Screening Issues and Controversy
Screening debate, pros and cons
One of the challenges of the increased frequency of chest CT scans being done for screening of people at higher risk of lung cancer, or done more commonly for chest symptoms, is that lung nodules are very commonly found, but most the time they aren’t cancer. Most studies show that >90% of lung nodules are benign, but the majority lead to additional work-up, and in nearly 100% of cases, they cause anxiety for the patient. What if a blood test could help clarify the probability that someone doesn’t have a lung cancer?
The most pivotal study supporting the value of screening for lung cancer is the National Lung cancer Screening Trial (NLST), which revealed a 20% improvement in overall survival in patients with sufficiently high risk of lung cancer and who underwent an annual chest CT scans vs. chest x-ray over a three year period. This significant benefit was seen in patients who were sufficiently high risk for lung cancer — patients age 55-75 and with at least a 30 “pack-year” smoking history (the product of number of years smoking x average number of packs smoked per day).
But even after this survival benefit was seen,there has been plenty of controversy that followed. Screening chest CT scans detects not only some true, life threatening lung cancer but also many, many benign lung nodules in people who undergo these scans. News of such nodules often cause people cause tremendous anxiety, along with a need for additional imaging and often invasive procedures to clarify whether the detected nodules are more likely to represent a benign finding or a real cancer.
Some patients and many institutions favor extending the screening of high risk patients to those at significantly lower risk, such as those who are younger, have minimal smoking history, perhaps even a never-smoker with a family history. But there is a real danger that if screening is applied people at low risk of actually having lung cancer, it’s far more likely that any nodules detected will be benign but will still lead to all of the anxiety, extra scans, and sometimes invasive procedures… just not to lives saved from lung cancer.
Why do screening on people who are at lower risk? Many people are nervous about lung cancer, and some institutions that make money by doing scans and procedures may be more than happy to oblige them or even feed their fears. We need to be judicious about how to use CT screening for lung cancer in a way that can save the most lives but lead to a minimal amount of extra scans, unneeded biopsies, and profound anxiety.
What is remarkably instructive as we struggle with these issues is a a new analysis of the results from the NLST study that stratified eligible patients by level of risk, which demonstrates the real risks of lung cancer vs. “false positives” – cases where the nodules required action and probably caused anxiety, but it wasn’t cancer. The investigators looked at a wide range of relevant variables for risk of lung cancer (age, sex, years since quitting, pack-years of tobacco exposure, family history, etc.), then divided the participants into 5 quintiles (5 equally sized groups). As we would expect, major differences were noted in the efficacy and significance of an abnormal result depending on whether people eligible for the NLST were higher or lower on the risk spectrum. Continue reading
I just did a brief video for Swedish Medical Center on the issue of low dose CT screening for lung cancer, which has been proven to improve survival. Though Dr. Otis Brawley, Chief Medical Officer of the American Cancer Society, just wrote a book about the risk of over-diagnosis of cancer, the ACS has just officially endorsed lung cancer screening, recognizing its value.
The only problem is that it really isn’t being done. I discuss a bit on the resistance to screening here:
A post on About.com makes the case that screening the higher risk population of just those people 55-75 with a significant smoking history, as was done in the influential National Lung Cancer Screening Trial (NLST) published last year in the New England Journal of Medicine, would miss nearly 3 of 4 lung cancers even as this effort improves lung cancer survival by 20% in the screened population. This piece implies that broader screening across of a wider range of ages and smoking history would be appropriate in order to detect more lung cancer and improve outcomes. So let me make two points.
1) I am a proponent of lung cancer screening for an appropriate population and think it’s underutilized now.
2) It is categorically incorrect to presume that broadening screening to a wider population will lead to better outcomes.
We know that there is a big difference between a lung (or pulmonary) nodule and having cancer. Formal screening studies or just random CT scans done for other reasons will often show nodules that are of questionable significance, leading us to recommend either follow-up imaging or an immediate biopsy, depending on the level of suspicion. Often, the biopsy gives us an explanation for the nodule: perhaps cancer, but otherwise, perhaps just inflammatory or scar tissue, or else infection. That answer is usually the right answer, but not always. There is a chance that a result that comes back as “not cancer” is actually a false negative result: this happens there is actually cancer, but the correct answer wasn’t detected. What are the features that suggest a greater probability that we can’t necessarily be as confident of a biopsy result that comes back as something other than cancer?
We can get some insight about this question from the published experience from the radiology groups at Cornell University and Mt. Sinai Medical Centers in New York City, who just published on their results of the clinical and imaging features of their false negative CT-guided biopsy results over a three-year period from the beginning of 2002 to the end of 2004 (Dr. Yankelevitz, who has great experience as an expert in CT screening and biopsies and who did a terrific webinar for us on detecting and evaluating lung nodules last year, is the senior author of this paper). To do this, they reviewed the results from 170 patients in that interval who had an initial biopsy that was reported as negative initially who were then either found to:
Many people in the lung cancer world consider the National Lung Screening Trial (NLST) that demonstrated a 20% improvement in survival from CT-screening higher risk people for lung cancer as a major advance in the field, befitting coverage in Dr. Weiss’s summary of lung cancer highlights from 2011, but this hasn’t yet led to wholesale adoption of the practice. Why not? Some people say that it’s just one study and that we need more evidence, but it’s hard not to believe that implications for health care resource utilization (i.e., cost and practical implementation) aren’t a big part of the challenge. Annual CT scans will/would add a lot of cost when applied for the millions of people just in the US who would be appropriate candidates by the definition of the study (age 55-75 and with a 30 pack-year smoking history). In addition, we know that CT screening detects a lot of nodules that require plenty of follow-up scans and cause significant anxiety but ultimately prove to not be cancer. What if we could add another factor that could raise or lower our suspicion and potentially enable us to modify the frequency of scanning and/or our enthusiasm for escalating the workup?
I’ve covered one such approach in a prior post describing a test analyzing chemical compounds in the exhaled breath of patients, and this research is ongoing. But another strategy is to analyze the blood of patients in search of preliminary evidence of cancer that might be detectable at the time of or even before the earliest imaging findings suggestive of cancer. The EarlyCDT-Lung test is designed to do this by looking for immuno-biomarkers (“auto-antibodies” created by the body in reaction to a protein detected within), any of a panel of 6-7 that could signify early cancer if one or more of these is elevated.
This is the third and final part of Dr. Weiss’s presentation on “Highlights in Lung Cancer, 2011″. After focusing on developments in relatively narrow subpopulations with distinct molecular markers in the first two parts of his webinar, Dr. Weiss closed with his coverage of a couple of issues with broader applicability: the new data supporting CT screening for higher risk people with a significant smoking history, and also some new data addressing the question of whether elderly patients are best served by receiving single agent or doublet chemotherapy.
Below you’ll find the podcast of the program in audio and video formats, as well as the transcript and figures for this activity.
Here’s the podcast from the recent webinar by Dr. David Yankelevitz, Professor of Radiology at Mount Sinai Medical Center in New York City, on the subject of “Pulmonary Nodules: Evaluation and Management”. He took us through a wonderful review of many recent developments in CT scans, both in screening programs and informal workup of many other medical settings, as well as how the best radiologists distinguish higher from lower risk nodules. He also covered the work-up of higher risk nodules with CT-guided biopsies.
One key point: a huge proportion of lung nodules aren’t cancer, and as our CT scanners get more sensitive, we’re going to be finding nodules in just about everyone. But when they’re that common, it’s not really appropriate to call them abnormal.
Below is the audio and video versions of the podcast, as well as the transcript and figures:
This was another webinar in the terrific expert series that we developed in partnership with LUNGevity Foundation. Thanks to both Dr. Yankelevitz and LUNGevity for making this great program possible. I hope it’s helpful.
The National Lung Screening Trial (NLST), a protocol with over 50,000 former or current smokers between ages 55 and 75, justifiably became a major news story when the results demonstrated a significant improvement in lung cancer-specific and all-cause mortality of 20% and 6.7%, respectively. However, now even a year after the initial press releases about the positive results and several months after its publication in the New England Journal of Medicine (marking it as a practice-changing finding), CT screening for lung cancer hasn’t yet become routine practice. Why not? In contrast with screening results in breast or colon cancer, where positive results have led to a change in policy, the cost of implementing a broad screening policy today entails a public debate about the feasibility, which largely centers around costs.
In this context, a paper by McMahon and colleagues in the Journal of Thoracic Oncology provides a valuable analysis. The authors created a data-based simulation of cohorts of men and women of ages 50, 60, and 70 (six distinct cohorts) with a significant smoking history that would reflect the range of patients included in a screening program instituted based on the NLST. Calculating results based on the data from this simulation, they then analyzed the cost-effectiveness in the common term for this measurement of “costs per quality-adjusted life-year gained ($/QALY)” (essentially, how much does it cost to improve one person’s life by a year of functional, “good” time?) for these cohorts when modeling estimated outcomes for CT screening, smoking cessation interventions (with a range of abstinence ranging from 4 to 30% at one year), and a combination of these two approaches.