Utility Of Tumor Markers In Diagnosis And Treatment In Patients With Small Cell Lung Cancer Or Advanced Lung Adenocarcinoma

Background and objectiveAmong frequently-used tumor markers in lung cancer,carcinoembryonic antigen(CEA)and carbohydrate antigen-125(CA125),cytokeratin 19(CYFRA21-1)and squamous carcinoma antigen(SCC),neuron specific enolase(NSE)and pro-gastrin-releasing peptide(ProGRP)are respectively expressed highly in lung adenocarcinoma,lung squamous carcinoma and small cell lung cancer.Small cell lung cancer(SCLC)is a rapidly growing tumor with characteristic of neuroendocrine cellular function.NSE,ProGRP and lactic dehydrogenase(LDH)are valuable in diagnosis and treatment of SCLC.By analyzing the variation of NSE,ProGRP and LDH before and after treatment,this study aims to investigate the efficacy of tumor markers in diagnostic staging,therapeutic evaluation and prediction of disease relapsing.By comparing patients with multiple increased tumor markers(group A)and patients with increase of CEA and/or CA125(group B),this study aims to investigate the utility of multiple increased tumor markers in therapeutic evaluation and prediction of disease relapsing in patients with advanced lung adenocarcinoma.MethodsPatients with SCLC who receiving the first line chemotherapy in Cancer Hospital,Chinese Academy of Medical Sciences were enrolled and retrospectively analyzed.Clinical characteristic(includes NSE,ProGRP and LDH level before and after 2 cycles chemotherapy),efficacy evaluation,progression-free survival(PFS)were analyzed.Patients with stage IV lung adenocarcinoma who receiving the first line chemotherapy in Cancer Hospital,Chinese Academy of Medical Sciences were enrolled and retrospectively analyzed.Clinical characteristic,serum tumor markers before chemotherapy,efficacy evaluation,progression-free survival(PFS)were analyzed.ResultsBefore treatment,Serum NSE,ProGRP and LDH in patients with extensive disease(ED)were significantly higher than those with limited disease(LD)(all P<0.005);NSE level increased obviously accompanied by increase of lymph nodes stage in LD group(P=0.010);Patients with weight reduction when diagnosis had higher NSE and LDH than those without loss of weight(P=0.032,0.014).After 2 cycles chemotherapy,decrease of NSE and ProGRP in effective group was higher than which in stable and ineffective groups(P=0.015,0.002).The relapse risk was lower in patients who accepted>4 cycles chemotherapy and with obvious decrease of ProGRP than those who accepted≤4 cycles chemotherapy and with less obvious decrease of ProGRP in LD group;ED patients with no more than 2 distant metastasis,normal LDH level before treatment and obvious decrease of ProGRP after chemotherapy had lower short term relapse risk.In addition,the types of relapse(sensitive relapse,drug resistance relapse and refractory relapse)were negatively correlated with decrease of ProGRP(P=0.044).By multivariate analysis,numbers of chemotherapy cycle was independent prognostic factor for PFS in LD SCLC;numbers of distant metastasis and decrease of ProGRP were independent prognostic factors for PFS in ED SCLC.Except CEA and CA125,the highest ratio of increased tumor markers in group A was CYFRA21-1(93%),then was NSE(36%),SCC(13%)and ProGRP(12%).Patients with multiple increased tumor markers tend to have more distant metastasis(P<0.001)and shorter PFS(median PFS 5.3 months vs 7.3 months,P=0.016).The relapse risk was lower in patients who accepted maintenance therapy than those who didn’t accept maintenance therapy in both groups(P<0.001).ConclusionIncrease level of serum tumor markers is related to tumor burden in SCLC.Decrease level of ProGRP after treatment may prognose efficacy and relapse risk.Patients with multiple increased tumor markers have high risk of relapse,and maintenance therapy can reduce relapse risk.