Page 29 - MemoriaES-Eng

www.ciberes.org

ó

Lung Cancer

CLINICAL AND MOLECULAR CHARACTERIZATION OF EARLY-
Coordinator
STAGE LUNG CANCER (LC).
Dr. Eduard Mons

LC is an important disease on account of its high incidence and severity, and on the level
of associated mortality. In contrast to the response obtained with other solid tumours and

despite an enormous research effort, the prognosis for LC has improved only slightly in
recent decades, with a 5-year survival less than 15%.

The typology of LC is defined by anatomo-pathological criteria that initially differentiate

LC as small cell carcinoma and NSCLC, with the latter further classified as adenocarci-

noma, squamous cell carcinoma and large cell carcinoma. In a proportion of NSCLC cases
this differentiation is not possible, with the carcinoma remaining as undifferentiated. Im-

munohistochemical markers can be used to clarify in part the situation, but uncertainty

in the estimation of prognosis and response to treatment is high. The incorporation of
prognostic molecular markers, such as epidermal growth factor receptor (EGFR) in tu-

mour cells, which modulates a different therapeutic response when a mutation is present,
has led to significant changes in treatment regimens used in NSCLC, which have been

incorporated into clinical guidelines.

Early identification of the disease favours the use of therapeutic interventions associated

with prolonged survival. The TNM system of staging according to the degree of exten-
sion of the primary tumour (T), lymph nodes (N) and metastasis (M) has been and is

important, but is imprecise in relation to the prognosis and treatment selection. The
percentage variation in survival with the TNM model is only 30%, with each patient’s

prognosis depending on poorly known determinants. In fact, in patients considered to

have early-stage LC, there has barely been any reduction over the last 30 years in mor-
tality and relapse. In cases that have been resected and staged as Ip, without evidence

of lymph node or systemic metastases at baseline, very high rates (35-50%) of mortality

or relapse are seen during follow-up. Moreover, despite the benefits seen with the use of 13
platinum-based adjuvant chemotherapy in cases of advanced stages, the available data 20
T
do not support the use of such treatment in patients with stage IA cancer and show very OR
It seems clear that TNM staging P
questionable results in patients with stage IB cancer. RE
based on tumour extension conceals in its apparent homogeneity a considera- L
A
ble level of biological heterogeneity of the tumour or tumour-host relationship, NU
which is evidenced in terms of prognosis and prediction.
N
A
The inclusion of new predictive molecular variables to the staging of LC could be S /
E
a promising approach to improve establishment of the prognosis and prediction of treat- ER
B
ment response, in addition and complementarily to the TNM; such an approach could be CI
easily incorporated into clinical practice guidelines and could enable alternative therapies

to be defined beyond those currently in use. Numerous studies have addressed this prob-
lem, with inconclusive or contradictory outcomes. The cause resides in complexity and
29