Treatment options for isolated locoregional recurrences of nonsmall cell lung cancer after surgery: yes, radiation therapy too!

To the Editor:

In a recent article, Subotic et al. [1] summarised the importance of salvage surgery in treating local or loco-regional, post-surgical recurrences in patients with, mostly, early stage nonsmall cell lung cancer (NSCLC). While the feasibility of such an approach is indisputable, we believe that the readership of the European Respiratory Journal should be made aware of another treatment option already successfully used in this setting, namely, radiation therapy. This is especially important in patients with less favourable features, where secondary surgery may not be an option. Other authors have already shown that such patients comprise the majority of the patient population, with salvage surgery being possible in just 4% of cases. Taking this into consideration may give the treating physicians a better perspective and also enable a more meaningful discussion on optimising both the standard clinical and investigational approaches in any future endeavours in this setting.

Traditionally, loco/regional recurrence may be divided into chest wall/pleural, parenchymal, bronchial stump, mediastinal lymph node recurrence or a combination of any of these. Radiation therapy has already been successfully used previously in all of the aforementioned settings and its value in the treatment of recurrent NSCLC is recognised and well described in the literature. Earlier studies [2], as well as newer reports on radiation therapy alone or combined with chemotherapy [3, 4], showed it to be both effective and safe, with low toxicity in this setting. These studies also provided a framework that enabled an important observation, namely that the location of recurrence may ultimately influence the treatment outcome; recurrences located in the bronchial stump were associated with a much better prognosis than recurrences located in the chest wall/pleura or mediastinal lymph nodes.

Focusing on isolated bronchial stump recurrences, Jeremic and Bamberg [3] documented excellent median survival of ∼28.5 months and a 5-year survival >30%. Furthermore, in a subset of patients with T2N0 bronchial stump recurrences in the study of Jeremic et al. [5], high-dose radiation therapy (≥60 Gy) achieved excellent survival (5-year overall survival 57%), not inferior to survival obtainable with surgery alone or combined with other therapeutic modalities in newly diagnosed NSCLC of the same stage [6, 7].

Even when considering cases with a “more extensive” bronchial or tracheal component of the disease (with no nodal or other components present) [8] a median survival time of 19 months and 3-year survival of 12.5% can be achieved. Contrary to that, when bronchial stump recurrence was accompanied with nodal recurrences, the outcome became dismal [5, 9].

However, newer studies showed better survival in patients with a mediastinal recurrence [10]. Cai et al. [7] compared the survival of post-resection recurrent versus newly diagnosed NSCLC patients treated with radiation therapy combined with radio- or chemotherapy in 661 patients, of which 54 had post-resection recurrent and 607 had newly diagnosed NSCLC. The median survival time and 5-year overall survival rates (19.8 months and 14.8% versus 12.2 months and 11.0% for the two treatment groups, respectively (p=0.037)) clearly favoured the recurrent cancers, but for stages I–III there was no statistically significant difference observed in the 5-year overall survival (p=0.297) or progression-free survival (p=0.935) between recurrent and newly diagnosed patients.

Finally, a recently published study from Takenaka et al. [4] showed that combined radio-/chemotherapy is a promising option for patients with post-surgical recurrence. In this single institution study, 35 patients (24 nodal, six bone and five lung) were treated with a curative intent and a median dose of 60 Gy combined with a platinum-based chemotherapy regimen. This concept resulted in a median post-recurrence survival of 31 (range 5–127) months with survival being better in patients with nodal recurrence.

In conclusion, the available evidence shows that patients with post-resection recurrent NSCLC can achieve excellent results when treated with radiation therapy alone or with radio-chemotherapy. It reiterates that patients with post-resection recurrent cancers should be treated as aggressively as those with newly diagnosed disease.

Furthermore, the significant perioperative mortality together with the limited patient collective, where a surgical approach is applicable, proof that radiation therapy alone or combined with chemotherapy as an attractive alternative must be considered.