GRACE :: Lung Cancer
Dr West

Can Lung Cancer be Clinically Insignificant? The Case for “Overdiagnosis” and “Overtreatment” of Lung Cancer

Share
download as a pdf file Download PDF of this page

For all too many people with lung cancer or caring for someone with it, the concept that lung cancer may not be threatening may seem sacrilegious.  It is, after all, by far the leading cause of cancer deaths in the US in both men and women, far ahead of both breast cancer and prostate cancer in its fatality rate, though breast cancers and prostate cancers are more commonly diagnosed in women and men respectively.  Yes, lung cancer is far more deadly than those two cancers, but both breast and prostate cancer are diagnosed in tens of thousands of people who aren’t truly threatened by it.   The world has been slow to recognize that lung cancer can also sometimes be minimally threatening, but it’s worth discussing that possibility.  And it shouldn’t lead us to minimize the danger of lung cancer any more than we should become complacent about handling deadly snakes just because there are some that are are perfectly safe.  In the real world, a far greater proportion of lung cancers than snakes are deadly, but the main idea is that we should consider each based on individual characteristics.  It is absolutely possible to “over-treat” a lung cancer.

This issue became newsworthy because of a new article in JAMA Internal Medicine that did a very complex calculated analysis (i.e., I didn’t understand it) of the lung cancers detected in the National Lung Screening Trial (NLST) and concluded that 18.5% of the lung cancers detected by chest CT screening and 22.5% of non-small cell lung cancers represented an “overdiagnosis” — a cancer that was detected but that would not be clinically relevant (as the numbers reflect, this is rarely a concern for small cell lung cancer).  For bronchioloalveolar carcinoma (BAC), which is often indolent (and especially likely when detected as a solitary lesion), up to nearly 80% of these lesions were potentially overdiagnosed cancer. 

As someone who sees the clinical behavior of hundreds of cases of lung cancer ever year, I’m here to tell you that this seems about right. This doesn’t mean that I don’t believe in CT screening for lung cancer: the NLST trial showed a 20% improvement in lung cancer-specific survival, which to me illustrates that screening for lung cancer is valuable. But it’s also worth knowing two things:

1) Not all lung cancers are life threatening.

2) There is a real risk of overtreating some lung cancers, causing more harm than benefit by treating it.

How might this happen? First, the truth is that very small lung nodules, especially nodules biopsied as showing BAC or designated in a new terminology as adenocarcinoma in situ (AIS), meaning that it’s a pre-cancerous lesion, pose an extremely minimal threat to survival over the next 5-10 years. It’s worth clarifying whether they are growing, whether they are growing at a meaningful rate (can you see a change over 6 months, or does it take 2 years for it to grow a millimeter in diameter?), and whether the threat of the cancer is a realistic concern relative to a patient’s other medical problems. If I see a lesion grow from 8 to 14 mm in 6 months, that’s a lesion that should be resected. But I will tell you that there are many 78 year old patients with heart disease “saved” from a cancer growing from 8 to 9 mm over 18 months.  That’s like saving someone from a box turtle approaching from two blocks away.   And for the lung cancer, that involves a surgery in which the risk from anesthesia and the cancer itself probably exceeded the risk from the cancer over the next 5 years.

Though not relevant to screening, this also comes up in multifocal/advanced lung cancer. Most lung cancers progress at a rate that is a real threat, but a minority grow slowly enough that the risk and side effects of the treatment exceed the symptoms of the cancer over the foreseeable future.  This is more likely for BACs, but other lung cancers can be quite indolent, and we get a hint of this when we see that a patient feels well and hasn’t had a real change in their cancer over scans done a few months apart.

My key point is that it’s important to tailor the treatment to the individual patient’s cancer. Even with lung cancer, we need to ensure that the treatment is appropriate for the disease, and there is a potential risk of overtreatment and not just undertreatment.

What do you think? Do you find this believable, or is it too hard to imagine such a thing as a non-threatening lung cancer?


35 Responses to Can Lung Cancer be Clinically Insignificant? The Case for “Overdiagnosis” and “Overtreatment” of Lung Cancer

  • golfadkt says:

    As I have ( as you know) what in two years seems to a very indolent BAC I want to desperately believe this!!

  • Lembird says:

    Dr West,

    I am still sitting here writing to you 4 years after my diagnosis and initial treatment. I never thought I would even be here, never mind in very good physical condition. I will add that it is the mental aspect of this diagnosis that works on me at times. I feel and look well but LC always pops into my mind when I start making plans……so, I try to live in the moment as much as possible,
    Learning to live each day fully may be the upside (if an upside is possible) to BAC.

    Thank you, again, for all you do.
    Lembird

  • tracey59 says:

    Dear Dr. West:

    When I was diagnosed I thought I probably would have about six months. It has been 18 months now since my diagonsis of stage IV adenocarcinoma and most of the time I am feeling normal and I have been working full-time. Now I am travelling alone in Western Europe. So, sure, I think your argument is convincing, and much more positive, unlike some other doctors in HK who just tell us that we are hopeless as the disease is not curable.

    Thank you so much for your bright and positive advice, and wish you a Merry Xmas and a very happy New Year!

    Best wishes,

    Tracey

  • themag62 says:

    Dear Dr.

    The vagueness of some of your terms make this article less helpful than it could be. First of all, what do you consider to be “very small” size for a lung nodule? You don’t specify. At what size, and other factors, should it be considered too risky to follow and be removed? How does one know a nodule is indolent BAC unless it is biopsied or removed by VATS? Is it true that a needle biopsy can potentially miss cells that would show true adenocarcinoma and miss node involvement?

    Do you reply to comments? Thanks. I am scheduled for VATS on 1/3/14

  • Dr West
    Dr West says:

    Thanks for all of your comments.

    As for the vagueness, that’s deliberate, because there isn’t a specific definition or threshold at which a nodule goes from being very small to substantial. I would consider a 4 or 5 mm nodule very small, and certainly anything smaller than that, but if I see a patient’s scans having grown from 8 to 9 mm over 12 months, that’s also very indolent to me, even if it’s larger than 4-5 mm. Even a 20 or 30 mm (2-3 cm) lesion can be indolent if it changes extremely little over a long time.

    My best working definition of indolent is if you can’t perceive or can barely perceive any change (squinting or using electronic measurements on a screen) in a lesion over 6 months or more. There’s nothing magical or absolute about that, but it puts a general concept into functional terms.

    As for BAC, it’s not the definition of it under a microscope that makes it indolent. I don’t care whether a lesion is called BAC or invasive adenocarcinoma or squamous carcinoma or sarcomatoid carcinoma: if it doesn’t change or barely changes over 6 months or longer, it’s acting in an indolent fashion. So the issue is how it behaves far more than what a pathologist calls it.

    -Dr. West

  • doubletime says:

    I lost my mother to BAC in her 40’s, she was a light tobacco smoker. I am 31 and heavy marijuana users, however due to edibles I cut my smoking by 90%.

    I wonder if they will revise guidelines to those with family history of LC at a young age. I frequent lung cancer forums on various cancer discussion forums. I am seeing a trend of children and parents with same lung cancer, however the child of parent gets diagnosed usually 10-15 years before their parents do.

    I would like to get screened yearly. But will the radiation end up giving someone LC in the long run?

  • Dr West
    Dr West says:

    There is a mildly increased risk of lung cancer among people who have a first degree family member (parent, sibling, or child) with lung cancer, especially if that person was a never-smoker. However, that risk is still quite low for people who don’t have a significant smoking history, and there is no evidence that the benefit of lung cancer screening exceeds the risk from having many scans or likely identifying one or several nodules that aren’t cancer but end up needing a full workup and potentially invasive interventions like biopsy or surgery. At this point, screening CT scans for people who don’t meet the criteria for high enough risk based on smoking history and age are not really recommended, though it’s a good next question to ask in screening.

    Good luck.

    -Dr. West

  • doubletime says:

    Thanks Dr for quick reply.

    It’s just that after reading this study, it really heightened my anxiety of an increased risk.

    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3445438/

    Increased risk of lung cancer in individuals with a family history of the disease

    “Individuals with family history in a first-degree relative are at an approximate 50% increased risk of lung cancer compared to those without a family history, and this association remains regardless of gender, race/ethnicity, histological type and after adjusting for other known lung cancer risk factors.”

  • Dr West
    Dr West says:

    50% increased risk of a very low number is still a very low number. Smoking history combined with age remains a much stronger predictor of ABSOLUTE risk, not just RELATIVE risk (yes, risk is greater with family history, but that’s higher relative to a potentially very low risk).

    -Dr. West

  • suka says:

    I had a left pneumonectomy October 2009 and a year ago last March they discovered GGO and 3 nodules in my right lung. Without a biopsy, my oncologist said it is AIS/MIA. One lesion is 24 mm and another 16 mm. They have not grown at all in a year. Needless to say, it’s difficult not doing anything when you have only one lung. I understand that resection would be a drastic measure and there is a possibility of developing other lesions. I had my CAT scan in June and don’t go back until next June. Is this the right protocol to follow? I have developed a phlegmy cough, which my oncologist says is due to my reflux. Your advice?

  • suka says:

    Dr. West – can you please reply?

  • Dr West
    Dr West says:

    I am not permitted to give medical advice to people who aren’t my patient.

    I see this often; this is clearly a multifocal process, and the pattern is that whatever you do to those new lesions, there will be more. The process is very slow progression, and I think that any lung you remove or destroy with radiation will be missed later — especially after a prior pneumonectomy.

    Please refer to my algorithm on indolent lung cancers: essentially, it says that if a lung cancer is multifocal, local therapy isn’t likely to be beneficial unless one area is progressing quickly and far ahead of everything else. You’re describing a very slow process that would likely be associated with new lesions after these are resected or radiated. The main treatments in the algorithm I advocate are systemic therapy for cancer that is progressing at a clinically significant pace, or restraint and just observation if the progression is very slow. It’s very possible that the more you intervene, the worse things will end up when you have very little lung tissue left that hasn’t been removed or now involved with recurrent disease.

    -Dr. West

  • suka says:

    Thank you Dr. West. I know this is the right path to follow: Just watch and wait but sometimes I just have a hard time with that and keep thinking that there just has to be something they can do. I do appreciate your response.

  • laxmi1975 says:

    Dear Dr West

    I was diagnosed with BAC of lung in January 2015.I had Left lung lower lobectomy in Mar 2015. Subsequently I completed 6 cycles of adjuvant chemotherapy with pemetrexed plus carboplatin and 6 cycles of maintenance chemotherapy with pemetrexed alone; total being 12 cycles by 13.2.2016.

    Following this treatment, PET CT was taken in Feb 2016 and the report gives the impression of multiple metabolically active bilateral pulmonary nodules- largest in right lower lobe measuring 13mm (SUV Max: 2.6-4.5) &small volume mediastinal nodes (SUV Max: 2.6-4.5) with no other metabolically active disease in the rest of the body but shows increase in number & size of pulmonary nodules compared to CT scan Dec 2015. Medical oncologist advised 2nd line chemotherapy with the following medications.

    Gemcitabine + Carboplatin or Docetaxel + Carboplatin

    Scared of side effects of more chemotherapy I decided to give a break of two months to the treatment.
    Kindly Advise

    1.Should we continue further treatment as per advice of medical oncologist as India does not have Immunotherapy treatment options as available in advanced countries. If so which option is suitable?
    2. Any risk from metabolically active lymph nodes. Could they become metastatic?
    3. Whether surgical intervention would be right option to remove largest nodule of 13 mm reported in right lung.

  • Dr West
    Dr West says:

    I don’t know if your tumor has been tested for an EGFR mutation. If not, an EGFR inhibitor could potentially be very beneficial if you have an EGFR mutation and maybe modestly helpful even if you don’t. I think it could also be helpful to check for an ALK or ROS1 rearrangement. I don’t know if an agent like Xalkori c(crizotinib) is available in India, but it can be very effective in people whose cancer harbors an ALK or ROS1 rearrangement.

    Further chemotherapy could potentially be helpful. The agent with the strongest track record in patients who have received prior chemotherapy is Taxotere (docetaxel). It could potentially be paired with carboplatin, and there is some evidence to suggest it can be a bit more effective when Taxotere is combined with Cyramza (ramicirumab), though this agent is very likely not available in India.

    The involvement of cancer in the lymph nodes does show that the cancer has an invasive component and may spread elsewhere.

    I would say that there is no reason to think that surgery for a single nodule will have any beneficial impact when there are many growing lung nodules.

    Good luck.

    -Dr. West

  • laxmi1975 says:

    Thanks for your valuable comment sir. I would like to get a consultation from you regarding my case as i hail from India. Is there any possibility for tele or remote consultation.

    Thanks

  • Dr West
    Dr West says:

    I would love to do that and am actually leading a working group on telemedicine consultations at my institution, trying to get this service going. I hope to offer it in the next few months but unfortunately can’t do that at this time.

    Good luck.

    -Dr. West

  • alexandra says:

    Hello Dr.West
    I would really appreciate if could advise me about the complicated health situation that my dad is going through. and give me your opinion.
    In 2009 my Dad was diagnosed with Chronic Lymphocyte Leukemia (HLL) which is in remission now for the last 7 years. Because the disease is not progressing or bothersome symptoms appear, there is no treatment to him, which is a good thing.
    Two mounts ago, my dad was diagnosed with a heart disease. He needs to go under a coronary artery bypass graft (CABG). Meanwhile, also a “shadow” was found on his right lung.
    A 21x30mm nodule was found on the right lower lung. CT, bronchoscopy and biopsy confirmed it’s about pure Bronchioloalveolar cancer (BAC). He has no metastasis on other parts of the organs.
    My question is , which health issue (BAC cancer or the CABG)should be treated first ?Do you advice Cyber knife ( Gamma Knife) for this kind of cancer and the overall health condition in which is my dad?
    Thank You in advance for Your answer!
    Best Regards,
    Alexandra

  • Dr West
    Dr West says:

    BAC is likely to be an indolent process that is a lower priority than any active cardiac issues.

    Focal radiation is emerging as a very strong option for many patients with an isolated, clinically node-negative (no enlarged or hypermetabolic lymph nodes on imaging). It may well be comparable to surgery for even patients who are fine candidates for surgery but is certainly a leading option for patients in whom surgery poses significant risks.

    Good luck.

    -Dr. West

  • alexandra says:

    Dr.West,

    Than you very much for Your quick answer!
    Can I just ask one more question…If my dad firstly goes under CABG surgery, is it possible the cancerous cells from the lung to be spread through the other parts of the body? As I read on the Internet, after CABG, the patient is on a “machine” for the next 2 hours, and that “machine” runs the blood through the body.

    Thank you!

  • Dr West
    Dr West says:

    No more likely than when the heart pumps blood through the body. The machine is just mimicking what the heart does. Blood needs to pump through the body one way or another.

  • alexandra says:

    Dear Dr.West,

    I’m very thankful for your quick detailed professional answers. Before writing you, me and my family were feeling completely helpless and desperate. As you advised, my dad made an appointment for the next CT which will be in 4mounths…

    I hope won’t be any problem to write you again for advice…

    Thank You again for the dedicated time.

    Regards,
    Aleksandra

  • lani1321 says:

    Dear Dr. West,
    I just joined cancer grace and I’m encouraged by all the insight. I was wondering if you could give me some insight. My father-in-law was diagnosed three months ago with stage IV nonsmall celll lung cancer with an EGFR mutation. When he was diagnosed, the cancer had started in his lungs and metastasized to other areas, including the brain. He has gone through two treatments of gamma knife and is now in a clinical trial using Afatnib.
    He’s been in this trial for a month and a half and got new results back to his scans and al spots had shrunk by 50% or more, a few even completely disappeared. Then two days later he had a partial onset seizure. He was feeling great, his speech was back to normal and he had so much energy (he was even Referreing soccer games). Ever since the seizure, his speech has been sub par but the doctors say nothing’s wrong. What could the sudden change in speech be caused by? Especially after receiving such great news from the clinica trial.
    Any insight would help. MRI didn’t show anything different and the EEG showed some activity in his left brain (where the largest lesion in his brain is). Our family is at a loss right now. Not sure if we should be happy or worried. Could the decline in speech and partial onset seizure be caused by some of the lesions disappearing in his brain?
    Anything would help right about now,
    Thanks!
    Lani

  • Dr West
    Dr West says:

    I’m afraid that I’m not equipped to offer any further insights. This question is really one best handled by a neurologist, and particularly someone with access to his MRI and all of the details of his case. Moreover, while GRACE is really a great forum for providing general information about lung cancer and other cancer situations, the internet isn’t really ideal for getting treatment recommendations for an individual patient’s case when the other person has none of the critical details.

    I’m sorry I can’t offer any further thoughts beyond those provided by his own doctors.

    Good luck.

    -Dr. West

  • lani1321 says:

    I completely understand. Thought I’d give it a shot. Thanks!

  • alexandra says:

    Hello Dr.West,
    As I had mention before, my dad is a complicated pation with CLL,needs CABG and was diagnosed with BAC. His oncologist suggested to start with chemotherapy (cisplatine+gemocitabine).So, after the first chemo and just after few hours, he got a attack of suffocation (i don’t know if i write it correcth). He was immediately transfer to the hospital(cardiology) and stayed there for 7days. For one day he was staying on intensive care.The doctors diagnosed that he got water in the lungs/heart. Before he left the hospital, the doctors didn’t want to check him again,to make once again eho of the lungs/EKG, therefore to check if there is some water left again…Isn’t that strange?? Also they didn’t give us an answer if that water was from the chemo maybe..Can you,please give me Your opinion as oncologist? Have you ever met similar health issues?
    I’m really worried about my father.

    Best Regards,
    Alexandra.

  • Dr West
    Dr West says:

    I suspect this is related to the large amount of fluid given with cisplatin. If it is from that, which the doctors should have some idea of (it should look like congestive heart failure on x-rays, and an echocardiogram may show diminished squeezing capacity of the heart), then switching to a different drug than cisplatin, such as carboplatin, may be much better tolerated. Alternatively, some patients develop a hypersensitivity reaction to gemcitabine, though this is very uncommon.

    Good luck.

    -Dr. West

  • alexandra says:

    Thank You Dr.West for Your quick and professional answer!

    We got the results, and as you are saying, the echo cardiogram shows diminished squeezing capacity of the heart. For now, until he doesn’t get stabilized, the doctors here in my country, are not recommending continuing the chemo. I’m just wondering, how long should it take to throw out from his body all those chemo-meds ? Should we expect more suffocation ?

    Thank you very much!
    Alexandra

  • Dr West
    Dr West says:

    No, this is likely directly related to the fluids he received, so it shouldn’t be an ongoing issue unless he gets too large a volume of fluids in a short time. However, I should say that of course I have none of the details of his situation and that a far more appropriate source of information would be his own doctor(s).

    Good luck.

  • asil66 says:

    Hi Dr West,

    Thanks for publishing your article. This is really insightful and I am actually thinking bout the same thing. I am not too sure if those treatments are doing more harm than good to my boyfriend, who was diagnosed with stage 4 adenocarcinoma in August last year. This is because he has been suffering from many side effects from the treatments. He was given chemo (carbo + Alimta) between Sep – Dec 2015, radiation to spine in early February 2016 and 4 infusions of Nivolumab. He has had mixed response to both chemo and Nivolumab.Unfortunately, the latest scan done last week showed progression in the lungs whereas the other mets to the spine are stable.

    He has not been eating and sleeping well for the past 2 months and the medications (nexium, meteoclopromide) given by his doc doesn’t seem to work. This really stressed him out as he doesn’t seem to get enough rest despite sleeping for a long time. His digestion seems to be getting worse as he cant hold in food without throwing up without taking meteoclopromide.

    We are currently thinking to stop treatment and find ways to improve his digestion and resolve his sleep problem before continuing. Would you have any ideas on what could be wrong with his digestion and what can we do about it? It’s really stressing me out seeing him becoming weaker day by day.

  • Dr West
    Dr West says:

    Unfortunately, it’s really not feasible for me to assess what’s happening with so many variables and not being directly involved. I think one of the most important things would be to prune back some of the medications to rule out that one or more aren’t the cause, and this is something that seems especially appropriate if the treatment isn’t clearly effective. Chemo and nivolumab can each be associated with nausea.

    Radiation to the spine may involve some of the bowel or liver, which can cause nausea, but it is late for that to still be a problem if the radiation was completed in February.

    Otherwise, it’s possible that the cancer itself is causing fatigue and nausea, but a good way to clarify if it’s the disease or the treatment is to hold the treatment and see whether things improve or not.

    Good luck.

    -Dr. West

  • eandkbranham says:

    Dr. West,
    A month ago, my husband had a solid pulmonary nodule in his right lower lobe detected as an incidental finding on abdominal CT. It measure 2.5×2.6×2.2cm. PET was negative, but did show “minimal fdg uptake not significantly above background” radiologist stated that although there was not significant accumulation, appearance of nodule remains concerning for AIS(nodule has irregular border and central micro cavitation). We met with surgeon and plan is for VATs in 2 weeks. Wedge resection if path in OR is benign, but lobectomy if AIS. He is 42 with absolutely no symptoms and 100% lung function on his pulmonary function tests. After reading this article, I’m concerned that lobectomy could be problematic down the road if recurrence. But pulmonollogist recommended VATs over needle aspiration due to possibility of false negative with biopsy. Would CT monitoring over a course of 3 months be wise with a lesion this large not knowing its growth rate?

  • Dr West
    Dr West says:

    I think that at age 42, that’s a lot of surveillance for a very long time, and I would be very surprised if there’s never anything that leads someone to favor taking it out. Particularly if there’s a single focus, I think it’s very appropriate to deal with it definitively. My comments are more relevant in a case of a much older person who may have a very, very slowly changing process over many years that will probably not be relevant even if it grows over the next 10-20 or more years. At 42, your husband has decades to be at risk for it progressing.

    The other setting in which I think a very indolent process is especially relevant is if you know there are several areas of disease but nothing is moving at a pace that is likely to be threatening.

    But if there is a single area of disease in someone who is very young and therefore has a long time to be vulnerable to progression of that lesion, we are more inclined to favor being more aggressive to both get a better sense of what it truly is and to hope to treat it definitively. I would be far more cautious if another lesion appears a few years from now. That’s when you’d have a clearer sense of a need to be judicious about the risk of over-treatment in a multifocal process. Here, there’s no evidence it’s multifocal.

    Good luck.
    -Dr. West

  • alexandra says:

    Hello Dr.West,

    I’m writing you again hoping to give me some of your advice… Because we are facing new situation with my father (he was diagnosed with BAC-nonmucinous , CL-chronic lymphocyte leukemia and heart disease), I would really need your opinion what do you think. The blood results showed elevated WBL to 80 000 and elevated D-Dmer to 4400 (yesterday were 1700/also yesterday he made some blood analyses). Is this means that the cancer is spreading? Because on the last CT made in June 2016(the previous one was made in February 2016), doctors can’t say for sure that is spreading (the border is not so clean)..
    Also, I would really really appreciate if somehow I can contact you and send you the CT of my father’s lungs from February and the last one made in June, so you can check it? I don’t trust to the health system in my country! No matter that I’m contacting you via forum, I trust you more than any doctor that I had meet until now!Please, let me contact you!
    Thank you in advance,
    Aleksandra S.(my email is: aleksandra.stavreva@gmail.com)

  • Dr West
    Dr West says:

    I’m sorry, but this is really exactly what I am not able to do. GRACE is here to provide general information for patients and caregivers. I am not able to give personal recommendations on individual cases, and it is illegal for me to do so for people who are not my patient. Thank you for understanding that his oncologist is the person who is the one that should be managing these issues.

    -Dr. West

Leave a Reply

Ask Us, Q&A
Lung/Thoracic Cancer Expert Content

Archives

Share
download as a pdf file Download PDF of this page

GRACE Cancer Video Library - Lung Cancer Videos

 

2015_Immunotherapy_Forum_Videos

 

2015 Acquired Resistance in Lung Cancer Patient Forum Videos

Share
download as a pdf file Download PDF of this page

Join the GRACE Faculty

Breast Cancer Blog
Pancreatic Cancer Blog
Kidney Cancer Blog
Bladder Cancer Blog
Head/Neck Cancer Blog
Share
download as a pdf file Download PDF of this page

Subscribe to the GRACEcast Podcast on iTunes

Share
download as a pdf file Download PDF of this page

Email Newsletter icon, E-mail Newsletter icon, Email List icon, E-mail List icon

Subscribe to
GRACE Notes
   (Free Newsletter)

Other Resources

Share
download as a pdf file Download PDF of this page

ClinicalTrials.gov


Biomedical Learning Institute

peerview_institute_logo_243