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Monash Medical Centre
Clayton, VIC


Surgical resection of lung cancer has cured millions of people worldwide since its principles were established in the early part of the last century, however most lung cancers cannot be resected at the time of presentation and diagnosis. Thus chemotherapy, radiotherapy and palliative care have played a major role in treating symptoms of more advanced disease and to enhance quality of life in those who can’t be cured. This vast experience worldwide of trying to get on top of the problem has made all those involved with treating lung cancer aware that the adage “prevention is better than cure” relates to this situation perhaps more than any other preventable disease. In fact, it would not be an understatement to say that smoking has caused the greatest public health problem in the history of the world. It is obvious that its addictive properties have held people firmly in its grip, so that smoking cessation programs require just as much energy to implement to effect change as all the treatment regimes used to treat its harmful effects.

However, smoking cessation must be a priority for all countries. When one sees patients who have lost their health from smoking, then see people smoking from a box of cigarettes with “Smoking Kills” written in big letters, it leaves you asking the same question for both situations – why? Do people want health? There is a time however when reality strikes – when a person is faced with the reality that they have an untreatable lung cancer and it is the end. As doctors you can’t help feeling an intense despair at the situation – especially if, as a surgeon, you have to tell patients you can’t operate on them for one reason or another. You wonder, with all the information available, why cigarette companies don’t run workshops to support people they’ve made addicted – why we as doctors have to mop up after them while they sell products which create so much havoc for humanity. As if giving up smoking is not enough, 50% of lung cancers arise in people who have stopped smoking years before. Does anyone really want to have cancer?

This issue of Cancer Forum addresses all the current issues relevant to specialists treating lung cancer, and coincides with the final stages of the development of the first NHMRC/ACN Clinical Practice Guidelines for the Management of Lung Cancer.

Guidelines are evidence-based, but these articles cover a much broader range of areas with discussion and interpretations by the individual contributors.

In Australia, the beginning of the new millennium has started with the recognition of the need for surgeons to have good oncologic principles leading to the formation of the Surgical Oncology section of the Royal Australasian College of Surgeons. Many other Australasian organisations specially dedicated to cancer management such as the Australian Cancer Network and COSA and the Lung Cancer Consultative Group of the Australian Lung Foundation work together to support specialists treating lung cancer, and are forming a stronger voice for issues relating to lung cancer. Incredible advances have been made over just a few years to stop smoking in the workplace and public places, and more recently in gambling facilities. This has had a dramatic effect in Australia on smoking awareness, which will benefit everyone from now on, and help promote health rather than inevitable illness.

Management of lung cancer has improved so much due to expanding knowledge in all areas. In relation to surgery for lung cancer, principles established early in the last century still hold, and form the basis for current treatment. Compared to 100 years ago, dramatic developments in technology have changed the whole practice of surgery. Rubins1 pointed out however that the survival of stage 1 lung cancer in the two periods 1947 to 1969 and 1981 to 1994 were the same although perioperative mortality dropped significantly. Preoperative assessment, cardiac evaluation and surgery, inotropes, intensive care, antibiotics, CT scanning, PET scanning and above all, pulse oximetry and computers have been pivotal in this improvement in surgical survival.

Current issues

1. Correct diagnosis and delayed diagnosis

Currently there are several issues being discussed worldwide to improve lung cancer management. Firstly there is the issue of correct diagnosis of lung cancers. Liu Yurun2, in Beijing, in a review of 1061 cases of primary lung cancer misdiagnosed as other diseases addressed this issue of the difficulties of diagnosis. Treatment delays, resulting from different reasons have been looked at in a UK study by Bozcuk3, and in a Japanese mass screening group by Kashiwabara4. It was suggested that survival in lung cancer, apart from classical prognosticators, was strongly dependant on route of referral in early stages and use of combined-modality treatment in locally advanced disease, and that a one-year delay in detection of cancers under 2cm on mass screening did not affect prognosis.

2. Population-based screening for lung cancer

Early detection – using helical CT population-based screening – is addressed by another author in the following articles.

3. Management of small lung cancers – thoracoscopic wedge resection or lobectomy?

Although the Lung Cancer Study Group’s research5 found that lobectomy was better than wedge resection, many writers continue to evaluate the same issue hoping lesser procedures can be done for screening detected small cancers. In fact, just looking at 1cm cancers, Miller6 found 18 patients developed recurrent cancer, and node metastases were detected in seven of 100 patients, leading them to the conclusion that lobectomy was still the operation of choice. It is still a contentious issue however for screen-detected cancers, and will take further studies to convince everybody.

Is it possible to detect pre-cancerous nodules? It is of interest that cancers showing pure ground glass attenuation on CT are being detected more and more and formed the basis of several reports7,8. That by Kodama7 suggested that some of these will never progress to clinical disease, however a prior history of lung cancer raised the possibility of cancer as a diagnosis in some of their patients, leading to their excision. Because of difficulties in pre and intraoperative diagnosis, minimally invasive surgery may be appropriate to diagnose and cure such lesions.

4. Can investigative procedures be improved upon?

Is fluorescence bronchoscopy and virtual bronchoscopy with 3D visualisation of images going to help? Another author in the following articles addresses these issues.

5. TNM staging difficulties

Is current staging adequate? The current TNM classification has obvious strengths and along the way there are always difficulties with some tumours’ classifications. As the system is based on prognoses of different combinations being the same, time will show how to classify some rare situations when data are mature. One area of common interest to surgeons is pleural involvement (T2). A study by Saito9 looked at Touch Cytology of pleural surfaces over lung cancers. Overall, taking an impression of the surface of the lung using a glass slide at the time of surgery and staining it, revealed malignant cells in 17% of cases compared to 7% of pleural lavage. As well, malignant cells were identified in a significant number of patients without pleural malignancy detected on standard histology. This is one advance which may further tighten diagnostic criteria for T2, and is easily applied.

6. Technique of surgical resection

Is an open thoracotomy and node dissection better than thoracoscopic lobectomy (VATS ) and node dissection, or vice versa? So far only good results for thoracoscopic surgery have been presented10,11 and show virtually no difference between the gold standard of open resection and thoracoscopic resection, in terms of cancer outcomes. In a prospective trial aimed to determine the long-term prognosis of video-assisted thoracoscopic lobectomy versus conventional lobectomy for patients with clinical stage 1 T1N0 lung cancer, Sugi and colleagues10 studied 100 consecutive patients. Lymphnode dissections were performed in a similar manner in both groups, with no differences in the number of dissected nodes in the two groups. The conclusion was that VATS lobectomy with node dissection achieved an excellent five-year survival, similar to open lobectomy. Some dispute the safety of this procedure however, and surgeons are a little hesitant of the potential morbidity and the difficulty in teaching and training in this area to take it on in most units. Time will tell how this current vogue develops. Cost of staples for endoscopic procedures is limiting in countries trying to reduce costs, and as time in hospital is not magically reduced by the procedure to compensate for the expense, there may not actually be a reason to embark on these procedures. If the overall outcomes are the same, then, in terms of cancer management, this is purely a technical question relating to patient preference and surgeons’ skill to perform the surgery.

7. Understanding lung cancer biology

How can tumours be better characterised? Are serum and tissue biomarkers of the cancer cells predictive of outcomes, or is there a need for adjuvant treatment post-surgery? Bozzetti12 studied the biological parameters on CT-guided fine needle aspirates from peripheral primary non-small cell lung cancers, showing it is possible to get information other than histology from a needle biopsy. Buccheri13 also studied serum biomarkers in early stage lung cancer in an effort to guide selection of surgical candidates. They studied CEA and Tissue Polypeptide Antigen in patients with operable non-small cell lung cancer. Other biological assessments of lung cancers are ongoing to characterise patients better, and this area will become more relevant to surgeons as different interventions may result from the biological marker assessment. As well, early detection may be a possibility with a serum biomarker.

8. Management of stage 3a N2

Is the current surgical approach for stage 3a N2 correct? Ever since the Roth14 and Roselle15 studies were published on the management of stage 3a disease, indicating that neoadjuvant therapy then surgery is appropriate for resectable lung cancers with ipsilateral mediastinal node involvement, more experience has been gained. Ichinose16 from the Japanese Clinical Oncology Group reported recently on 466 completely resected stage 3a N2 patients, and Bedini et al17 reported their experience with maximal loco-regional treatment with cisplatin-enhanced high dose radiotherapy then surgery for initially non-respectable stage 3 lung cancer. Obviously with their successes, this treatment is becoming the acceptable way of dealing with this advanced disease. What is important is to appreciate that since these studies have been done, PET scanning has been introduced and this will probably be shown to be of vital importance in showing if a tumour is active or not after the chemo/radiation treatment. This may result in less surgical intervention if PET activity of the tumour and mediastinum was not demonstrable post-treatment, and if survival were shown to be the same, then this would be a significant achievement.

9. Use of PET and PET/CT in the surgical management of lung cancer

This brings us to the issue of PET scanning and its place in surgical management. This forms the basis for a separate discussion so I will not further elaborate.

In the following articles, specialists address the issues current in their specialties. It is hoped with pooling of all our resources in Australia, smoking-related lung cancer can be eradicated. The significant changes in society regarding smoking indicate people understand they can make a decision about their own health, and that no matter what has happened in the past with advertising and recommending smoking, times have changed and this is no longer fashionable. When completed, the use of the Clinical Guidelines for Lung Cancer Management, and recognition of our major advances in treating lung cancer in this country, brings us to the forefront in lung cancer management in the world. However, as long as people keep succumbing to lung cancer, we have to both increase preventive measures and use the newest treatment modalities available. Multidisciplinary management will ensure there is the best care for the patient throughout any of these treatment programs.

References

1. J Rubens, S Ewing, S Leroy, E Humphrey, V Morrison. “Temporal trends in survival after surgical resection of localized non-small cell lung cancer”. Lung Cancer. 28 (2000): 21-7.

2. Y Liu. “1061 case primary lung cancers were misdiagnosed as other diseases.” Lung Cancer, 34, Supplement 1 (2001): S35.

3. H Bozcuk, C Martin. “Does treatment delay affect survival in non-small cell lung cancer? A retrospective analysis from a single UK centre.” Lung Cancer, 34 (2001): 243-52.

4. K Kashiwabara et al. “Outcome in patients with lung cancer found retrospectively to have had evidence of disease on past lung cancer mass screening roentgenograms.” Lung Cancer, 35 (2002): 237-41.

5. D Miller, C Rowland et al. “Surgical treatment of non-small cell lung cancer 1cm or less in diameter.” Ann Thorac Surg, 73 (2002): 1545-51.

6. K Kodama, M Higashiyama et al. “Natural History of Pure Ground Glass Opacity after long term follow up of more than 2 years.” Ann Thorac Surg, 73 (2002): 386-93.

7. S Watanabe, T Watanabe et al. “Results of wedge resection for focal bronchioloalveolar carcinoma showing pure ground glass attenuation on computed tomography.” Ann Thorac Surg, 73 (2002): 1071-5.

8. Y Saito, Y Yamakawa, M Kiriyama et al. “Diagnosis of visceral pleural invasion by lung cancer using intraoperative touch cytology.” Ann Thorac Surg, 73 (2002): 1552-7.

9. Lung Cancer Study Group. “Randomised trial of Lobectomy versus limited resection for T1 N0 Non-small cell Lung Cancer.” Ann Thorac Surg, 60 (1995): 615-23.

10. K Sugi, Y Kaneda, K Esato. “Video assisted thoracoscopic lobectomy achieves a satisfactory long-term prognosis in patients with clinical stage 1A lung cancer.” World J Surg, 24, 1 (2000): 27-30.

11. S Sagawa et al. “A prospective trial of systematic nodal dissection for lung cancer by video assisted thoracic surgery: Can it be perfect?” Ann Thorac Surg, 73 (2002): 900-4.

12. C Bozzetti et al. “Biological parameters on computed tomography guided fine needle aspiration biopsy from peripheral primary non-small cell lung cancer.” Lung Cancer, 35 (2002): 243-7.

13. G Buccheri, D Ferrigno et al. “Serum biomarkers facilitate the recognition of early stage cancer and may guide the selection of surgical candidates: A study of cea and tissue polypeptide antigen in patients with operable non small cell lung cancer.” CVS 122, 5 (2001): 891-9.

14. J Roth et al. “A Randomized trial comparing perioperative chemotherapy and surgery with surgery alone in resectable stage III: A non-small-cell lung cancer.” J Natl Cancer Inst, 86 (1994): 673-80.

15. R Rosell et al. “A Randomised trial comparting preoperative chemotherapy plus surgery with surgery alone in patients with non-small-cell lung cancer.” N Engl J Med, 330 (1994):153-8.

16. Y Ichinose et al. “Overall survival and local recurrence of 466 completely resected stage IIIA N2 non-small-cell lung cancer patients questionnaire survey of the Japan Clinical Oncology Group to plan for clinical trials.” Lung Cancer, 34 (2001): 29-36.

17. A Bedini et al. “Surgical results of maximal local-regional treatment (cis-platinum high dose radiotherapy and adjuvant surgery)in initially non-resectable stage III lung cancer.” Lung Cancer, 35 (2002): 271-7.

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