Importance Cl v Path staging for T3 CRC patients?

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greens
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Importance Cl v Path staging for T3 CRC patients?

Postby greens » Mon Nov 07, 2011 5:11 pm

Hello Colon Clubbers


I am a T3 N2 diagnosed CRC patient in July who has completed 6 week chemo rad and has recently been re-staged as T3 N0 on basis that tumor has shrunk from 5cm to 3cm, the nodes have shrunk albeit there remains intermittent breaches of the muscular propria ( less so than previous).

Although I am very thankful for this and in particular that I appear to no longer have a threatened margin, I do understand it is only a clinical diagnosis and that crunch is the pathology report. Having said that I hope that the nodes have been sterlilised and that the tumor will continue to retrest from the muscular propria in the next 8 weeks befor my LAR.

I came across this report which studies the factors that affect prognosis for T3 N0 CRC path tumors who do not undertake adjuvant chemo lhttp://www.ro-journal.com/content/5/1/118 and it would appear low tumor location, low P21 expression, and high CD44v6 expression) is higher risk and low risk involves having no or one adverse risk factor (with rspect to recurrence).

Can anyone explain what is meant by P21 expression and CD44v6 expression in the context of T3 CRC and adjuvant chemotherapy for T3 N0 patients ? (albeit I may well not be as my path stage may or may not reveal pos nodes)

What is the general protocol for adjuvant chemo for pT3 N0 patients? (I know there has been a discussion similar led by Augustine but believe this was colon not CRC)



Best wishes

Charlie
Last edited by greens on Tue Nov 08, 2011 8:41 am, edited 2 times in total.

beth568
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Re: P21 and CD44v6 impact on T3 CRC patients?

Postby beth568 » Mon Nov 07, 2011 5:50 pm

Here's the thing: the difference between T3N2M0 and T3N0M0 is a big one - stage IIIB vs. stage IIA. My docs told me that they'd treat me based on my initial clinical staging, even if chemoradiation affected my tumor significantly and appeared to "downstage" it. It's always been my understanding that your staging doesn't change after diagnosis. So, if you are stage III and then, a year later, have liver mets, you don't become a Stage IV - you're classified as Stage III with recurrent cancer. If you are a Stage III at diagnosis and chemorad shrinks a tumor, you don't become a Stage II. Pathological staging assesses the effectiveness of treatment and can be indicative of a better or worse prognosis, but I don't believe it necessarily affects post-surgical treatment.

Given that, I would expect you to be staged IIIB and treated with adjuvant chemotherapy, either FOLFOX or XELOX.

The genetic markers you're talking about (that's what P21 and CD44v6 refer to) are relevant to stage II patients, and the study suggests that particular genetic expressions might influence a decision whether to give a stage II patient - someone whose original diagnosis was T3N0, and who had no preoperative treatment - adjuvant chemo. That testing is not necessarily part of the routine pathology that you'd get as part of the ordinary course of treatment.

I think the question you need to ask your oncologist is whether s/he will treat you as a Stage III patient because of your clinical diagnosis. If so, then chemo is in your future. My docs planned to do chemo even if my neoadjuvant chemoradiation killed all the cancer in nodes that appeared "suspicious" on my scans.

Does that make sense? Perhaps I'm wrong about the staging thing, and if so someone can correct me.
Beth
dx @age 42, Jan '11 RC, T2or3NxM0 (stage IIIA/IIIB)
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LAR 5/23/11, staged T2N1bM0 (2 of 15 nodes positive)
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CRguy
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Re: P21 and CD44v6 impact on T3 CRC patients?

Postby CRguy » Mon Nov 07, 2011 6:54 pm

beth568 wrote:Does that make sense? Perhaps I'm wrong about the staging thing, and if so someone can correct me.

I think the terminology and abbreviations thread would concur. Check the "STAGING" section.
Also of consideration is the fact that we are talking rectal vs colon.. ?????
In my experience the docs take a more aggressive course on rectal vs colon of a similar "Stage". I was "upstaged" therapeutically because of rectosigmoid primary, and even though neoadjuvant chemoradiation nuked my primary to "complete pathological response"... I still did adjuavnt chemo and resection...... AND still had a recurrence three years later.

IMO..can't do enough to nuke the beast, so I would push for the best care you can get and frequent follow up monitoring scans and Onc rechecks.

Well JMHO, butt...BTDT :mrgreen: and just sharing so hopefully you won't have to !

Cheers on the Journey
CRguy

((PS : I would also have to consider the fact that with some folks ..... BBagger and me to name just 2 ....that there is a situation whereby the original Dx may be a Stage III...BUT... BUTT... with mets developing in the process - which are NOT yet recognizable on any current scans, or scans misread or not done...SO actually a Stage IV all along, but original Dx as Stage III. Maybe splitting hairs, but since WE have to end up dealing with whatever situation we are presented..and the uncertainty...I "created" the psychological Stage 3.5...The Three-Five-0 Club for just such occasions. Yes we are a Stage III...but OOOPS :shock: something else is up...Sooooooooo back to the drawing board. YUP BTDT too. ))
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better, faster, cheaper

Postby rp1954 » Tue Nov 08, 2011 12:32 am

You might want to search around about "Tagamet" and "cimetidine" for 1-2 years use before/during/after surgery for stage III or stage II, especially with above average CA19-9. Also used with chemo and other adjuncts. Many wish they had heard earlier. I've seen some stage IVs add it, doing better than expected.
watchful, active researcher and caregiver for stage IVb/c CC. surgeries 4/10 sigmoid etc & 5/11 para-aortic LN cluster; 8 yrs immuno-Chemo for mCRC; now no chemo
most of 2010 Life Extension recommendations and possibilities + more, some (much) higher, peaking ~2011-12, taper to almost nothing mid 2018, mostly IV C

greens
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Re: P21 and CD44v6 impact on T3 CRC patients?

Postby greens » Tue Nov 08, 2011 6:56 am

Thanks for the replies.


It is often siad that staging is driven by the original diagnosis but having read the viewtopic.php?f=1&t=5366 thread I am a bit confused as it suggests that the TNM staging is based "after surgery"

It seem to me that there are 3 times that a CRC is staged iniitially:

1) At diagnosis (C)
2) Post neo-adjuvant chemradiationbut before surgery (C)
3) After surgery (P)


My questions are:

1) Is over all prognosis based upon path findings?

2) Certainly a huge number of studies I have read tend to refer to path findings ALONE when correlating with LR, DFS and OS. In one study which I believe is very authorative for stage 2/3 CRC patients research shows http://www.wjso.com/content/8/1/27 that node positive patients at diagnosis before neo-adjuvant treatment but node negative at path fared equally as well as those who were node negative at all times.

This begs the question if you take two patients who are the same pathalogical stage but one was cT3 N2 at diagnosis and the other was cT3 N0, what impact does the cT3 N2 staging have on over all prognosis for a patient staged pT3 N0?

3) If treatment is based upon c staging rather than p staging then this would tend to suggest that patients with a different p stage could end up being either over treated or undertreated as it would tend to suggest that prognosis is correlated to diagnosis stage?

4) Does downstaging say from c T3 N2 to c T3 N0 ie post neo-adjuvant but pre surgery tell us anything substantial, particularly as clinical scans may indicate improvement in or around the tumor yet the "damage" may already have incurred via sell escape from pelvis and so the downstage may be to quote an English phrase "shutting the stable door after the horse has bolted"?

Some of the points slightly over lap but any feedback from clubbers on their expereince would help

Best wishes


Charlie

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Re: Importance Cl v Path staging for T3 CRC patients?

Postby justin case » Tue Nov 08, 2011 7:10 am

I'm T3N0M0, clinical staging. I've had 3 tx folfox, I'm in chemo/rad right now. I will have surgery, then more folfox. What's wrong with being on the safe side, as opposed to playing with the consequences?
Regards,
Michael
7/11 diagnosed Stage 2 colon and rectal cancer
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Last treatment July 2012

greens
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Re: Importance Cl v Path staging for T3 CRC patients?

Postby greens » Tue Nov 08, 2011 7:13 am

No too right Michael I agree with you but still want to understand some of the issues around my question from any clubbers who have feedback.

best wishes

Charlie

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Gaelen
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Re: P21 and CD44v6 impact on T3 CRC patients?

Postby Gaelen » Tue Nov 08, 2011 7:41 am

greens wrote:My questions are:

1) Is over all prognosis based upon path findings? ---No. It's based on clinical stage unless there was a gross error in clinical stage which UPstages you after surgery (like unseen-on-scan liver mets)

2) Certainly a huge number of studies I have read tend to refer to path findings ALONE when correlating with LR, DFS and OS. In one study which I believe is very authorative for stage 2/3 CRC patients research shows http://www.wjso.com/content/8/1/27 that node positive patients at diagnosis before neo-adjuvant treatment but node negative at path fared equally as well as those who were node negative at all times.

This begs the question if you take two patients who are the same pathalogical stage but one was cT3 N2 at diagnosis and the other was cT3 N0, what impact does the cT3 N2 staging have on over all prognosis for a patient staged pT3 N0? --- They have a worse prognosis - that of the cT3 N2 stage, which is the only one relevant at this time.

3) If treatment is based upon c staging rather than p staging then this would tend to suggest that patients with a different p stage could end up being either over treated or undertreated as it would tend to suggest that prognosis is correlated to diagnosis stage? ---"Overtreatment" is a matter of opinion. No one would be undertreated since anything seen surgically or pathologically that was more serious than the initial clinical stage would UPstage the patient since s/he had been misdx'd clinically.

4) Does downstaging say from c T3 N2 to c T3 N0 ie post neo-adjuvant but pre surgery tell us anything substantial, particularly as clinical scans may indicate improvement in or around the tumor yet the "damage" may already have incurred via sell escape from pelvis and so the downstage may be to quote an English phrase "shutting the stable door after the horse has bolted"? ---in my opinion, no - it tells us nothing and just clouds the issue. YMMV.


And as a side note, you are WAY overthinking this. ;) You're not going to be able to get definitive, irrefutably conclusive answers to any of these questions. I'm all about being and getting informed, but you're not going to learn everything your docs know about CRC treatment from the unschooled answers of patients and caregivers who respond to a few forum posts, nor from digging up and reading every research article ever written.

There is a point when it's time to turn off the computer, go outside and enjoy the day. When you start worrying about the ramifications of clinical vs. pathological stage with theorectical patient treatment regimens, you're there. ;)
Be in harmony with your expectations. - Life Out Loud
4/04: dx'd @48 StageIV RectalCA w/9 liver mets. 8 chemos, 4 surgeries, last remission 34 mos.
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Re: Importance Cl v Path staging for T3 CRC patients?

Postby Surroundedbylove » Tue Nov 08, 2011 7:49 am

Hi Greens,

I haven't read all of the threads but I did want to comment. The fact that it appears that your lymph nodes have responded to treatment is good but the terminiology used sometimes can confuse the issue in rectal cancer. Rectal cancer is treated based on the clinical staging - not the pathological staging after treatment. I'm a similar example - T3N2 at clinical diagnosis. At surgery I was ypT3N0 - but I am still treated as a Stage 3 patient. Chemo and all. I'm thankful for that.

SBL
Surroundedbylove

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greens
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Re: Importance Cl v Path staging for T3 CRC patients?

Postby greens » Tue Nov 08, 2011 8:40 am

Thanks Gaelen

Appreciate your reply and insight.

Whilst I totally get that the answers to these questions are not definitive etc I'm not sure I agree that by raising them I am "over thinking". They do matter and they are important and although one or two posters have appeared to suggest I ask two many questions in the past, I have learnt a lot fromposters on their site and the widom they can pass on from their ONC's to these sorts of issues:

If, as you say, prognosis is based upon clinical rather than path findings is there another reason why the studies, almost without exception, tend to focus on path findings when reporting survival criteria. There is probably a reason that I have missed?

Where you say "They have a worse prognosis - that of the cT3 N2 stage, which is the only one relevant at this time" why would it be the only relevant one if the path findings had confirmed pT3N0?

Where you say "Overtreatment" is a matter of opinion - am I wrong in thinking that chemo alone will increase chances of cancer in longe term by a few percent which unless the benefits outweigh the risk substantially this would amount to overtreatment in cases where it was not really required?

Gaelen you are much respected on this site and thank you for participating in the thread. Unfortunately I am no scientist but must make it my business to understand this disease and I must learn on the basis that no question is too stupid!

Best wishes


Charlie

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Re: Importance Cl v Path staging for T3 CRC patients?

Postby thelongglass » Tue Nov 08, 2011 10:04 am

greens wrote:I am a T3 N2 diagnosed CRC patient in July who has completed 6 week chemo rad and has recently been re-staged as T3 N0 on basis that tumor has shrunk from 5cm to 3cm, the nodes have shrunk albeit there remains intermittent breaches of the muscular propria ( less so than previous).

Although I am very thankful for this and in particular that I appear to no longer have a threatened margin, I do understand it is only a clinical diagnosis and that crunch is the pathology report. Having said that I hope that the nodes have been sterlilised and that the tumor will continue to retrest from the muscular propria in the next 8 weeks befor my LAR.


If staging was downgraded during treatment, it would negate the whole logic for having adjuvant therapy. The reason why those of us with Stage III have adjuvant therapy is because cancer cells could have travelled through the lymph system during the months/years before we were diagnosed/received neoadjuvant therapy. Scans can only reliably identify 1 cm tumors or larger, so even though we have a stage III diagnosis, the risk of having pockets of cancer elsewhere, undetected is high. Hence the adjuvant therapy, regardless of how the cancer reacts to neoadjuvant therapy.

After going through five weeks of chemoradiation and eight weeks of waiting before surgery, my 5 cm tumor disappeared, no lymph nodes were involved, and I had a complete response. That was fabulous, but didn't change the fact that my body had cancer in the lymph system for possibly years prior. Restaging me at that point as if I had no cancer would have been counterintuitive, as the risk was still just as real as before. They continue to do research as to what length of adjuvant therapy is necessary (used to be 12 months), but the recurrence rates show that adjuvant therapy is advisable for us stage III patients.

greens wrote:Can anyone explain what is meant by P21 expression and CD44v6 expression in the context of T3 CRC and adjuvant chemotherapy for T3 N0 patients ? (albeit I may well not be as my path stage may or may not reveal pos nodes)


Hopefully someone else can help you with the terminology. I have never come across it. You should probably ask a doctor. However, I don't think the study would be relevant, since you should be using the initial staging prior to treatment.
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Re: Importance Cl v Path staging for T3 CRC patients?

Postby weisssoccermom » Tue Nov 08, 2011 11:16 am

I might take some heat for this reply but I have been following your questions, greens, and yes, IMO, you are overanalyzing this situation. PLEASE don't take offense.....and I am NOT trying to imply that this is a dx that shouldn't be taken seriously, etc. However, your diagnosis IS what is IS and you cannot change that. Simply put, rectal cancer is staged by your clinical diagnosis, UNLESS the pathological diagnosis supports an UPSTAGING. This would be done, for example, in the case of a patient who, upon all the clinical findings, testings, etc. who showed no lymph nodes but....the pathological findings showed otherwise. It would also apply, again for example, on a patient who presented clinically with ONE node but the pathological findings showed (again, just an example) SIX nodes. Does it happen - certainly it does.

The whole point of chemoradiation is: (a) to potentially shrink the tumor and/or (b) kill off the nodes. If the treatments do their 100% best - GREAT!! Does that mean that patient has a better prognosis? Maybe, but certainly not enough to totally eliminate all adjuvant treatments. The fact is that when any patient clinically presents with enlarged lymph nodes, that patient has the very real potential for having cancer cells that 'could' travel to other parts of the body. That's an entirely different story from the patient who presents clinically with NO lymph nodes. Even still, there is always the possibility that there are microscopic cells in a lymph node but the node is not yet enlarged which is precisely why adjuvant chemo is generally undertaken. You seem to be focusing on the whole clinical v pathological staging process - but why???

I understand wanting to be informed - truly I do - and I am a huge advocate for being proactive in your care but....truly what does all of this matter?? Are you going to take a pass on adjuvant chemo because your nodes appeared to have been blasted by the chemo?? Would your post treatment pathology report make any different in which chemo you take?? Are you still going to go ahead with the surgery? IMO, you're only going to make yourself crazy worrying about this study or that study.....wondering if this bit of positive news (with respect to your chemorad treatments and the ensuing results) will ultimately make a difference overal in the long run. First of all, you're not that far out from your chemorad treatments and your body is still responding to the effects of the treatments.

Putting it simply - is it a 'good' thing if your tumor/nodes respond to the chemorad? Sure it is...it means that your tumor, at least initially, 'can' be killed off with treatments. Does it mean that later on nothing else will occur? NO, it doesn't. You tested positive for nodal involvement and just because the pelvic nodes 'appear' to have been sterilized, there is no guarantee that cancer cells, prior to the advent of chemoradiation, didn't travel outside the pelvic region.

You seem to be neglecting one factor here. While your pathological staging might very well be T3N0M0 - your report would NOT appear that way. It would say: ypT3N0M0 which is VERY different from a cT3N0M0. Put simply, that small 'y' designation says that this is what the report is AFTER treatment. Let's look at me. I was originally clinically diagnosed (my surgeon later amended the pre-chemoradiation report) as a cT3N0M0 after undergoing a CT scan & an endorectal ultrasound. That initial diagnosis put me at a stage IIA with an entirely different prognosis than yours at a cT3N2M0. Even if your pathological staging does turn out to be ypT3N0M0 - it will NOT be the same as my clinical diagnosis. You're trying to compare apples to oranges and you just can't do that. I'm NOT saying that the treatments and ensuing shrinkage aren't worth it - certainly they are but....again, I repeat, it's NOT the same. One last thing....even though my surgeon, after looking at the ORIGINAL, PRE-TREATMENT ultrasound pictures, 'reclassified' my "T" stage to a T2 - it did NOT change a thing with respect to my chemo treatments. I was treated as a stage IIA & will be followed up as though I was a stage IIA.

Once the cancer presents itself in your lymph nodes, you open your body up to the potential for more spread. Your lymph system is like a major highway system with on/off ramps all over the place. All it takes is ONE cell to decide to take an off ramp somewhere and take a 'rest' in some other organ and you've got an entirely different problem. Are you willilng to take that very real risk?? Let's remember something else. A patient you has a clinical staging of T3N0M0 who then undergoes chemoradiation truly can never be 100% certain that there wasn't one node harboring cancer at dx. It simply may have been that the node wasn't yet enlarged enough to be classified as 'suspicious'.
Rectal cancer, merely by it's location (in close proximity to major blood/lymph system 'hubs') tends to have higher rates of recurrences than colon cancer which is precisely why the oncs tend to be more aggresive with rectal cancer in the stage II setting.

Only you can decide how much worrying and analyzing you're willing to do. The fact is, you clincally are a stage IIIB or IIIC (depending on the exact number of nodes - are you an N2a or an N2b?) and nothing will change that. You can respond well to treatments (what everyone wants/hopes for) but your classification will NOT change no matter how well you respond. Your prognosis truly isn't affected by the response to neoadjuvant chemoradiation but is determined by your initial staging. You may have a good response (great) but it doesn't change the fact that you presented with nodal involvement and you need to be treated accordingly.
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Re: Importance Cl v Path staging for T3 CRC patients?

Postby Ktwirls » Tue Nov 08, 2011 2:57 pm

<<<<Your prognosis truly isn't affected by the response to neoadjuvant chemoradiation but is determined by your initial staging.>>>

While I agree that prognosis can be determined by initial staging (and you don't change stages because of a good response) BUT so does response to neoadjuvant chemoradiation affect prognosis as shown in many studies. The standard is no matter what the response is to chemo/rad the initial staging determines the course of action suggested by doctors.

I also believe no stupid questions and how ever you feel the need to deal with this more power to you, we all get comfort it different ways and none is right or wrong. Some prefer no/little info and some perfer lots. The best to you!
Kim Ann, mom to 6
dx May 2010 age 37 (symptoms started in pregnancy age 36)
Rectal Cancer stage 3b T4,N1
FolFox 8, chem/rad 6wks
It came back March 2014
APR w/ PPE surgery, now on chemo, latest scan NED
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stu

Re: Importance Cl v Path staging for T3 CRC patients?

Postby stu » Tue Nov 08, 2011 5:55 pm

Just checking your ok Green.
I agree too, not a stupid question and your an autonomous individual .
Best wishes.

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Gaelen
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Re: Importance Cl v Path staging for T3 CRC patients?

Postby Gaelen » Tue Nov 08, 2011 7:17 pm

Folks - there is a huge (BiG, really BIG) difference between "overthinking" or over-analyzing something and asking questions that will actually shed light on a subject.

Overthinking borders on obsession. It's when you can't see the forest for the trees, maybe can't even see the whole tree because of your hyper-focus on a single leaf - even though the thing you're hyper-focused on is only one teeny tiny facet of the whole that is the tree and the bog picture of the forest.

Nobody in this thread has said Greens' questions are stupid, or even that there are too many of them. But what has been said, and is valid, is that clinical stage is the basis of treatment, and in that context, the other questions are basically rhetorical, because they don't affect what his treatment will be.

Yes, some studies will show improved prognosis for good response to preaiod chemo/rad...but the recognized groups who publish prognosis indications don't include that variable because it's too individualized and there's not enough data yet.

Learning about cancer and treatments is a big deal and takes a lot of effort. It's very easy, it's almost predictable which posters will fall into the traps that newly dx'd patients seem to self-discover like obsessing, overthinking, believing they are unique in the overall picture of disease and potential results or of side effects - and in the other direction, denial, positivity at all costs, etc. What more experienced patients can tell you - but most newbies won't listen until they get to realization on their own two feet - is that sometimes a cigar is just a cigar, and that no matter how many questions you ask, you're not going to necessarily have a clearer idea than when you started.

Oh - and yeah, anyone who's been around support forums long enough can (or ought to be able to) spot the moment when the ring of knowledge seeking begins to corrupt the seeker, becoming one of Tolkien's seven rings of power - and not in a good way. To be honest, we'd be remiss if we didn't point that out, and maybe help divert someone from flaming out in his/her quest to know everything.

The doctors (and some of us) have studied CRC for years - and they don't know everything. There's nothing wrong with wanting to learn. Knowledge is power. But the quest for knowledge/power can drive you crazy, and those of us who've been there are just trying to add that self-realization to the newly dx'd knowledge base. Knowing when you're overthinking is as valuable a skill as knowing how to ask better questions and when to ask them.
Be in harmony with your expectations. - Life Out Loud
4/04: dx'd @48 StageIV RectalCA w/9 liver mets. 8 chemos, 4 surgeries, last remission 34 mos.
2/11 recurrence R lung, spinal bone mets - chemo, RFA lung mets
4/12 stopped treatment


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