1. The document provides recommendations for using tumor markers in lung cancer, including that single tumor markers should not be used for screening but can help identify tumor type before treatment.
2. It recommends measuring CYFRA 21-1, CEA, NSE, and ProGRP before first treatment and all four if no histology is available, as raised NSE and ProGRP suggest small cell lung cancer while raised SCCA suggests squamous cell cancer.
3. Serial marker measurements may help assess recurrence after primary therapy but criteria for biochemical progression are still needed to use markers to initiate intervention trials.
1. The document provides recommendations for using tumor markers in lung cancer, including that single tumor markers should not be used for screening but can help identify tumor type before treatment.
2. It recommends measuring CYFRA 21-1, CEA, NSE, and ProGRP before first treatment and all four if no histology is available, as raised NSE and ProGRP suggest small cell lung cancer while raised SCCA suggests squamous cell cancer.
3. Serial marker measurements may help assess recurrence after primary therapy but criteria for biochemical progression are still needed to use markers to initiate intervention trials.
1. The document provides recommendations for using tumor markers in lung cancer, including that single tumor markers should not be used for screening but can help identify tumor type before treatment.
2. It recommends measuring CYFRA 21-1, CEA, NSE, and ProGRP before first treatment and all four if no histology is available, as raised NSE and ProGRP suggest small cell lung cancer while raised SCCA suggests squamous cell cancer.
3. Serial marker measurements may help assess recurrence after primary therapy but criteria for biochemical progression are still needed to use markers to initiate intervention trials.
1. The document provides recommendations for using tumor markers in lung cancer, including that single tumor markers should not be used for screening but can help identify tumor type before treatment.
2. It recommends measuring CYFRA 21-1, CEA, NSE, and ProGRP before first treatment and all four if no histology is available, as raised NSE and ProGRP suggest small cell lung cancer while raised SCCA suggests squamous cell cancer.
3. Serial marker measurements may help assess recurrence after primary therapy but criteria for biochemical progression are still needed to use markers to initiate intervention trials.
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NACB: Practice Guidelines And Recommendations For Use Of Tumor Markers In The Clinic 1
Lung Cancer (Section 3P)
Tumor Markers in Lung Cancer Based on these pragmatic considerations the following recommendations can be made regarding the use of serum tumor markers in lung cancer:
1. Currently, single tumor markers, such as CYFRA 21-1, CEA, NSE, and ProGRP should not be used for screening purposes either in asymptomatic populations or in those at high risk for lung cancer (e.g. smokers).
2. Depending on histology, determination of CYFRA 21-1, CEA, NSE and/or ProGRP may be helpful in lung cancer patients prior to the first therapy. Where no histology can be obtained before surgery, measurement of all four markers is necessary to identify the leading marker (usually that present in highest concentration).
3. Where inoperable lung cancer is suspected but no histology is available, raised serum NSE and especially ProGRP are highly suggestive of small cell lung cancer while raised serum SCCA is suggestive of squamous cell cancer.
NACB: Practice Guidelines And Recommendations For Use Of Tumor Markers In The Clinic 2 Lung Cancer (Section 3P)
4. Follow-up of asymptomatic patients after primary therapy of lung cancer is controversial. However serial determinations of the appropriate tumor marker may help assess the completeness of tumor removal and provide early indication of recurrence.
5. CEA and CYFRA 21-1 can be measured during systemic treatment of non-small cell lung cancer, NSE and ProGRP during systemic treatment of small cell lung cancer to reflect response to therapy and to document progressive disease. Reliable criteria for biochemical progression are still required to initiate tumor marker-based intervention trials in future.
6. Careful attention to pre-analytical factors is essential. Specimens for NSE determination should be separated from the clot within 60 minutes of collection, and haemolysed samples should not be assayed. Vigorous mixing of serum samples after thawing should be avoided for cytokeratin measurements. Contamination of samples with skin or saliva must be avoided for SCCA measurements. Samples may be stored at +4C (short term) and at -70C (long term).
NACB: Practice Guidelines And Recommendations For Use Of Tumor Markers In The Clinic 3
7. Serial measurements should be performed using the same tumour marker test, which should be indicated on the laboratory report and documented in the patients medical records. 8. NACB: Practice Guidelines And Recommendations For Use Of Tumor Markers In The Clinic 4 Lung Cancer (Section 3P)
Table 1. Useful and potentially useful markers for lung cancer.
Cancer Marker Proposed Use/Uses Phase of Development LOE 1
NSE Differential diagnosis of lung masses when biopsy is not available: in high levels high specificity for small cell carcinoma; in SCLC, additive information to ProGRP In clinical use, but value not validated in a high-level evidence study III Assessing prognosis. High levels predict adverse outcome in SCLC
In clinical use, but value not validated in a high-level evidence study II-III Assessing prognosis. High levels predict adverse outcome in NSCLC
In clinical use, but value not validated in a high-level evidence study II-III Monitoring therapy in SCLC In clinical use, but value not validated in a high-level evidence study III Monitoring therapy in advanced disease (NSCLC)
Not in clinical use IV-V NACB: Practice Guidelines And Recommendations For Use Of Tumor Markers In The Clinic 5 Lung Cancer (Section 3P)
Detection of recurrent disease. Increasing kinetics indicate progressive disease in SCLC
In clinical use, but value not validated in a high-level evidence study IV CEA Differential diagnosis of lung masses when biopsy is not available; in high levels high specificity for adenocarcinoma; in NSCLC, additive information to CYFRA 21-1
In clinical use, but value not validated in a high-level evidence study. III Assessing prognosis. High levels predict adverse outcome in early and advanced stage NSCLC
Not in clinical use III-IV Monitoring therapy in advanced disease (NSCLC and SCLC)
Not in clinical use IV Detection of recurrent disease. Increasing kinetics indicate progressive disease in NSCLC, part. in adeno cancer.
Not in clinical use III-IV
NACB: Practice Guidelines And Recommendations For Use Of Tumor Markers In The Clinic 6 Lung Cancer (Section 3P)
CYFRA 21-1 Differential diagnosis of lung masses when biopsy is not available: in high levels high specificity for squamous cell carcinoma; best marker for NSCLC
In clinical use, but value not validated in a high-level evidence study. III Assessing prognosis. High levels predict adverse outcome in early and advanced NSCLC
Recommended for clinical use I-II
Assessing prognosis. High levels predict adverse outcome in SCLC
Not in clinical use III
Monitoring therapy in advanced disease (NSCLC)
In clinical use, but value not validated in a high-level evidence study. II-III
Early prediction of therapy response in
Not in clinical use yet, II-III NACB: Practice Guidelines And Recommendations For Use Of Tumor Markers In The Clinic 7 Lung Cancer (Section 3P)
advanced disease (NSCLC)
undergoing further validation
Detection of recurrent disease. Increasing kinetics indicate progressive disease in NSCLC, part in squamous cell cancer.
In clinical use, but value not validated in a high-level evidence study. III
ProGRP
Differential diagnosis of lung masses when biopsy is not available: in high levels high specificity for small cell carcinoma; best marker for SCLC; additive information to NSE
In clinical use, but value not validated in a high-level evidence study. III
Assessing prognosis. High levels predict adverse outcome in SCLC
Not in clinical use IV III NACB: Practice Guidelines And Recommendations For Use Of Tumor Markers In The Clinic 8 Lung Cancer (Section 3P)
Monitoring therapy in SCLC
In clinical use, but value not validated in a high-level evidence study.
Detection of recurrent disease. Increasing kinetics indicate progressive disease in SCLC.
In clinical use, but value not validated in a high-level evidence study. III SCCA Differential diagnosis of lung masses when biopsy is not available: in high levels high specificity for squamous cell carcinoma; in SQC additive information to CYFRA 21-1 Abnormal levels are associated with a high probability of NSCLC, mainly squamous tumors
In clinical use, but value not validated in a high-level evidence study. III
Assessing prognosis. High levels predict adverse outcome in NSCLC
Not in clinical use III-IV NACB: Practice Guidelines And Recommendations For Use Of Tumor Markers In The Clinic 9 Lung Cancer (Section 3P)
CA 125
Differential diagnosis of lung masses when biopsy is not available; in high levels relative specificity for
Not in clinical use III
adenocarcinoma, large cell carcinoma
Assessing prognosis in NSCLC. High levels predict adverse outcome in NSCLC
Not in clinical use IV
Monitoring therapy in advanced disease (NSCLC)
Not in clinical use IV
Early prediction of therapy response in advanced disease (NSCLC) Not in clinical use IV NACB: Practice Guidelines And Recommendations For Use Of Tumor Markers In The Clinic 10 Lung Cancer (Section 3P)
Chromogranin A
Differential diagnosis of lung masses when biopsy is not available; particularly for neuroendocrine tumors
In clinical use, but value not validated in a high-level evidence study. III
Assessing prognosis. High levels predict adverse outcome in SCLC and in neuroendocrine tumors
Not in clinical use III-IV
Monitoring therapy in neuroendocrine tumors
Not in clinical use IV
HER2-neu
Not appropriate for differential diagnosis
Not in clinical use III NACB: Practice Guidelines And Recommendations For Use Of Tumor Markers In The Clinic 11 Lung Cancer (Section 3P)
Assessing prognosis. High levels predict adverse outcome in advanced NSCLC: conflicting data
Not in clinical use IV
Monitoring therapy in NSCLC not possible
Not in clinical use IV DNA fragments
Assessing diagnosis; correlation with stage
Not in clinical use yet, undergoing further validation III
Assessing prognosis. High levels predict adverse outcome
Not in clinical use yet, undergoing further validation II-IV
Monitoring therapy in advanced disease (NSCLC)
Not in clinical use yet, undergoing further validation II-IV NACB: Practice Guidelines And Recommendations For Use Of Tumor Markers In The Clinic 12 Lung Cancer (Section 3P)
Early prediction of therapy response in advanced disease (NSCLC)
Not in clinical use yet, undergoing further validation II-III
Detection of recurrent disease. Increasing kinetics indicate progressive disease in NSCLC
Not in clinical use III TPA Differential diagnosis of lung masses when biopsy is not available
Not in clinical use, undergoing further validation III
Assessing prognosis. High preoperative levels predict adverse outcome in NSCLC
Not in clinical use III-IV TPS Assessing diagnosis (inferior to CYFRA 21-1 and TPA); correlation with stage
Not in clinical use IV NACB: Practice Guidelines And Recommendations For Use Of Tumor Markers In The Clinic 13 Lung Cancer (Section 3P)
Assessing prognosis. High levels predict adverse outcome in NSCLC
Not in clinical use III-IV
Assessing prognosis. High levels predict adverse outcome in SCLC
III-IV
Monitoring therapy in advanced disease (NSCLC)
Not in clinical use III
Early prediction of therapy response in SCLC
Not in clinical use
III-IV
Detection of recurrent disease. Increasing kinetics indicate progressive disease in NSCLC.
Not in clinical use III TU M2-PK Assessing diagnosis; inconsistent data are Not in clinical use IV NACB: Practice Guidelines And Recommendations For Use Of Tumor Markers In The Clinic 14 Lung Cancer (Section 3P)
available
Monitoring therapy in NSCLC and SCLC
Not in clinical use IV Detection of recurrent disease. Increasing kinetics indicate progressive disease in NSCLC and SCLC
Not in clinical use IV
CEA, carcinoembryonic antigen;
CYFRA 21-1, cytokeratin 19 fragments;
HER2-neu; shed form of Her2-receptor;
NSE, neuron specific enolase;
ProGRP, progastrin-releasing peptide;
SCCA; squamous cancer cell antigen; NACB: Practice Guidelines And Recommendations For Use Of Tumor Markers In The Clinic 15 Lung Cancer (Section 3P)
TPA, tissue polypeptide antigen,
cytokeratin fragments 8, 18, and 19;
TPS, tissue polypeptide specific-antigen;
cytokeratin fragments 18;
TU M2-PK, tumor M2 pyruvate kinase;
NACB: Practice Guidelines And Recommendations For Use Of Tumor Markers In The Clinic 16 Lung Cancer (Section 3P)
Table 2. Recommendations for use of markers in lung cancer by different expert groups.* [See Final Comments, p.9 for discussion of caveats relating to the recommendations in this Table.]
Marker Application EGTM 1999
NACB 2005 NSE For differential diagnosis Yes, for SCLC Yes, for SCLC For prognosis None published None published For post-operative surveillance Yes, in SCLC Yes, in SCLC For monitoring therapy in advanced disease Yes, in SCLC Yes, in SCLC For detection of recurrent disease Yes, in SCLC Yes, in SCLC CEA For differential diagnosis Yes, for NSCLC Yes, for NSCLC For prognosis None published None published For post-operative surveillance Yes, in adenocarcinoma Yes, in NSCLC For monitoring therapy in advanced disease Yes, in adenocarcinoma Yes, in NSCLC For detection of recurrent disease Yes, in adenocarcinoma Yes, in NSCLC CYFRA 21-1 For differential diagnosis Yes, for NSCLC Yes, for NSCLC NACB: Practice Guidelines And Recommendations For Use Of Tumor Markers In The Clinic 17 Lung Cancer (Section 3P)
For prognosis None published Yes, in NSCLC For post-operative surveillance Yes, in all NSCLC and SCLC Yes, in NSCLC For monitoring therapy in advanced disease Yes, in all NSCLC and SCLC Yes, in NSCLC For detection of recurrent disease Yes, in all NSCLC and SCLC Yes, in NSCLC ProGRP For differential diagnosis None published Yes, for SCLC For prognosis None published None published For post-operative surveillance None published Yes, in SCLC For monitoring therapy in advanced disease None published Yes, in SCLC For detection of recurrent disease None published Yes, in SCLC *The American Cancer Society (ACS) and the American Society of Clinical Oncology (ASCO) have not as yet published recommendations relating to the use of tumor markers in lung cancer.
NACB: Practice Guidelines And Recommendations For Use Of Tumor Markers In The Clinic 18 Lung Cancer (Section 3P)
Abbreviations: EGTM, European Group on Tumor Markers; NACB, National Academy of Clinical Biochemistry; NSE, neuron specific enolase; CEA, carcinoembryonic antigen; CYFRA 21-1, cytokeratin 19 fragments; ProGRP, progastrin-releasing peptide; SCLC; small cell lung cancer; NSCLC; non-small cell lung cancer. NACB: Practice Guidelines And Recommendations For Use Of Tumor Markers In The Clinic 19 NACB: Practice Guidelines And Recommendations For Use Of Tumor Markers In The Clinic Lung Cancer (Section 3P)
Table 3. Recommendations for use of markers according to histologies of lung cancer and application forms.
Histology Before therapy Post-therapy follow-up Unknown CYFRA 21-1, CEA, NSE, ProGRP After surgery: following histology In advanced disease: using the leading marker Adenocarcinoma CYFRA 21-1 and CEA CYFRA 21-1 and/or CEA NACB: Practice Guidelines And Recommendations For Use Of Tumor Markers In The Clinic 20 Squamous cell carcinoma CYFRA 21-1 and CEA (and SCCA) CYFRA 21-1 and/or CEA (and/or SCCA) Large cell carcinoma CYFRA 21-1 and CEA CYFRA 21-1 and/or CEA Small cell carcinoma NSE and ProGRP NSE and/or ProGRP CEA, carcino embryonic antigen; CYFRA 21-1, cytokeratin 19 fragments; NSE, neuron specific enolase; ProGRP, progastrin-releasing peptide; SCCA, squamous cell carcinoma antigen
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