I’m completing a chapter in a key lung cancer textbook on managing multi-focal bronchioloalveolar carcinoma, a clinical entity that is in the process of being re-labeled lepidic predominant adenocarcinoma (LPA) (lepidic meaning scale-like, which is the classic way that the cells are defined as spreading when looked at under a microscope). I suspect that it will continue to be called multifocal or advanced BAC for a long time (after all, the formal staging of small cell lung cancer goes from stages 1 to 4, but nobody ever uses that, classifying it as just limited or extensive stage).
When asked to write this chapter, I faced the challenge of there being very little actual hard data on managing multifocal BAC. Though many experts have a very similar approach, this is actually based on expertise, good judgment, and clinical experience more than data we can point to, and I don’t think this approach has ever been articulated in a scientific paper or book chapter, so I’m hoping this will be a valuable addition to the literature.
As I reviewed the papers out there, what struck me most are two things:
1) There is incredible variability in the appearance and clinical behavior of what is called advanced BAC in the clinical world — some of it is aggressive and imminently threatening, and much of it is very slow growing and among the least threatening cases ever labeled as lung cancer.
2) People with a very slow growth rate are likely to do very, very well no matter what treatments they get, as much despite as because of those treatments. In many cases, interventions are pursued on patients who are destined to do very well, and then when their short term survival is good, the people who did that intervention write a paper saying how their approach is feasible and attractive because the patients did well — not recognizing, or at least glossing over the idea, that they were going to do very well anyway.
I would say that in no other area of lung cancer care is it more important to distinguish between what can be done and what should be done. And the real experts know when to not intervene.
So here is the algorithm I developed, which isn’t beautiful, but you can see that it focuses on seeing what is actually changing rather than treating reflexively based on a label on a pathology report or single a scan finding. Essentially, it says to try to avoid intervening at all unless or until you see clinically significant change (which I would consider as something that is readily apparent as progression on scans done 6 months apart or less), and then if you see progression, clarify whether it’s limited to one lesion or progressing more diffusely in multiple areas.
Also, if patients need systemic therapy, you use the same approach that you would for another non-squamous NSCLC. BAC today should be tested for the key molecular markers that can change management, most particularly EGFR mutation and ALK rearrangement, with the decision of chemo or targeted therapy as first line treatment really dictated by the molecular profile, just the way we’d approach an invasive lung adenocarcinoma.
Finally, I’ll say that this concept isn’t or shouldn’t be unique to multifocal BAC. There are other slow-growing cancers, and if I see someone with a slow growing mesothelioma or invasive lung cancer or bladder cancer or prostate cancer, the question of whether there is clinically significant progression should come up. Though there are many people who absolutely need all of the aggressive anti-cancer treatment they can get, we treat lots of people with more therapy than is there best interests: part of that is a cultural bias among patients and doctors that we must go in, guns blazing, to meet our enemy full force. Part is that the incentives, in the US health care system at least, is to give the most care that is defensible and will be paid for.
I don’t know if most people in this situation can accept remaining untreated for months or years at a time, even knowing that they have an indolent cancer. But I would advise people to think about some of these slower-growing cancers like diabetes, high cholesterol, or obesity. They represent a chronic risk to survival over years and often decades, but most people don’t lose sleep over obesity or their cholesterol levels and don’t rush into a triple bypass done 10 years before it might be needed just because a paper might show that people who undergo a prophylactic cardiac bypass 10 years before they would have had a clinical issue are still doing well 3 years after the surgery.
What do you think? Could you accept surveillance scans and no treatment if you were told that you have what is technically an advanced cancer, but one that is likely slow-growing and for which early intervention offers no clear benefit over later intervention? Do you believe that the treatment might be worse than the disease?
Great article Dr West
This applies to my diagnosis and yes I choose to wait it out!
I am currently following this treatment plan. Scans every 3 months, and if nothing is changing, then watch and wait. Already tested negative for mutations, so the first line treatment if and when something changes looks to be chemo.
I am also following this treatment plan. Tested negative for EGFR, waiting for ALK results. If ALK is negative, it looks like I will be starting chemo treatments probably within the year. I have asked about photo dynamic therapy but have been told it is only used in early stage. I wonder why they don’t try it for multi focal, bilateral stage, maybe it would still help shrink the lesions?
No, I think that PDT wouldn’t be a feasible approach at all for multifocal BAC, given how diffuse it often is and how far out into the lungs the lesions appear. Having just written the chapter on it, not only did it not get a mention, it has never come up in any research, nor have I ever spent any time wondering whether it would be a good idea. Based on how it works, I can’t imagine that it would be an effective option for multifocal BAC.
-Dr. West
Thank you for the comment Dr. West. I guess a part of me wants to try everything and anything. One of the Oncologists in Vancouver said the same and he does PDT. I was hoping there would be an alternative to chemo.
This is a hard question. I think I may fall into this category. I am just at my 2 year mark from the end of chemo,2 1/2 from diagnosis and on maintenance only. What’s left of my cancer has not changed at all in 2 years. I am on Avastin and I can’t be sure that it’s the maintenance keeping me stable or if it would be stable anyway. I think about stopping the maintenance sometimes but get so frightened of it just starting up and the doctor not being able to stop it again. I have been tested for the mutations and am triple negative so I don’t have one of those options. That’s the rub…….I just don’t now.
That’s why I think it’s so incredibly important to use the information from before treatment was started to try to determine whether the cancer’s particular natural history is consistent with it being incredibly indolent anyway, which is completely possible with BAC, or it was growing and then stopped only when the treatment was added.
I’d have to say that I don’t think the data with maintenance Avastin (bevacizumab) alone is especially strong, which would make me suspicious that it’s not doing much, if anything. There’s a small risk — I would say VERY small — and I think it may be more than counterbalanced by the risk of side effects, either acute or chronic, from being on Avastin for a very long time.
-Dr. West
I had stage II colon cancer (adenocarcinoma) at age 38, 15 years ago. I have Lynch syndrome which means that I have a mismatch repair gene abnormality which makes me susceptible for colon cancer.
Found a ~3cm+ spot on lower left lobe of lung which shows GGO. Bronchoscope biopsy showed no evidence of cancer but definite inflamation. Pathologist said it “appears to be reactive”. For past 6 months the spot on chest x rays does not appear to be changing very much. Pulmonologist thinks it would be reasonable to have a VATS biopsy to see what is there. Possible BAC?
It is not small, certainly. However it does not appear to be growing, either. I have had plenty of surgeries over the years, and having another one doesn’t thrill me. On the other hand, “something” appears to be going on, and it would be nice to have a definitive diagnosis.
Does it make sense to have the VATS biopsy done? Any advice from anyone would be most welcome.
I think I’m following this regimen as well, and am happy with it. Dxd with BAC in 2009 following biopsy at university medical school/hospital of one of two nodules in left upper lobe and mediastinal lymph nodes. Had concurrent chemo-&-radiation (cisplatin+etopiside), no change in nodule size. EGFR positive; nodules enlarged while on Tarceva 3 months. DC’d Tarceva and started Alimta; no change. Compared with 7 years of pre-diagnosis CT & PET scans every 3-6 months, very slow progression. Since then CT every 3 months for 2 years, now every 6 months. Still indolent. Recent Papillary Thyroid Cancer with tall cell and follicular features resulted in completion thyroidectomy 1 month ago (half the thyroid was removed for goiter when I was 15); radioiodine ablation to take place in another month. If it isn’t one thing it’s another, but I’m feeling okay for a 75-year-old female with lupus and arthritis.
Had VATs in Jan 2010, have taken a wait and see approach for the NSCLC indolent BAC, stage IV. None of the molecular studies came back to my benefit so we waited. Just started Alimta without anything else. I haven’t seen much about BAC/Alimta approach. I also have fibrosis due to scleroderma so its difficult to say what is cancer and what is fibrosis. Any thoughts on Alimta?
Not a lot of data, but Alimta (pemetrexed) appears to be at least as good as any other chemo, very possibly the best among them. Alimta is recognized as being particularly effective in lung adenocarcinomas, and BAC is actually a subset of that histology.
Good luck.
-Dr. West
Thanks so much for this very clear article about treatment options. I was diagnosed with BAC last year (woman, mid-fifties) and had VATS to remove 4 nodules on right lung. Nodules on left lung are progressing slowly and I’m anticipating another surgery this fall after another CT scan. Radiofrequency ablation has been suggested as an alternative to surgery and I wonder if your research turned up any insights on this. Since I have multifocal, bilateral disease I’m of the impression I may need multiple “interventions” so I wonder if RFA is a good option. EGFR was negative as was ALK I think.
I’m sorry to say that for multifocal BAC, RFA represents another completely futile option that we would have no reason to think would be any more appropriate than multiple surgeries. In other words, it’s something to do just for the sake of doing something, but which I suspect will end up being more harmful than probably doing nothing at all if the disease is slow-growing. If the disease is indolent and growing in multiple locations, the leading options are systemic therapy and nothing but observation — ANY other local therapy is simply adding more alternatives driven by either an ill-conceived reflex to treat no matter how poor the rationale for doing so, or just financial motivation of the people who make money by doing interventions that may be profitable but make no sense.
I truly don’t mean to be too harsh. I just hate to see expensive, utterly useless and even harmful interventions performed because we just feel we MUST do something, even when a careful consideration of the alternatives should lead us to anticipate that there will be no benefit from pursuing them.
-Dr. West
Thanks so much for the really fast reply!! Not harsh at all – strong opinions are welcome! My question was really RFA compared to VATS, but I have the impression you were thinking that RFA was suggested as an alternative to doing nothing. That’s not the case here. Another related question: how do you define “slow growing”? I’ve had scans at 6 month intervals. In Feb 2013 the doctor recommended surgery on the left lung based on slow growth (of one nodule in particular) since the prior scan in Aug 2012. I asked him if we could wait 6 months to the scan in Aug 2013 to do anything and he said that would be “low risk” so that’s what I’m doing. But he also stated definitely that the nodule “has to come out.” If the August scan shows continuing growth (how much?) would RFA be an alternative to surgery or is surgery the most effective? FYI, I recently saw the radiologist’s report from the Feb scan and it referred to the left lung nodules as “indolent” and “unchanged.” I questioned my doctor on this and he said it’s clear from the images they are growing. Another doctor who saw my scans concurred. I believe them and assume the radiologist’s report is wrong, but it’s unnerving, which is why I’m asking how much growth is cause for intervention. Thanks again, very much, for your response and for this site.
No, I’m actually saying that neither RFA nor surgery have any anticipated value if there are multiple growing nodules. Instead, the preferred approach should be systemic therapy if progression is significant or observation alone if the progression is minimal.
How much progression makes it significant? There’s no clear answer: it’s in the eye of the beholder, but I very often disagree with the premise that “it’s growing, so it MUST come out”. Frankly, if a nodule is growing by 1-2 mm every year or two, that might be a threat in 10 or 20 or 40 years, and removing the nodule and the surrounding perfectly functional lung tissue may well be more of a threat to lung function and even survival over the next 5-10 years. I understand that some surgeons favor doing surgery, but that’s a very short term benefit of just being able to congratulate yourself that a nodule is now gone…which shouldn’t be mistaken for having improved survival in any remote way. If the pace of the growth is enough that you can see visible growth within 3-6 months, that’s probably clinically relevant and worth dealing with, but as I note in the algorithm, if more than one nodule is growing, it makes little or no sense to focus on one nodule or even to take out multiple nodules, since more nodules will nearly invariably follow if there are multiple nodules growing now.
-Dr. West
Thanks so much. This is *very* helpful!
Dr West, on May 27,2013 I wrote about starting on Alimta for my NSCLC indolent BAC, stage IV. Unfortunately after two rounds, 21 days apart, the CT showed no change and my oncologist determined what was growing is my fibrosis (I have CREST form of scleroderma). I feel like a ship without a rudder since I have taken 4 years of wait and see, only to find out that the cancer is still indolent but I’m being attacked by an untreatable fibrosis. My health is still good, my O2 absorption is very good, I cough a lot and get fatigued but in general I’m doing well. My biggest issue is pneumonia, twice this year, 6 months apart.
I know you can’t diagnose or recommend a treatment plan but what do patients with my set of issues do at this stage of the game? Can you recommend a research/medical center that is known for scleroderma – CREST focusing on lung fibrosis/lung cancer?
Thank you for your comments.
carol
I’m sorry, but I’m pretty sure that there’s no center and no person on the planet who has an expertise in the combination of CREST and lung cancer. As an oncologist, I don’t have a particular expertise of CREST, so I think it makes the most sense to just approach each of these issues separately, essentially fighting the urge to (over)treat the BAC if it’s really very indolent.
Good luck.
-Dr. West
I was diagnosed with stage 1B NSCLC 2002. Had traditional surgery to remove LUL with a rather large (3x5cm), single tumor. Subsequent path review revealed “well-differentiated NSCLC with BAC tendencies”. My onc at that time was not a thoracic specialist and chose to follow me with PET rather than CT. But my very first follow-up scan WAS a CT, six months post-op & when looking back, it is now clear that a very small 2mm lesion was present in my right upper lobe, though not noted on the scan because of its size. So I was followed, from that point forward for 2 1/2 yrs w/PET until that lesion finally lit up. We continued to follow for another 2 1/2 yrs until a second lesion appeared. At that point I had a needle biopsy just to confirm that is was the same cancer, I changed oncologists and was followed by CT for another 3 years. A total of 8 years of watchful waiting & living with disease. I admit it was difficult emotionally at times, but eventually I got used to my predicament and while watching so many friends from support groups suffer and loose their battles, I became grateful for what I had. IN 2010, I had 2 nanoknife procedures to the 2 right lobe lesions. The upper lesion was obliterated by the nanoknife, the lower lesion didn’t respond as well. I then began a course of Tarceva. I have an EGFR mutation, though it is not at exon 19 (it’s at 18 & 21) and I did not tolerate the Tarceva well. After 1 1/2 yrs on the drug at 100mg, I stopped taking it and was advised to undergo cyberknife radiation to the lower R lobe lesion – this was the worst possible thing I could have done. Not only has it left me with a permanent, severe cough and SOB (it’s been a year), but now there are multiple new lesions surrounding the area treated. I am weighing my options of either afatinib (starting at 20mgs), or alimta/avastin. Any thoughts??
I think my leading thought is that it sounds like you’re suffering more from the treatments than from the disease that has been extremely indolent. I guess I’m unclear why, after suffering from so many complications from treatments that haven’t been especially effective, the assumption is that more aggressive treatments are the answer. Perhaps things would go far better without them, at least right now. Is the disease growing at a significant rate, because I’m not getting that sense.
-Dr. West
Sorry if I was unclear in my original post, let me add some detail. In 2 scans I had post cyberknife (at about 3 months, then again at 9 months) there was too much inflammation to really see much of anything on the scans. I was scheduled for a follow-up scan last November which would have put me at 1 yr out from cyberknife, but I opted to wait until Feb. which meant that the time between the last scan and most current was 6 months. On this latest scan it looks like the progression of disease has picked up its pace. This is fairly clear, based upon comparisons to my long history of scans. You can see the changes easily with the naked eye and there are additional new lesions. While I believe some of this increased activity is attributable to tarceva “waking things up” it really doesn’t matter. I am now unfortunately in a place where doing nothing is no longer an option. I fear afatinib will be too much for me given my severe intestinal issues with 100mg of tarceva but as I am otherwise chemo naive, I’m not sure if I’d be better off on the infusion drugs. Bottom line is that the radiation left me in a far more compromised state than I ever imagined and I’m trying to balance quality of life with effective treatment choices.
I don’t have much enthusiasm for afatinib after Tarceva. The evidence suggests it’s not especially helpful in the vast majority of patients. I would also not discount the potential value of chemotherapy, which is a fine option if treatment is truly warranted.
Good luck.
-Dr. West
The only time when I think it would make sense to treat one spot in the setting of known multifocal disease is if there is nothing else growing over a very long period of time, and you see that one spot is overwhelmingly outpacing everything else in the background. I would actually say that seeing a spot grow by 3 mm could be significant if that progression is over a year or less, in which case it might make sense to intervene AS LONG AS THERE AREN’T OTHER LESIONS GROWING at a comparable rate. But that’s still pretty borderline and may well be at a pace at which it might only pose a real risk more than a decade from now, perhaps 15-20 years from now. So I think it makes sense to use the time of ongoing follow up to clarify whether new nodules are going to be emerging.
If there are multiple growing lesions, the point of a multifocal process is that the treatment of any single focus isn’t going to make the critical difference. Please forgive me, but I’d say that you’re thinking about it all wrong if you expect additional nodules to appear and yet think surgery will help. The fact that additional nodules are expected to appear means that surgery, or any other local/focal therapy, will NOT help. Instead, you’ll have some good lung removed or radiated for any treatment to a single spot, and then you’ll end up missing and wishing you had the functional lung tissue when the real problem is caused by the additional nodules that emerge later, eventually leading to a shortage of functional lung tissue. When treating one or two spots is not going to solve the problem, why damage/sacrifice lung tissue to treat one or two spots?
To answer your question, there is no size cutoff where a lesion suddenly leads to a major risk. If an 8 cm lesion/infiltrate were only growing by 2 mm every few years, it wouldn’t necessarily merit treatment, especially if someone is at real risk of dying from some other cause in the next 10-20 years.
-Dr. West
I have had a CT scan with contrast dye. Findings: right upper lobe has a 1.5cm predominantly ground glass opacity with a partial more solid appearing component. There is also a partially visualized groundglass nodule within the anterior right upper lobe and a faint 3mm subplural posterior in the right lower lobe. Thoracic surgeon #1 recommended an upper right lobectomy plus removal of lymph nodes ASAP if the pathologist confirms carcinoma during surgery. Thoracic surgeon #2 recommended 3-4 month follow up CAT scan to evaluate progression. If surgery is indicated due to progression he would do a segmentectomy of the 1.5cm nodule. After reading your article I am inclined to choose the second surgeon. In your opinion, what rate of growth would indicate the need for surgical intervention? Also, given that this may be a multifocal cancer- if future CAT scans show a multifocal presentation what would your recommendations be regarding interventions and do you feel surgical intervention would be the best way to go?
I really tried to articulate my general approach in the algorithm, but beyond that, it gets into the range of making a medical recommendation on an individual patient. In the setting of multifocal disease with one dominant lesion growing (and really NOT when there are several lesions growing at a similar rate), I favor the least invasive, least aggressive approach necessary to remove the dominant growing lesion.
Overall, though, these are situations in which you need to see the scans and speak with and see the person in question.
Good luck.
-Dr. West
Thank you . You are so kind!
Dr West, I am so grateful to have found you. So much of what you share resonates. My mother had a CT scan 5 years ago and they found a nodule that was 1.1cm – they did another CT scan 2 years later and it hadn’t changed. They dismissed it as being nothing. Then, 2 weeks ago she was in the hospital for a UTI and caught pneumonia. They did a CT scan and the nodule had grown to 1.4cm. It grew from 1.1cm to 1.4cm in 5 years. Her doctor ordered a PET scan and it came back as active. They suspect it to be slow growing BAC. My mother is 75 years old, and quite compromised with kidney failure (25% function), heart failure, and COPD. Her pulmonologist wants her to see an oncologist to discuss radiation. I am so resistant to this! Your thoughts would be SO appreciated?!? Thank you so much! Sarah
Radiation is usually very well tolerated and is an obvious compromise between observation and intervening with something as potentially risky as surgery. It satisfies the compulsion to DO SOMETHING when you get a diagnosis of something that is technically called cancer under the microscope but your brain tells you that treatment is very possibly if not probably unwarranted. Usually, the radiation oncologists are only willing to do radiation if a spot is biopsy-proven as a cancer, and I think that if a medical team feels a patient isn’t able to get that biopsy, or the patient is unwilling to do so, it doesn’t make sense to undergo a treatment intervention. Radiation is EXTREMELY likely to lead to hazy ambiguity in the treated area for the next several years, so it doesn’t obviate additional follow-up scans that are very likely to provide completely inconclusive results. However, it’s very likely to more than do the job of treating the area, which, as you’ve concluded, is very, very unlikely to be a real threat in the next several years.
The challenge is that there’s always a small chance that it will change its behavior and become more threatening, but that is a very small risk. I’m not sure the risk of complications from treatment, even very small risks, aren’t greater than the risks posed by a very indolent-appearing nodule in a 75 year-old with many other competing and likely more threatening medical issues. We discuss cases like your mother’s in our lung cancer tumor board every week, and even the surgeons and radiation oncologists often fall on the side of ongoing observation rather than reflexive intervention.
Good luck.
-Dr. West
I would only add that the PET uptake may also be instructive, as it tends to be associated with the growth rate of a lesion.. A “maximum SUV” of under 2-3 is suggestive of a very indolent process, but if it’s over 4 or 5, it suggests that it may be transitioning to a less indolent process that may merit treatment. I’m not sure how “positive” the PET scan really is — being detectable on the PET isn’t the same as being suggestive of threatening behavior.