Prognostic factors in resected lung carcinomas

A prognostic factor is one which determines or is related to the natural history of a disease, in the absence of diseasemodifying therapy. A literature search provides innumerable studies purporting to describe such factors prognostic for patients with lung cancer. The potential significance of virtually every conceivable histopathological feature and molecular biomarker has been reported in thousands of studies. Yet in clinical practice, the only prognostic features which are regularly used in clinical decision-making are the tumour stage and the patient’s performance status. This paper will address prognostic factors which are features of the tumour, relating to surgically resected lung cancer. It will not discuss those features of the individual patient which have prognostic significance related to the outcome. The potential value of efficient prognostication in this particular clinical setting is to enable appropriate selection of patients for adjuvant therapy, determining who should benefit from systemic therapy, with that benefit likely to outweigh potential toxicity. To a lesser extent, knowledge of a prognostic factor before surgery may influence the type or extent of surgery which is carried out, but related practice change is still under trial. Adjuvant treatment is aimed at eliminating clinically undetectable micro-metastatic disease which, if present, may be responsible for tumour relapse. Prognostic factors are therefore predictors of a higher or lower probability of disease relapse and indicators of the likelihood that the surgery alone has cured the patient. Adjuvant therapy is therefore speculative. Currently, adjuvant cytotoxic chemotherapy is offered to patients with pathological Stage II–III non-small-cell lung carcinoma (NSCLC) and reduces the risk of death by approximately 20% [1]. Trials have demonstrated that surgery effectively cures 64% of patients with p-Stage 1B disease and 39% and 26% respectively of patients with p-Stage II and III disease. Only an additional 3% of p-Stage 1B patients, and 10%/13% respectively of p-Stage II/III patients, will be alive as a result of adjuvant chemotherapy. Adjuvant chemotherapy in p-Stage 1B patients cannot be justified by this modest gain in survival [1–3]. Despite adjuvant chemotherapy, 33% of p-Stage IB, 51% of p-Stage II and 61% of p-Stage III patients succumb to recurrent disease. The implication of these figures is that current decisionmaking should be improved to optimise whom and how to treat in the adjuvant setting. Prognostic factors that predict more accurately for postoperative disease relapse could improve selection of those patients most likely to benefit from adjuvant chemotherapy and – equally importantly – where it should be avoided. Factors that predict for effectiveness of individual drugs, which are outside the scope of this review, could be used to decide how to select chemotherapy for those who need adjuvant treatment.