Screening Issues and Controversy
Screening debate, pros and cons
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Growing Endorsement of Chest CT Screening for Lung Cancer: Why Aren’t We Doing It?
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:
Why shouldn’t we do screening for lung cancer on everyone?
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.
Why?
What are the Characteristics of the Nodules that are Biopsied but Mistakenly Called Benign?
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:
- have a lung cancer later diagnosed
- have a subsequent procedure (such as a surgery) that confirmed a benign cause, or
- showed resolution of the questionable nodule, or
- showed stable findings over at least two years of follow-up that would be considered very consistent with a benign nodule
Refining CT based lung cancer screening with a blood test?
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.
Dr. Weiss’s “Highlights in Lung Cancer, 2011″: CT Screening & Optimal Management of Elderly Patients with Advanced NSCLC
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.
Dr. Weiss Highlights in Lung Cancer 2011, Pt. 3 CT Screening and LC in Elderly Audio Podcast
Dr. Weiss Highlights in Lung Cancer 2011, Pt. 3 CT Screening and LC in Elderly Transcript
Dr Weiss Highlights in Lung Cancer 2011, Pt. 3 CT Screening and LC in Elderly Figs
Podcast: Play in new window | Download (Duration: 13:57 — 40.8MB) | Embed
Dr. David Yankelevitz on Evaluation and Management of Pulmonary Nodules
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:
dr-yankelevitz-pulm-nodules-evaluation-and-management-audio-podcast
dr-yankelevitz-pulm-nodules-evaluation-and-management-transcript
dr-yankelevitz-pulm-nodules-evaluation-and-management-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.
Podcast: Play in new window | Download (85.6MB) | Embed
Capitalizing on a “Teachable Moment”: Lung Cancer Screening, Smoking Cessation, and Cost-Effectiveness
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.
The National Lung Screening Trial: Results are in
The much-anticipated manuscript from the NCI-sponsored National Lung Screening Trial (NLST) was just published on line in the New England Journal of Medicine, with an editorial by Dr. Harold Sox. As Dr. West outlined in a previous post, we’ve known since last year that this trial demonstrated an improvement in lung-cancer specific survival with low-dose spiral CT screening of high-risk individuals. However, we have not had access to the details of this study until now. One of the fundamental problems we face is that lung cancer is most often diagnosed in an advanced stage. This has generated intense interest in screening and early detection. However until this trial, no screening test has been shown to reduce the risk from dying from lung cancer, which is the benchmark we use to judge the effectiveness of any screening modality. As the first trial that shows lung cancer screening can save lives, the NLST will no doubt have a significant impact on how we practice in this country and should be viewed as a very hopeful result for lung cancer advocates. However, many questions remain and as is the case with any medical intervention, individuals considering low dose CT screening will need to weigh not only the potential benefit (as defined for the first time by this trial), but also the potential risks associated with this approach. The NLST will go a long way towards informing this decision.
Lung Cancer Screening Saves Lives!
For years and years, lung cancer advocates have often aggressively championed screening for lung cancer, while many in the medical “establishment” and policy-makers expressed reservations that, while there were encouraging indicators of benefit, there was not evidence that lung cancer screening saves lives, so we really couldn’t make a blanket statement encouraging lung cancer screening. That has now changed, as the NCI-sponsored National Lung Screening Trial (NLST) has now been reported to demonstrate a 20% improvement in lung cancer-specific survival. A preliminary but detailed manuscript describing the trial itself is published in the journal Radiology and is available at no charge.
The trial was started in 2002 and randomized over 53,000 patients who were 55-75 and had at least a 30 pack-year smoking history (pack-years being the product of average number of packs of cigarettes smoked per day x number of years smoking) to either annual low-dose spiral CT scans for three consecutive years or a chest x-ray on the same interval. These screening CT scans are done without IV contrast and are done within a single breath hold (up to 15 seconds) but can fully view the lung fields.
The Data Safety Monitoring Committee that regualrly reviews the trial results over the course of a study’s ongoing conduct recently reviewed the most current results and noted a statistically significant improvement in the lung cancer-specific survival of people were were randomized to screening CT scans. Specifically, there were 354 deaths from lung cancer on the CT arm, vs. 442 deaths from lung cancer on the arm assigned to chest x-rays, a 20.3% reduction. In addition, the CT screened patients had a 7% reduction in “all cause mortality” (not just lung cancer, but deaths for any reason), with only 25% of the deaths in the overall trial due to lung cancer. This was likely due to detection of issues such as cardiovascular disease and other incidental but significant medical problems with CT but not chest x-ray screening.
Dr. Kristin Manning: Introduction to Imaging for Lung Cancer
A radiologist, the person who specializes in reviewing imaging studies in medicine, is often someone you notice if they’re unusually bad or unusually good. They perform a service and you presume that they’re good at it, but a few are so sharp that the other doctors they work with notice it at every tumor board discussion or one on one exchange.
Dr. Manning is one of those special radiologists. She had trained at the University of Washington while I was completing my medical oncology training there, and when she left to join Seattle Radiology, a private group based at Swedish Hospital in Seattle, I was among the many doctors who felt the body blow of losing her talent. On the other hand, when I later joined the medical oncology group at Swedish, I was very happy to have the opportunity to be reunited with her.
But talk is cheap, so I’ll also add that when I developed a cough that lasted for months a few years ago, and one of the thoracic surgeons I work with said I needed to get a chest CT to check it out (as I joked that his practice was slow and that he was trying to drum up business), it was Dr. Manning who read my own scans for me (and fortunately, they were OK).
She remains a terrific resource, and one too valuable to not share with others. She was kind enough to sit down with me for a discussion of current issues in imaging, with a particular focus on issues related to lung cancer. Here’s the first part of our discussion, which covers a bit on screening, the issues related to assessing and following lung nodules, and some basics of the work-up and ongoing follow-up of patients with lung cancer. Below you’ll find the audio and video versions of the podcast, the transcript, and a copy of the very few figures associated with the audio component:
dr-manning-imaging-intro-part-1-audio-podcast
dr-manning-imaging-intro-part-1-transcript
dr-manning-imaging-intro-part-1-figures
Podcast: Play in new window | Download (0.3KB) | Embed
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