Management of Lung Cancer in 2004
Wilson Ko, M.D.
(presented at the 2004 CAMS Annual Scientific Meeting)
Lung cancer is the leading cause of cancer death for men and women in the United States, accounting for more than 140,000 annual cancer related deaths and more than the total number of cancer deaths for the next three most common cancers combined (colon, breast and prostate). There is over one million lung cancer deaths worldwide annually. With these numbers in mind, one may argue that lung cancer has not gotten the attention from the public media that it deserves. The incidence of lung cancer increased exponentially during the 1960’s to 1970’s, and reached a plateau during the last decade. We do not have data on the ethnic differences between Chinese Americans and the general U.S. population.. However, the World Heath Organization publishes the incidence of lung cancer among many countries world wide. If we use Hong Kong as a benchmark, the incidence of lung cancer among Chinese males is almost identical to, and among Chinese females is slightly worse than that of the U.S. general population. We were taught in medical school that the smoking related squamous cell carcinoma was the most common histologic type of lung cancer, exceeding the other two, namely adenocarcinoma, and large cell carcinoma. However, the distribution of these three histologic types has changed over the last two decades. It is now known that adenocarcinoma is the most common type, accounting for close to half of the current cases. Having been involved in the large Chinese community in New York, my personal experience with lung cancer among Chinese Americans is very different from the rest of the New York population. The patients that come to my attention for surgical resection have predominately adenocarcinoma, and the prevalence among women is higher than man. This point was discussed among the participants in this meeting. Possible etiologies other than smoking were discussed. They included second hand smoking, unique cooking habits such as open fire stir frying. The discussion concluded in a recommendation to study the unique ethnic differences among Chinese Americans in the large community in New York. Suggestion was made for CAMS to sponsor such a study with the collaboration of the many well established Chinese pulmonologists in New York.
The overall five year survivals for lung, colon, breast, and prostate cancer are 15%, 61%, 86%, and 96%, respectively. These statistics underscore the dismal prognosis of the lung cancer patients compared to other common cancers. The median 1 year survival for metastatic lung cancer (stage IV) is merely 5 months. With modern chemotherapy and radiation, it is extended by 3 more months according to 2004 data. The 5 year survival for stages I, Ib, II a, II b, IIIa disease are 67%, 57%, 55%, 39% and 23%, respectively. It is unfortunate that even for the earliest lesion (less than 3 cm, with no lymph node metastasis) that come to a complete resection with intent to cure, about one third of them will still die of the disease. There is a trend to look at lung cancer more like breast cancer, in that perhaps it is more disseminated than we thought even at the earliest stage. This is probably more and more true with the increasing incidence of adenocarcinoma supplanting squamous cell carcinoma.
Modern thoracic surgery for lung cancer was not developed until the 1960s, not until the concepts of endotracheal intubation and positive pressure ventilation were developed into standard practice which allow the surgeon to expose the lung, normally under negative pressure, to the atmosphere. The survival impact of thoracic surgery accounts for 7% of all newly diagnosed lung cancer (12,000 cases annually) patients who would not have survived in 1960. Only 20% of all lung cancer patients are referred to the thoracic surgeon. Half of these patients undergo some sort of diagnostic or palliative procedures, and the other half (of 10% of total) will undergo surgical resection with the intent for cure. Only 70% of these (or 7% of total) will become long term survival after curative surgery.
With this dismal overall long term survival rate, we must ask ourselves how we can do better in screening, early diagnosis, accurate staging, aggressive surgical resection, chemotherapy, and radiation.
Pap smears, mammogram, and colonoscopy have been accepted as important screening tools for cancers. Despite many years of research, there is still no supportive data for any screening for lung cancer according to the American College of Chest Physician guidelines. The Early Lung Cancer Action Project led by Dr. Henesche at Cornell has documented the efficacy of using low radiation CT scan to screen high risk patients for lung cancer . In this study, there was a 3% yield from the initial screen. They were all not seen on CXR, and 85% were stage I. Therefore, we can only hope that CT scan will be approved by the government to be used as a screening for high risk patients.
CT scan, by far, is the most important imaging tool for evaluation. From it, the location, size, associated hilar and mediastinal lymph node involvement are determined. Based on its location and proximity to other vital organs, the most appropriate approach to establish tissue diagnosis, and its resectability can be determined.
The addition of PET scan has been very useful in the initial and post-treatment evaluation of lung cancer patients. Excellent data has demonstrated that a negative PET scan outside of the primary lesion correlates very well (>90% accurate) with localized disease. It is invaluable in assessing the mediastinal lymph nodes and distant metastasis, metachronous lung nodules/masses, and to detect local recurrence after successful resection. Bone scan is no longer necessary. In an important study conducted by the American College of Surgeon, the data suggests that up to 1/5th of unnecessary thoracotomy can be avoided by preoperative PET scan. A few caveats: PET scan cannot evaluate the brain because of its high metabolic rate . A negative PET scan should never be taken as definitive to exclude the diagnosis of cancer in solitary pulmonary nodules. The likelihood of it being cancer is best assessed by the experienced thoracic surgeon based on its CT scan appearance. For example, adenocarcinoma is well known to be negative on the PET scan.
In addition to bronchoscopic biopsy, the thoracic surgeon has to his disposal transthoracic needle biopsy, mediastinoscopy, and thoracoscopy for diagnosis and staging. The most important differentiation in patients without distant metastasis, is to determine whether or not there is mediastinal lymph node metastasis. Patients with ipsilateral involvement should undergo pre-operative chemotherapy, and surgical resection is only indicated for those who responded. Patients with contralateral lymph node involvement were not thought to have any chance for long term survival and therefore surgery was not recommended. However, recent data suggest that there are few patients who responded well to chemotherapy with complete resolution of mediastinal disease and should undergo resection with the intent to cure. In my 10 years of practice, I have only encountered two of such patients who were so fortunate to have come back for surgery after successful chemotherapy.
Video assisted thoracoscopic (VAT) surgery has been refined over the last 10 years. VAT lobectomy is now possible for a subset of patients. The advantages include a small cosmetic incision, less postoperative pain?(not proven), quicker recovery and return to work (likely will bear out to be true). However, the current techniques of VAT lobectomy does not allow a full mediastinal lymph node dissection, which is accepted to be an important part of the operation with intent to cure. Therefore, current recommendation limits this technique to “small” stage I patients (<2 cm), with negative PET scan to document the absence of mediastinal lymph node involvement.
Robotic surgery has been sensationalized in the mass media recently. It was originally an idea conceived for cardiac surgery, but it is now also being investigated for lung surgery and others. The extraordinary costs ($1.5 million for the hardware, $200,000 for annual maintenance, about $5,000 for disposables per case) and the limited safety profile of the first generation device would categorize it as purely investigational. It is being used by hospital administrators for marketing purposes. How can we justify such astronomical costs in the face of ever diminishing reimbursements for hospitals and physicians?
With the support of industries, there are now several products designed specifically for the thoracic surgeon to provide palliation for the end staged patients. These techniques include Laser ablation, bronchscopic high pressure balloon dilatation, and stent placement for tracheo-bronchial obstruction. Many of these techniques were transferred from coronary angioplasty.
The publication in NEJM in Jan of 2004 regarding the use of Cisplatin based chemotherapy being able to prolong survival of lung cancer patients across all stages has received much attention. The survival benefits were only a few percentage points. Until now, stage I and II patients were not recommended for postoperative chemotherapy. In light of the new findings, we are obligated to refer all postoperative patients for a consultation with oncology. There is now enormous interest among several biotechnology companies in the development of so called “targeted” chemothereapeutic agents. Finally, molecular biology is being applied rigorously. Most of these new agents center around the biologic pathways of growth hormones and angiogenesis and their respective receptors. Iressa has been approved for salvage treatment of adenocarcinoma of the lung, especially the bronchioalveolar type. The responders tend to be women, and non-smokers. Others include Avastin and Erbitux that will likely to be approved for advanced stage lung cancer. These specific and less toxic systemic therapy holds the hopes for eradicating all cancer cells even for the earliest staged patient. They hold the promise to bring the survival rates of lung cancer patients to the level of other cancers such as breast and colon.
Lastly, three-dimensional image guided radiotherapy has allowed this targeted therapy to be more effective with less chance of damage to adjacent vital organ. For example, we should no longer lose hope on a patient who developed recurrent mediastinal nodal disease years after a curative lung resection.
It is very important to emphasize the importance of the comprehensive approach in the management of lung cancer. The thoracic surgeon is now seen as a central figure in coordinating the care of the lung cancer patients from the various discipline; he is given the responsibility of the ultimate expert in this regard. Lastly, the basic requisite for cure is anatomical and complete lung resection as dictated by modern thoracic surgical techniques. The very low operative mortality (<1% for lobectomy) is afforded not just by the surgeon, but a comprehensive thoracic surgical program consisting of also dedicated thoracic anesthesia, critical postoperative care, pain management, physical therapy, and specialized nursing care. Thoracic surgery has come a very long way over the last decade.
Dr. Ko is Associate Professor of Cardiothoracic Surgery, Weill Medical College of Cornell University and Attending Cardiothoracic Surgeon at New York Presbyterian Hospital-Cornell Medical Center, and Director of Cardiothoracic Surgery at New York Hospital Queens
