Características del procedimiento

CAPÍTULO IV. ANÁLISIS Y DISCUSIÓN DE LOS RESULTADOS

IV.4 Características del procedimiento

Work-up

Lung Cancer

06

32 Lung Cancer: Initial Diagnosis and Work-up

33 Adjuvant Treatment for Resected Non-small Cell Lung Cancer

34 Advanced Non-small Cell Lung Cancer

35 Small Cell Carcinoma of the Lung

P R O B L E M

Case History

A reasonably fit 62-year-old smoker presents with persistent cough. Bronchoscopy reveals an obstructing endobronchial tumour in the right middle lobe bronchus, 1 cm from the subcarina. Biopsy confirms squamous cell carcinoma. A computed tomography (CT) staging scan shows collapse/consolidation in the right middle lobe distal to a 2.5 cm tumour and several 1.5–2 cm lymph nodes in the mediastinum in the N1 and N2 positions. No metastatic nodules are visualized within the other lobes of the lung, and there are no distant metastases.

What is the bronchoscopic and radiological stage of this tumour? What are the implications for management?

Background

What is the bronchoscopic and radiological stage of this tumour?

Accurate staging in patients with non-small cell lung cancer (NSCLC) has a critical role in determining optimal therapy (Tables 32.1 and 32.2). It reflects the nature and extent of disease and provides important prognostic information. Surgery remains the treatment

of choice for early-stage NSCLC, and the likelihood of curative surgery depends on the local extent of the primary tumour and presence of any distant metastases.1,2

Bronchoscopy is both a diagnostic and staging investigation, in this case revealing a T1 tumour. CT is used to define the extent of disease and determine whether the primary tumour is resectable. Magnetic resonance imaging (MRI) of the chest does not offer improvement in the accuracy of primary tumour staging3_{and is not routinely done.}

Discussion

What are the implications for management?

Figure 32.1 provides an algorithm for the management of NSCLC.

Primary tumour (T)

Tx Primary tumour cannot be assessed or tumour proven by the presence of malignant cells in sputum or bronchial washings but not visualized by imaging or bronchoscopy

T0 No evidence of primary tumour Tis Carcinoma in situ

T1 Tumour <3 cm in greatest dimension, surrounded by lung or visceral pleura, without bronchoscopic evidence of invasion more proximal than the lobar bronchus

T2 Tumour with any of the following features of size or extent: 쎲 >3 cm in greatest dimension

쎲 involves main bronchus >2 cm distal to the carina 쎲 invades the visceral pleura

쎲 associated with atelectasis or obstructive pneumonitis that extends to the hilar region but does not involve the entire lung

T3 Tumour of any size that directly invades the following: chest wall (including superior sulcus tumours), diaphragm, mediastinal pleura, parietal pericardium; or tumour in the main bronchus <2 cm distal to the carina but without involvement of the carina; or associated atelectasis or obstructive pneumonitis of the entire lung

T4 Tumour of any size that involves any of the following: mediastinum, heart, great vessels, trachea, oesophagus, vertebral body, carina; or tumour with a malignant pleural or pericardial effusion, or with satellite tumour nodule(s) within the ipsilateral primary tumour lobe of the lung

Regional lymph nodes (N)

Nx Regional lymph nodes cannot be assessed N0 No regional lymph node metastases

N1 Metastases to ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and intrapulmonary nodes involved by direct extension of primary tumour

N2 Metastases to ipsilateral mediastinal and/or subcarinal lymph nodes

N3 Metastases to contralateral mediastinal, contralateral hilar, ipsilateral or contralateral

Distant metastases (M)

Mx Presence of distant metastases cannot be assessed M0 No distant metastases

M1 Distant metastases present

This patient’s primary lesion is amenable to lobectomy. However, he has abnormally enlarged nodes in the N1 and N2 positions, i.e. radiological stage IIIA disease. Nodal staging is important in patients with NSCLC as it has important implications for suitabil- ity for curative surgery.4_{Patients who have stage IIIA disease with N2 node involvement}

have a poorer prognosis and are unlikely to be cured by surgery alone.4,5_{The survival rate}

for N2 disease, however, depends on whether this is a radiological, mediastinoscopic or postoperative histological finding. Some postoperative survival statistics include patients in whom preoperatively unsuspected N2 disease was diagnosed only microscopically in a few N2 nodes resected at operation. These patients’ survival, clearly, is superior to that of most stage IIIA patients. Patients with N3 node-positive disease are not suitable for curative surgery.5

Nodal disease assessment is difficult, as enlarged nodes on chest radiograph or CT scan do not necessarily imply nodal metastases. Accuracy of CT for nodal staging is not high, with sensitivity and specificity of 60–65% and 60–70%, respectively.5_{Nodes may be}

enlarged due to inflammatory or other benign processes and conversely, normal-sized nodes may contain malignant cells. The large N1 and N2 nodes in this case may be due to malignant involvement or because of inflammation reactive to the obstructive pneumonitis.

Mediastinoscopy or, occasionally, transcarinal bronchoscopic fine needle aspiration (FNA) may be done to obtain histological or cytological confirmation of intrathoracic lymph node involvement. Mediastinoscopy remains the most accurate method of nodal staging but may be associated with a small but important morbidity and mortality.6–8

Some surgical centres offer one-step staging and definitive surgery, i.e. mediastinoscopy

Stage grouping TNM subsets

0 Carcinoma in situ IA T1 N0 M0 IB T2 N0 M0 IIA T1 N1 M0 IIB T2 N1 M0 T3 N0 M0 IIIA T3 N1 M0 T1 N2 M0 T2 N2 M0 T3 N2 M0 IIIB T4 N0 M0 T4 N1 M0 T1 N3 M0 T2 N3 M0 T3 N3 M0 T4 N3 M0 IV Any T Any N M1

Table 32.2Staging of non-small cell lung cancer

and frozen section of lymph nodes, proceeding to thoracotomy and definitive surgery if nodes are reactive rather than malignant.

There has been increasing interest in non-invasive staging using whole-body positron emission tomography (PET) with 18-FDG ([18F] fluoro-2-deoxyglucose), which has a higher rate of detection of mediastinal nodes as well as extrathoracic metastases.8–10

Studies have shown PET scan to be consistently more accurate than CT for mediastinal node staging with negative predictive values >90%.9_{It has been suggested that in some}

YES

(occasional, controversial)

(Alternative: transcarinal FNA)

NO NO May require N2 staging anyway Treat as advanced NSCLC Are enlarged N2 nodes

malignant

Chemoradiotherapy Radical

surgery

Patient fit for radical surgery? Optimize status? Other treatments Distant metastases Confirm Chemoradiotherapy N3 nodes PET positive N2 nodes PET positive N2 nodes PET negative Bronchoscopy and CT scan T1N2 NSCLC PET N2 nodes malignant Mediastinoscopy N2 nodes benign

Figure 32.1 Algorithm for the management of non-small cell lung cancer (NSCLC). CT, computed

cases mediastinoscopy is not necessary if the mediastinum is PET negative.11

Incorporating PET into conventional staging also upstages approximately 25% of patients, detecting unsuspected extrathoracic metastases in around 10%.10,12_{The cost of}

PET may be compensated by more appropriate patient selection and avoidance of futile surgery.13,14

PET has some limitations. 18-FDG is taken up by muscles and by areas of active inflammation, which may give false-positive results. Furthermore, precise location of focal abnormalities is difficult to determine on PET, needing visual correlation with CT. Integrated PET-CT has been shown to be superior in determining stage of NSCLC com- pared with other radiological modalities.15_{However, PET-CT is not widely available. If}

the PET scan in the case study patient did not reveal unsuspected distant metastases, it is likely that mediastinoscopy and pathological staging of the lymph nodes would be indicated in any case, as the only radiological contraindication for potentially curative surgery is presence of ‘radiologically abnormal nodes’.

If clinical assessment or PET suggests metastatic disease not revealed on staging CT then additional site-specific tests, such as isotope bone scan and CT/MRI of the brain could be useful. However, in general, these are not indicated in asymptomatic patients. Some centres, however, are adopting the practice of a CT brain scan for lung adenocarci- noma before resection, because of the relatively high rate of unsuspected brain metastases in this subset of patients. Others advocate that patients with N2 nodes undergo ultrasound of the supraclavicular area and FNA of any nodes thus revealed, as this yields a positive result in a subset of patients for whom radical surgery is therefore not appropriate.

Finally, we must also take into account the patient’s fitness for surgery. Patients with poor performance status and those with history of marked weight loss are more likely to have advanced disease and should be staged particularly carefully. Many patients with NSCLC have coexisting smoking-related chronic obstructive airways disease and/or ath- erosclerotic cardiovascular disease, so careful preoperative assessment of their pul- monary function and cardiovascular risk factors is necessary.1,2

Conclusion

Surgery remains the treatment of choice for early-stage NSCLC. In this case, the decision whether the patient has surgery or not will depend on whether the N2 nodes, enlarged on CT, prove malignant or not.

Case History

A 69-year-old man is referred by a thoracic surgeon following complete resection of T2 N1 squamous cell carcinoma of the lung. Resection margins are clear.

What trials form the evidence base for adjuvant chemotherapy in this situation? What factors would you take into account when deciding whether to offer this patient adjuvant chemotherapy?

What will you tell the patient?

If you and the patient decide that chemotherapy should be given, what regimen(s) and duration would you choose and why?

Background

What trials form the evidence base for adjuvant chemotherapy in this situation?

In 1995, a meta-analysis of updated data from 52 randomized clinical trials (1394 patients) indicated that adjuvant chemotherapy in surgically resected stage IB, II and IIIA non-small cell lung cancer (NSCLC) did not appreciably improve overall survival. There was, however, a trend in favour of chemotherapy regimens that included cisplatin. This analysis led to the development of several subsequent adjuvant chemotherapy trials with improved patient selection and refined drug regimens.

The International Adjuvant Lung Cancer Trial (IALT) showed that adjuvant cisplatin- based chemotherapy improved relapse-free survival by 5.1% and overall survival by 4.1% at 5 years. The IALT included 1867 patients and investigated stage IA–IIIA disease, comparing three or four cycles of adjuvant combination chemotherapy including cisplatin combined with either etoposide, vinorelbine, vinblastine or vindesine, against observation.1 _The

National Cancer Institute of Canada (NCIC) JBR.10 trial showed a 15% improvement in overall survival in the chemotherapy-treated group at 5 years. This trial included 482 patients and investigated stage IB–II disease, comparing four cycles of a combination of vinorelbine and cisplatin against observation.2 _{The Adjuvant Navelbine International}

Trialist Association (ANITA) trial (including 840 patients, again comparing a combination of vinorelbine and cisplatin against observation in patients with stage IB–IIIA disease) showed an improvement in overall survival of 8.6% at 5 years, maintained at 7 years.3

On the other hand, early reports of the Cancer and Leukaemia Group B (CALGB)

33 Adjuvant Treatment for Resected Non-

small Cell Lung Cancer

In document UNIVERSIDAD DE CIENCIAS MÉDICAS DE LA HABANA ICBP Victoria de Girón Facultad Playa. Centro de Investigaciones Médico Quirúrgicas. (página 73-77)

CAPÍTULO IV. ANÁLISIS Y DISCUSIÓN DE LOS RESULTADOS

IV.4 Características del procedimiento

Work-up

Lung Cancer

06

Case History

Background

Discussion

Conclusion

Further Reading

Case History

Background

33

Adjuvant Treatment for Resected Non-

small Cell Lung Cancer