REVIEW ARTICLE Lung cancer what the surgeon needs to know Martyn Payne MB ChB, FFRad (D) (SA) Levin and Panners Constantiaberg Mediclinic Cape Town Anthony G Linegar MB ChB, FCS (SA) N1 City Hospital Cape Town Introduction Lung cancer is the commonest cause of death from cancer, account- ing for over 900 000 of the estimated 5.2 million cancer-related deaths worldwide.' South Africa is the only developing country with a cancer death rate approximately the same as that of the developed world." Approximately 80% of lung can- cers are categorised as non-small cell tumours (NSCLCA) and the rest (20%) are small cell tumours. NSCLCA can be cytologically subdi- vided, with adenocarcinoma being the commonest (40%) followed by squamous cell carcinoma (30%) and large cell undifferentiated carcinomas (10%). There are also tumours with mixed cell types where two different tumour cell types are identified in a single tumour (e.g. adenosquamous carcinoma). Primary surgery is universally accepted as the treatment of choice in early stage (cStage I and cStage II) NSCLCA in selected patients with the physiological reserves to undergo the operation and maintain a reasonable quality of life thereafter. The purpose of surgery is curative, and this requires careful patient selection if fruitless interventions are to be avoided. The overall cure rate after complete resec- tion is 13%.3 Staging Staging the tumour is crucial to planning of treatment, prognostica- tion, and the final interpretation of the results of therapy. Non-invasive imaging techniques (i.e. spiral CT scanning with contrast enhancement) are used to determine the anatomical extent of the disease and thereby to enable clinical staging according to the tumour node metastasis (TNM) stag- ing system.' Clinical staging refers to staging prior to surgery and is prefixed by the letter 'c' (cTNM) whilst patho- logical staging (pTNM) refers to the pathological staging achieved by sys- tematic surgical exploration. International staging system The TNM system (Table I) pro- vides a reproducible description of the anatomical extent of the disease and was most recently updated in 1997.4 The T descriptor refers to tumour size, anatomical extent and relation- ship to adjacent structures. The N descriptor refers to extent of nodal 30 SA JOURNAL OF RADIOLOGY • February 2003 disease. The M descriptor refers to presence or absence of metastases. Imaging assessment of Stage The chest radiograph (high kVp 120 - 130, PA and lateral) is the way in which most lung cancers are detected and is useful in preliminary clinical staging. T criteria such as size and location of the tumour, atelectasis, pleural effusion and chest wall inva- sion with rib destruction can be assessed. However, it is insensitive to small nodules and to small to moder- ate sized lymph node involvement, and is unreliable in ascertaining extent of mediastinal invasion (Fig. I). It is therefore insufficient in determining resectability extent in cases of clearly advanced disease. Fig. 1. CXR showing LUL mass adjacent to the mediastinum. Invasion cannot be assessed. Surgically proven resectable adenocarcinoma. CT scanning is the dominant imaging modality and should be rou- tinely performed.' The examination must extend inferiorly to include the adrenal glands and liver, which are common sites of distant metastases. It should be performed with intra- REVIEW ARTICLE Table I. TNM staging system Thmour status (T descriptor) Tx Primary tumour cannot be assessed, or tumour proven by malignant cells in sputum but not seen on imaging or bronchoscopy TO No evidence of primary tumour Tis Carinoma in situ Tl Tumour 3 em or less in greatest dimension, surrounded by lung or vis- ceral pleura, without bronchoscopie evidence of invasion more proximal than the lobar bronchus (i.e. not in the main bronchus)" T2 Tumour with any of the following features of size or extent: More than 3 em in greatest dimension Involves the main bronchus, 2 em or more distal to the carina Invades the visceral pleura Associated with atelectasis or obstructive pneumonitis that extends to the hilar region and does not involve the entire lung T3 Tumour of any size that directly invades any of the following: Chest wall (including superior sulcus tumours), diaphragm, mediastinal pleura, parietal pericardium Or tumour in the main bronchus < 2 em distal to the carina, but without involvement of the carina Or atelectasis or obstructive pneumonitis of the entire lung Tumour of any size that invades any of the following: Mediastinum, heart, great vessels, trachea, carina, oesophagus, vertebral body Or tumour with a malignant pleural or perieardial effusion' Or with satellite nodule(s) within the primary tumour lobe of the lung T4 Regional lymph nodes (N descriptor) Nodes cannot be assessed No lymph node metastases Metastases to ipsilateral peribronchial and or ipsilateral hilar lymph- nodes, and intrapulmonary nodes involved by direct extension of the primary tumour Metastases to ipsilateral mediastinal and or subcarinal lymph nodes Metastases to contralateral mediastinal, hilar or scalene or supraclavicular nodes Distant metastasis status (M descriptor) Mx Cannot be assessed Nx NO Nl N2 N3 MO Ml No distant metastases Distant metastases present" "The uncommon superficial tumour of nny size with its invasive component limited to the bronchial wall, which may extend proximal to the main bronchus, is also classified ac;TI. [Most pleura] effusions in association with a cancer are malignant and caused by the tumour. However. Il few patjent'S have multiple cytology examinations of the pleural fluid that are negative for tumour. In these cases the fluid is ncr bloody and is nol an exudate. When these elements and clinical judgement dictate that the effusiou is not related to the turnour.the effusion should be excluded as a staging clement. and the patient staged Tl, 2 or 3, Pericardlal effusion is classified according to tJ1C same rules, tSeparnte metastatic turnour nodulels) in the ipsilateral non-primary tumour lobe of the lung are also classified Ml. venous contrast to allow accurate dif- ferentiation of mediastinal and hilar vascular structures from nodal tissue and tumour. The scan must also be displayed with lung and soft tissue set- tings. CT assessment of T descriptor Staging of the T descriptor has an accuracyof85% (Fig. 2).6Grossmedi- astinal invasion can be confidently 31 SA JOURNAL OF RADIOLOGY • February2003 Fig. 2. CT of Tt NO adenocarcinoma Fig. 3. CT showing obvious mediastinal invasion. diagnosed, but it can be difficult to distinguish between tumour contigu- ity and extension into mediastinal structures (Fig. 3). Intact fat plane, contact of 3 cm or less with the medi- astinum and less than 90° contact with the aorta suggest no invasion, whereas greater than 180° contact with the mediastinal structures usual- ly indicates invasion.' CT assessment of N descriptor N assessment relies on node size with a short axis diameter of greater than 1 cm being considered positive for nodal metastases (Fig. 4). How- ever, small nodes can contain micro- scopic tumour deposits (producing a false-negative assessment in 20% of cases) and conversely large nodes may be clear of metastases (producing a false-positive assessment in 20% of cases for glands greater than 2 cm)," A REVI'EW ARTICLE Fig. 4. T2N2: lymph nodes measure greater than 1 em In short axis. systematic approach using one of the accepted lymph node maps should be utilised to describe disease in hilar (Nl), ipsilateral mediastinal (N2) and contralateral mediastinal (N3) sta- tions." The profoundly negative impact on survival of nodal metastases is well documented, but the identification of hilar nodal (Nl) disease remains a weakness in the clinical assessment. CT assessment of M descriptor The search for metastases is initial- ly limited to the chest and the upper abdomen unless clinical information indicates the need for brain and or bone scanning which are not routine- ly performed. Low density liver lesions are frequently encountered. These are most often benign cysts. Ultrasound can be useful in differenti- ating cystic from solid lesions. Isolated adrenal masses are usually benign adenomas. Unenhanced CT attenuation of 10 HU or less, or more than 50% washout on ID-minute delayed enhanced CT are highly spe- cific for benign adrenal adenomas. to MR. This is of similar accuracy to CT in assessing the T and M descriptors, but may offer an advantage over CT in assessing mediastinal and chest wall invasion, particularly in superior sul- cus tumours.' Chemical shift MR! accurately differentiates metastases from benign adrenal adenomas. I I Positron emission tomography PET scanning relies on the increased metabolism of glucose in tumour cells to characterise glands and masses. Its role in routine pre- operative staging is yet to be fully defined, but may prove to be useful in enhancing the CT assessment, in examining the Nl hilar nodes, and for evaluation of any contralateral parenchymal nodules." Stage grouping Stage groups were developed on retrospective survival data.' 5-Year lNMsubset survival (%) Ca- in situ TlNOMO 60 T2NOMO 38 TlNIMO 34 T2NIMO 24 T3NOMO 22 T3NIMO 9 TlN2MO l3 T2N2MO l3 T3N2MO l3 T4anyN 7 N3anyT 3 Ml anyT, anyN Stage o IA IB IIA lIB IlIA IIIB N 32 SA JOURNAL OF RADIOLOGY. February 2003 The major prognostic factor is the ability to achieve a complete resection (RO). Limited invasion of the medi- astinum or of the chest wall (T3) does not prohibit complete resection, and provided the mediastinal glands are not involved S-year survivals of up to 40% can be achieved. Pleural effusions in the presence of a lung tumour are almost always malignant and should be considered to be so unless careful cytological analysis of the fluid as well as thor- ough thoracoscopic examination reveals no malignancy in the pleural space. This is unlikely in advanced T and N categories. Malignant effusions confer a T4 status on the tumour and these patients are not surgical candi- dates. The purpose of detecting medi- astinal nodal disease preoperatively is to avoid unnecessary operations that will not favourably influence survival. Where large mediastinal glands are recognised on the CT scan, biopsy by mediastinoscopy and or mediastin- otomy is undertaken, where these glands are within reach of the medi- astinoscope. Mediastinoscopy will produce a false-negative result in 25% of cases." Clinical staging under stages the full extent of the disease in at least 25% of cases which explains why the overallS-year survival in TINO is only 60% (i.e only 60% were in fact TINO and the rest had more advanced dis- ease). Additional information Chest radiograph and CT scanning will provide other valuable informa- tion that may influence surgical plan- REVIE\N ARTICLE ning. Background lung disease such as COPD, scarring, likely presence of adhesions from previous pleural dis- ease, and cardiac disease can be assessed and factored into the overall risk assessment for surgery (Fig. 5). The site and size of the tumour and some anatomical factors identified on the scan can assist in estimating the likely extent of the resection necessary to achieve a complete resection (i.e. lobectomy or pneumonectomy) (Fig.6). Fig. 5. TI tumour, but note background of COPO which may complicate surgical approach. Fig. 6. Small tumour LLL but close to LUL bronchus therefore pneumonectomy rather than lobectomy required. Conclusion The radiological assessment of lung cancer requires an understand- ing of the biological behaviour of the disease, and a knowledge of the meth- ods available to study it. Critical infor- mation required by the surgeon revolves around staging the primary tumour and assessing its resectability based on the information provided above. Accurate interpretation of the information requires practice and team work between the radiologist and the thoracic surgeon. Although clinical staging under stages the disease in approximately 25% of cases, it is not an unacceptable situation, as it means that with the current system no patient with resectable disease will be denied a potentially curative resection. 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