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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

Advances in the treatment of lung cancer have been
precious and few over the past 40 years, as reflected in the minimal rise in
overall survival from this disease since 1960. Significant progress has occurred
in staging accuracy, surgical morbidity, radiation delivery, and new
chemotherapeutics. And yet, patients with stage II disease have a 5-year
survival rate of 50% or less, while patients with stage III disease fare poorly
overall.

Technologic advances have greatly reduced risk in the surgical resection of
lung cancer. Improved staging and knowledge of surgical outcomes in locally
advanced disease have helped to reduce unnecessary surgery and have led to the
integration of surgical resection into multimodality frameworks. We can operate
on sicker patients, and intraoperative decisions are now based on better
knowledge of the disease process. But the actual mechanics and extent of lung
cancer resection today have not significantly changed since the 1960s.

Negative or Equivalent Trials Predominate

As we look back on the first century of mass nicotine addiction and its
lethal offspring, our knowledge of the role of adjuvant therapy in resected
stage II/IIIA non-small-cell lung cancer (NSCLC) is dominated by trials
with negative or equivalent results. Dr. Movsas has elegantly summarized the
important studies in this area, which constitute a tremendous effort on the part
of surgical, radiation, and medical oncologists to improve the outlook for
patients with lung cancer.

The only major positive finding at this point is that postoperative radiation
therapy reduces local recurrence in resected stage III NSCLC. Dr. Movsas’
critique of the postoperative radiotherapy (PORT) meta-analysis is important
because, taken at face value, the results of that study can be misleading; upon
closer scrutiny, however, they do not contradict current conventional wisdom.
Postoperative radiation in stage I/II lung cancer is without proven benefit and
may be harmful, but prevention of local recurrence, which is most often seen in
resected stage III patients, results in improved quality of life in many cases.

Survival Benefits of Mediastinal Lymphadenectomy?

The idea that "cleaning out" the mediastinal lymphatics confers a
survival advantage is not entirely without merit. It is worth noting that the
control arm of Intergroup trial 0115/Eastern Cooperative Oncology Group trial
3590 (testing radiation alone) had a median survival of 39 months (61 months for
stage II and 33 months for stage IIIA) and a 5-year survival of about 40%. These
data represent an improvement on historical results in this cohort of
patients.[1] This is likely due to selection bias from accurate surgical staging
rather than better surgery or radiation, but without a randomized trial using
surgery alone as the control, the question of a survival benefit remains open.

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