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Role of Adjuvant Therapy in Resected Stage II/IIIA Non-Small-Cell Lung Cancer

Role of Adjuvant Therapy in Resected Stage II/IIIA Non-Small-Cell Lung Cancer

The search for effective postoperative adjuvant therapy
for patients with resected non-small-cell lung cancer (NSCLC) has been spurred
by a high rate of failure after definitive surgery. Except for patients with
resected T1, N0, M0 lesions, failure rates exceed 30%. Widespread application of
adjuvant therapy has been reined in by a disappointing lack of effectiveness in
this setting.

The article by Dr. Movsas provides an evenhanded review of some of the key
controversies currently bedeviling the clinician faced with making a
recommendation for the patient with resected node-positive NSCLC. The article is
gratifying in its desire to stay close to the evidence rather than join the
polemics that often surround such discussions, and it largely succeeds in this
goal. What is disappointing is that the present data do not allow the author, or
a fair-minded reader, to make any firm conclusions and treatment
recommendations.

How is it that we know so little about optimal adjuvant therapy for a cancer
that each year kills more people in the United States than cancers of the
breast, prostate, and colon combined? What has brought us to this sorry state
where medical and radiation oncologists spend time disputing meta-analyses of
decade-old data, and how can we move off this sticking point in the next decade?

Large Adjuvant Trials Lacking

There has been a tendency in designing adjuvant trials to think that our
therapeutic interventions are likely to be of great benefit, improving overall
or relapse-free survival by 10% or more. It is highly unlikely that this will be
the case, and a lesser degree of benefit (eg, an absolute gain of 5% in
survival) would be considered clinically worthwhile by many patients and
physicians.[1,2]

Even the demonstration of such small differences, however, requires large
trials, and until relatively recently, there has been a reluctance to implement
such large studies, at least in the United States. Several European trials of
adjuvant therapy have recently been completed, with relatively broad eligibility
requirements and flexibility in the choice of chemotherapeutic regimen. The
results of these trials are awaited with great interest. At best, however, they
will give provisional answers about the value of what is rapidly becoming
yesterday’s chemotherapy. We have probably missed the window in which a
modestly but significantly effective adjuvant chemotherapeutic regimen could
become a broad-spectrum standard analogous to what fluorouracil (5-FU)/leucovorin
in colorectal cancer or CAF (cyclophosphamide, doxorubicin [Adriamycin], 5-FU)
had been in breast cancer 5 years ago. We are approaching a time when
therapeutic recommendations will be much more individualized.

Another course of action is to develop tools that better define patients at
highest risk for relapse and to develop adjuvant therapies targeted more
specifically against the molecular features of their tumors. We are rapidly
approaching the time when such strategies will be feasible in the clinic.

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