Radiation & surgery do not prolong survival in de novo MBC

I was eagerly waiting for a surgery date when I saw this yesterday. I am like the participants in the study except my primary tumour is not palpable or visible on scans after systemic treatment. I am now almost certainly going to cancel my surgery! My doctors had said there was no evidence that surgery prolonged survival, but I took that to mean that evidence was lacking. That, combined with anecdotes on my support groups, led me to prefer surgery. However, I now believe the evidence is in that it DOESN'T improve survival (on average, but this is exactly how our drugs are approved).

I have examined the study thoroughly at the clinical trial link and it is of good design, including being stratified for disease subtype and burden. The sample size is sufficiently powered to show the difference they expected to find but surprisingly didn't. Instead the result accords with the 2015 Indian Badwe study (and although the Indian study strangely didn't give HER2+ people HER2+ therapy, its arms were properly divided; whereas the Turkish Soran 2018 study that supported surgery appears biased as it had more people in its surgery arm likely to live longer based on their disease characteristics). Moreover, this latest trial included only women with intact/residual primary tumours, and despite that, not removing them did not improve survival.

PS retrospective studies are no good in this area because there will be inherent selection biases (those who get surgery have the best prognosis). Hence, doctors have been waiting for years for the results of this randomised control trial (RCT) to actually answer the question.

FYI below is a meta analysis of the previous two RCTs

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6494198/

Yeah - this is a sticky subject with me. I was also de novo but with a retracted nipple and while I can tell the drugs are working, I hate looking at the thing and from a psychological perspective would rather have a lumpectomy and radiation just to feel that it is out of me. Rosie24 got hers done after 9 or 12 months or so and has done well, but different medical systems and oncs etc. Im still jealous!

And then I see some of the longer-term de novo ladies popping up and you look at their stats and they all had surgery and radiation and chemo etc. I know that is a selection bias, but still - it would be a bit more reassuring if a de novo lady who DIDNT have all that done came along at ten years or whatever and was still around. But again, selection bias - that is just what was done in those years,and there probably aren't any around if the guidance has changed in recent years.

Piggy pointed out some time ago that she still has hers and her MO is using it as the canary in teh coal mine so to speak, and I can see that argument too. But I do wonder that if you are in your late 30s and early 40s at a high grade and are stuck with this thing its a bit different than someone in their 70s/80s with a low grade at de novo. Mentally I want it off/out - my breasts are already scarred from a reduction 20 years ago, I would feel more comfortable with a bit of recontouring than feeling like such a failure seeing that boob every day. Also, its obvious in some shirts/bras and swimsuits

interesting. My breast tumor is no longer detectable on scans. My medical oncologist did discuss surgery with me last year, saying they could do a lumpectomy and that we would have genomic testing done on whatever tissue was there. I think it might be beneficial to have that info for future treatment decisions. However, I did not see a surgeon to further discuss it.

Hard to say about this question- the study cited was done well and results are clear, but what if some great treatment pops up that significantly extends survival? Primary tumor is a source of cancer stem cells, that might make a difference to survival that shows up over a longer period of time..

On the other hand, pre-clinical studies showed that responses to immunotherapy were greater if the primary was still there, probably by providing a big source of cancer cells to prime the immune system to go hunt down mets. But this can be circumvented by blasting open cancer cells with radiation, and there are so many other work-arounds being tested for I-O that it probably just won't matter, either way?

"I think those Her2 positive may benefit from surgery because the Her2 drugs are so effective for years." "what if some great treatment pops up that significantly extends survival?"

One doesn't necessarily follow from the other: yes, HER2 drugs can be effective for years, but it doesn't follow that surgery of the primary tumour is beneficial. Indeed, this new study would seem to indicate that surgery didn't add (survival) benefit. However, I concede that many of the retrospective analyses are making assertions like that - e.g., that due to improved survival a sub group of patients would benefit from aggressive surgical approaches - without really explaining why that conclusion follows.

Meanwhile, I found another randomised prospective study yesterday from 2018 (https://pubmed.ncbi.nlm.nih.gov/31082916/) that stopped accrual early at 90 people, but showed no benefit derived from surgery and in fact a detriment to some, akin to the 2015 Badwe study. This new 2020 study also showed a detriment to 20 patients with triple negative disease. I wonder if the detriment relates to possible detrimental triggering of the immune response, etc, as has been seen in mouse studies.

So that's four randomised prospective trials I've now found, three of which point against surgery with possible slight detriment. The one that points towards it (Soran 2018) had biased sampling with more people with good prognosis in the surgery arm, and patients were randomised before starting any systemic treatment rather than being selected for being the respondents to the administered first-line treatment.

The difficulty is that a person can't perform a clinical trial against themself, e.g. do surgery and not do it and see which worked. Therefore, we rely on clinical trials like this. That's how we end up with our drug treatment regimes.

They called me yesterday to tell me my surgery is scheduled for next Thursday... they're holding it for me...

Hi 42young, I just responded to that exact point in my previous post: from the fact that HER2+ has good overall survival due to systemic treatment does not follow that surgery of the primary tumour benefits survival.

Oh yes, I totally agree actually. My tumour is not palpable - if it was I would remove it. My fear is of course that it becomes palpable later and then grows rapidly, but on the other hand it might not be there at all!

I spoke to my onc today and he said he agreed, surgery should not be done for survival benefit. He agreed the study was well done and it pretty clearly changed things from 'there is no evidence that it increases survival' to 'it doesn't increase survival'. It's also contemporary, unlike the older studies, so everyone got the latest systemic treatment. He said breast surgery could be done in cases - especially HR+/HER2- cases - where the tumour is not under control for local control, but that doesn't apply where the tumour is under control, especially if not visible on scans.

When I asked if we could operate quickly if it grew, he said 'yes' in principle - he just couldn't guarantee how long I'd have to wait (although the scheduling of this mastectomy was relatively quick), but said that if I went to a private hospital and paid $ then I could get it done very quickly (I go to a public hospital and get everything free). And in general, he said he/everyone at my hospital will treat 'oligo progression' (progression in one area - even if it's liver or bone - only) locally, e.g. with radiation or surgery rather than change all systemic treatment. With the breast, it could actually be treated with radiation instead of surgery. I am glad of this stance, as I see so often women online who have their whole treatment changed due to breast progression only. He said he wouldn't do that. He did, however, say that with HER2+ it would be highly unlikely that I would have breast-only progression.

What do you find controversial about the literature? Keep in mind that retrospective studies are not helpful in this case because surgery is usually done on people with the best survival prospects and it is apparently impossible to adjust for that inherent bias without a randomised controlled trial.