Clinical case management - IIIA NSCLC

[deleted1002574]

This is something that I've realized is extremely regional and doesn't seem to follow anything except what the group has decided they'd like to do. At residency we treated one way, first job treated another way, and now another way.

Example case: 64 year old man with 35 pack year history presents with cough and slight worsening of SOB. CXR shows right hilar mass, CT shows 3.5cm suprahilar mass and enlarged (1.8cm) right paratracheal LN. EBUS/bx performed for dx and both the suprahilar mass and the right paratracheal LN come back as adenocarcinoma. PET-CT confirms these findings. No distant disease. MRI negative for brain mets. PFTs are good and would be operable candidate.

In residency, this patient would get chemotherapy, then surgery, then consideration of radiation depending on response/findings, but usually would get PORT.

In first job, surgeons preferred we take them to full dose if operable and minimal nodal disease (1 or 2 nodes, nothing greater 2cm), 60ish Gy with carbo/taxol and then they'd operate.

New job, definitive CRT to 60-66 Gy.

My preference is option 2, based on Vyfhuis data. I think the "negative" study is because 45 Gy is a homeopathic (not that there's anything wrong with that) dose. And you shouldn't take out people's whole lungs. Not cool.

Option 1 or 3, not unreasonable. Option 3, especially after RTOG 0617 where 60 Gy + chemo gets you median survival of 29 months (way higher than RTOG9410!). Option 1 makes some oncologic sense to get full dose chemo in.

What do you guys do and why?

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[xrthopeful]

in academics- this would be trimodality all the way. (whether pre-op chemoRT per Albain or pre-op chemo or pre-op chemo/IO on trial depends on where you are)

in community - this is almost always PACIFIC

 

[FrostyHammer]

Surgery is so BS for IIIA NSCLC. Especially after Pacific (which was nonop). By operating, you're basically actively withholding a level 1 evidence therapy proven to increase OS.

 

[medgator]

Our surgeons generally don't operate on IIIA disease

66 Gy + carbo/taxol (or cis/vp-16 if fit) for everyone. Wish 0617 looked at doses people actually used a lot in practice like 63-66, the 60 vs 74 debate doesn't jive with my GI tract/instincts. I am tight with heart mean doses and routinely use of IMRT these days given the 0617 secondary data in JCO.

Everyone gets durva for a year, preferably 2-4 weeks post chemo/xrt. Given the evolving durva data, not sure why anyone should go to surgery these days

 

[yeasterbunny]

I've never done the Albain way, neither in residency nor in practice. Our old thoracic surgeon was more hands-off and nearly all IIIA patients would get definitive CXRT, but for the last few years our new guy prefers upfront chemo -> surgery -> PORT depending on path

 

[deleted1002574]

Surgery is so BS for IIIA NSCLC. Especially after Pacific (which was nonop). By operating, you're basically actively withholding a level 1 evidence therapy proven to increase OS.

Pacific trial specifically excluded patients that are resectable. You're not comparing apples to apples. I'm talking about potentially resectable cases.

 

[BobbyHeenan]

Our surgeons generally don't operate on IIIA disease

66 Gy + carbo/taxol (or cis/vp-16 if fit) for everyone. Wish 0617 looked at doses people actually used a lot in practice like 63-66, the 60 vs 74 debate doesn't jive with my GI tract/instincts. I am tight with heart mean doses and routinely use of IMRT these days given the 0617 secondary data in JCO.

Everyone gets durva for a year, preferably 2-4 weeks post chemo/xrt. Given the evolving durva data, not sure why anyone should go to surgery these days

This is exactly what I do at a large multi disciplinary cancer center, non academic.

Our CT surgeons rarely will consider surgery in a single station N2 case but this is not common.

 

[medgator]

This is exactly what I do at a large multi disciplinary cancer center, non academic.

Our CT surgeons rarely will consider surgery in a single station N2 case but this is not common.

What do people do when the surgeon takes out n2 disease after chemo and rt??? Seems like a CF. PORT seems more tough too for pts post chemo and surgery in my limited experience

 

[deleted1002574]

Even high volume community centers are doing trimodality with full dose RT. Good results, talking 55 month median survivals. Many long term cures. Shouldn't be calling "different" treatment strategies BS ... it's "a" standard of care. That's why the discussion is happening Having been to several places, academic, private, and academic-ish, have to learn to understand that there are valid differences of opinion.

 

[BobbyHeenan]

Even high volume community centers are doing trimodality with full dose RT. Good results, talking 55 month median survivals. Many long term cures. Shouldn't be calling "different" treatment strategies BS ... it's "a" standard of care. That's why the discussion is happening Having been to several places, academic, private, and academic-ish, have to learn to understand that there are valid differences of opinion.

Really hard to compare across trials, but my *bias* is to think that the surgery is not worth the loss of immunotherapy. Had a recent N2 patient s/p surgery where med onc wanted to extrapolate and consider durvalumab after their post op XRT but couldn't get it approved.

So hard to know what is better - PACIFIC versus some flavor or chemo-->surg--> PORT.

 

[medgator]

Theoretically, what is the surgeon exactly accomplishing removing disease that will require adjuvant rt afterwards.

Couldn't you argue the urologists have a point to "debulk" high volume, high risk PCa and then fu with port? Only thing lacking there is the data of course....

 

[deleted1002574]

Really hard to compare across trials, but my *bias* is to think that the surgery is not worth the loss of immunotherapy. Had a recent N2 patient s/p surgery where med onc wanted to extrapolate and consider durvalumab after their post op XRT but couldn't get it approved.

So hard to know what is better - PACIFIC versus some flavor or chemo-->surg--> PORT.

I knooooowwwwwwwwww.... but that trial was UNRESECTABLE. By definition, if these patients are able to be operated on, they are not eligible for trials that only allow UNRESECTABLE patients.

 

[medgator]

I knooooowwwwwwwwww.... but that trial was UNRESECTABLE. By definition, if these patients are able to be operated on, they are not eligible for trials that only allow UNRESECTABLE patients.

Eye of the beholder. How was it defined? Surgeon's decision I imagine

 

[deleted1002574]

Theoretically, what is the surgeon exactly accomplishing removing disease that will require adjuvant rt afterwards.

Couldn't you argue the urologists have a point to "debulk" high volume, high risk PCa and then fu with port? Only thing lacking there is the data of course....

I cannot argue that. Prostate cancer can be treated with nothing and survival can exceed 90%. Lung cancer can be treated optimally and survival is 10% at 5 years. We are talking about two different diseases.

 

[medgator]

I cannot argue that. Prostate cancer can be treated with nothing and survival can exceed 90%. Lung cancer can be treated optimally and survival is 10% at 5 years. We are talking about two different diseases.

I'm talking high risk PCa. The rationale to take out disease knowing you will need to radiate, urologists tell me they do the same for high risk disease because they think the outcome might be better by "debulking" the pt first

 

[deleted1002574]

Eye of the beholder. How was it defined? Surgeon's decision I imagine

There are definitions. I.e. - NCCN says if single station and smaller than 3cm, can be considered for surgery.

 

[BobbyHeenan]

I knooooowwwwwwwwww.... but that trial was UNRESECTABLE. By definition, if these patients are able to be operated on, they are not eligible for trials that only allow UNRESECTABLE patients.

Unresectable to one CT surgeon is very different to another. I don't know the definitions of unresectable per Pacific trial (?central review versus site review?, ?some PFT standards? or up to discretion of institution surgeon?) I completely get what you're saying though.

No one knows for sure what the best management is for these patients, it's why we're all here talking about it. It's not like I put up a big fight (or get a second opinion) when the CT surgeon at thoracic tumor board is telling me he doesn't want to operate on the 2 cm squamous cell with an EBUS + level 7 node as only site of N2 disease. We've got one CT surgeon who would reluctantly consider surgery, and another that will say ("it's stage III, I don't operate on that"), and another that doesn't care and wants to operate on everything. All surgeons though prefer to not operate if full 60-66 Gy is given - in the instance of pre-op XRT they specifically prefer 45-50.4 Gy

 

[FrostyHammer]

Pacific trial specifically excluded patients that are resectable. You're not comparing apples to apples. I'm talking about potentially resectable cases.

View attachment 285676

Great point but this is a semantics issue. Unresectable does not mean that you consider resection first, then if not resectable you take the Pacific route. All unresectable cases can't be treated surgically, but the same isn't true for potentially resectable cases. In other words, a potentially resectable case can be treated with surgical based options, or unresectable options like Pacific. The NEJM papers should really have changed their terminology to "unresected" and not "unresectable". "Unresectable" is largely a surgical opinion. One surgeon who's aggressive will call very few IIIA cases "unresectable" versus many surgeons mentioned above who don't want to operate for IIIA NSCLC will still call the patient "unresectable" despite technically being able to operate if they wanted to.

 

[FrostyHammer]

Really hard to compare across trials, but my *bias* is to think that the surgery is not worth the loss of immunotherapy. Had a recent N2 patient s/p surgery where med onc wanted to extrapolate and consider durvalumab after their post op XRT but couldn't get it approved.

So hard to know what is better - PACIFIC versus some flavor or chemo-->surg--> PORT.

Totally agree with you, but consider that at least the Pacific method has level 1 evidence, unlike the chemo/surg/PORT route.

I feel very strongly about this, but the only pts who could benefit from surgery are those with a low distant met risk + larger local burden. Meaning large T tumors, little N involvement. The futility of surgery (and withholding immunotherapy) is directly related to the DM risk. More nodal involvement means more DM risk. The benefit of surgery is directly related to local disease burden, since CRT may not adequately control a humongous primary tumor as well as whacking it out. Thus, I would not consider surgery in any case unless the primary is on the larger end ("larger" open to debate) AND there's at most 1 smaller N2 node ("smaller" also open to debate).

 

[deleted1002574]

Great point but this is a semantics issue. Unresectable does not mean that you consider resection first, then if not resectable you take the Pacific route. All unresectable cases can't be treated surgically, but the same isn't true for potentially resectable cases. In other words, a potentially resectable case can be treated with surgical based options, or unresectable options like Pacific. The NEJM papers should really have changed their terminology to "unresected" and not "unresectable". "Unresectable" is largely a surgical opinion. One surgeon who's aggressive will call very few IIIA cases "unresectable" versus many surgeons mentioned above who don't want to operate for IIIA NSCLC will still call the patient "unresectable" despite technically being able to operate if they wanted to.

But they didn't call it unresected. They called it unresectable. I don't think that's semantic. Whoever was screening the patients made a decision on eligibility and one of the criteria was resectability.

Where did you get that definition? I'm just asking. NCCN has a definition for IIIA. UpToDate has a very similar definition for IIIA. I'm fairly sure that the IIIA patients on PACIFIC were not resectable, meaning they didn't fall into one of those categories.

 

[medgator]

Totally agree with you, but consider that at least the Pacific method has level 1 evidence, unlike the chemo/surg/PORT route.

I feel very strongly about this, but the only pts who could benefit from surgery are those with a low distant met risk + larger local burden. Meaning large T tumors, little N involvement. The futility of surgery (and withholding immunotherapy) is directly related to the DM risk. More nodal involvement means more DM risk. The benefit of surgery is directly related to local disease burden, since CRT may not adequately control a humongous primary tumor as well as whacking it out. Thus, I would not consider surgery in any case unless the primary is on the larger end ("larger" open to debate) AND there's at most 1 smaller N2 node ("smaller" also open to debate).

Yup. Data regarding LC with xrt and tumor size is known from SBRT data. Same principles for chemo rt imo

 

[medgator]

But they didn't call it unresected. They called it unresectable. I don't think that's semantic. Whoever was screening the patients made a decision on eligibility and one of the criteria was resectability.

It's not as objective. Unlike an say a T4 glottic with full thickness thyroid cartilage invasion

 

[deleted1002574]

But they didn't call it unresected. They called it unresectable. I don't think that's semantic. Whoever was screening the patients made a decision on eligibility and one of the criteria was resectability.

It's not as objective. Unlike an say a T4 glottic with full thickness thyroid cartilage invasion

It is as objective. Single station N2 node, <3cm, not T4 (typically). I'm not sure how to make this any more clear. It's listed in NCCN and UpToDate.

 

[FrostyHammer]

But they didn't call it unresected. They called it unresectable. I don't think that's semantic. Whoever was screening the patients made a decision on eligibility and one of the criteria was resectability.

I reread the massive protocol to answer your question. Feel free to corroborate. There was NO central review of operability / defining someone "unresectable". There are tons of recs of defining unresectable, but at the end of the day it's the surgeon call. Because there was no central review, what likely happened was that each center's surgeons called it whatever way they wanted per their preference and practice, and they all came in to screening portion of the trial having been labeled as "unresectable". Ergo, the results apply to a population that's "unresected" which is how nearly everyone uses the Pacific data anyway.

 

[deleted1002574]

I reread the massive protocol to answer your question. Feel free to corroborate. There was NO central review of operability / defining someone "unresectable". There are tons of recs of defining unresectable, but at the end of the day it's the surgeon call. Because there was no central review, what likely happened was that each center's surgeons called it whatever way they wanted per their preference and practice, and they all came in to screening portion of the trial having been labeled as "unresectable". Ergo, the results apply to a population that's "unresected" which is how nearly everyone uses the Pacific data anyway.

I'm telling you not "everybody" does. There is regional variation in practice. The certainty is inspiring, though! Glad you feel so strongly ... more I see, the less I feel I know.

 

[medgator]

It is as objective. Single station N2 node, <3cm, not T4 (typically). I'm not sure how to make this any more clear. It's listed in NCCN and UpToDate.

Not how it was defined in Pacific, unless you're reading something I'm not in the protocol PDF available from nejm.

As frosty stated, this is very subjective and up to the surgeon.

 

[xrthopeful]

we all know that many aggressive academic surgeons operate on multi-station N2.

this is a pointless argument.

 

[BobbyHeenan]

...also, as noted above, the Vyfhuis data looks great, but it's a retrospective review of patients. So many caveats there.

We've now proven that chemo/XRT/IO is better than chemo/XRT. So at least we have data that one form of treatment is better than another. Of course the surgery question wasn't asked, but there's a randomized benefit of superiority that met pre specified criteria.

Unless I'm unaware of the data, I'm not aware of that level of evidence existing for surgery in stage III lung cancer. We very well might get there with pre-op chemo with immuonotherapy followed by surgery with selective post op XRT....but let's run the trials to figure it out.

 

[medgator]

...also, as noted above, the Vyfhuis data looks great, but it's a retrospective review of patients. So many caveats there.

We've now proven that chemo/XRT/IO is better than chemo/XRT. So at least we have data that one form of treatment is better than another. Of course the surgery question wasn't asked, but there's a randomized benefit of superiority that met pre specified criteria.

Unless I'm unaware of the data, I'm not aware of that level of evidence existing for surgery in stage III lung cancer. We very well might get there with pre-op chemo with immuonotherapy followed by surgery with selective post op XRT....but let's run the trials to figure it out.

Albain/rtog, which was negative

 

[FrostyHammer]

Albain/rtog, which was negative

In fact there are like 7 randomized trials. None have shown benefits to surgery, and Albain I think was the only one to show a post-hoc benefit. Espatue is another well known trial that didn't show differences.

 

[deleted1002574]

Okay okay let's not bring ESPATUE in there, they did BID 45 Gy/30 fx and there was induction before the concurrent...

Yes, 9309 negative, and yes it was post-hoc analysis. But, I"m not the NCCN, and they list it as an option AND I'm talking about full dose, not wimpy 45 Gy.

As I said, our current practice is to do CRT definitive (as you all do), but for my own self, I'd like 60/C/T + take it out. They wouldn't list 2B recommendations if they weren't a possible standard of care. CONSENSUS REACHED. Now, let's all share some paella, because it's communal and festive.

 

[medgator]

Okay okay let's not bring ESPATUE in there, they did BID 45 Gy/30 fx and there was induction before the concurrent...

Yes, 9309 negative, and yes it was post-hoc analysis. But, I"m not the NCCN, and they list it as an option AND I'm talking about full dose, not wimpy 45 Gy.

As I said, our current practice is to do CRT definitive (as you all do), but for my own self, I'd like 60/C/T + take it out. They wouldn't list 2B recommendations if they weren't a possible standard of care.

Do you offer upfront prostatectomy to G9 pca with ece/svi noted on mpMRI? It's a standard of care, as recognized by the nccn...

 

[deleted1002574]

I cannot operate, kind sir. I don't find it optimal, but I don't think it's 100% wrong, especially if noted by the NCCN. There are some places with people smarter than me that think surgery is better (I don't). I don't think people are dumb for not doing exactly what I do.

 

[FrostyHammer]

Okay okay let's not bring ESPATUE in there, they did BID 45 Gy/30 fx and there was induction before the concurrent...

Yes, 9309 negative, and yes it was post-hoc analysis. But, I"m not the NCCN, and they list it as an option AND I'm talking about full dose, not wimpy 45 Gy.

As I said, our current practice is to do CRT definitive (as you all do), but for my own self, I'd like 60/C/T + take it out. They wouldn't list 2B recommendations if they weren't a possible standard of care. CONSENSUS REACHED. Now, let's all share some paella, because it's communal and festive.

NCCN is great but remember that it hedges a LOT. NCCN also can't substitute for knowing the actual data. NCCN tell you what you CAN do but not what you SHOULD do. I'll pick the proven benefit of durva over surgery any day of the week.

 

[mavrik13]

The most interesting aspect of this is seeing how different practice is for something like this. Our surgeons wouldn't operate upfront or ask for neoadjuvant CRT. Post-PACIFIC, they are operating even less (even if techincally operable, they believe immuno > surgery. I'd tend to agree (anecdotally)

 

[Mandelin Rain]

The met rate is so high in stage III nsclc, maximizing systemic therapy makes good sense to me

 

[FrostyHammer]

The met rate is so high in stage III nsclc, maximizing systemic therapy makes good sense to me

Tell that to some surgeons. These people are so anti logic and sadistic sometimes... They'll throw data out the window to satisfy their urges to cut and keep the RVUs flowing. Especially academic surgeons, who are canonically "supposed" to know the data better than community practitioners #smh

 

[medgator]

Tell that to some surgeons. These people are so anti logic and sadistic sometimes... They'll throw data out the window to satisfy their urges to cut and keep the RVUs flowing. Especially academic surgeons, who are canonically "supposed" to know the data better than community practitioners #smh

Same crap with h&n. Apparently a radical TORS is de-escalation of therapy for p16+ pts, esp when they end up needing adjuvant therapy anyways

 

[Mandelin Rain]

I sent someone with a t1n1 hpv+ tonsil for TORS. Surgeon thought the margin was threatened so sent him back for xrt.

regretted every moment on sending him for surgery. Probably won’t do it again. Even without chemo, he did awful.

 

[FrostyHammer]

Same crap with h&n. Apparently a radical TORS is de-escalation of therapy for p16+ pts, esp when they end up needing adjuvant therapy anyways

Amen. Who says you need randomized data to do anything?? Not the ENTs...

 

[xrthopeful]

Honestly the chemo/IO induction data looks fantastic

The role for RT in potentially resectable stage III May be going away

 

[Mandelin Rain]

Honestly the chemo/IO induction data looks fantastic

The role for RT in potentially resectable stage III May be going away

As noted above, resectable stage 3 is almost an oxymoron in the community.

but obviously yet ANOTHER theeatened indication for xrt.

 

[FrostyHammer]

As noted above, resectable stage 3 is almost an oxymoron in the community.

but obviously yet ANOTHER theeatened indication for xrt.

Also on the surgeons. There's multiple randomized trials, albeit without OS advantages, but that's not why RT is added to the neoadj setting. Surgeons often whine and moan that their surgical fields become harder to operate on if RT is given prior. Always thinking about themselves. Cry me a river.

 

[medgator]

Also on the surgeons. There's multiple randomized trials, albeit without OS advantages, but that's not why RT is added to the neoadj setting. Surgeons often whine and moan that their surgical fields become harder to operate on if RT is given prior. Always thinking about themselves. Cry me a river.

Plus how do you deal with it if the pt is still N2+ after neoadjuvant chemo/rt? Yeah no thanks, didn't want to give it to begin with

 

[deleted1002574]

Plus how do you deal with it if the pt is still N2+ after neoadjuvant chemo/rt? Yeah no thanks, didn't want to give it to begin with

I don’t know why people keep saying that. If you believe that surgery works (as some people do), then that removes residual disease. Yes, no prospective data. But, yes, it’s a possible way of treating.

One thing that sucks, students, about this field is not many people don’t understand regional variances in treating and if people don’t agree with their way, then they are BS or dumb or whatever. Get used to a lot of righteousness!! Actually, don’t. Stay away, because you won’t have a job.

 

[medgator]

I don’t know why people keep saying that. If you believe that surgery works (as some people do), then that removes residual disease. Yes, no prospective data. But, yes, it’s a possible way of treating.

So residual, viable pN2 post XRT is oncologically addressed with the mediastinal lymphadenectomy?

Seriously, if you follow the pts long term and the paradigm works, more to power to you. Not trying to be righteous, it just doesn't make sense to me. At least when nodes are positive post chemo with ece in breast cancer, I feel like I'm doing something by offering post op XRT. My point was regarding XRT upfront.

Actually, don’t. Stay away, because you won’t have a job.

Unfortunately, some in academics won't believe that until there is 5-10 years of prospective data..

 

[BobbyHeenan]

Honestly the chemo/IO induction data looks fantastic

The role for RT in potentially resectable stage III May be going away

I agree with these. Compelling data .

Enough that I think we need to see chemo/IO then surgery then selective xrt (?maybe ECE on node, multiple nodes +) versus chemoRT+IO in a phase 3.

 

[RickyScott]

Haven’t read the thread, but if surgery precludes io, than it real is disservice to pts as 80% fail distantly even in low volume disease.

 

[deleted1002574]

Yes, it’s retrospective. Yes, it’s somewhat out of the box. But, it’s done a lot in the northeast... 355 patients, 60 month median survival. It’s nothing to sneeze at. And if durvu works after 60 Gy without surgery, why not with?

We need a study.. just saying it’s an option !!

So residual, viable pN2 post XRT is oncologically addressed with the mediastinal lymphadenectomy?

Seriously, if you follow the pts long term and the paradigm works, more to power to you. Not trying to be righteous, it just doesn't make sense to me. At least when nodes are positive post chemo with ece in breast cancer, I feel like I'm doing something by offering post op XRT. My point was regarding XRT upfront.



Unfortunately, some in academics won't believe that until there is 5-10 years of prospective data..

 

[FrostyHammer]

Plus how do you deal with it if the pt is still N2+ after neoadjuvant chemo/rt? Yeah no thanks, didn't want to give it to begin with

If it's still N2 after neo CRT, then that's just bad biology. Especially with the level of evidence for PORT, it would nearly certainly be useless for those cases too. If it's that bad biology, the met risk is certainly very high and they should get durva. But alas, they operated and can't do that anymore. Better solution? Don't wait to find out about biology, don't operate, and give durva.