as many as possible.  I can't believe they are taking out 20+ nodes....

Tony Crispino
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   Posted 4/7/2011 6:52 PM (GMT -6)   
Thanks for the post.

It's in line with what I saw presented at our UsTOO meeting when we had a top surgeon come in. The more nodes the better.

Tony
Advanced Prostate Cancer at age 44 (I am 48 now)
pT3b,N0,Mx (original PSA was 19.8) EPE, PM, SVI. Gleason 4+3=7

Treatments:
Da Vinci Surgery ~ 2/16/2007
Adjuvant Radiation Therapy ~ IMRT Completed 8/07
Adjuvant Hormone Therapy ~ 28 months on Casodex and Lupron.
Undetectable PSA.

Blog: www.caringbridge.org/visit/tonycrispino

proscapt
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   Posted 4/7/2011 6:54 PM (GMT -6)   
Yes it seems like a lot of nodes to remove for, say, a g6 patient with 1-2 positive cores!! From the abstract I couldn't tell if they had stratified the sample properly; it's always possible that there are other explanations for the result -- like, for example, all of the survival advantage was localized in people who either had higher PSA's or more extensive cancer on biopsy or high PSA. I just can't tell from the abstract. This will likely be very controversial.
DX age 54 12/2009
PSA 5.6, DRE-, high pre-op PSAV. Clinical stage T1c
Biopsy: Gleason 3+4 with PNI / 6 of 14 cores + / 10% of total length + / worst 45% +
DaVinci RP 2/2010
pT2cNx / Gleason 3+4 / PNI+ / SM- / SV- / EPE- / Tumor vol 3cc / vol 40cc / 63 gm
PSA - 4/10 <0.01, 8/10 0.01, 12/10 0.01, 3/11 0.01

Tony Crispino
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   Posted 4/7/2011 8:11 PM (GMT -6)   
Chris R,
You posted the AUA Brosman report here (18.6 year RP follow up). That report was adamant on lymph node dissection showing extensively better results particularly in intermediate and high risk cases. It did downplay the benefits in G6 cases but there was a reward there too. Just not as extensive as the other risks. But they showed near 75% disease control rates at 15 years for high risk stage 3 and 4.

Tony

reachout
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   Posted 4/7/2011 8:29 PM (GMT -6)   
There's something here that doesn't add up. The study had a 25% BCR for patients with <20 nodes removed at 10 years. But according to the Sloan Kettering calculator, the probability of BCR at the 10 year point for low risk patients is at most around 10%. That calculator has no entry for the number of nodes removed, only whether or not they were positive. Since not many patients have over 20 nodes removed, and if 25% of those had BCR, the overall BCR rate should be well above 10% in the SK calculator if the results of that study were consistent with the results from the patients used for the SK nomograms. So which is correct, the study or the calculator? Or, better, why are the two patient populations so different?

proscapt
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   Posted 4/7/2011 8:49 PM (GMT -6)   
reachout - the difference is probably explainable by the nature of the sample. This sample was not entirely low risk patients, it was a mix of patients of different risk levels. They were all PT2, N0, SM-. But some were G4+3=7 and higher. Some had PSA>10. Some may have had other negative features on their pathology such as EPE+, SV+. See below, from the abstract:

The abstract said...

The study included 1,368 consecutive patients with pT2, N0 and surgical margin negative (SM-) CaP treated with extended PLND (ePLND) and RP for clinically localized CaP at a single referral center. All patients underwent an anatomically defined ePLND (including removal of obturator, external iliac and hypogastric nodes). Patients were divided into two groups according to the extent of PLND: <20 and ≥20 lymph nodes removed. Pre-operative as well as pathological variables were available for all patients. BCR at 2, 5 and 8 years after surgery in the overall patient population and in each group was calculated. The association between the extent of PLND and BCR - after accounting for pre-operative PSA and age at surgery, prostate weight and pathological Gleason score - was determined. Overall, mean number of nodes removed was 16.6, and pathological Gleason sum was 6, 3+4 ,4+3 and 8-10 in 56.1, 32.4, 8.4 and 3.1% of patients, respectively. Mean PSA was 7.86 ng/ml and mean prostate weight was 53.2 grams. No patient received any adjuvant treatment.

Post Edited (proscapt) : 4/7/2011 7:54:35 PM (GMT-6)


reachout
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   Posted 4/7/2011 9:02 PM (GMT -6)   
Proscapt, that's what I thought as well, but the numbers still don't add up. It's late and I'm tired so maybe I'm missing something, but go into the calculator and put in G 4+3 and PSA around 7 with everything negative and you will get around a 10% BCR at 10 years. This is the upper end of the patients used in the study except for the G 8-10 but they account for only 3.1%, not enough to drive the overall BCR from 10 to over 20%. I admit I'm reading between the lines and have not read beyond the abstract, but I still don't get the high BCR they report.
Age: 66
Pre-surgery PSA: 7 tests over 2 years bounced around from 2.6 to 5.6
Biopsy 8 of 12 positive, Gleason 3+4, T2a
DaVinci August 2009, pathology Gleason 4+3, neg margins, T2c
Post-surgery PSA one year of zeros.
Continent right away.
Viagra and other pills only gave me headache
Trimix working great!

proscapt
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Date Joined Aug 2010
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   Posted 4/7/2011 9:04 PM (GMT -6)   
Here's a good articulation of the contrary view:

www.ncbi.nlm.nih.gov/pmc/articles/PMC2997839/ **FREE**


Should all men having a radical prostatectomy have a pelvic lymph node dissection? No


... said...

However, even if we assume that PLND does have a beneficial cancer control effect, the very low LNI rate in contemporary patients may eliminate any meaningful benefit. Kawakami and colleagues18 examined the CaPSURE database; according to the D’Amico risk classification,19 they reported LNI rates of 0.8, 2.0 and 7.1% for low, intermediate and high-risk PCa patients, respectively. Based on a 10% biochemical-free survival reported by Masterson and colleagues,16 the “number needed to treat” to achieve this beneficial effect in 1 individual is 1250, 500 and 140 PLNDs for low, intermediate, and high-risk patients, respectively. It may be hard to defend performing 1250, 500 or even 140 PLNDs to improve the biochemical recurrence-free rate by 10% in 1 individual. In that light, omitting the PLND appears to represent a much better option.


I'm not saying I buy this line of argument (I don't) but there you have it.

Post Edited (proscapt) : 4/7/2011 8:07:35 PM (GMT-6)


proscapt
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   Posted 4/7/2011 9:14 PM (GMT -6)   
reachout, you make a good point and without getting into the data in full source document it's hard to explore further. The author is based at an institution in Milan; perhaps their experiences is very different: either their patients are sicker, their technique not as good, or their threshhold for defining BCR is a lot lower. Or something else. Good question. In any case, the fact that there is a difference between the two groups remains noteworthy even if the baseline numbers are very different from what SMK reports.
DX age 54 12/2009
PSA 5.6, DRE-, high pre-op PSAV. Clinical stage T1c
Biopsy: Gleason 3+4 with PNI / 6 of 14 cores + / 10% of total length + / worst 45% +
DaVinci RP 2/2010
pT2cNx / Gleason 3+4 / PNI+ / SM- / SV- / EPE- / Tumor vol 3cc / vol 40cc / 63 gm
PSA - 4/10 <0.01, 8/10 0.01, 12/10 0.01, 3/11 0.01

John T
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Date Joined Nov 2008
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   Posted 4/7/2011 10:56 PM (GMT -6)   
I think I would like to know a lot more about the effects of removing lymphnodes. I know that a lot of breast cancer patients have to wear an arm sleeve and have loss of motion due to node removal.
Does anyone know the effects of removing pelvic nodes? I suspect leg swelling. What may be an acceptable risk for high risk patients may not be for low and intermediate risk ones.
I would be more inclined to get the new IPSO imaging from Sand Lake Imaging, the replacement for Combidex, that uses the Feraleme contrasting agent. I understand it cost $750, which is a smoking deal.
JT
65 years old, rising psa for 10 years from 4 to 40; 12 biopsies and MRIS all negative. Oct 2009 DXed with G6 <5%. Color Doppler biopsy found 2.5 cm G4+3. Combidex clear. Seeds and IMRT, no side affects and psa .1 at 1.5 years.

proscapt
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   Posted 4/7/2011 11:11 PM (GMT -6)   
John T - there are a few articles on the specific complications. For example:

Urology. 1990 Mar;35(3):223-7.
Intraoperative and early complications of staging pelvic lymph node dissection in prostatic adenocarcinoma.

Donohue RE, Mani JH, Whitesel JA, Augspurger RR, Williams G, Fauver HE. University of Colorado Health Sciences Center, Denver.

Pelvic lymphadenectomy is the final staging procedure before institution of therapy for patients with clinically locally confined adenocarcinoma of the prostate, a normal acid phosphatase, and a bone scan free of metastatic disease. The pathologic information it provides cannot be accurately acquired at the present time by any other method. Extraperitoneal lymphadenectomy is associated with some morbidity intraoperatively and in the early postoperative period. We enumerate our results with 284 extraperitoneal lymphadenectomies.

PMID: 2316085 [PubMed - indexed for MEDLINE]

Where do you have to go to get the new imaging you mentioned?
DX age 54 12/2009
PSA 5.6, DRE-, high pre-op PSAV. Clinical stage T1c
Biopsy: Gleason 3+4 with PNI / 6 of 14 cores + / 10% of total length + / worst 45% +
DaVinci RP 2/2010
pT2cNx / Gleason 3+4 / PNI+ / SM- / SV- / EPE- / Tumor vol 3cc / vol 40cc / 63 gm
PSA - 4/10 <0.01, 8/10 0.01, 12/10 0.01, 3/11 0.01

Purgatory
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Date Joined Oct 2008
Total Posts : 25393
   Posted 4/7/2011 11:33 PM (GMT -6)   
My uro/surgeon and I talked about this very subject once, more than a year ago. He said that he typically only removes what is needed in the lymph nodes, they do a spot check during surgery, and it the closest ones appear "clean", they don't remove any more. Sure this varies on the number and conditon of the particular patient. He said removing all of them, if not needed, isn't  worththe  risk of possible deep infections and complications after the fact. Kind of made sense to me.

David

Post Edited (Purgatory) : 4/7/2011 10:54:07 PM (GMT-6)


John T
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   Posted 4/7/2011 11:46 PM (GMT -6)   
Sand Lake is somewhere in Fla; I don't know what city. The last data I saw on Combidex was a 96% detection rate and a 6% false positive. Nothing else even came close, even sampling from surgical removal had a much lower detection rate because there are lymphnodes that cannot be surgically sampled and these nodes are especially suspect if you have SVI. These were confirmed by surgical removal and pathology after the scan and run by several different hospitals in Germany and Holland as part of the trials. If the newer scan is anything close it would be a very important staging tool for any high risk patient. Try googling Sand Lake Imaging. The last I heard they were only taking patient referrals from Drs Myers, Strum and Dattoli; I don't know if things have changed. I can't believe the $750 charge; I paid $2400 for the combidex and $4200 for an MRIS. The $750 came from a patient that had the scan in Jan 2010.
JT
65 years old, rising psa for 10 years from 4 to 40; 12 biopsies and MRIS all negative. Oct 2009 DXed with G6 <5%. Color Doppler biopsy found 2.5 cm G4+3. Combidex clear. Seeds and IMRT, no side affects and psa .1 at 1.5 years.

Tim G
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   Posted 4/8/2011 12:49 AM (GMT -6)   
My uro/surgeon and I talked about this very subject once, more than a year ago. He said that he typically only removes what is needed in the lymph nodes, they do a spot check during surgery, and it the closest ones appear "clean", they don't remove any more. Sure this varies on the number and conditon of the particular patient. He said removing all of them, if not needed, isn't  worth the  risk of possible deep infections and complications after the fact. Kind of made sense to me.

David
 
This is exactly what my surgeon did.
 
Tim

PSA quadrupled in one year (0.6 to 2.6)
DRE negative Retested at 3 months
1 of 12 biopsies positive (< 5%) G6
RP open surgery June 2006 at age 57
Bilateral nerve-sparing
Organ-confined to one minuscule area, downgraded to G5
Prostate weight 34 grams
PSAs < 0.1

reachout
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Date Joined May 2009
Total Posts : 739
   Posted 4/8/2011 7:33 AM (GMT -6)   
So, based on this study, initial spread to the lymph nodes may be common with many BCR cases. I wonder, for patients who have had no or few lymph nodes removed and encounter BCR, has there been any discussion of additional surgery to remove lymph nodes before going to SRT? Or would it too late for that?
Age: 66
Pre-surgery PSA: 7 tests over 2 years bounced around from 2.6 to 5.6
Biopsy 8 of 12 positive, Gleason 3+4, T2a
DaVinci August 2009, pathology Gleason 4+3, neg margins, T2c
Post-surgery PSA one year of zeros.
Continent right away.
Viagra and other pills only gave me headache
Trimix working great!

John T
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Date Joined Nov 2008
Total Posts : 4269
   Posted 4/8/2011 12:00 PM (GMT -6)   
Reachout,
You have to identify the infected nodes because you can't remove all of them. Dr Myers went through this early in his battle, he had some identified nodes surgically removed and had radiation to others. You can specifically target individual nodes with radiation and that works really well, but 1st you have to identify which nodes are affected and which are clear. The other option is wide area radiation to the pelvic region and sometimes to the upper body.
JT
65 years old, rising psa for 10 years from 4 to 40; 12 biopsies and MRIS all negative. Oct 2009 DXed with G6 <5%. Color Doppler biopsy found 2.5 cm G4+3. Combidex clear. Seeds and IMRT, no side affects and psa .1 at 1.5 years.

Newporter
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Date Joined Sep 2010
Total Posts : 225
   Posted 4/8/2011 12:38 PM (GMT -6)   
They must be talking about open surgery. I have not come across robotic surgeons taking out 20 as a matter of routine surgery. In my case, mine took out 4, examined them and when all were negative, then stopped.

Here is my speculation of why US surgeons do not like to take them out unnecessarily, other than the risk of BCR is low:

If the surgeon takes out lymph nodes, there is usually a drain tube put in to drain off the excess fluid. However, they usually close the drain before your discharge from the hospital. I think there is a higher risk of infection if lymph nodes are taken out. Abdominal sepsis is a risk factor at the initial post surgery period as the fluid could accumulate in the abdominal cavity after you left the hospital and causes infection. This is rare but the more lymph nodes remove, the more fluid could accumulate.

Tony Crispino
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   Posted 4/8/2011 12:47 PM (GMT -6)   
Newporter,
My robotic surgeron told me when he came out to do a guest speaking engagement that if he knew more at the time when he did my surgery that he would have removed more in my case. But he also said that he was glad that I went with a radiation protocol that hit remaining lymph nodes (WPRT or whole pelvic region treatment ~ designed to hit the prostate bed and remaining illiac lymph nodes). And this was after he removed ten in the RALP. Robotic surgery does not limit the ability to remove lymph nodes in fact he said it enhances the ability to find them.

Images of the lymphatic system:
sparkcharts.sparknotes.com/health/generalanatomy/section7.php

Tony

Post Edited (TC-LasVegas) : 4/8/2011 12:42:01 PM (GMT-6)


142
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   Posted 4/8/2011 2:18 PM (GMT -6)   
John T,
I wonder about the test cost. If someone tells me $750 these days, I expect that they mean how much it cost them out of pocket after insurance / agreed prices kick in ???

John T
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   Posted 4/8/2011 2:26 PM (GMT -6)   
142,
I don't know, but since this is experimental I doubt that insurance would cover it. The MRI is standard, so insurance may pick up the MRI cost and the $750 would be for the contrast agent. I really don't know.
JT
65 years old, rising psa for 10 years from 4 to 40; 12 biopsies and MRIS all negative. Oct 2009 DXed with G6 <5%. Color Doppler biopsy found 2.5 cm G4+3. Combidex clear. Seeds and IMRT, no side affects and psa .1 at 1.5 years.

Carlos
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Date Joined Nov 2009
Total Posts : 486
   Posted 4/8/2011 3:04 PM (GMT -6)   
142,  A recent article about Feraheme said the manufacturer had posted about a $400/vial wholesale aquisition cost.  The analyst thought the actual price might be closer to $300/vial.  Two vials are required for FDA approved kidney disease treatment but there was no mention of the dose for MRI contrast agent.  There is a clinical trial evaluating Feraheme as a contrast agent for evaluating brain tumors.  No mention of any plan for PCa imaging.
 
Carlos

Dx 2/2008, age 71, PSA 9.1, G8, T1c
daVinci surgery 5/2008, G8(5+3), pT2c
BCR 2 1/2 yrs after surgery
IMRT, 68.4 Gy, 12/2010 - 2/2011
PSA 0.16 six wks after IMRT

proscapt
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   Posted 4/8/2011 3:51 PM (GMT -6)   
Today's UroToday news highlights a study that answers several questions about morbidity rates associated with LN removal and dissection:

Complications of pelvic lymphadenectomy in clinically localised prostate cancer: Different techniques in comparison and dependency on the number of removed lymph nodes

www.urotoday.com/prostate-cancer-1014/complications-of-pelvic-lymphadenectomy-in-clinically-localised-prostate-cancer-different-techniques-in-comparison-and-dependency-on-the-number-of-removed-lymph-nodes-abstract.html **FREE ABSTRACT - REGISTRATION REQUIRED**

It contrasts what they call ePLND (extended pelvic lymph node dissection) with SLND (sentinal lymph node dissection, in which a few nodes are taken, examined while the pt is still on the operating table, then more nodes are taken if needed. The SLND has about half the complication rate of the ePLND (11% vs. 21-22%) and so it is recommended as a good compromise between better cancer control and lower side effects.

Tony Crispino
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Date Joined Dec 2006
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   Posted 4/8/2011 4:46 PM (GMT -6)   
It is appearing that lymph node dissection and/or irradiating them is becoming an even more important strategy especially for guys that are not low risk. I am seeing a lot of data to that affect today where I was seeing just marginal data when I started out. It also appears that when surgeons do not remove at least "sentinal" nodes regardless of risk that it is an inferior practice.

Interestingly, if one chooses surgery and has higher risk characteristics, would lymph node scans be even needed. We know that Combidex, or it's newer version, can detect most nodes that are possibly positive, but in the studies the dissection of nodes positively affects outcomes even when they test negative for prostate cancer. Clearly if one chooses radiation it may be good strategy to be asking the RO about WPRT. And if they do not understand it, it may be time to get that second opinion.

Tony

Newporter
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Date Joined Sep 2010
Total Posts : 225
   Posted 4/8/2011 5:55 PM (GMT -6)   
Tony,

Thank you for the information. I learn something new today.

Regards
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