Friday, April 26, 2013

Lung Cancer Part 2 - Early Diagnosis

Most patients found to have lung cancer die within a year largely because their tumor has already spread, making treatment difficult. Now there is real reason to believe that lung cancer can be detected early and with it witness an improvement in cure. Given that 160,000 Americans die each year - more than the next four cancers combined – early diagnosis followed by curative treatment would be a major advance. 

For many years it was considered useless to screen individuals for lung cancer with chest x-rays in a manner comparable to mammography for breast cancer, PAP smears for cervical cancer  or colonoscopy for colon cancer because a chest X-ray only detected lung cancer when it was far advanced, which rarely meant detecting a cancer that could be cured. Over the past decade it has been postulated that CT scanning could detect lung cancer while it was still small and localized. Now as a result of careful randomized controlled studies, low dose CT (LDCT) scanning has proven effective in screening for lung cancer in high-risk populations. 

The largest LDCT study, the National Lung Screening Trial or NLST, was sponsored by the National Cancer Institute. Between 2002 and 2004 some 53,454 individuals were randomly allocated to be screened annually for three years with either routine chest X-ray or with low dose CT scans with data collected through the end of 2009.  The screening criteria were high-risk individuals, i.e.,  between the ages of 55-74, current or former smoker, 30+ pack years and still smoking until at least 15 years before. The results suggest that not only can early lung cancer be detected by LDCT but also that mortality can be reduced.  

For each annual scan, about twenty of every 100 (20 percent) of individuals will be found to have a nodule. But only one patient of every 100 will have lung cancer; that is only 5 percent (one of 20) of those with a nodule will be due to cancer, the other 19 of the twenty nodules (95 percent) are benign. To establish which are cancer and which are not, the next step is to follow the nodule with repeat CT scans or to do a biopsy.  

In an effort to avoid an invasive procedure to obtain the biopsy, the usual approach was to schedule repeat scans at three or six month intervals. Many individuals were given a scare before they were told all was okay many months or a year later when the repeat CT scans showed that the lesion either was stable or disappeared.  

The value of screening was demonstrated by the observation that 63% of cancers detected by LDCT were Stage IA or IB, distinctly different from the norm where most are found at advanced stages. When cancer was found, surgical resection with or without adjuvant chemotherapy or radiation therapy was the usual treatment. Overall, deaths from lung cancer were reduced by about 20% by using the LDCT scanning as described compared to chest X-ray screening. 

A few examples of false positives are illustrative of the dilemma:

A middle aged lady who had quit smoking ten years before was attracted by an offer at a local hospital to be scanned for only $75. She got a letter in the mail some weeks later saying she had a very small nodule that required follow-up. Naturally she was upset. Six months later she had another CT. At that screening she was told her scan was normal but that she should get screened again in six months “just to be on the safe side.” Ultimately she chose not to have any additional screening and remains fine albeit having had a tortuous path.

Another lady had a similar experience. Her nodule was larger and she had a year of every 3 months getting a CT scan and then after a year, every 6 months for two years at which point she was told that it was likely not cancer but that she should continue screening for another year. She has remained disease free.

An elderly gentleman with chronic lung disease who had been a heavy smoker for over 30 years had a lung nodule detected on CT scan. He was told it was highly suspicious for cancer. He had surgery to establish the diagnosis resulting in a collapsed lung with a difficult recovery.  The pathology showed that the nodule was not cancer but rather histoplasmosis in need of no therapy.

It is this high false positive rate that raises questions of risk benefit and cost effectiveness. The opportunity for early diagnosis of lung cancer raises important issues. The NLST studied only older individuals with a long and heavy smoking history, i.e., those at highest risk. For those, over 20 percent were found to have a pulmonary lesion of which 1 in 20 were ultimately found to be cancer. And those who were screened with CT scanning ultimately had a 20% reduction in lung cancer mortality compared to those screened with regular chest X-rays. If the screening criteria were loosened to include a broader base (as in the hospital above that offered inexpensive screening for any current or former smoker), would the result still be a high lesion discovery but a proportionately much smaller number of cancers discovered? Whether or not the screening criteria are expanded, the high rate of non-cancer/benign diagnoses requires careful consideration. These are individuals who, based on their smoking history, have a high prevalence of chronic lung disease and possibly cardiac disease, together making them less amenable to invasive procedures to confirm or eliminate a cancer diagnosis. As a result, more patients in the study were followed with repeat CT scans to determine if the lesion progressed – an approach linked to high stress levels for the individual patient and for the patient’s family. Clearly, an approach capable of resolving the diagnostic dilemma that is less invasive than needle biopsy or surgical incision is required. Some new technologies may soon be forthcoming in this regard.  

Taking all of this data into consideration, many professional societies such as the American Cancer Society, the American College of Chest Physicians and the American Society of Clinical Oncology have endorsed offering LDCT scanning for these high-risk individuals but only provided that there is first a thorough discussion of risks and rewards between physician and patient. 

For now, those who are at high risk for lung cancer, i.e., the criteria used in the NLST, should consult with their physician and carefully weigh the pros and cons of screening. Clearly, LDCT can detect lung cancer and detect it early when treatment options are much better. But the risks including anxiety related to a positive scan which may be a false positive are real.  If scanning is opted for, it should only be accomplished at an institution with high levels of expertise and experience. And should cancer be ultimately detected, it is best to be treated at an institution that not only has staff with the necessary expertise and experience but also utilizes the multi-disciplinary approach where thoracic surgeon, radiation oncologist and medical oncologist all interact with the patient together and offer a unified plan of care. 

The finding that LDCT can detect lung cancer while it is still small and localized is a major advance. Study patients were 20% less likely to die of lung cancer compared to those who were screened with regular chest X-rays. It opens the opportunity for cure with a combination of surgical resection or radiation therapy plus adjuvant combination chemotherapy. It also suggests the opportunity to begin, at an earlier stage, effective treatment for those found to have some overt spread of disease. Hopefully new non or less invasive yet rapid diagnostic venues will be shortly brought to bear on differentiating which lesions are cancer and which are benign.
Note: I first presented this five part series in Medical News Today at  

Tuesday, April 23, 2013

Lung Cancer Overview - Part 1 of 5

There has been some remarkable progress in recent years in the diagnosis and treatment of lung cancer. 160,000 Americans die annually from lung cancer making it second only to heart disease as a cause of death and slightly more than the next four cancers combined – breast, colon, pancreas and prostate.  This is largely because lung cancer is usually discovered only after it has spread. Now CT scanning has been shown to detect lung cancer when it is still small and localized. Further there have been major advances in treatment with radiation, with combination drug therapy and with new compounds targeted at “driver mutations”. Although cures are rare still they are growing in number. For those with extensive disease, there are useful responses to newer therapies that prolong survival and improve the quality of life. As a result, there now appears to be some light at the end of this very long tunnel. 

Facts and Figures - About 225,000 individuals will develop lung cancer in 2013. The incidence among men is higher than among women (76 and 53 per 100,000 respectively, age adjusted.) This is presumably due to the greater past use of tobacco by men over the years. The lifetime risk for men and women combined is about seven percent. That translates to one of every 14 individuals will develop lung cancer sometime during life. The incidence rises substantially with age. About one third of cases develop below the age of 65, one third between 65 and 75 and one third above age 75. The median age of onset is 70 years.  

It is certainly no surprise that smoking is the leading cause of lung cancer; about 80 percent of individuals are current (20 percent) or former (60 percent) smokers. Smoking increases a person’s lifetime risk by a factor of 20 times. Other causes are radon, second hand smoke, asbestos (especially when combined with smoking) and a variety of other environmental factors including arsenic, nickel and chromium. But there are those, especially younger women, who are developing lung cancer despite no known exposures. Lung cancer among both men and women who have never smoked is the sixth leading cause of cancer deaths with about 28,000 dying annually, about the same as prostate cancer caused deaths. 

The incidence of lung cancer has plateaued or even dropped slightly for men but is continuing to rise for women. This reflects the fact that a leveling off of smoking occurred sooner for men than women.

Most lung cancers are diagnosed after it has already spread past the lungs. As a result, surgery alone uncommonly leads to cure and unfortunately most patients are not even candidates for surgery due to local, regional or distant spread at diagnosis. Only about 15 percent of lung cancers are diagnosed when still localized to its pulmonary site of origin; the rest have already spread regionally (22 percent) or distantly (56 percent) with the remainder uncertain as to stage. Compare this to breast cancer or prostate cancer where about 60 percent and 80 percent respectively are localized at diagnosis. This makes for a huge difference in the ability to treat successfully. For women, it means that 73,000 die of lung cancer compared to 40,000 for breast cancer each year despite the fact the age adjusted incidence of the two diseases are 53 per 100,000 and 124 per 100,000, respectively.  

Lung cancer, with its 160,000 annual deaths, accounts for nearly 30 percent of all cancer deaths and is somewhat more than the combined mortality of the next four leading causes of cancer deaths - colon (about 56,000 deaths per year), breast (40,000), pancreas (37,000) and prostate (28,000).  

Survival is generally short with only about 15 percent five-year survivors (5 year survival rates are commonly used measures of successful therapy for cancer). Compare this to the rates of cure for breast cancer (about 90 percent), prostate cancer (nearly 100 percent), and colon cancer (65 percent). Given that the long phase of initiation of smoking to cancer diagnosis is many decades and given that 20 percent of Americans smoke regularly today it is reasonable to forecast that by 2030 the number of cases will increase by about 50 percent for both men and women.  

Categories and Early Detection - Lung cancers are categorized as either small cell or non-small cell lung cancer (SCLC, NSCLC) and the NSCLC are further defined by both their appearance under the microscope as squamous, adeno or large cell and increasingly by genomic analysis. Lung cancer can now be detected early with low dose CT scanning. This means that more individuals are potentially amenable to having their cancer cured. The demonstration that adjuvant chemotherapy for those with possible distant microscopic disease increases the rate of cure for resected NSCLC is a major advance.  But for each cancer lesion detected early by CT scans, 19 benign lesions are also detected which are usually not easily distinguishable from cancerous ones. This results in a dilemma for the patient and the physician – to have an invasive procedure to get a definitive answer or to have regular CT follow-up to see if the lesion progresses, stays stable or regresses. Clearly, new rapid, effective yet less invasive approaches to resolving this dilemma are critical.
Treatment - The opportunity to detect the cancer early means more individuals can be cured with surgical excision or with radiation therapy. Either can be followed by adjuvant chemotherapy for those with a high likelihood of microscopic disease spread. The combination of chemotherapy with radiation therapy has curative potential in locally advanced NSCLC and in limited stage SCLC. New approaches to radiation therapy allow for much higher doses of radiation to the tumor with much less damage to surrounding normal tissues. Current chemotherapy drugs, usually used in combination with one another, have clearly improved the quality of life for patients with more advanced disease, slowed progression of the tumor and created definite a, albeit relatively short, survival advantage.
Of interest in drug therapy today is the advent of “targeted drugs,” ones that inhibit a specific abnormal protein in the tumor cell that is a “driver” of the cancer. These are the products of DNA mutations or DNA rearrangements and are uncovered by genomic analysis. Because the new drugs are quite specific, they affect the tumor but cause proportionally less side effects. Responses among patients with the DNA mutations in their cancers tend to occur rapidly and often with marked regression of the tumor. Unfortunately, relapses eventually occur as resistance develops and the drugs are quite expensive. There is an important proof of principle here that has been accomplished and improvements in targeted treatment are coming fast and furiously.
There is good evidence that the best results with early diagnosis and with effective treatment lies in organizations that have high levels of expertise and utilize a multi-disciplinary approach to care wherein the patients is seen concurrently by surgeon, radiation therapist and medical oncologist to devise the most appropriate approach to care. Added to this, palliative care begun at the time of diagnosis adds to patient comfort, lessens anxiety, and reduces overall costs while improving satisfaction with caregivers and therapies.
With the advent of early diagnosis with CT screening, more effective yet less damaging approaches to radiation therapy, effective chemotherapy, targeted drug therapy for those with driver mutations, all initiated in experienced hands with a multi-disciplinary approach and early institution of palliative care, perhaps the light is now actually beginning to glow at the end of the tunnel for lung cancer patients and their families.
Four follow-on articles will discuss in more depth early diagnosis, treatment options of surgery, radiation and drugs, the use of multi-disciplinary team care and the value of palliative care teams. This five part series first appeared in Medical News Today at   

Praise for Dr Schimpff

The craft of science writing requires skills that are arguably the most underestimated and misunderstood in the media world. Dumbing down all too often gets mistaken for clarity. Showmanship frequently masks a poor presentation of scientific issues. Factoids are paraded in lieu of ideas. Answers are marketed at the expense of searching questions. By contrast, Steve Schimpff provides a fine combination of enlightenment and reading satisfaction. As a medical scientist he brings his readers encyclopedic knowledge of his subject. As a teacher and as a medical ambassador to other disciplines he's learned how to explain medical breakthroughs without unnecessary jargon. As an advisor to policymakers he's acquired the knack of cutting directly to the practical effects, showing how advances in medical science affect the big lifestyle and economic questions that concern us all. But Schimpff's greatest strength as a writer is that he's a physician through and through, caring above all for the person. His engaging conversational style, insights and fascinating treasury of cutting-edge information leave both lay readers and medical professionals turning his pages. In his hands the impact of new medical technologies and discoveries becomes an engrossing story about what lies ahead for us in the 21st century: as healthy people, as patients of all ages, as children, as parents, as taxpayers, as both consumers and providers of health services. There can be few greater stories than the adventure of what awaits our minds, bodies, budgets, lifespans and societies as new technologies change our world. Schimpff tells it with passion, vision, sweep, intelligence and an urgency that none of us can ignore.

-- N.J. Slabbert, science writer, co-author of Innovation, The Key to Prosperity: Technology & America's Role in the 21st Century Global Economy (with Aris Melissaratos, director of technology enterprise at the John Hopkins University).