Thoughts from a PGY-5

[RickyScott]

We are talking about lung screening effect (and scarb’s Nonsense) not the smoking use decline, which will decrease a number of cancer diagnoses hopefullly.

Scarb only Real assumption is that 90%+ of lung cas detected on screening do not get Sbrt. This is my experience as well.

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[PhotonBomb]

Right. we all agree that most don't get SBRT. But if screening leads to 100 more stage I lung cancers getting diagnosed, maybe ten percent of this population will be deemed medically inoperable, and that is 10 more patients getting radiation.

 

[RadOncMegatron]

Thanks @scarbrtj for dropping knowledge including in other thread RE other specialities use of RT (unfortunately you're right sigh)

@Mandelin Rain I don't think what you are saying is controversial

Lung cancer screening is either likely good overall or possibly modest to no benefit to society (see Twitter thread by Vinay Prasad, David Palma)

Also agree with you that screening will likely decrease the number of RT cases due to stage migration + since vast majority of screen detected lung cancer undergoes Sx.

For patients this is no issue, but for determining number of radoncs needed in USA, it does make a difference.

Not sure where I stand yet, but definitely something to think about. Here is the thread quoted above that I do recommend reading:

 

[RadOncG]

Right. we all agree that most don't get SBRT. But if screening leads to 100 more stage I lung cancers getting diagnosed, maybe ten percent of this population will be deemed medically inoperable, and that is 10 more patients getting radiation.

Aren't you assuming they would have never been diagnosed were it not for screening?

I am not convinced that screening is finding this hidden swath of lung cancers that would never manifest. That is ironically what happened with breast and prostate cancer screening.

 

[RadOncG]

Not sure where I stand yet, but definitely something to think about. Here is the thread quoted above that I do recommend reading:

I think Vinay Prasad is absolutely correct. Overall mortality is exactly the same in either group.

Lung cancer specific mortality is not an endpoint that matters. The harms of false positives and over treatment are significant. So significant in fact that they wash out these tiny disease specific survival benefits when looking at overall mortality.

If my life expectancy is 13.5 years whether I get screening or not why would I subject myself to this testing?

 

[PhotonBomb]

I think Vinay Prasad is absolutely correct. Overall mortality is exactly the same in either group.

Lung cancer specific mortality is not an endpoint that matters. The harms of false positives and over treatment are significant. So significant in fact that they wash out these tiny disease specific survival benefits when looking at overall mortality.

If my life expectancy is 13.5 years whether I get screening or not why would I subject myself to this testing?

I agree that the fact that overall mortality or even OVERALL CANCER-specific mortality is not improved gives reason to pause about the utility of screening.

HOWEVER, there is no evidence that over-treatment or false positive cause a significant enough harm that wash out the lung cancer Disease-specific benefit. This statement is not supported by the data at all.

I think what the data overall says is that diagnosing and curing lung cancers in this high-risk population does not improve their chance of living longer or improve their chance of dying from a non-cancer cause because this population still has a high enough competing risk of dying of stuff like heart failure, diabetes etc or another tobacco-associated cancer.

 

[Palex80]

HOWEVER, there is no evidence that over-treatment or false positive cause a significant enough harm that wash out the lung cancer Disease-specific benefit. This statement is not supported by the data at all.

I'm not sure about that. What about costs? Are we willing to pay any price for screening as long as there is tiny bit of overall survival benefit?

Ok, let me propose a 6-monthly whole body MRI starting at year 40 fpr EVERYBODY. It will probably produce a significant overall survival benefit.

Costs you say? Who cares?

 

[RadOncG]

HOWEVER, there is no evidence that over-treatment or false positive cause a significant enough harm that wash out the lung cancer Disease-specific benefit. This statement is not supported by the data at all.

I agree. This is one theory by Vinay Prasad as to the discrepancy. It seems to make sense to me as a possible theory. When the benefit is so incredibly small for disease specific survival (less than one percent) the small risks from needle biopsies, VATS, etc start to matter. If surgical mortality for diagnostic purposes is on the order of a few tenths of a percent then it could impact a disease specific survival advantage that is on the order of less than one percent.

I think what the data overall says is that diagnosing and curing lung cancers in this high-risk population does not improve their chance of living longer or improve their chance of dying from a non-cancer cause because this population still has a high enough competing risk of dying of stuff like heart failure, diabetes etc or another tobacco-associated cancer.

Also agree with this statement. In totality cancer screening data has been a huge disappointment when is comes to helping people live longer lives with better quality of lives (the only endpoints that matter).

 

[scarbrtj]

Right. we all agree that most don't get SBRT. But if screening leads to 100 more stage I lung cancers getting diagnosed, maybe ten percent of this population will be deemed medically inoperable, and that is 10 more patients getting radiation.

EDIT TL;DR It may add 10 in the new 100; but it might subtract 100 from the "pre-existing cache" of 1000
OK, now you're showing your IQ. If you screen heavily, you're going on the assumption that the medically inoperable/operable ratio will stay steady within the Stage I group. So this is not what the data is showing, I say again, paradoxically. (Paradoxes even trip up the highest IQs.)
And I'm not saying things will be this way. Just that they could.
The utilization rate of SBRT in Stage I NSCLC is around 25%, nationally (highest number I've thus far seen quoted).
However we have data that within a screening program, the utilization rate of SBRT for Stage I lung CA is ~14%.
Now I woulda thunk, prior to seeing the data, that screening will increase SBRT prevalence by finding more Stage I. It will (maybe, keep in mind smoking decrease) find more Stage I, but it may "find them for the surgeons" to a greater degree/proportion than what we see now. It all makes one think, regardless one's IQ, that screening migrates more Stage I lung patients away from SBRT.

Dropping knowledge with papyrus font.

Or is it? What font is that?

Oregon LDO DemiBold

 

[RickyScott]

EDIT TL;DR It may add 10 in the new 100; but it might subtract 100 from the "pre-existing cache" of 1000
OK, now you're showing your IQ. If you screen heavily, you're going on the assumption that the medically inoperable/operable ratio will stay steady within the Stage I group. So this is not what the data is showing, I say again, paradoxically. (Paradoxes even trip up the highest IQs.)
And I'm not saying things will be this way. Just that they could.
The utilization rate of SBRT in Stage I NSCLC is around 25%, nationally (highest number I've thus far seen quoted).
However we have data that within a screening program, the utilization rate of SBRT for Stage I lung CA is ~14%.
Now I woulda thunk, prior to seeing the data, that screening will increase SBRT prevalence by finding more Stage I. It will (maybe, keep in mind smoking decrease) find more Stage I, but it may "find them for the surgeons" to a greater degree/proportion than what we see now. It all makes one think, regardless one's IQ, that screening migrates more Stage I lung patients away from SBRT.

Oregon LDO DemiBold

What you are essentially saying:
if pt were not screened, more likely to present at more advanced age/progressed copd when they are more likely to be medically inoperable. These guys get plenty of x rays cts for copd flairs so persistent nodule will show up sooner or later.

 

[scarbrtj]

What you are essentially saying:
if pt were not screened, more likely to present at more advanced age/progressed copd when they are more likely to be medically inoperable. These guys get plenty of x rays cts for copd flairs so persistent nodule will show up sooner or later.

Yes. But I'm not making any "assumptions" about the why's (although you mention good why's). I'm just quoting data that shows screening puts all patients at higher risk of surgery/no-RT even within each stage group, Stage I included. Yes, it will migrate more patients into Stage I, and will find more Stage I in general probably. But this higher risk of surgery because of screening may offset the amount of raw numbers of new Stage I cancers found such that screening might (if it ever happens "widespreadly") cause rad oncs to do less SBRT for Stage I than they do now. Thus countering the "the more lung cancers diagnosed, the more that need [radiation] treatment" thesis.

 

[PhotonBomb]

I'm not sure about that. What about costs? Are we willing to pay any price for screening as long as there is tiny bit of overall survival benefit?

Ok, let me propose a 6-monthly whole body MRI starting at year 40 fpr EVERYBODY. It will probably produce a significant overall survival benefit.

Costs you say? Who cares?

That doesn’t have anything to do with what I said

 

[RadRadRad]

I don’t think any screening studies are powered for overall survival advantage. Mammograms, psa (if you believe Europe data), and lung ct are all cancer specific mortality benefits not overall survival.

 

[PhotonBomb]

I don’t think any screening studies are powered for overall survival advantage. Mammograms, psa (if you believe Europe data), and lung ct are all cancer specific mortality benefits not overall survival.

Lung CT screening did NOT improve cancer specific mortality overall. It did improve lung cancer mortality.

 

[RadRadRad]

To be clear
Mammograms reduce breast cancer specific mortality
Psa reduces prostate cancer specific mortality (euro data)
Lung ct reduces lung cancer specific mortality

this thread seems to imply that lack of overall survival advantage is a weakness of lung screening ct

Are we now against all screening?

 

[RickyScott]

1 billlion cells in 1 cm3. At that point it’s going to do what it’s going to do.

 

[RadRadRad]

Fisher vs halstead vs Hellman

 

[scarbrtj]

1 billlion cells in 1 cm3. At that point it’s going to do what it’s going to do.

IMHO lung CT not way to screen for lung CA in future.
Let's leave it to the dogs.

 

[elementaryschooleconomics]

IMHO lung CT not way to screen for lung CA in future.
Let's leave it to the dogs.

Dogs can learn to detect cancer? Learning algorithm is a black box?

Dogs = deep learning confirmed.

 

[RadOncG]

To be clear
Mammograms reduce breast cancer specific mortality
Psa reduces prostate cancer specific mortality (euro data)
Lung ct reduces lung cancer specific mortality

this thread seems to imply that lack of overall survival advantage is a weakness of lung screening ct

Are we now against all screening?

I'm against all screening that does not improve overall mortality or quality of life. I personally will not get cancer screening for a cause specific mortality benefit alone given the risks of overdiagnosis/overtreatment.

Vinay Prasad has had a big impact on many on this forum. His ability to critically evaluate these trials is second to none IMO.

 

[RadOncG]

I don’t think any screening studies are powered for overall survival advantage. Mammograms, psa (if you believe Europe data), and lung ct are all cancer specific mortality benefits not overall survival.

Does it say something about the screening test being employed that trials with tens of thousands of patients aren't enough to power for overall mortality?

 

[RadRadRad]

Does it say something about the screening test being employed that trials with tens of thousands of patients aren't enough to power for overall mortality?

A Medonc against early detection of cancer....stage 4 does allow for more drug therapy

 

[Lamount]

IMHO lung CT not way to screen for lung CA in future.
Let's leave it to the dogs.

One day, our toilets will tell use when we have Kras mutant circulating DNA... until then, we are stuck with LDCT

 

[RadRadRad]

I'm against all screening that does not improve overall mortality or quality of life. I personally will not get cancer screening for a cause specific mortality benefit alone given the risks of overdiagnosis/overtreatment.

Vinay Prasad has had a big impact on many on this forum. His ability to critically evaluate these trials is second to none IMO.

Are you advocating against screening for all cancers at your institution? Are you in the radiology department asking them to shut down their screening mammography program?

 

[RadOncDoc21]

Leaving all data aside, I know SBRT hasn’t been shown to be as good as a lobectomy....yet but from strictly a marketing perspective. If we have a modality that can “cure” with significantly less toxicity, local control rate around 90%, why are we still holding out against offering SBRT as a frontline option?

Again, I know there are ongoing trials comparing the two treatments with at least two closed studies (due to poor accrual) because why? Thoracic surgeons do not want to enroll patients.

Correct me if I’m wrong Palex but I think in Europe, SBRT is being offered as front line treatment with surgery as a salvage option.

Just saying, we lack the balls to just do what other specialties have been doing.

 

[Palex80]

Correct me if I’m wrong Palex but I think in Europe, SBRT is being offered as front line treatment with surgery as a salvage option.

It all depends on what institution you work at and how "strong" your thoracic surgeons are.
The thoracic surgeons at my institution are quite ambitious (but they are also good at what they do too).

So, like some here, we only get a handful or referrals for SBRT of NSCLC Stage I per year.

The patients of 2019, which I can recall:
a) 92 year old gentleman with a walker and some dementia
b) 73 year old lady with a terminal COPD
c) 68 year old lady with only one lung (7 yers post pneumonectomy for a stage II NSCLC on the contralateral side)

I believe we treat less than 10 patients with SBRT for stage I NSCLC per year. The rest of our lung SBRTs are for oligometastatic disease and seldom a local recurrence post surgery/CRT for higher stage disease.

Unless we can produce high-level evidence that SBRT offers comparable results to lobectomy with less morbidity / costs and better QoL, we are never going to establish it as standard of care.

The "operable patient" definition has also shifted in thoracic surgery over the years, SBRT is not the sole new component of the last two decades in treating early lung cancer. Despite the negative randomized trial of the 90s comparing sub-lobar resection with lobectomy, thoracic surgeons have produced good trial results, showing that:
a) VATS-lobectomy is equivalent in terms of oncologic outcome to open lobectomy (--> shorter hospitalization time, less morbidity, possibly better QoL)
b) segmentectomy in selected patients is equivalent in terms of oncologic outcome to lobectomy (--> which in turn opens the window for surgery to patients, who were not eligible for lobectomy before due to having an inadequate predicted post-operative lung function). [This is still not considered s.o.c., but may change soon].

The main argument which I hear every week at the tumor board and which I cannot rule out is the fact that a surgical procedure has one distinct benefit over SBRT: resection / staging of lymph nodes. Althouth the isolated lymph node recurrence rate post SBRT is low (in the range of 5% at most), the surgeons can point out at numerous studies showing that despite comprehensive pre-operative staging of nodes (including PET-CT, EBUS/mediastinoscopy) there may still be quite a few patients with tumor cells in their nodes, which will go undetected if not resected. The big question is whether or those those small lymph node metastases (often micrometastases or simply isolated cells) play a prognostic role if they are resected during surgery. Will every resected lymph node containing a micrometastasis result in a failure-event being prevented? Probably not.
However, identifying those cells will allow you to guide adjuvant therapy. Now, adjuvant therapy for NSCLC is not that "big" in terms of overall survival benefit and certainly not "easy" therapy with 3 cycles of cisplatin-based chemotherapy, so that perhaps it's not that import to know if the 82 year old Mr. Parker has N1-disease, since he wont be getting any cisplatin/navelbine anyway, however:
a) perhaps resecting that N1-node, even when not giving adjuvant chemotherapy, allowed Mr. Parker to live longer / prevented a recurrence or metastasis
b) perhaps in 5 years from now patients with resected N1-disease will be getting immunotherapy as adjuvant treatment (and pembrolizumab monotherapy for 1 year is probably easier to get through than 3x cisplatin/navelbine in a 82 year old).

It's a bit like melanoma, I guess. Most of us think (and it has been shown in trials too), that resecting occult nodal disease does not add any benefit in terms of survival. But we still need to do it in order to guide adjuvant treatment options.

 

[OTN]

It all depends on what institution you work at and how "strong" your thoracic surgeons are.
The thoracic surgeons at my institution are quite ambitious (but they are also good at what they do too).

So, like some here, we only get a handful or referrals for SBRT of NSCLC Stage I per year.

The patients of 2019, which I can recall:
a) 92 year old gentleman with a walker and some dementia
b) 73 year old lady with a terminal COPD
c) 68 year old lady with only one lung (7 yers post pneumonectomy for a stage II NSCLC on the contralateral side)

I believe we treat less than 10 patients with SBRT for stage I NSCLC per year. The rest of our lung SBRTs are for oligometastatic disease and seldom a local recurrence post surgery/CRT for higher stage disease.

Unless we can produce high-level evidence that SBRT offers comparable results to lobectomy with less morbidity / costs and better QoL, we are never going to establish it as standard of care.

The "operable patient" definition has also shifted in thoracic surgery over the years, SBRT is not the sole new component of the last two decades in treating early lung cancer. Despite the negative randomized trial of the 90s comparing sub-lobar resection with lobectomy, thoracic surgeons have produced good trial results, showing that:
a) VATS-lobectomy is equivalent in terms of oncologic outcome to open lobectomy (--> shorter hospitalization time, less morbidity, possibly better QoL)
b) segmentectomy in selected patients is equivalent in terms of oncologic outcome to lobectomy (--> which in turn opens the window for surgery to patients, who were not eligible for lobectomy before due to having an inadequate predicted post-operative lung function). [This is still not considered s.o.c., but may change soon].

The main argument which I hear every week at the tumor board and which I cannot rule out is the fact that a surgical procedure has one distinct benefit over SBRT: resection / staging of lymph nodes. Althouth the isolated lymph node recurrence rate post SBRT is low (in the range of 5% at most), the surgeons can point out at numerous studies showing that despite comprehensive pre-operative staging of nodes (including PET-CT, EBUS/mediastinoscopy) there may still be quite a few patients with tumor cells in their nodes, which will go undetected if not resected. The big question is whether or those those small lymph node metastases (often micrometastases or simply isolated cells) play a prognostic role if they are resected during surgery. Will every resected lymph node containing a micrometastasis result in a failure-event being prevented? Probably not.
However, identifying those cells will allow you to guide adjuvant therapy. Now, adjuvant therapy for NSCLC is not that "big" in terms of overall survival benefit and certainly not "easy" therapy with 3 cycles of cisplatin-based chemotherapy, so that perhaps it's not that import to know if the 82 year old Mr. Parker has N1-disease, since he wont be getting any cisplatin/navelbine anyway, however:
a) perhaps resecting that N1-node, even when not giving adjuvant chemotherapy, allowed Mr. Parker to live longer / prevented a recurrence or metastasis
b) perhaps in 5 years from now patients with resected N1-disease will be getting immunotherapy as adjuvant treatment (and pembrolizumab monotherapy for 1 year is probably easier to get through than 3x cisplatin/navelbine in a 82 year old).

It's a bit like melanoma, I guess. Most of us think (and it has been shown in trials too), that resecting occult nodal disease does not add any benefit in terms of survival. But we still need to do it in order to guide adjuvant treatment options.

We are opening a trial soon for SBRT + pembro for stage I NSCLC. Should be interesting.

 

[scarbrtj]

Leaving all data aside, I know SBRT hasn’t been shown to be as good as a lobectomy....yet but from strictly a marketing perspective. If we have a modality that can “cure” with significantly less toxicity, local control rate around 90%, why are we still holding out against offering SBRT as a frontline option?

Again, I know there are ongoing trials comparing the two treatments with at least two closed studies (due to poor accrual) because why? Thoracic surgeons do not want to enroll patients.

Correct me if I’m wrong Palex but I think in Europe, SBRT is being offered as front line treatment with surgery as a salvage option.

Just saying, we lack the balls to just do what other specialties have been doing.

The only way to make SBRT supplant or co-equalize with surgery is have a (robust, non-piddling) trial that is citable as being evidence of equivalence or superiority to surgery. There are about 1000 new Stage I lung CA per year, per state, in the US, so in theory you'd think that wouldn't be hard to do. However now thanks to a few retrospective analyses, and the poorly conceived MISSILE, anti-RT naysayers (aka surgeons) can call into question equipoise. Thus cojones not the problem as much as data. Surgeons cite a ~40% locoregional failure rate with SBRT.

 

[RadOncDoc21]

The only way to make SBRT supplant or co-equalize with surgery is have a (robust, non-piddling) trial that is citable as being evidence of equivalence or superiority to surgery. There are about 1000 new Stage I lung CA per year, per state, in the US, so in theory you'd think that wouldn't be hard to do. However now thanks to a few retrospective analyses, and the poorly conceived MISSILE, anti-RT naysayers (aka surgeons) can call into question equipoise. Thus cojones not the problem as much as data. Surgeons cite a ~40% locoregional failure rate with SBRT.

I said no data! I’m talking about first dibs on patients, aka urologist doing prostatectomies, ablations, thoracic surgeons doing upfront wedges, no regards to standard of care, tumor board, etc. Think sleezy Florida rad onc on a billboard advertising “surgery without the scar” on tv every news cycle.

I think we are too data driven. Yes, we know all the studies, indications and workup but if we are not seeing patients what’s the point?

 

[PhotonBomb]

I said no data! I’m talking about first dibs on patients, aka urologist doing prostatectomies, ablations, thoracic surgeons doing upfront wedges, no regards to standard of care, tumor board, etc. Think sleezy Florida rad onc on a billboard advertising “surgery without the scar” on tv every news cycle.

I think we are too data driven. Yes, we know all the studies, indications and workup but if we are not seeing patients what’s the point?

If you want to be sleazy and ignore data or what’s right for the patient - do that. You can.

 

[RadOncG]

A Medonc against early detection of cancer....stage 4 does allow for more drug therapy

You haven't reviewed his work or the conclusions of large meta-analysis on cancer screening. Look over his twitter and listen to some of his podcasts then we can discuss it more. You will learn he is not a friend of big pharma either.

If we were converting stage 4 to stage 1 we would see a mortality benefit.

 

[RadOncG]

Are you advocating against screening for all cancers at your institution? Are you in the radiology department asking them to shut down their screening mammography program?

No. I am not as brave as Vinay Prasad. I have only agreed with him anonymously on here.

Our specialty would be toast without cancer screening. That still does not mean it is an evidence based practice. This is not my opinion by the way. Please review the Cochrane meta-analysis on PSA and mammography.

 

[RadOncDoc21]

If you want to be sleazy and ignore data or what’s right for the patient - do that. You can.

Were you bullied or something as a kid?

 

[PhotonBomb]

Were you bullied or something as a kid?

Lol just pointing out what you’re advocating for. My point is you can do that in your Sphere if you think you can pull It off , but that’s never going to be whole-sale endorsed.

 

[PhotonBomb]

You haven't reviewed his work or the conclusions of large meta-analysis on cancer screening. Look over his twitter and listen to some of his podcasts then we can discuss it more. You will learn he is not a friend of big pharma either.

If we were converting stage 4 to stage 1 we would see a mortality benefit.

Mostly agree with you that Vinay Prasad has an important voice on these issues.

I do think that screening is converting enough stage 4 patients to curable patients - this is why there is a Lung Cancer mortality improvement. This is clear to me.

The stickler is that these patients are STILL dying of CANCER overall at the same rates, let alone dying of any cause at the same rate. So what are we doing for them?

 

[RickyScott]

Fisher vs halstead vs Hellman

Been a long time, but my impression was that at least when it comes to breast cancer- and probably a general trend for cancers in general- 80% -90% of time fisher, 10% of time halstead/Hellman, which is why screening has such a limited benefit unless you are catching precancers like cervix or colon.

 

[Palex80]

We are opening a trial soon for SBRT + pembro for stage I NSCLC. Should be interesting.

Great news!

AstraZeneca is running a trial like that too with Durvalumab.

ClinicalTrials.gov

clinicaltrials.gov

 

[medgator]

I said no data! I’m talking about first dibs on patients, aka urologist doing prostatectomies, ablations, thoracic surgeons doing upfront wedges, no regards to standard of care, tumor board, etc. Think sleezy Florida rad onc on a billboard advertising “surgery without the scar” on tv every news cycle.

I think we are too data driven. Yes, we know all the studies, indications and workup but if we are not seeing patients what’s the point?

Exactly. Although lung is easier to address. Often pcps and Pulmonary are the gatekeepers to Thoracic and rad onc. Many of my sbrt referrals come straight from Pulmonary

No such luck in prostate.

 

[RadOncG]

I do think that screening is converting enough stage 4 patients to curable patients - this is why there is a Lung Cancer mortality improvement. This is clear to me.

It isn't as clear to me. Mortality data for NLST was reported when non-lung cancer deaths were higher in the control arm. When you removed non-lung cancer deaths the 0.46% mortality benefit of CT vs. CXR disappeared.

To be convinced there is a mortality benefit I think you would have to say lung cancer screening decreases non-lung cancer deaths. Updated mortality data has never been published even though lung cancer specific data has been updated.

 

[RadOncG]

Great news!

AstraZeneca is running a trial like that too with Durvalumab.

ClinicalTrials.gov

clinicaltrials.gov

I can get surgery and be done or I can get radiation plus 24 months of IV injections?

Hope it works out. From a patient perspective it seems we are making an easy treatment as inconvenient and extended as possible.

 

[PhotonBomb]

It isn't as clear to me. Mortality data for NLST was reported when non-lung cancer deaths were higher in the control arm. When you removed non-lung cancer deaths the 0.46% mortality benefit of CT vs. CXR disappeared.

To be convinced there is a mortality benefit I think you would have to say lung cancer screening decreases non-lung cancer deaths. Updated mortality data has never been published even though lung cancer specific data has been updated.

Look at the NELSON trial. Lung cancer specific morality reduced with Screening. Cancer morality was unchanged, overall morality was unchanged.

 

[PhotonBomb]

I can get surgery and be done or I can get radiation plus 24 months of IV injections?

Hope it works out. From a patient perspective it seems we are making an easy treatment as inconvenient and extended as possible.

The point of the adjuvant IO is to reduce the chance of distant failure in high risk patients, which is driving their overall morality risk.

 

[RadOncG]

Look at the NELSON trial. Lung cancer specific morality reduced with Screening. Cancer morality was unchanged, overall morality was unchanged.

Sorry I reread and realized you were talking about lung cancer specific mortality. Some screening trials do pass this threshold. I think the crux of the question is does this endpoint matter.

A reasonable patient may say "Doctor, you are telling me I live 13.5 years with screening and 13.5 years without screening. Why would I get screened?"

How would you answer?

 

[RadOncG]

The point of the adjuvant IO is to reduce the chance of distant failure in high risk patients, which is driving their overall morality risk.

I understand that. Just commenting that 24 months seems long. For stage III it is 12 months right? Are these stage I/II patients at higher risk of distant failure?

 

[PhotonBomb]

A reasonable patient may say "Doctor, you are telling me I live 13.5 years with screening and 13.5 years without screening. Why would I get screened?"

How would you answer?

That’s my point!

 

[PhotonBomb]

I understand that. Just commenting that 24 months seems long. For stage III it is 12 months right? Are these stage I/II patients at higher risk of distant failure?

Yeah I agree two years too long. Pharma is gonna Pharma

 

[Palex80]

I can get surgery and be done or I can get radiation plus 24 months of IV injections?

Hope it works out. From a patient perspective it seems we are making an easy treatment as inconvenient and extended as possible.

Well, the "hope" from the radiation oncologist view is that:
a) Surgery + Immuntherapy = Surgery [trials are runing looking this combination]
, but;
b) SBRT + Immunotherapy > SBRT
and
c) SBRT + Immunotherapy > Surgery.

So, let's just keep our fingers crossed...


It is important to state that while immunotherapy has improved OS for numerous diseases, it's has only shown an OS benefit after curative-intent treatment in only two scenarios so far:
a) adjuvant immuntherapy after resection of high-risk melanoma
b) adjuvant immunotherapy after RCT for Stage III NSCLC (PACIFIC)

No other trial has shown a survival benefit in the adjuvant setting so far. Perhaps it's too early to tell, perhaps there is no effect noted (yet).
We do not really know.

But there are numerous cancers where we know that immunotherapy works well in the metastatic setting and where it is being tested in the adjuvant setting (MSI-high CRC, renal cancer, bladder cancer, head&neck cancer). And although immunotherapy does not work like targetted therapy, it is important to bear in mind that the promising and often used targetted agents (TKIs) have not shown a survival benefit in the adjuvant setting with the exception of Glivec for GIST. Ten years ago many people would have probably told you that in 2020 all high-risk renal cancer patients post surgery would be getting Sutent for a year or two as adjuvant treatment. Didn't happen.

 

[deleted774703]

The point of the adjuvant IO is to reduce the chance of distant failure in high risk patients, which is driving their overall morality risk.

Yes but 2 years doesn’t make sense when the pacific trial did not include durva up to two years

 

[w00tz]

Yes but 2 years doesn’t make sense when the pacific trial did not include durva up to two years

Yea, but if positive trial, then $$$$$$$$ x 2

 

[PhotonBomb]

Yes but 2 years doesn’t make sense when the pacific trial did not include durva up to two years

Obviously