Adequacy of axillary lymph node dissection

[Treat]

Hi all,

I'd like to know what threshold people use to determine the adequacy of an axillary dissection, in deciding whether or not to give an axillary boost.

10 nodes? 8? 6?

I'd be most grateful if you could also point me towards any supporting literature.

Thanks!

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[Palex80]

My general cut-off is 10. However, I also like to look into the macroscopic description of the pathology report.
My pathologists have often told me that the number of identified lymph nodes can be variable according to "how hard" the pathologist will look for.

So if you have a large axillary tissue sample described in the macroscopic description but only a few lymph nodes identified, you may want to call the pathologist and ask him to look again for further nodes. Sometimes they may find the extra 2-3 nodes that will allow you to reach your threshold.
If the pathologist is not compliant, you can always tell him "Oh well, if you can't find any, I will probably have to subject this patient to perhaps unnecessary radiation treatment." Pathologists can be very cooperative when they actually get the impression that their extra work will have a direct clinical impact for the patient.

 

[Treat]

Thanks Palex!

As always, I appreciate your willingness to share your experience.

Under what circumstances would you accept a number below this 10 lymph node threshold?

 

[Palex80]

I think there are quite a few factors to take into account in situations like these.

The question "how many lymph nodes are enough" arises when you have one or more positive lymph nodes in an axillary dissection (but not 10) and you question yourself whether or not you should target the axilla.
Following factors play role IMHO and please do add more, should I have missed any.

a) Did the patient receive neoadjuvant treatment? Obviously if you end up with ypN1 (1/8), you have a difference situation than if you did the axillary dissection prior to neoadjuvant treatment. That ypN1 could have been pN1 (3/8) prior to neoadjuvant treatment.

b) Are there additional factors for an increased risk of axillary involvement? Size of primary tumor, histology grading, premenopausal status, luminal B tumor, lymphovascular involvement, etc...

c) What was the extent of axillary lymph node involvement? Was it a pN1 with 1, 2 or 3 nodes? Was there ECE present? Was the metastasis small, even pN1mi or was it a larger metastasis?

d) What does the nomogram say? The MSKCC nomogram is designed to find out the risk of additional involved non-sentinel nodes.

Breast Cancer Nomogram: Breast Additional Non SLN Metastases | Memorial Sloan Kettering Cancer Center

nomograms.mskcc.org

That is not same scenario as when you perform an axillary dissection but end up with a less than desirable amount of total resected nodes, but it can still help you. However, use it with caution, I presume its accurary drops once you enter a higher number of non-involved nodes (it does say "Negative Sentinel Lymph Nodes" which is not the same as "Negative Additional Lymph Nodes").

e) What type of surgery was performed? Was it a full axillary dissection, were >1 levels assessed or did the surgeon only dissect one level (usually level 1)? Was it a targetted axillary dissection? We are currently participating in a trial which looks into the role of RT for pN1 disease without full axillary dissection.
However it's trial for cN1 patients, not patients that were cN0 and turned out to be pN1, which is the most common scenario. Usually with a cN1 tumor the surgeon will resect "enough" to give you 10 nodes. Tailored AXIllary Surgery With or Without Axillary Lymph Node Dissection Followed by Radiotherapy in Patients With Clinically Node-positive Breast Cancer (TAXIS) - Full Text View - ClinicalTrials.gov

f) Which side is the one we are talking about? Is is the right side on a right-handed person? Or was it the left side on a left-handed person? Does the patient use its arm a lot for example during work? Is there lymphedema already present?

g) Will coverage of the right axilla substantially increase the heart dose? Does the patient have a preexisting heart disease? Are there risks for pneumonitis in the patient?

 

[scarbrtj]

From the back of the room guy raises his hand...

In what situation is the axilla a therapeutic target? I.e., what is doing anything to the axilla—harvesting many or few of its nodes, irradiating its contents—changing the patient's outcome? We have hints that that "standard thought" about what we thought we knew about the dissected axilla might have been way off. Maybe we ought to rethink a few things.
Most women don't need the axilla dissected at all nowadays, right? Even if we know one or two lymph nodes have disease in them already?
And why is "10" a "magic number?" Do we fart in 9's general direction? Where does this data come from? From a very old era, all the way in the last century, like when Reagan was President? When the USSR was a threat and breast cancer treatment was quite different? Was this good data? Robust data? Is it almost oncolore now? Are there any ... alternative ... contradictory ... data? Dissecting more nodes causes more toxicity. I wish we had some GOOD data to more truly know the risks/benefits.
Why does the axilla get "picked on" as a site to treat in breast cancer? Are other lymph node sites (almost) just as likely to have positive nodes, or to have metachronous positive nodes "pop up," as the axilla? Why don't we dissect the supraclav region? Dissect the IMN region?
How often is the axilla an isolated site of recurrence? One in a thousand cases? Doesn't that alone suggest "boosting the axilla" is sisyphean?
I would (controversially) suggest that irradiating an axilla just because it "only" had 7 LNs dissected is masochistic/needlessly lymphedemogenic. An MD, e.g., who decides to irradiate an axilla, "boost it," in a woman that's cN+ and HER2+ who gets a CR and pN0 after neoadj chemo and has 0/7 LN's positive needs... help. This will be a guy who referring docs might think has more side effects in his patients than other guys'.

Sorry to interrupt.

Does the patient use its arm a lot for example during work?

Because I'm irreverent I couldn't help but picture...
"Ma'am, do you use your arm a lot?"
"No, I barely ever use it. I am not really an 'arm' person."
"OK, cool cool, I'm gonna irradiate your axilla then."

 

[medgator]

g) Will coverage of the right axilla substantially increase the heart dose? Does the patient have a preexisting heart disease? Are there risks for pneumonitis in the patient?

Do you mean left?

 

[Palex80]

Do you mean left?

Do you mean left?

Ooops, sorry, mistyped that.

 

[Palex80]

Because I'm irreverent I couldn't help but picture...
"Ma'am, do you use your arm a lot?"
"No, I barely ever use it. I am not really an 'arm' person."
"OK, cool cool, I'm gonna irradiate your axilla then."

Well this is actually not something I discuss with the patient, but it is something I consider when I consult them.
Some patients need their arms alot more during work and use them in such a way that the risk of lymphedema can be increased.
A patient who irons clothes for a living is at a higher risk for lympedema than the typical teacher for example. Or perhaps let me rephrase that: The typical teacher can adapt her type of work and her habits at work in order to minimize her risk for lymphedema. The patient that irons clothes cannot do it as easily.

 

[scarbrtj]

Well this is actually not something I discuss with the patient, but it is something I consider when I consult them.
Some patients need their arms alot more during work and use them in such a way that the risk of lymphedema can be increased.
A patient who irons clothes for a living is at a higher risk for lympedema than the typical teacher for example. Or perhaps let me rephrase that: The typical teacher can adapt her type of work and her habits at work in order to minimize her risk for lymphedema. The patient that irons clothes cannot do it as easily.

Who knew dissected number of axillary lymph nodes in breast cancer could be such a humerus situation?
Teachers use their arms a lot at school btw. So does the lunch lady. And people iron clothes for a living? Like... an iron lady?

g) Will coverage of the right axilla substantially increase the heart dose? Does the patient have a preexisting heart disease? Are there risks for pneumonitis in the patient?

How would adding axillary irradiation increase exposure the heart to any appreciable extent (even L axilla) in the setting of already irradiating the breast or CW. I can't easily picture that. Nor can I easily picture substantially upping the pneumonitis risk w/ axillary RT.

Again, whether a teacher, or an iron lady, or a smoker, or if there's situs inversus, I can't see how any of this influences axillary RT or not.

e) What type of surgery was performed? Was it a full axillary dissection, were >1 levels assessed or did the surgeon only dissect one level (usually level 1)? Was it a targetted axillary dissection? We are currently participating in a trial which looks into the role of RT for pN1 disease without full axillary dissection.
However it's trial for cN1 patients, not patients that were cN0 and turned out to be pN1, which is the most common scenario. Usually with a cN1 tumor the surgeon will resect "enough" to give you 10 nodes. Tailored AXIllary Surgery With or Without Axillary Lymph Node Dissection Followed by Radiotherapy in Patients With Clinically Node-positive Breast Cancer (TAXIS) - Full Text View - ClinicalTrials.gov

Good trial. Congrats for participating (I kid, I kid... it's more than I do!). But this trial is totally non-germane to OP's original question re: the adequacy of an axillary dissection: 1) the trial allows any number of axillary nodes to be dissected and doesn't define adequacy, 2) no one AFAIK is doing "tailored" axillary surgery outside of trials, and 3) the study has an estimated completion date in the year 2043(!).

At end of day, here's what I internalized from Z0011 and AMAROS: let's quit it with the axillary schwarmerei (EDIT: this too as mentioned). Whether you irradiate the axilla or not, whether you dissect it or not (everyone in AMAROS had to have 10 or more LNs dissected), whether you irradiate it or dissect it, it doesn't move any needles except that 1) intentionally irradiating the axilla significantly increases the incidence of contralateral breast cancer and 2) irradiating axilla w/ 50Gy/25fx instead of dissecting 10 or more LNs gives less lymphedema than dissecting 10 or more LNs. (If you're "boosting" the axilla per OP's question, you will get more lymphedema than not boosting IMHO.) There is no magic number for axillary dissection adequacy. The surgery is pretty standard ("they get what they get"); the pathologist plays an outsize role as you pointed out. We don't have to worry <4 or ≥4 nodes positive anymore (for PMRT e.g.); the axilla is positive, or it's not. There are exceptions to all rules, but it's the rarest of rare cases when I fret about number of axillary LNs obtained at surgery.

 

[nkmiami]

Agree with scarbtj. AND is not therapeutic.

 

[scarbrtj]

Agree with scarbtj. AND is not therapeutic.

Thanks man. Now you and I aren't saying it's 100% non-therapeutic. You have a big palpable axillary node, bx-positive, let's get it out. That's therapeutic.
But if you "discover" positive nodes, like at surgery, it takes a lot more than just 10 nodes in total to get comfortable that there aren't more "unharvested" lymph nodes lurking in there making you all uncomfortable and what not. Like in Palex's case....

Did the patient receive neoadjuvant treatment? Obviously if you end up with ypN1 (1/8), you have a difference situation than if you did the axillary dissection prior to neoadjuvant treatment. That ypN1 could have been pN1 (3/8) prior to neoadjuvant treatment.

Who cares? Seriously. Fowble suggested you have to get like **20** total nodes out of the axilla, when 3 are positive, to get comfortable that there's not a 4th in there. E.g., 3/8 LN+... getting 12/12 additional nodes negative is rare-ish, but "needed" to really find the "truth."
When a LN is positive in the axilla, the more you dissect, the more likely you will find more positive nodes. Why stop at 10? Why not get AS MANY AS POSSIBLE.
I say ignoramus et ignorabimus. I'm a grumpy old man lol.

 

[evilbooyaa]

I generally prefer 10 LNs out on ax Dissection to have an accurate assessment, but if they have 7 I'm not going to treat the 'dissected' axilla just because they have 7. There are very, very few clinical scenarios where I purposefully treat a dissected axilla at all. I agree that for cN0, AND is a staging procedure 99% of the time. The rare times it may be therapeutic is if an otherwise low-risk patient has 1 LN positive out of 10+ dissected, clinically, I may be able to justifying not treating regional lymph nodes. Versus if the patient had 1/3 LNs + on SLNB and didn't have an Ax dissection, I'm probably doing RNI.

This does not apply to people only getting sentinel lymph node biopsy. If nodal coverage is indicated in a positive SLNB, they get coverage of the entirety of the axilla.

What do you mean by an Axillary boost? Are people treating to higher than 50Gy in a dissected axilla? If so, why? Only

People do axillary boosts (posterior axillary boost, anterior axillary boost) to get the dose in the nodes (usually to the undissected axilla and SCV) to close to prescription dose, because a standard 6x AP prescribed isn't going to give you adequate coverage of CT-sim drawn lymph node regions in 90%+ of patients if you care about the max hot-spot at all.

 

[Palex80]

Who knew dissected number of axillary lymph nodes in breast cancer could be such a humerus situation?
Teachers use their arms a lot at school btw. So does the lunch lady. And people iron clothes for a living? Like... an iron

Yes, people do iron clothes for a living. I presume you do not iron your business shirts yourself, do you?
If you don‘t like that example, think of a bus driver. She will also use her hands alot and keep them in a position where the risk of lymphedema is increased (lower than the heart and bent). A teachef also uses her hands, but not all the time and not in the same position and not using a lot of strength. She can also adapt her way of work to decrease the risk (take pauses from using her arms). A bus driver cannot do that.

How would adding axillary irradiation increase exposure the heart to any appreciable extent (even L axilla) in the setting of already irradiating the breast or CW. I can't easily picture that. Nor can I easily picture substantially upping the pneumonitis risk w/ axillary RT.

I mistyped Right, i wanted to type Left, I already made a comment on that before you replied.
Treating the left axilla can increase your heart dose according to the technique you use. You will have to have a more „dorsal“ field edge for your lateral border, meaning your tangent will be steeper, which will increase heart exposure.
Again, as I typed before, it depends on technique. If you block out heart (and PTV) or if you use DIBH the effect will be small.
Regional nodal irradiation leads to higher doses to the lungs and more pneumonitis. MA20 reported on that. MA20 included axillary irradiation in only part of the patients, but as with the heart, the principle is clear. „More“ OAR in the tangents ––> more side effects.
I do tell my patients than treating the lymphatics will expose the lungs to more dose, don‘t you?

Again, whether a teacher, or an iron lady, or a smoker, or if there's situs inversus, I can't see how any of this influences axillary RT or not.

The indication for axillary RT is not solely bound on tumor factors. I do weigh in additional patient-specific factors. It's common practice in radiation oncology to look into other factors too which are not tumor specific when you decide upon treatment.
It's why you would think twice about indication neoadjuvant RT in a 28 year old woman who has a cT3 cN0 rectal cancer and who wants to perhaps have kids. You will look at the MRI hard and try to figure out the CRM, talk with the surgeon if he thinks he can perform primary resection. At the end of the day, you may end up irradiating her tumor anyway, but you will take her age and wish to have kids as non-tumor-specific factors into account.

Good trial. Congrats for participating (I kid, I kid... it's more than I do!). But this trial is totally non-germane to OP's original question re: the adequacy of an axillary dissection: 1) the trial allows any number of axillary nodes to be dissected and doesn't define adequacy, 2) no one AFAIK is doing "tailored" axillary surgery outside of trials, and 3) the study has an estimated completion date in the year 2043(!).

Indeed. As I already pointed out, the trial addresses cN1 patients and does not address the question of axillary treatment in cN0 patients which turned out to be pN1. I wrote that.
Tatgetted axillary dissection is a thing here in Europe. It is being done alot outside of trials too but only for cN1 patients.
The argument is simple: If you know before surgery that the radiation oncology will indicare RNI, why perform a complete axillary dissection and not just take the few enlarged nodes (and affected) nodes out, then go on to RT? It can only be done in cN1 disease and you need quite a workup (preoperative FNP of the nodes, clipping of the nodes, etc...).

At end of day, here's what I internalized from Z0011 and AMAROS: let's quit it with the axillary schwarmerei (EDIT: this too as mentioned). Whether you irradiate the axilla or not, whether you dissect it or not (everyone in AMAROS had to have 10 or more LNs dissected), whether you irradiate it or dissect it, it doesn't move any needles except that 1) intentionally irradiating the axilla significantly increases the incidence of contralateral breast cancer and 2) irradiating axilla w/ 50Gy/25fx instead of dissecting 10 or more LNs gives less lymphedema than dissecting 10 or more LNs. (If you're "boosting" the axilla per OP's question, you will get more lymphedema than not boosting IMHO.) There is no magic number for axillary dissection adequacy. The surgery is pretty standard ("they get what they get"); the pathologist plays an outsize role as you pointed out. We don't have to worry <4 or ≥4 nodes positive anymore (for PMRT e.g.); the axilla is positive, or it's not.

I am sorry, but that is wrong.
Not „everyone“ had to have 10 nodes dissected in AMAROS. The axillary radiotherapy group had only sentinel nodes removed.

Other than that, I am interested in the numbers of nodes removed in order to establish or not the necessity to irradiate the axilla.

There are exceptions to all rules, but it's the rarest of rare cases when I fret about number of axillary LNs obtained at surgery.

Oh, really?

Case 1:
55 year old lady, pT1c (17 mm) pN1 (2/6; 8mm, no ECE) cM0 G2 ER+ PR- Her2neu- OncotypeDx low risk, treated with BCS and SLNB followed by axillary dissection, will receive letrozole
What are you treating?
I have no idea, why they only got 6 nodes out. S**t happens...

Case 2:
55 year old lady, pT1c (17 mm) pN1 (2/18; 8mm, no ECE) cM0 G2 ER+ PR- Her2neu- OncotypeDx low risk, treeated with BCS and SLNB followed by axillary dissection, will receive letrozole
What are you treating?

 

[Palex80]

Thanks man. Now you and I aren't saying it's 100% non-therapeutic. You have a big palpable axillary node, bx-positive, let's get it out. That's therapeutic.
But if you "discover" positive nodes, like at surgery, it takes a lot more than just 10 nodes in total to get comfortable that there aren't more "unharvested" lymph nodes lurking in there making you all uncomfortable and what not. Like in Palex's case....

Allow me to disagree.
Both in cN0 and cN1 patients axillary dissection is diagnostic and therapeutic.
In cN0 you get the information of whether or not the axilla is involved. In cN1 patients you get the information on "how much" it is involved.
In both cases you can utilize this infomation to guide further treatment, both locoregional and systemic.

Resecting further, non-enlarged nodes in cN0 and cN1 patients can be therapeutic too if they are involved. If applying local treatment to microscopic disease was never therapeutic then all the trials on RNI would also have come up negative. Affected but clinically negative nodes in the axilla are as dangerous as affected but clinically negative nodes in the supraclavicular fossa. I do not have the data to show for the same thing in surgery, I grant you that. But saying that surgically treating clinically negative nodes in (breast) cancer is only diagnostic is in my opinion a matter of debate.

When a LN is positive in the axilla, the more you dissect, the more likely you will find more positive nodes. Why stop at 10? Why not get AS MANY AS POSSIBLE.
I say ignoramus et ignorabimus. I'm a grumpy old man lol.

Feel free to set your own threshold. I feel comfortable with 10 in cN0-patients.
Getting as many as possible lymph nodes usually translates in getting as much as possible lymphedema...

 

[scarbrtj]

Yes, people do iron clothes for a living. I presume you do not iron your business shirts yourself, do you?
If you don‘t like that example, think of a bus driver. She will also use her hands alot and keep them in a position where the risk of lymphedema is increased (lower than the heart and bent). A teachef also uses her hands, but not all the time and not in the same position and not using a lot of strength. She can also adapt her way of work to decrease the risk (take pauses from using her arms). A bus driver cannot do that.

The funny thing about arms is, you never know when you're gonna need 'em.
I just make the blanket assumption for all patients: "This lady is gonna need her arms one day even if she doesn't today."
It's like the double stitch in your pants.

Not „everyone“ had to have 10 nodes dissected in AMAROS. The axillary radiotherapy group had only sentinel nodes removed.

You know what I mean wiseguy

Case 1:
55 year old lady, pT1c (17 mm) pN1 (2/6; 8mm, no ECE) cM0 G2 ER+ PR- Her2neu- OncotypeDx low risk, treated with BCS and SLNB followed by axillary dissection, will receive letrozole
What are you treating?
I have no idea, why they only got 6 nodes out. S**t happens...

Case 2:
55 year old lady, pT1c (17 mm) pN1 (2/18; 8mm, no ECE) cM0 G2 ER+ PR- Her2neu- OncotypeDx low risk, treeated with BCS and SLNB followed by axillary dissection, will receive letrozole
What are you treating?

Why did they even get axillary dissections? They should not have: not oncologically helpful, needlessly toxic, etc. You know this!
What am I treating? Tangents and s'clav in both cases.

Both in cN0 and cN1 patients axillary dissection is diagnostic and therapeutic.
In cN0 you get the information of whether or not the axilla is involved. In cN1 patients you get the information on "how much" it is involved.
In both cases you can utilize this infomation to guide further treatment, both locoregional and systemic.

A serum PSA in a prostate CA patient * is not* therapeutic just because it provides info to guide local and systemic treatment.

Resecting further, non-enlarged nodes in cN0 ... patients can be therapeutic too if they are involved.

Now wait a sec. Didn't Z0011 disprove this? Am I wrong?

Affected but clinically negative nodes in the axilla are as dangerous as affected but clinically negative nodes in the supraclavicular fossa.

Do you TRULY believe that.
You're making a bunch of noise about axillary dissections, whilst at the same time the s'clav is NEVER dissected, anywhere, by anyone. "A node by any other name would not be as sweet..." Carrying forth the "axilla needs a good dissection" logic means the s'clav (and IMNs) do too. A reductio ad absurdum.

If applying local treatment to microscopic disease was never therapeutic then all the trials on RNI would also have come up negative.

Some statisticians would argue they are negative.
They were negative for survival advantages (p=0.06 to 0.4).
They were anemically positive for DFS and local controls.
The biggest, most impressive statistical differences from "all the trials on RNI" (2 trials? 3?): doing RNI always adds more toxicity (p<0.001).
And in AMAROS, adding in axillary RT is associated with a higher risk of contralateral breast CA. Can you think why? I'm just a paranoid kinda guy.

Every action has an equal and opposite reaction.

 

[evilbooyaa]

Good trial. Congrats for participating (I kid, I kid... it's more than I do!). But this trial is totally non-germane to OP's original question re: the adequacy of an axillary dissection: 1) the trial allows any number of axillary nodes to be dissected and doesn't define adequacy, 2) no one AFAIK is doing "tailored" axillary surgery outside of trials, and 3) the study has an estimated completion date in the year 2043(!).

In regards to bolded, this is standard practice at my institution for cN1 people that have core needle/FNA confirmation getting neoadjuvant chemotherapy not planned for full ax dissection. You basically do a SLNB as well as removal of the clipped node that was biopsied prior to NAC.

https://ascopubs.org/doi/10.1200/JCO.2015.64.0094

Case 1:
55 year old lady, pT1c (17 mm) pN1 (2/6; 8mm, no ECE) cM0 G2 ER+ PR- Her2neu- OncotypeDx low risk, treated with BCS and SLNB followed by axillary dissection, will receive letrozole
What are you treating?
I have no idea, why they only got 6 nodes out. S**t happens...

Case 2:
55 year old lady, pT1c (17 mm) pN1 (2/18; 8mm, no ECE) cM0 G2 ER+ PR- Her2neu- OncotypeDx low risk, treeated with BCS and SLNB followed by axillary dissection, will receive letrozole
What are you treating?

I know the question is to scarbrtj but....

Case 1: Why did she get an ALND? BCS + SLNB followed by adjuvant RT is fine per Z11 (even if you do high tangents or add a SCV field, which is where a potential argument could be). With the patient as is, I am treating tangents + SCV, with NO purposeful coverage of the dissected axilla. Whatever happens to get in at the tangents is fine, but I'm not contouring dissected axilla.

Case 2: Again, why did she get an ALND? With 2 positive LNs I'm doing the exact same RT fields as Case 1. I think recurrence free survival is a worthwhile end-point. My personal cut-off for 'ignoring' LNs is 10% involvement - meaning 1/10 usually. Whether RT can be omitted to RNI based on low risk OncoType DX is an ongoing study question of the TAILOR-RT trial (also known as MA.39).

This concept of SLNB followed by completion ALND has been shown as unnecessary by Z11, and needs to stop in patients that are cN0.

From z0011:
Subjective lymphedema at 12 months
6% (SLNB+RT) vs. 19% (ALND+RT) (P<0.0001)

 

[scarbrtj]

From z0011:
Subjective lymphedema at 12 months
6% (SLNB+RT) vs. 19% (ALND+RT) (P<0.0001)

Sad stat. All pain & no gain... in 10 years, out of ~450 women who had cancer in their sentinel nodes, and didn't get ALND, and didn't get "intentional" axillary RT... there was one woman with an axillary recurrence.
(Of course the ALND fans will say the ALND patients had zero axillary recurrences.)

 

[Palex80]

A serum PSA in a prostate CA patient * is not* therapeutic just because it provides info to guide local and systemic treatment.

If you are going to answer with arguments like that, please do quote the entire passage I wrote, rather than snipping out a part.
I wrote:

Both in cN0 and cN1 patients axillary dissection is diagnostic and therapeutic.
In cN0 you get the information of whether or not the axilla is involved. In cN1 patients you get the information on "how much" it is involved.
In both cases you can utilize this infomation to guide further treatment, both locoregional and systemic.

Resecting further, non-enlarged nodes in cN0 and cN1 patients can be therapeutic too if they are involved. If applying local treatment to microscopic disease was never therapeutic then all the trials on RNI would also have come up negative. Affected but clinically negative nodes in the axilla are as dangerous as affected but clinically negative nodes in the supraclavicular fossa. I do not have the data to show for the same thing in surgery, I grant you that. But saying that surgically treating clinically negative nodes in (breast) cancer is only diagnostic is in my opinion a matter of debate.

Is that clear now? The first passage addresses the diagnostic, the second the therapeutic value.

Now wait a sec. Didn't Z0011 disprove this? Am I wrong?

Z0011 is one of the most misinterpreted trials.
Noone really knows what radiotherapy was used in Z0011 because surgeons designed and ran the trial without talking with radiation oncologists. No complete documentation of treated fields, no quality review, no guidelines for contouring. When a subset of patients was analyzed, results were appalling.

Radiation field design in the ACOSOG Z0011 (Alliance) Trial - PubMed

Most patients treated in Z0011 received tangential RT alone, and some received no RT at all. Some patients received directed nodal irradiation via a third field. Further research is necessary to determine the optimal RT approach in patients with low-volume axillary disease treated with SLND alone.

www.ncbi.nlm.nih.gov

The trial recruited poorly and was shut down before reaching its recruitment goal, 38% of the patients only had micrometastasis in the nodes.

And in AMAROS, adding in axillary RT is associated with a higher risk of contralateral breast CA. Can you think why? I'm just a paranoid kinda guy.

I have no idea. Perhaps just bad luck?
I cannot imagine how axillary RT can lead to a higher incidence of contralateral breast cancer.
If you look at the data in the paper you may notice that the rate of invasive lobular carcinoma was slightly higher in the RT group and antihormonal treatment was delivered slightly less often in the RT group too. We have no information on the adherence to antihormonal treatment. Perhaps the patients that got the more "extensive" RT thought they wouldn't need to take anti-hormonal treatment for that long?
We have seen that happen in DCIS. Patients who opt for adjuvant RT in DCIS without Tamoxifen end up having a higher rate of contralateral DCIS than ipsilateral DCIS recurrence.

Do you TRULY believe that.
You're making a bunch of noise about axillary dissections, whilst at the same time the s'clav is NEVER dissected, anywhere, by anyone. "A node by any other name would not be as sweet..." Carrying forth the "axilla needs a good dissection" logic means the s'clav (and IMNs) do too. A reductio ad absurdum.

Some statisticians would argue they are negative.
They were negative for survival advantages (p=0.06 to 0.4).
They were anemically positive for DFS and local controls.
The biggest, most impressive statistical differences from "all the trials on RNI" (2 trials? 3?): doing RNI always adds more toxicity (p<0.001).

Let me get back to the two cases I put up:

Case 1:
55 year old lady, pT1c (17 mm) pN1 (2/6; 8mm, no ECE) cM0 G2 ER+ PR- Her2neu- OncotypeDx low risk, treated with BCS and SLNB followed by axillary dissection, will receive letrozole
What are you treating?
I have no idea, why they only got 6 nodes out. S**t happens...

Case 2:
55 year old lady, pT1c (17 mm) pN1 (2/18; 8mm, no ECE) cM0 G2 ER+ PR- Her2neu- OncotypeDx low risk, treeated with BCS and SLNB followed by axillary dissection, will receive letrozole
What are you treating?

Both Scarbtj and Evilbooyaa would treat them the same: Tangents + SCV. Whether or not it's high tangents or not, is not clear to me, but it's not really relevant.

No why would you treat them like that?
Tangents for breast are a no-brainer. Ok.
Why target SCV though?

Let's run the MSKCC & MD Anderson nomogram.

Case 1 (with only 6 resected nodes) has a chance of further axillary nodes of 27% per MSKCC and 10% per MD Anderson.
Case 2 (with 18 resected nodes) has a chance of further axillary nodes of 13% per MSKCC and 0% per MD Anderson. (The risk is probably even lower, since both nomograms allow to enter a lower maximum number of resected nodes)

Now let's presume that the truth is somewhere in between:

Case 1 has a 18% probability for additional nodes, Case 2 has a 7% chance.

So... Let's presume that axillary radiotherapy and antihormonal treatment will both reduce the risk of recurrence by 1/3. Some may even say that they would each halve it. We know they do in the primary, so why should it not happen in the axilla too?
That means that Case 1 is left with 6% and Case 2 with 2% risk for recurrence. Not delivering radiotherapy will lead to a risk of 12% and 4% respectively.

So, the treatment you are both not willing to give for Case 1 leads to a 6% higher chance of recurrence. According to this calculation, but you can very well provide your own.

Yet, you are treating the SCV. Based on what evidence? MA20 and EORTC 22922. Great! Both cases would fit the trial, early breast cancer with limited axillary involvement (albeit EORTC asked for a full ALND).
Both trials treated breast +/- SCV/IM. And what the difference? 5% for MA20 and 3% for EORTC in terms of DFS.
If you take a look at the underpowered subgroup analysis no hint is there showing that this rather favorable patient in terms of biology (luminal A, postmenopausal) will benefit more; she's probably at the lower end in terms of DFS benefit based on those trials. And I am not going to break it down to SCV/IM, let's just say that all the benefit comes from SCV.

What is my point?
I would treat case 1 with RT to the breast, axilla, SCV. Why? Because there is a substantial chance of additional positive nodes in the axilla. And why am I treating the SCV? Because there is quite some chance that this lady may have >3 nodes in the axilla, in which case its quite clear she would benefit from SCV-irradiation.
I would treat case 2 with tangets to the breast only. Why? I think that this patient with a favorable biology has a small risk for occult disease in regional nodes. After ALND with a quite high number of nodes her risk for lymphedema with RNI will be elevated.

I know that's not NCCN-conform.

 

[scarbrtj]

Z0011 is one of the most misinterpreted trials.
Noone really knows what radiotherapy was used in Z0011 because surgeons designed and ran the trial without talking with radiation oncologists. No complete documentation of treated fields, no quality review, no guidelines for contouring. When a subset of patients was analyzed, results were appalling.

You could be the only guy on the planet using words "Z0011" and "appalling" in same sentence. "No complete documentation of treated fields, no quality review, no guidelines for contouring." And 1— one!—out of 500 women with positive nodes in this mishmashed higgledy-piggledy hodgpodge of RT approaches who didn't get a dissection had an axillary recurrence. Lots of undissected positive nodes in this trial... vanishing small number of recurrences. What you call appalling I call comforting. But in all honesty, no more 10+ node ALND for cT1-2N0 patients.

Case 1:
55 year old lady, pT1c (17 mm) pN1 (2/6; 8mm, no ECE) cM0 G2 ER+ PR- Her2neu- OncotypeDx low risk, treated with BCS and SLNB followed by axillary dissection, will receive letrozole
What are you treating?
I have no idea, why they only got 6 nodes out. S**t happens...

Case 2:
55 year old lady, pT1c (17 mm) pN1 (2/18; 8mm, no ECE) cM0 G2 ER+ PR- Her2neu- OncotypeDx low risk, treeated with BCS and SLNB followed by axillary dissection, will receive letrozole

Case 1 has a 18% probability for additional nodes, Case 2 has a 7% chance.

So... Let's presume that axillary radiotherapy and antihormonal treatment will both reduce the risk of recurrence by 1/3. Some may even say that they would each halve it. We know they do in the primary, so why should it not happen in the axilla too?
That means that Case 1 is left with 6% and Case 2 with 2% risk for recurrence.

I know of no modern cases series or randomized trial arm where the axillary recurrence rate was 6% for T1cN0 ER+ patients. Nor even 2%. Nor one where ALND caused the axillary recurrence rate to go down by 4 absolute percentage points as you posit. WHAT IS GOING ON lol. The nomograms have ruined your logic.

 

[evilbooyaa]

This is for @Palex80

Your main problematic assumption is that all unresected lymph nodes turn into axillary recurrences. That's mostly what Z0011 argues against. By treating the dissected axilla in both cases you are further increasing this patient's risk of lymphedema. Coverage of the dissected axilla (as you seem to be pushing for) increases lymphedema risk quite significantly. To use it frequently is IMO, being on the wrong end of the toxicity vs benefit spectrum.

https://www.redjournal.org/article/S0360-3016(18)30597-2/fulltext

All of these patients received RNI. 84% got ALND. Group 1 (not covering level 1 and 2 axilla) had lower rates of lymphedema than Group 2 or 3 (both included coverage of lower axilla, difference was whether it was AP or AP/PA). Rates were 7% for Group 1 vs 37% for Group 2/3.... which is probably a bigger difference than real life, but it's some data. Held up on multivariate analysis as well.

If you feel that 6 LNs is essentially a glorified SLNB and/or if the nodes weren't removed as a packet (but rather piece meal) then go ahead. This is why 10 LN as an 'adequate' ALND was defined for the EBCTCG meta-analysis that proved survival benefit of RNI (albeit in the mastectomy setting), because people criticized Danish 82b and c for 'inadequate' LN dissection. In fairness to you, re-reviewing MA.20 methods, I found this:
"For patients who had fewer than 10 axillary nodes removed or more than 3 positive axillary nodes, the lateral aspect of the field was extended laterally to include the level I and II axillary lymph nodes".

So I suppose if you're saying 6 LNs is less than 10, then you should cover under the humeral head. OK, this is reasonable as that's how MA.20 treated, if you would like.

For case 2, if you don't want to treat SCV, then fine, it's a grey area. You can go based on an unplanned subset analysis that showed no difference or you can go with the main trial results.

If I'm doing a SCV field then I'm not doing high tangents. We do mono-isocentric 3-field technique so it's either high tangents OR a SCV field. I'm not even sure how high tangents and SCV together makes sense (if that's what you were proposing - otherwise never mind).

At the end of the day, I think what you are proposing for either case is not 'wrong' per se, just as I think that my answers are not 'wrong', and it's really just variation in practice. I don't toe the 10 LNs or bust line all that much. I read the OP report - did the surgeon remove the axillary LNs as a packet, or did they randomly pluck some things (like a sampling) and call it a dissection? Usually for something like Case 1, if you ask the pathologist to look closer, they can pull out an additional 4 LNs to get you to your magic number, as you previously mentioned in this thread.

However, I do really try to avoid treating dissected axilla if at all possible based on the study that I linked, and I will usually recommend 3-field any node positive patient based on MA.20, EORTC, and EBCTCG meta-analysis. I believe in preventing recurrence (either local or distant) in early breast cancer as being a valuable endpoint and am not seriously concerned about heart dose given modern management techniques (DIBH and keeping mean heart < 3-4 Gy at my institution). I do counsel patients of a slight increase in lymphedema risk (4.5% w/ WBI alone vs 8.1% WBI + RNI per MA.20).

 

[Palex80]

You could be the only guy on the planet using words "Z0011" and "appalling" in same sentence. "No complete documentation of treated fields, no quality review, no guidelines for contouring." And 1— one!—out of 500 women with positive nodes in this mishmashed higgledy-piggledy hodgpodge of RT approaches who didn't get a dissection had an axillary recurrence. Lots of undissected positive nodes in this trial... vanishing small number of recurrences. What you call appalling I call comforting. But in all honesty, no more 10+ node ALND for cT1-2N0 patients.

I have heard alot of people describing the trial as bad. Appalling is strong wording, but I am not talking about the trial results as such. I am talking about the ignorance and inadequacy of the study team to include standardized RT in the trial. Appalling is what the analysis of the RT pointed at. Half of the patients getting high tangents, 20% getting comprehensive regional RT.

I know of no modern cases series or randomized trial arm where the axillary recurrence rate was 6% for T1cN0 ER+ patients. Nor even 2%. Nor one where ALND caused the axillary recurrence rate to go down by 4 absolute percentage points as you posit. WHAT IS GOING ON lol. The nomograms have ruined your logic.

Not all T1 cN0 ER+ breast cancers are the same.
The recurrence rate in Z0011 was 1.5% after SLNB and more than half of the patients did receive some sort of regional irradiation (high tangents +/- axillary fields) and it was 1.2% in AMAROS with full axillary RT.
But this is just the average recurrence risk. Subgroups of patients, like the 38% patients with pN1mi in Z0011 certainly have a lower risk for recurrence. Others however probably have a higher one, like the ones with >1 nodes with macrometastasis.
It's a mix. You shouldn't be looking at absolute risk reductions but rather at relative ones.

 

[Palex80]

This is for @Palex80

Your main problematic assumption is that all unresected lymph nodes turn into axillary recurrences. That's mostly what Z0011 argues against. By treating the dissected axilla in both cases you are further increasing this patient's risk of lymphedema. Coverage of the dissected axilla (as you seem to be pushing for) increases lymphedema risk quite significantly. To use it frequently is IMO, being on the wrong end of the toxicity vs benefit spectrum.

I generally only treat the axilla when there was substantial involvement with a high ratio of involved/total number of resected nodes and unfavorable biology or when the resection was inadequate and the nomograms point at a high chance of further nodes in the axilla. I do not have a clear cutoff there in terms of percentage, but I consider rates >15% for further nodes as candidates for axillary treatment.

This is actually in accordance to the S3 German Guideline:

https://www.leitlinienprogramm-onkologie.de/fileadmin/user_upload/Downloads/Leitlinien/Mammakarzinom_4_0/Version_4.1/LL_Mammakarzinom_Langversion_4.1.pdf

This is something like the NCCN guideline, albeit with a lot more text.
For those who are interested (you can probably use google translator for it) statements on axillary RT are on Page 156
Basically it says that radiation therapy can be considered for patients with 1-2 positive sentinel nodes who have not received ALND and the decision should be made in the interdisciplinary tumor board. Patients with more than 2 sentinel nodes without ALND should receive RT.

 

[Palex80]

Sad stat. All pain & no gain... in 10 years, out of ~450 women who had cancer in their sentinel nodes, and didn't get ALND, and didn't get "intentional" axillary RT... there was one woman with an axillary recurrence.
(Of course the ALND fans will say the ALND patients had zero axillary recurrences.)

I am sorry, but you are quoting it wrong.

It was 1 patient who developed a recurrence in the years 5 to 10 after treatment.

Effect of Axillary Dissection vs No Axillary Dissection on 10-Year Overall Survival Among Women With Invasive Breast Cancer and Sentinel Node Metastasis: The ACOSOG Z0011 (Alliance) Randomized Clinical Trial - PubMed

clinicaltrials.gov Identifier: NCT00003855.

www.ncbi.nlm.nih.gov

The rate is not 1/450 as you make it sound.

The cumulative rate is 1.5% with SLND and 0.5% with ALND at 10 years.

Locoregional Recurrence After Sentinel Lymph Node Dissection With or Without Axillary Dissection in Patients With Sentinel Lymph Node Metastases: Long-term Follow-up From the American College of Surgeons Oncology Group (Alliance) ACOSOG Z0011 Randomi

Despite the potential for residual axillary disease after SLND, SLND without ALND offers excellent regional control for selected patients with early metastatic breast cancer treated with breast-conserving therapy and adjuvant systemic therapy.

www.ncbi.nlm.nih.gov

 

[scarbrtj]

I am sorry, but you are quoting it wrong.

It was 1 patient who developed a recurrence in the years 5 to 10 after treatment.

Effect of Axillary Dissection vs No Axillary Dissection on 10-Year Overall Survival Among Women With Invasive Breast Cancer and Sentinel Node Metastasis: The ACOSOG Z0011 (Alliance) Randomized Clinical Trial - PubMed

clinicaltrials.gov Identifier: NCT00003855.

www.ncbi.nlm.nih.gov

The rate is not 1/450 as you make it sound.

The cumulative rate is 1.5% with SLND and 0.5% with ALND at 10 years.

Locoregional Recurrence After Sentinel Lymph Node Dissection With or Without Axillary Dissection in Patients With Sentinel Lymph Node Metastases: Long-term Follow-up From the American College of Surgeons Oncology Group (Alliance) ACOSOG Z0011 Randomi

Despite the potential for residual axillary disease after SLND, SLND without ALND offers excellent regional control for selected patients with early metastatic breast cancer treated with breast-conserving therapy and adjuvant systemic therapy.

www.ncbi.nlm.nih.gov

Yes I had that wrong, 1 nodal recurrence in the SNB group at 5+ years. "Cumulative incidence of regional recurrences at 10 years in the ipsilateral axilla were similar between each arm with 2 (0.5%) in the ALND group compared with 5 (1.5%) patients in the SLND alone group."

I was mixing my metaphors. I knew there was a very low rate of isolated axillary recurrence in the SNB group; I read that blurb re: "1 recurrence" to make sure and thought there was 1 recurrence. Forced error. In this follow-on MSKCC study there were zero isolated axillary recurrences in the SNB+/ALND- group, which I guess is ~0/700.

Zero. Not the end all be all but still makes one think.