The Risk of Overtreating Indolent Bronchioloalveolar Carcinoma

This is an oldie but goodie article from GRACE's archives. Enjoy!
H. Jack West, MD, Founder, President and CEO

 

 

Bronchioloalveolar carcinoma, or BAC, is a subtype of lung adenocarcinoma that has a tendency to progress more slowly, stage for stage, than other types of lung cancer. There are many patients who experience symptomatic and significant progression over months, and rarely patients have a very aggressive and fulminant form of the disease. However, many patients with BAC experience slow growth that raises the risk of potentially overtreating it, with the possibility of detrimental effects from that.

As someone with a particular interest and expertise in BAC, I see the situation with BAC as being similar to the issues we face with prostate cancer. Once a blood test for detecting prostate cancer emerged (prostatic serum antigen, or PSA), it became possible to identify 200,000 men in the US per year who had prostate cancer. The problem is while a huge proportion of men will develop prostate cancer as they get older, many will have an indolent cancer that will not really threaten their survival, and for which treatment with surgery or radiation can have significant long-term side effects. A low grade prostate cancer is well known for being a cancer men can “die with, but not of”. In other words, men can have a prostate cancer that would never directly threaten them, and they can go on to a ripe old age before succumbing to heart disease or another non-cancerous condition.

I haven’t forgotten that this website is about lung cancer and not prostate cancer. My point is that BAC, unlike other forms of lung cancer, brings up the same kind of dilemma. We know that there are some very threatening, aggressive cases of BAC, but many others can be incidentally detected and be very…pokey (not a technical term). So treating BAC like every other kind of lung cancer, which would involve removing a lobe of the lung or perhaps the entire lung, has a real risk of making the treatment worse than the disease. BAC tumors have a tendency to grow slowly over time, and if they’re surgically removed, you can have another BAC come up many years later, unlike other types of lung cancer where you either develop a recurrence within the first 2-3 years or you probably never will. With BAC, you can develop another, likely related BAC lesion 5 or more years later. But it may grow so slowly that it causes no symptoms and is no threat to a person’s life for another 5, 10, 15 years, or perhaps until that person is over 90. But you can make that person symptomatic if you remove enough good lung tissue every time they develop a 5-10 mm BAC lesion. That patient may find themself really missing that good lung tissue that was surgically removed as a lobectomy 5 years ago (perhaps their 2nd lobectomy for BAC) if they develop new BAC in the remaining lung.

A case in point is a 75 year old man with several significant medical problems, including heart disease and diabetes, who had undergone a left upper lobectomy for a small (1.1 cm) BAC 4 years before I met him. In regular follow-up after that, a new right upper lobe nodule was detected, and over the next two years it grew from 5.5 to 7.5 cm. It was in the center of the lung, therefore not easy to biopsy.

While we would standardly want to biopsy this and remove it surgically if it is cancer, and that is definitely a reasonable option, I would just note that at the very slow rate of growth we’re seeing, his other medical problems will likely provde to be the greater threats over the next 5-10 years. This is very likely a recurrence of BAC, but if we watch it, it is likely to remain an asymptomatic small nodule for years to come. That said, removing it is certainly reasonable, although I would strongly urge that if surgery is pursued, a wedge resection to minimize loss of good lung tissue would be my preferred approach over a lobectomy.

Japanese researchers have been the ones who have primarily recognized that well-differentiated BAC lesions are very unlikely to progress into lymph nodes or spread outside of the chest. They have been doing studies with smaller surgeries for BAC, but at this point we don’t have proof that they produce equivalent results to the more extensive standard surgeries we usually do for lung cancer. In the US, there are studies just getting started asking similar questions of whether less extensive surgeries are appropriate for such cases.

At the same time, there are patients with multiple nodules that recur after surgery for BAC. In such cases, surgery is really not feasible for multiple spots, and the cornerstone of treatment is chemotherapy or targeted therapy like EGFR inhibitors/tarceva. However, I often recommend to asymptomatic patients that we follow scans off of treatment initially, generally every 3-6 months to start with. In many of my patients, they feel completely well and show minimal change on scans for years at a time, without any treatment. We could start chemo or tarceva immediately, but I wouldn’t want to waste a potentially valuable treatment, still likely to have some side effects, if a patient may go years before needing any treatment. Since tumors tend to become resistant to all of these therapies after months or years at most, I’d rather keep them available for when things are growing and we really need them.

The observation approach isn’t right for every patient. I wouldn’t want my patient to be disabled by anxiety due to “not doing anything” about their cancer. But BAC, unlike most other lung cancer types, has the potential to be a chronic disease, and that means that it makes sense to consider when to use the finite resources of effective treatments available, and also to see whether it will actually impact a patient’s health in the context of their entire clinical picture.

 

25 Responses to The Risk of Overtreating Indolent Bronchioloalveolar Carcinoma

 
 
  •  
    dusty says:

    Interesting and unique opinion.

    Dusty Donaldson

     
     
     
  •  
    Dr West says:

    Dusty,
    OK, that sounds like a euphemism…
    At the risk of seeming defensive, I’ll just say that my recognition that BAC might be treated different is not unique and that I’m no maverick. The idea of doing smaller resections comes from Japan, where they lead the world with their huge experience with BAC. And my view comes as person with a major experience with BAC, not someone treating BAC reflexively like every other cancer. I led the largest trial ever done on BAC thus far, and I recently was asked to lecture on “State of the Art Management of BAC” at the conference of International Association for the Study of Lung Cancer conference in Chicago in October. So this is at least a well-informed opinion.

    I know that many people seeking info on the internet are actually on the more aggressive side, and I wouldn’t suggest this is for everyone. But breaking out BAC and not treating it by the exact same rules as other cancers is a growing trend in lung cancer, which started with dedicating clinical trials to this unique population.

    -Dr. West

     
     
     
  •  
    ortizbazurto says:

    Dear Dr. West:

    I am very interested in your observations on the differences in the clinical evolution of BAC carcinomas with respect to other adenocarcinomas.

    My wife was diagnosed with adenocarcinoma with BAC features. I was wondering if these adenocarcinomas with BAC features also exhibit a similar indolent behavior as the pure BAC carcinomas.

    A more general questions is what features/patterns of the BAC carcinomas are also present in adenocarcinomas with BAC features. In particular, I heard that BAC seems to be not very responsive to standard chemotherapy doublets. Is this true? And if so, does this also holds for adenocarcinomas with BAC features?

    Thanks much! and keep up the good work.

    Carlos O.

     
     
     
  •  
    Dr West says:

    Carlos,

    Adenocarcinoma with BAC features is a mix, and it can act more like a classic BAC syndrome and grow slowly in the chest only, or it can have a bit of BAC but really act like a regular invasive NSCLC (adenocarcinoma). Conventional chemo tends to work best on faster growing cancers, so I believe that some of the problem with less responsive BAC tumors is that they are so indolent that they aren’t very vulnerable to chemo. However, adeno with BAC features can be as aggressive as any other NSCLC, or pretty slow. Often how the patient is doing over time (one month to the next, for instance) and/or how much scans have changed, especially in between treatments, can give a hint.

    If an adeno with BAC features looked more like a solid mass and was growing quickly, I’d be inclined to treat it like a standard NSCLC. On the other hand, if it appeared as multiple ground-glass opacities throughout the lung on CT that changed slowly over a couple of months, I’d think of it more along the lines of a BAC.

    Importantly, most of the trials we’ve designed for BAC now specifically include patients with adenocarcinoma with BAC features, because we know that they are often some of the ones who respond best to “BAC treatments”.

    You can check out some of my prior posts in the BAC section of the Subject Archive for more discussion of BAC and the spectrum between pure BAC and invasive adenocarcinoma.

    Thanks for your interest. Good luck to you and your wife.

    -Dr. West

     
     
     
  •  
    sally says:

    Here is another variation on this: I have what seems to me to be a large solid tumor (5.5 cm) in addition to the GGOs. How dangerous is this tumor? I am not seeking unreasonably aggressive treatment—I am just afraid of that thing and keep thinking that if it weren’t there I would be safer. However, I need to understand how dangerous it is. I believe because it is big it could metastasize at any time. (It has been basically stable for a year.)

     
     
     
  •  
    Dr West says:

    Sally,

    Good question. In someone with multifocal (advanced) NSCLC, including BAC or adeno/BAC mix, there is no evidence or even clear suggestion that removing one lesion in a setting of multifocal disease would provide benefit. The only setting where I might consider it compelling to treat a single focus is if that spot were the only area growing, and all of the other lesions had resolved. Even in that case, it would be “pushing the envelope” but might be considered as having a compelling rationale.

    If the solitary solid mass were stable, there is a realistic possibility that the adverse effects of local treatment, whether surgery or radiation, could outweigh the questionable benefits (for instance, if the ground glass opacities progress and remaining lung function really needs to be maximized). We generally pursue local therapy only if it’s potentially curative or the localized area is causing symptoms. Otherwise, there’s too much concern that disease will progress outside of the treated area, in which case the benefit of local treatment will be very questionable.

    All in all, it’s appropriate to see how things are changing over time, but if the pulmonary nodules/GGOs progress before the more solid-appearing lesion, my perspective is that there would be no benefit and potential harm from treating the latter.

    -Dr. West

     
     
     
  •  
    eadvossler says:

    My sister was dx’ed with stage 1A lung cancer 10/04. CT scan : 3cm nodule with several small satellite areas in LUL. Path report: adenocarcinoma of lung, papillary type, well diff.
    She had a LUL lobectomy late in 10/04 followed by 4 cycles of chemo (carbo/taxol). She had a series of CT scans in 2006 that show multiple bilateral nodules (2-5mm).
    She was advised to watch and wait, that the nodules were too small. In November she went to another state and had a biopsy that shows: “Adenocarcinoma with micropapillary and BAC features. The tumor cells demonstrate low nuclear grade”.
    Pet scan 12/06 is negative. Brain MRI 3/06 negative. She again is being advised to “watch and wait” and get another scan in early March. I am definitely uncomfortable with the watching and waiting. After reading your comment about BAC, maybe it is the thing to do, BUT my sister is in her early 40s with 3 young children and she wants to do whatever she needs to do stay ahead of this horrible disease.
    What would you do if this was your sister/wife?

    When do clinical trials fit in?

    Thanks for your input. I have found this site very helpful as well as your comments on the LCA site.

    Beth

     
     
     
  •  
    Dr West says:

    Beth,

    I understand about the desire to do more, but

    1) chemo doesn’t have a great track record against indolent cancers, and I would not be especially optimistic about chemo offering much, would only be inclined to use for symptomatic disease

    2) even for something that is sometimes effective like an EGFR inhibitor, just about everyone who responds eventually has the cancer become resistant.

    Every treatment is likely to have some side effects, and some can be serious. She may go a very, very long time without it affecting her quality of life or survival. The key question I think needs to be asked is not “should we do nothing or do something?”, but rather, “do you want to blow your best options while she’s feeling fine and potentially without symptoms for years, or do you want to save your treatments for when you need them?” It’s not now or never, but now or later. And how bad would it be if she went on a treatment and had a serious or fatal complication? Fortunately, that’s not likely, but it’s possible to have permanent problems or even die from chemo or tarceva or avastin complications. It’s tremendously unfortunate if it happens, but if it’s a setting of facing an imminent disease-induced problem, that’s less of a travesty than if we’re treating a scan rather than the person.

    Clinical trials are great, but many if not most are geared toward people who have had fewer rather than more treatments, so treating her just reflexively now could burn a bridge for a very appealing option later. All the more reason to treat her as judiciously as possible.

    I’m speaking as someone who watches patients run out of options and feel desperate to try anything, including many options which may be more harmful than beneficial. I would caution patients who might go years feeling great to strongly consider doing nothing until they need it. We will only learn more and have more treatment options in the future. It’s too easy to have treatments take their toll on a patient over years, when that person had no symptoms other than the side effects of therapy, and then be left with no appealing options when they really feel the effects of a growing cancer.

    -Dr. West

     
     
     
  •  
    blaze100 says:

    Hi Dr. West, I am probably one of those over treated BACs. Now 6 years out of surgery, I find my right coronary artery completely scarred.

    But I wanted to ask you what is the protocol for long term follow up after surgery? I’ve read the average time of recurrence is 300 weeks, so how often should a BAC survivor get scanned and for how many years should they be followed? Thanks. Barb

     
     
     
  •  
    Dr West says:

    Barb,

    BAC is really an uncharted world vs. other types of lung cancer. The risk of recurrence goes out pretty much forever with BAC, but the longer the interval, the less likely it will grow at a clinically meaningful rate. I’d recommend yearly surveillance CT scans and still say that even if there is evidence of a new lesion at some point many years later, if it has been 8 or 10 or 15 years, it just underscores how slow-moving the process can be and how questionable it would be to rush into an overly aggressive approach.

    -Dr. West

     
     
     
  •  
    blaze100 says:

    Thank you Dr. West. I know I breathed OK even with my large tumor, but I was continually catching colds and taking forever to get over them.

    Are there any BAC tumor locations or situations where it would be prudent to treat immediately?

    Barb

     
     
     
  •  
    Dr West says:

    Barb,

    No key location or threshold size. I have several patients with kind of scary looking CT scans, but they continue to feel well, their oxygen saturation (measured by a finger probe) is in the 90s (normal), and show very little change in the scans from one to the next. And several of these patients continue to do well year after year.

    I would use a trigger of problematic lung symptoms (usually cough or shortness of breath), convincing clinical decline of any type, and/or rapid clinical change on scans (which suggests a more aggressive cancer behavior and trouble coming soon), I’d recommend intervening with treatment.

    -Dr. West

     
     
     
  •  
    Bob Gamage says:

    Thanks for your excellent work here. You’re a Prince! After my first phase chemo treatment of 12 wks which held the BAC tumor stable, we refrained from any treatment for two months. The CT scan then showed a 20% growth of the tumor, and the 3 metastasised lymphnodes seemed to be increasing in number, but too small to know for sure. My question is: In two months is that what you’d call fast, medium or slow growth? It was 2 cm when we first found it and started the chemo.

     
     
     
  •  
    Dr West says:

    Here’s my opinion, in a field without lots of data:

    Any detectable progression in a two month period is probably in the medium range. I’d be looking for no perceptible change in 3-6 months to consider it slow. To me, visible change in a 2-4 month period is enough that I would be inclined to pursue treatment.

    Fast would be worsening symptoms or such clear progression on a CT scan after 2-3 months that you don’t need to do measurements to see it’s worse.

    -Dr. West

     
     
     
  •  
    jgr says:

    How much if any significance in the treat-no treat decision is a history of other cancers? (In this case an oddball thyroid cancer – oxyphyllic type; then an oddball combo of breast cancers – phyllodes and DCIS; then two skin cancers – basal and melanoma in situ, all within a six year period.)

     
     
     
  •  
    Dr West says:

    I’d consider that very unfortunate, but I would really consider those issues to be unrelated, so it wouldn’t make me any more inclined to treat a BAC. It sounds like all of these issues are likely in the past and not a significant threat for the future. In general, though, if someone had significant medical issues that compete with a slow-growing BAC, whether an active cancer or heart disease or whatever, it would probably lead me to be LESS inclined to treat the BAC because it would be even less likely to be the threat limiting survival.

    -Dr. West

     
     
     
  •  
    hubbie says:

    One of the unknowns in my wifes case is that her cancer was only defined after FNA as “poorly differentiated nonsmall cell lung cancer.” The largest mass and the one that was biopsied was up near the right shoulder and was only 2cm. There were too many spots throughout the right lung too count. One oncologist thought the growth pattern was suggestive of BAC and the other two we saw would only say it was not squamous. Can BAC be diagnosed with FNA or is a larger sample needed? My wife is a never smoker.

     
     
     
  •  
    Dr West says:

    There is some controversy, but most experts would say that BAC can’t be diagnosed from an FNA, but would require a bigger piece of tissue like a core biopsy. A never-smoking woman with innumerable lung nodules that are “not squamous” does fit with the BAC clinical picture, but BAC is typically well differentiated, not poorly differentiated. Still, I would probably base my treatment recommendations on her being a never-smoker and having a clinical and radiographic picture so consistent with a BAC syndrome.

    -Dr. West

     
     
     
  •  
    Barry Haigis says:

    In the reading of several posts on EGFR inhibitors I notice a distinction between adenocarcinoma with BAC (tendencies) and pure BAC. Would you please explain this distinction. And would your thoughts about a “watch and wait” approach to treatment apply equally?

    thank you

     
     
     
  •  
    Dr West says:

    The majority of what we talk about as BAC is actually not pure BAC but a mixture of the non-invasive form, which is more likely to be indolent, and the invasive, more common adenocarcinama. BAC is a kind of adenocarcinoma, so all BAC tumors are adenocarcinomas, but not all adenocarcinomas are BAC. There can be less aggressive tumors that are the invasive adenocarcinoma form, but the idea of watching and waiting, or at least being less aggressive, is an idea that applies more to pure BAC or a form where it is mostly BAC and just a small proportion of invasive adenocarcinoma. But I would use the change in scans over time, or lak thereof, as a more important factor than what the pathology showed.

    I describe the distinction of BAC vs. other forms of adenocarcinoma in a post here:
    http://cancergrace.org/lung/2006/10/11/bac-adeno-spectrum/

    I hope that helps.

    -Dr. West

     
     
     
  •  
    peter r says:

    Dr West,I will give a brief description of my lung cancer history and than a few questions.

    In 1996 due to a car accident I had a ct scan and 2 nodules were found one in each lung.I was told to have another scan in 6 months.I did not follow orders, as I was not smoker,but I did have another 3 years later in /99.I showed little change and the left lung nodule disappeared and a 6 mo. follow up recommended.Again I waited 1 yr.to 2000 and again no changes.I also had a PET scan in 2000 and nothing showed up.A 6 mo follow up was recomended.I had my third CT now in 2002 and a slight growth was noticed.

    In July 2002 I had surgery at MGH and a wedge excision was done. Lab report:Adenocarcinoma,poorly differentiated,mixed acinar and BAC subtypes 1.2 X 0.8 cm Resection margins are free of tumor.No vascular invasion,no pleural invasion.

    I have had only ct scans evey 6 mos since surgery.

    My questions:

    I am now 73, feel great and am very active,swimming,competitive tennis and work outs in the gym 2/3 times a week..After 5 years this July 1st do I need to keep getting CT scans with all its radiation?I must have had a 15/20 ct scans for varrious reasons but mostly for LC.

    I was never a smoker but was exposed to asbestos from auto parts, like brakes.My doctors believe this caused my LC.Does this make it more or less likey to reappear?

    Am I a 5 year survivor or a 11 year survivor from the first time a nodule was spotted in my lung by the CT scan ’96?

    Seeing my first nodule was slow growing,if another shows up in the lung should it be removed or just watch it with more CT scans? And how many CT scans can the body take before it does more harm than good?

    TIA and any other advice,is much appreaciated.

    Peter Reiss

     
     
     
  •  
    Dr West says:

    There are lots of different kinds of CT scans, and a screening CT scan has a pretty minimal amount of radiation associated with it. I am not an expert on that, but my view is that the risk of cumulative radiation problems from screening CTs is very unlikely to ever be clinically relevant, and even if it is, it’s likely to be an issue decades from now. There’s usually a lag of 20-30 years between radiation exposure and “secondary cancers” from that, but that applies far more to significant radiation exposure like atomic bombs or treatment levels of radiation than routine scans. Overall, I would say that the risk of missing a clinically relevant lung cancer is much greater than the more theoretical risk of a cancer or other problem from multiple CT scans over several decades.

    At 73, I do think there’s a real risk of overtreating a nodule if it grows from 8 to 9 mm over a couple of years. While I was specifically talking about well-differentiated BAC lesions, I’ve mentioned that the clinical behavior/imaging changes are much more important for my recommendations than the pathology results. Your case certainly sounds like one that isn’t very clinically threatening, but the fact that you’ve had a lung cancer puts you at higher risk of developing another in the future. After four years, the risk of a new cancer exceeds the risk of the old one returning.

    I am not sure about the increased risk of adenocarcinoma of the lung and asbestos. There are 20,000+ never-smokers in the US each year who develop lung cancer without any asbestos exposure, so it’s not the only explanation.

    I would be more inclined to call you a 5-year survivor, but it’s not like there are any official rules or terminology for your situation. I think it’s fair to say that your long follow-up gave a fair sense of the pace of the cancer, which was very slow.

    Anyway, the core of my answer is that I would estimate the risk of not doing CT scans to be greater than the risk of doing them, even though I agree that the clinical behavior of your cancer was pretty favorable.

    -Dr. West

     
     
     
  •  
    lindakirk says:

    I am in the interesting position of having 2 primary lung cancers: an adenocarcinom with bac features, 2.5cmm, discovered on routine chest xray last April(upper left lobectomty in June) and several small nodules throughout both lungs discovered on CAT scan workup. The ones in my lower left lung were removed during the surgey and were biopsied as pure non-mucinous bac. All nodes and margins were clean.

    So it was wait and see and have a CAT scan every 3 to 4 months. Okay until Feb. when a new 1 cm mass appeared in lower left lobe. Was unchanged 6 weeks later.

    So I’m scheduled for surgery to remove the new mass. What I’m wondering about is post-surgery. Yes, if this turns out to be one of the bac guys who got a little feisty, I guess I’m back to watchful waiting. What if it’s an adenocarcinoma like the original 2.5cm one? Doesn’t this mean that despite clean nodes and margins, some cells are floating around out there?

    Should I be considering some sort of chemo?

    I should add that I’m 63, female, ex-smoker (quit 30 yrs ago, smoked a pack a day for 15 years before that), in perfect health (if you don’t count the lung cancer) and had negative brain MRI and bone scans last July.

    Just wondering about your thoughts on this. Part of me thinks let’s zap those damn cells with everyhting we’ve got and part of me thinks, I just want to go back to work after surgery and I’ll deal with whatever else arises when and if it does.

    Thanks,
    Linda

     
     
     
  •  
    Dr. West says:

    Linda,

    Frankly, my leading suspicion would be that all of your lung nodules represent the same process, but some of those nodules act more like the adenocarcinoma part of the name, and some act more like the “with BAC features” part of the name. We know that adeno w/BAC features is a spectrum, and we often see that people have multiple nodules, some of which grow at a clinically meaningful pace, and some can grow at an amazingly slow pace. To me, that sounds exactly like your situation.

    I think it makes sense to follow nodules that haven’t been growing and treat with a systemic (whole body) therapy on an “as needed basis” in the event of progression of several nodules at a time (multifocal progression). The thing I’d be concerned about it that this IS a multifocal issue right now, and I don’t think you could be confident that surgery will end the issue. Because of that, there’s a danger in doing multiple surgeries over time and running out of good lung tissue when you take out one of these every few years with some surrounding good lung, especially if you do a lobectomy each time.

    -Dr. West

     
     
     
  •  
    lindakirk says:

    Dr. West,

    Thanks for th info and the quick reply!

    Linda

     
     
 
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