PACIFIC-2 is negative

[BobbyHeenan]

I’ve seen a couple very complex GI patients seen there and not get a multi-d evaluation
Whoever saw them first treated and didn’t even get opinions from colleagues . And these were true multi d cases .

My patient saw GI med onc and surg onc. Not a rad onc.

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[BobbyHeenan]

I hadn't really thought about the above - it is interesting that some how both OPRA and PROSPECT came out of the same institution. Two *very* different paradigms, enrolling potentially the same patient cohorts...

From discussion (though this is like 3rd hand info) from one of our surg oncs to one of their surg oncs....they have recently been taking the approach of anything mid or upper (ie no ostomy) then "majority" get XRT omission. Anything lower gets OPRA.

Again, that may be hearsay, but that was relayed to me.

 

[drowsy12]

im sure it depends on bulk and nodal burden too probably?

a high T3N0 tumor - I am totally fine with prospect.

 

[BobbyHeenan]

im sure it depends on bulk and nodal burden too probably?

a high T3N0 tumor - I am totally fine with prospect.

Yes, we've been comfortable with that for years even before prospect (especially the MRI T2's that were upstaged to T3 at surgery).

I'm sure there's nuance to it, but there are a lot of T2/T3N1 cases out there at our mutli-discp rectal conference and we're getting in some bigger dicussions than we ever did pre prospect. Seeing more radiation omission push. There are a lot of cases that come through our conference that meet prospect trial enrollment criteria.

We're also seeing discussion of the rare T2N0 that gets upstaged to T2N1 at surgery....so med onc/surg onc saying "extrapolate prospect" and omit radiation. I push back but doesn't always work.

I'm hoping we get some sub-group breakdown in future publications...though sub-group analysis wrought with all kinds of caveats....if a strong signal for recurrence with mid vs. high or N1 vs. N0 may help us tease it out.

 

[BobbyHeenan]

Yes, we've been comfortable with that for years even before prospect (especially the MRI T2's that were upstaged to T3 at surgery).

I'm sure there's nuance to it, but there are a lot of T2/T3N1 cases out there at our mutli-discp rectal conference and we're getting in some bigger dicussions than we ever did pre prospect. Seeing more radiation omission push. There are a lot of cases that come through our conference that meet prospect trial enrollment criteria.

We're also seeing discussion of the rare T2N0 that gets upstaged to T2N1 at surgery....so med onc/surg onc saying "extrapolate prospect" and omit radiation. I push back but doesn't always work.

I'm hoping we get some sub-group breakdown in future publications...though sub-group analysis wrought with all kinds of caveats....if a strong signal for recurrence with mid vs. high or N1 vs. N0 may help us tease it out.

Today at rectal conference...

mid cT2N0M0 upstaged at surgery to pT2N1M0. Rec from surg onc and med onc was radiation omission. This is within NCCN as "consider." They feel stronger about this after PROSPECT.

mid to upper cT3N0M0. Rec from surg onc and med onc was prospect treatment.

===

These rec's are completely reasonable...but they do impact absolute numbers of patients that need radiation.

 

[OTN]

Today at rectal conference...

mid cT2N0M0 upstaged at surgery to pT2N1M0. Rec from surg onc and med onc was radiation omission. This is within NCCN as "consider." They feel stronger about this after PROSPECT.

mid to upper cT3N0M0. Rec from surg onc and med onc was prospect treatment.

===

These rec's are completely reasonable...but they do impact absolute numbers of patients that need radiation.

Mid/high T3N0 reasonable to omit RT.

Node positive? Not reasonable.

 

[Palex80]

Today at rectal conference...

mid cT2N0M0 upstaged at surgery to pT2N1M0. Rec from surg onc and med onc was radiation omission. This is within NCCN as "consider." They feel stronger about this after PROSPECT.

mid to upper cT3N0M0. Rec from surg onc and med onc was prospect treatment.

===

These rec's are completely reasonable...but they do impact absolute numbers of patients that need radiation.

Good calls!

a) The patient with the incidental pN1 obviously needs adjuvant oxaliplatin-based chemotherapy. If the resection margins are clear, additional RCT on top of FOLFOX/CAPOX will add very little, but additional toxicity.

b) I also had a similar case last week in the tumor board. A 44 year old with an early cT3cN0 rectal cancer, 6 cm from anal verge and a clear CRM. The med onc looked at me and asked if I would be ok with omitting radiotherapy and I replied to her "Sure, this is the ideal candidate, that's why the trials were run." He is getting neodjuvant chemo, followed by resection.

 

[Doctorer]

Mid/high T3N0 reasonable to omit RT.

Node positive? Not reasonable.

The risk of LR with a T2, single node positive rectal cancer is under 10%. Omitting CRT in that setting isn't crazy.

 

[BobbyHeenan]

Good calls!

a) The patient with the incidental pN1 obviously needs adjuvant oxaliplatin-based chemotherapy. If the resection margins are clear, additional RCT on top of FOLFOX/CAPOX will add very little, but additional toxicity.

b) I also had a similar case last week in the tumor board. A 44 year old with an early cT3cN0 rectal cancer, 6 cm from anal verge and a clear CRM. The med onc looked at me and asked if I would be ok with omitting radiotherapy and I replied to her "Sure, this is the ideal candidate, that's why the trials were run." He is getting neodjuvant chemo, followed by resection.

The risk of LR with a T2, single node positive rectal cancer is under 10%. Omitting CRT in that setting isn't crazy.

1/22 nodes, 3mm of disease, no ECE on that T2N1 case.....so I have a hard time being dogmatic about giving post op XRT.

 

[RadRadRad]

My patient saw GI med onc and surg onc. Not a rad onc.

Mine saw radonc but not surg onc or Medonc
😂

 

[ramsesthenice]

Today at rectal conference...

mid cT2N0M0 upstaged at surgery to pT2N1M0. Rec from surg onc and med onc was radiation omission. This is within NCCN as "consider." They feel stronger about this after PROSPECT.

mid to upper cT3N0M0. Rec from surg onc and med onc was prospect treatment.

===

These rec's are completely reasonable...but they do impact absolute numbers of patients that need radiation.

Mid tumor with N+ disease could potentially go either way. Personally, I don't like doing post-op RT so I am ok with prospect here. We don't see these (as in maybe 1 a year) because of our surgeons. Unless the path and imaging look super rosy, they worry about upstaging and still offer chemoradiation to try to avoid an LAR in many cases.

The second case at my institution would depend on what surgery thought about surgery. Our surgeons are very aggressive about omitting surgery for complete responders with one exception: high tumors. Their (theoretical) concern is that they don't know if a recurrence would behave more like a rectal tumor (with localized recurrence) or a sigmoid tumor (less predictable pattern of nodal spread). If they feel like they are not someone they would consider watch and wait regardless of response, we might consider PROSPECT. You said mid to upper, so I bet w/w would be an option and we would go the TNT route.

Caveat: academic centers like mine are inherently a little more protected from PROSPECT because, NCCN appropriately says only consider PROSPECT if they do not have a threatened MRF. Being a referral center, we have a disproportionate number of these.

Everywhere (at least places with reasonable medical oncologists who actually do multi-D care): surgeons willingness not to operate is going to be key. About half of rectal patients probably don't need trimodality therapy and if they still think every early-ish mid/lower rectal tumor needs to come out regardless of response, your volume is going to get hurt.

 

[Palex80]

About half of rectal patients probably don't need trimodality therapy and if they still think every early-ish mid/lower rectal tumor needs to come out regardless of response, your volume is going to get hurt.

In my opinion, only 20-30% of all patients with rectal cancer need trimodality treatment.
And when I say trimodality, I mean:
a) several cycles of oxaliplatin/capecitabine
b) short course radiotherapy or long course radiochemotherapy plus
c) surgery

Only the really ugly one tumors (cT4/cN2/CRM involved) actually likely need this aggressive approach.
The rest can likely be safely treated with bimodality:
1) chemo --> surgery
2) short course radio / long course radiochemo --> surgery
3) TNT without surgery

The matter we are debating here is 1) vs. 2).

 

[ramsesthenice]

In my opinion, only 20-30% of all patients with rectal cancer need trimodality treatment.
And when I say trimodality, I mean:
a) several cycles of oxaliplatin/capecitabine
b) short course radiotherapy or long course radiochemotherapy plus
c) surgery

Only the really ugly one tumors (cT4/cN2/CRM involved) actually likely need this aggressive approach.
The rest can likely be safely treated with bimodality:
1) chemo --> surgery
2) short course radio / long course radiochemo --> surgery
3) TNT without surgery

The matter we are debating here is 1) vs. 2).

I think that only 20-30% "need" trimodality at diagnosis of course there is the caveat...only half of TNT patients are complete responders (depending on how your assess) so a higher proportion will ultimately end up getting it. I've heard PROSPECT zealots argue that PROSPECT should be preferable because most patients treated with PROSPECT will ultimately be able to avoid radiation. Which, if appropriately selected, is true. But it ignores the fact that surgery (even LAR) is the single greatest cause of long-term GI dysfunction. Many patients are highly, highly motivated to avoid surgery and happy to accept a higher chance of getting all 3 rather than resigning themselves to surgery from the beginning. Assuming they even know their options which many simply don't

 

[BobbyHeenan]

Mid tumor with N+ disease could potentially go either way. Personally, I don't like doing post-op RT so I am ok with prospect here. We don't see these (as in maybe 1 a year) because of our surgeons. Unless the path and imaging look super rosy, they worry about upstaging and still offer chemoradiation to try to avoid an LAR in many cases.

The second case at my institution would depend on what surgery thought about surgery. Our surgeons are very aggressive about omitting surgery for complete responders with one exception: high tumors. Their (theoretical) concern is that they don't know if a recurrence would behave more like a rectal tumor (with localized recurrence) or a sigmoid tumor (less predictable pattern of nodal spread). If they feel like they are not someone they would consider watch and wait regardless of response, we might consider PROSPECT. You said mid to upper, so I bet w/w would be an option and we would go the TNT route.

Caveat: academic centers like mine are inherently a little more protected from PROSPECT because, NCCN appropriately says only consider PROSPECT if they do not have a threatened MRF. Being a referral center, we have a disproportionate number of these.

Everywhere (at least places with reasonable medical oncologists who actually do multi-D care): surgeons willingness not to operate is going to be key. About half of rectal patients probably don't need trimodality therapy and if they still think every early-ish mid/lower rectal tumor needs to come out regardless of response, your volume is going to get hurt.

Thank you for the thoughtful comments.

Yes, our surgeons had been pretty progressive on TNT/watch and wait/surgical omission. Some of that enthusiasm died down after prospect.

One of the rectal surgeons on the T3N0 case said TNT/watch and wait...the other one (the one seeing the patient) rec'd Prospect.

It is very much surgeon driven in my experience.

I do think if you frame it to the patient that - if you do chemo and radiation there is a 50% chance you may not need surgery. But if you do need surgery then in retrospect maybe you never needed radiation to begin with. Some patients will roll the dice and go with TNT.

 

[Palex80]

But it ignores the fact that surgery (even LAR) is the single greatest cause of long-term GI dysfunction.

Well, there is caveat here as well...

If I had a mid, very early cT3 cN0 tumor, I could potentially get away with simply 5 x 5 Gy (confined to the mesorectum) + surgery or even (God forbid!) upfront surgery and possible adjuvant chemotherapy, depending on the final histology.
That is still surgey, but I would avoid any chemotherapy and large volume radiotherapy.

I understand the pro-TNT arguments, but multiple cycles of oxaliplatin can also bear some lasting toxicity (polyneuropathy) and getting my whole pelvis treated to 50 Gy is also not an atoxic treatment.

I do understand that surgery is the most GI-toxic treatment in the long term, but a full course radiochemotherapy + FOLFOX/CAPOX are also treatment. Add to that the issue of me having an only 50% chance of avoiding surgery at the end.

So, with an early cT3 cN0, I can twist the agument in both ways:
a) 50% avoid surgery with TNT, because they respond
b) 50% are potentially overtreated with TNT followed by surgery, because they don't respond. They may have been cured with upfront surgery.

 

[ramsesthenice]

Well, there is caveat here as well...

If I had a mid, very early cT3 cN0 tumor, I could potentially get away with simply 5 x 5 Gy (confined to the mesorectum) + surgery or even (God forbid!) upfront surgery and possible adjuvant chemotherapy, depending on the final histology.
That is still surgey, but I would avoid any chemotherapy and large volume radiotherapy.

I understand the pro-TNT arguments, but multiple cycles of oxaliplatin can also bear some lasting toxicity (polyneuropathy) and getting my whole pelvis treated to 50 Gy is also not an atoxic treatment.

I do understand that surgery is the most GI-toxic treatment in the long term, but a full course radiochemotherapy + FOLFOX/CAPOX are also treatment. Add to that the issue of me having an only 50% chance of avoiding surgery at the end.

So, with an early cT3 cN0, I can twist the agument in both ways:
a) 50% avoid surgery with TNT, because they respond
b) 50% are potentially overtreated with TNT followed by surgery, because they don't respond. They may have been cured with upfront surgery.

I agree with you whole heartedly but in my neck of the woods, data be damned, pretty much everyone is getting chemo. Your RT surgery option should be a good one in theory. But when the mindset is chemo for all, doing it all preop makes more sense.

 

[ramsesthenice]

I agree with you whole heartedly but in my neck of the woods, data be damned, pretty much everyone is getting chemo. Your RT surgery option should be a good one in theory. But when the mindset is chemo for all, doing it all preop makes more sense.

I shouldn't say nobody. Our med oncs are generally reasonable and there are times we don't do chemo but usually its for people with comorbidities which push us outside the box. Like, someone getting a TAMIS for what looks like a T1 tumor that has high risk features but surgeon doesn't think they are fit enough for an LAR or APR. Will recommend RT alone. But closely evaluating the adjuvant chemo trials, you can easily argue that many prospect eligible patients don't benefit from adding chemo after RT/CRT and surgery (as PALEX suggested).

 

[thesauce]

My patient saw GI med onc and surg onc. Not a rad onc.

Let me guess what their recommendation was…

 

[radiation]

Selective Personalized RadioImmunotherapy for Locally Advanced Non-Small-Cell Lung Cancer Trial (SPRINT) - PubMed

Pembrolizumab and risk-adapted radiotherapy, without chemotherapy, are a promising treatment approach for patients with LA-NSCLC with a PD-L1 TPS of ≥50%.

pubmed.ncbi.nlm.nih.gov

surprised this hasnt been discussed more - pretty good results for unresectable pts. Specifically gives radiation pathway for med oncs that want to give immuno upfront for high TPS pts