I have been listening to your podcasts and reading your articles since the regrettable indoor days of the pandemic. You are an important voice and I want to believe everything you say. The lung cancer information stings, though. My husband died from lung cancer in 2015 at age 58. He was a non-smoker, regular exerciser, healthy eater, slim, etc….but diagnosed at Stage 4 with lung cancer. He had symptoms for at least a year and sought input from his primary care doctor. But his symptoms could all be attributed to other things as well, like age and stress. Once he started losing lots of weight I panicked and made him beg the doctor to test him for cancer. By the time the diagnosis was made, he was 140 pounds at 5’1O” tall. He lived 2.5 years after diagnosis with treatments like Tarceva and others after Tarceva failed. He was grateful for those years and it helped us prepare and understand our finances and how I would best live without him. We had loads of time to talk; he even went back to work. I can’t help but think that if we had demanded the right screening earlier, like six months earlier, the cancer could have been caught at an earlier stage before it had spread to his liver and bones. I believe you when it’s other patients you are describing, but struggle when I apply it to my husband. I’m still listening and learning. I am a huge fan and supporter in spite of my personal experience.
Am sorry for your loss. But if he was not a smoker he would have not qualified for screening. You need to have smoked 1ppd for 20yrs to qualify and be aged 50-78. Even in the 3yrs during its trial 4% of patients had cancer. That’s a lot of cancer indeed but the smoking exposure was the risk factor. Lung cancer absolutely can happen even if no smoking (see Dr Paul Kalanithi - a late 20s neurosurgery resident who died of such) - but it’s very statistically rare. Perhaps a safe and clear screening modality will arise to detect it for non-smokers but we have not seen that be performed via strong evidence yet.
Yes unfortunately he wouldn’t qualify for screening being a non smoker, but he would have qualified for further work up of his symptoms, blood work, chest CT, etc. An X-ray may or may not have found something. So sorry for your loss! My grandpa died of lung cancer, he only lived about a year after his diagnosis and went through chemo and lobectomy. Knowing what I know now, I’m not sure why they did the lobectomy. A lot of pain and he still died of spread to his liver.
I generally agree with everything you say, however in this situation I find it hard to believe that finding a Stage 1 lung cancer on a screening study in a high risk individual is not beneficial. Sure there are complications of procedures that cause morbidity (I'm a retired IR and did thousands of lung biopsies over my career and caused plenty of pneumothoraces) but benefit/risk is very very high. And you know very well as an oncologist that a patient that has possible lung cancer on imaging almost always wants something done about it and is willing to take the risk to find out.
Thanks for the clarification. I am confused by one issue. In order for a determination of cancer specific death to be made, a provider must document that on the death certificate. I would think that with lung cancer, there would be a higher likelihood that it would be assigned as causal, as opposed to breast or prostate cancer where it would be more likely to go unmentioned as a “bystander” diagnosis. Does this issue in any way confound the way we think about this?
I think that is a fair criticism if the claim is that randomized trials directly proved a reduction in every measure of cancer morbidity. They did not. The major lung screening trials were powered primarily for mortality, and they did a poor job measuring outcomes such as hospitalization days, treatment toxicity, symptom burden, and time spent receiving cancer care.
But I also think it goes too far to say we therefore have no evidence that morbidity is reduced. NLST showed fewer lung cancer deaths and a substantial reduction in stage IV diagnoses in the screened group. As oncologists, we both know a stage IV lung cancer diagnosis has a very different burden of symptoms, metastatic complications, systemic therapy, hospitalization, and end-of-life care than a localized cancer found through screening.
Stage is still a surrogate, and screening has harms of its own. So I would phrase the conclusion like this: lung cancer screening has been proven to reduce mortality and advanced-stage disease, strongly suggesting a reduction in some cancer-related morbidity, although the size of that benefit has not been adequately measured.
I actually think the failure to measure those patient-centered outcomes is an important gap in the screening literature, rather than evidence that the benefit does not exist. And I agree that work should be done by the investigators. It might have been the biggest flaws of their studies not to collect and report that out.
Reduced lung-cancer mortality with low-dose computed tomographic screening
National Lung Screening Trial Research Team; Denise R Aberle, Amanda M Adams, Christine D Berg, William C Black, Jonathan D Clapp, Richard M Fagerstrom, llana F Gareen, Constantine Gatsonis, Pamela M Marcus, JoRean
Abstract
Background: The aggressive and heterogeneous nature of lung cancer has thwarted efforts to reduce mortality from this cancer through the use of screening. The advent of low-dose helical computed tomography (CT) altered the landscape of lung-cancer screening, with studies indicating that low-dose CT detects many tumors at early stages. The National Lung Screening Trial (NLST) was conducted to determine whether screening with low-dose CT could reduce mortality from lung cancer.
Methods: From August 2002 through April 2004, we enrolled 53,454 persons at high risk for lung cancer at 33 U.S. medical centers. Participants were randomly assigned to undergo three annual screenings with either low-dose CT (26,722 participants) or single-view posteroanterior chest radiography (26,732). Data were collected on cases of lung cancer and deaths from lung cancer that occurred through December 31, 2009.
Results: The rate of adherence to screening was more than 90%. The rate of positive screening tests was 24.2% with low-dose CT and 6.9% with radiography over all three rounds.
A total of 96.4% of the positive screening results in the low-dose CT group and 94.5% in the radiography group were false positive results. The incidence of lung cancer was 645 cases per 100,000 person-years (1060 cancers) in the low-dose CT group, as compared with 572 cases per 100,000 person-years (941 cancers) in the radiography group (rate ratio, 1.13; 95% confidence interval [CI], 1.03 to 1.23). There were 247 deaths from lung cancer per 100,000 person-years in the low-dose CT group and 309 deaths per 100,000 person-years in the radiography group, representing a relative reduction in mortality from lung cancer with low-dose CT screening of 20.0% (95% CI, 6.8 to 26.7; P=0.004). The rate of death from any cause was reduced in the low-dose CT group, as compared with the radiography group, by 6.7% (95% Cl, 1.2 to 13.6; P=0.02).
Conclusions: Screening with the use of low-dose CT reduces mortality from lung cancer.
(Funded by the National Cancer Institute; National Lung Screening Trial Clinical Trials.gov
I have been listening to your podcasts and reading your articles since the regrettable indoor days of the pandemic. You are an important voice and I want to believe everything you say. The lung cancer information stings, though. My husband died from lung cancer in 2015 at age 58. He was a non-smoker, regular exerciser, healthy eater, slim, etc….but diagnosed at Stage 4 with lung cancer. He had symptoms for at least a year and sought input from his primary care doctor. But his symptoms could all be attributed to other things as well, like age and stress. Once he started losing lots of weight I panicked and made him beg the doctor to test him for cancer. By the time the diagnosis was made, he was 140 pounds at 5’1O” tall. He lived 2.5 years after diagnosis with treatments like Tarceva and others after Tarceva failed. He was grateful for those years and it helped us prepare and understand our finances and how I would best live without him. We had loads of time to talk; he even went back to work. I can’t help but think that if we had demanded the right screening earlier, like six months earlier, the cancer could have been caught at an earlier stage before it had spread to his liver and bones. I believe you when it’s other patients you are describing, but struggle when I apply it to my husband. I’m still listening and learning. I am a huge fan and supporter in spite of my personal experience.
Am sorry for your loss. But if he was not a smoker he would have not qualified for screening. You need to have smoked 1ppd for 20yrs to qualify and be aged 50-78. Even in the 3yrs during its trial 4% of patients had cancer. That’s a lot of cancer indeed but the smoking exposure was the risk factor. Lung cancer absolutely can happen even if no smoking (see Dr Paul Kalanithi - a late 20s neurosurgery resident who died of such) - but it’s very statistically rare. Perhaps a safe and clear screening modality will arise to detect it for non-smokers but we have not seen that be performed via strong evidence yet.
Yes unfortunately he wouldn’t qualify for screening being a non smoker, but he would have qualified for further work up of his symptoms, blood work, chest CT, etc. An X-ray may or may not have found something. So sorry for your loss! My grandpa died of lung cancer, he only lived about a year after his diagnosis and went through chemo and lobectomy. Knowing what I know now, I’m not sure why they did the lobectomy. A lot of pain and he still died of spread to his liver.
I generally agree with everything you say, however in this situation I find it hard to believe that finding a Stage 1 lung cancer on a screening study in a high risk individual is not beneficial. Sure there are complications of procedures that cause morbidity (I'm a retired IR and did thousands of lung biopsies over my career and caused plenty of pneumothoraces) but benefit/risk is very very high. And you know very well as an oncologist that a patient that has possible lung cancer on imaging almost always wants something done about it and is willing to take the risk to find out.
Given the Welch study, is there comparable data that supports recommending routine mammography broadly?
Thanks for the clarification. I am confused by one issue. In order for a determination of cancer specific death to be made, a provider must document that on the death certificate. I would think that with lung cancer, there would be a higher likelihood that it would be assigned as causal, as opposed to breast or prostate cancer where it would be more likely to go unmentioned as a “bystander” diagnosis. Does this issue in any way confound the way we think about this?
As it has been said "If the cancer doesn't kill you the chemo will" . I have known a few now that that was the exact scenario for them.
I think that is a fair criticism if the claim is that randomized trials directly proved a reduction in every measure of cancer morbidity. They did not. The major lung screening trials were powered primarily for mortality, and they did a poor job measuring outcomes such as hospitalization days, treatment toxicity, symptom burden, and time spent receiving cancer care.
But I also think it goes too far to say we therefore have no evidence that morbidity is reduced. NLST showed fewer lung cancer deaths and a substantial reduction in stage IV diagnoses in the screened group. As oncologists, we both know a stage IV lung cancer diagnosis has a very different burden of symptoms, metastatic complications, systemic therapy, hospitalization, and end-of-life care than a localized cancer found through screening.
Stage is still a surrogate, and screening has harms of its own. So I would phrase the conclusion like this: lung cancer screening has been proven to reduce mortality and advanced-stage disease, strongly suggesting a reduction in some cancer-related morbidity, although the size of that benefit has not been adequately measured.
I actually think the failure to measure those patient-centered outcomes is an important gap in the screening literature, rather than evidence that the benefit does not exist. And I agree that work should be done by the investigators. It might have been the biggest flaws of their studies not to collect and report that out.
Reduced lung-cancer mortality with low-dose computed tomographic screening
National Lung Screening Trial Research Team; Denise R Aberle, Amanda M Adams, Christine D Berg, William C Black, Jonathan D Clapp, Richard M Fagerstrom, llana F Gareen, Constantine Gatsonis, Pamela M Marcus, JoRean
Abstract
Background: The aggressive and heterogeneous nature of lung cancer has thwarted efforts to reduce mortality from this cancer through the use of screening. The advent of low-dose helical computed tomography (CT) altered the landscape of lung-cancer screening, with studies indicating that low-dose CT detects many tumors at early stages. The National Lung Screening Trial (NLST) was conducted to determine whether screening with low-dose CT could reduce mortality from lung cancer.
Methods: From August 2002 through April 2004, we enrolled 53,454 persons at high risk for lung cancer at 33 U.S. medical centers. Participants were randomly assigned to undergo three annual screenings with either low-dose CT (26,722 participants) or single-view posteroanterior chest radiography (26,732). Data were collected on cases of lung cancer and deaths from lung cancer that occurred through December 31, 2009.
Results: The rate of adherence to screening was more than 90%. The rate of positive screening tests was 24.2% with low-dose CT and 6.9% with radiography over all three rounds.
A total of 96.4% of the positive screening results in the low-dose CT group and 94.5% in the radiography group were false positive results. The incidence of lung cancer was 645 cases per 100,000 person-years (1060 cancers) in the low-dose CT group, as compared with 572 cases per 100,000 person-years (941 cancers) in the radiography group (rate ratio, 1.13; 95% confidence interval [CI], 1.03 to 1.23). There were 247 deaths from lung cancer per 100,000 person-years in the low-dose CT group and 309 deaths per 100,000 person-years in the radiography group, representing a relative reduction in mortality from lung cancer with low-dose CT screening of 20.0% (95% CI, 6.8 to 26.7; P=0.004). The rate of death from any cause was reduced in the low-dose CT group, as compared with the radiography group, by 6.7% (95% Cl, 1.2 to 13.6; P=0.02).
Conclusions: Screening with the use of low-dose CT reduces mortality from lung cancer.
(Funded by the National Cancer Institute; National Lung Screening Trial Clinical Trials.gov
The NLST reported a 6.7% all cause mortality rate reduction for the CT screening group. Are you disputing the data, and if so, on what basis?
Vinay addressed this in the following paper (and elsewhere, IIRC):
Desai and Prasad, 2021 | Low-Dose Computed Tomographic Screening for Lung Cancer: Time to Implement or Unresolved Questions?
https://bit.ly/Desai2021