Postoperative Radiation Therapy: Passing the Baton for Local Control

In the article by Wang et al that accompanies this editorial, the authors harness data from a retrospective database in an effort to bolster the case for local control therapy after surgery—that is, postoperative radiation therapy (PORT). As with many retrospective reviews, there are numerous limitations in such an analysis, which the investigators do a good job of describing in their discussion. The patients that the authors included in their comparison of PORT versus no PORT were also fairly restrictive as a result of the authors’ attempt to have more uniform cohorts; however, interesting clinical scenarios, such as patients who have positive margins despite induction chemotherapy, are excluded from this report. Nevertheless, this work supports the stance of many oncologists who believe that aggressive attempts at local control benefit select patients with lung cancer. The authors point out that there is a paucity of data from clinical trials with primary end points that enable the direct assessment of PORT with respect to positive residual disease. From the perspective of a surgeon, certain natural human tendencies, such as avoidance of pain and lifestyle alterations, have made comparison of traditional open operations to less invasive surgeries challenging. Similarly, the question, “Did you get it all, doc?” looms large in patients’ minds and may similarly encumber prospective research that directly enables a PORT versus no PORT comparison. This is because patients who sense surgeons’ concerns regarding their possible occult residual diseases are unlikely to accept research random assignment to control (observation) group. Accordingly, I point out the diversity of clinical scenarios that can occur at the point of the handoff from surgeon to radiation oncologist; a better method of categorization and documentation for these scenarios is needed so that the PORT issue can be studied better by databases like that used by the authors. This comes naturally as an extension of the useful, but relatively crude, R0 (negative), R1 (microscopic ), and R2 (grossly ) designations. Obviously, there are many more nuanced patterns that connote a disease biology that might influence the surgeon to either remain optimistic or to be pessimistic with respect to local control after the operation. For instance, one scenario might involve a 1-cm region of peripheral gross tumor (R2) left on a T4 structure in a frail patient with N0 disease who is too weak for an extended resection. In this case, the surgeon begins the handoff to the radiation oncologist in the operating room by marking the target with radiopaque clips. In this situation, the local control team (surgeon and radiation oncologist) may expect a better survival for this frail patient (now designated as having R2 disease) than a healthy patient with N0 disease who has an aggressive wide area of microscopic (R1) disease. Another common, important, nuanced difference occurs with the types of positive bronchial margins. For a number of reasons that are largely related to comorbidities, surgeons may leave microscopic, focally positive, bronchial mucosal margins of juxtaposed, lower stage, less aggressive tumors to be reliably controlled by radiation rather than performing a complex airway reconstruction. Alternatively, a surgeon may leave a focally positive margin in the peribronchial tissues of a patient (who could easily tolerate any formal resection) because the aggressive primary is far away but demonstrating aggressive widespread lymphovascular invasion. Considering these scenarios might help explain certain conundrums in the study by Wang et al, which, because of its neoadjuvant exclusion, has studied a population whose care was coordinated initially by the surgeon. In the first of the comparative examples above, the surgeon is likely to strongly recommend radiation therapy as an important continuation of the curative operative treatment that the patient may have traveled a long distance to receive. The more aggressive, systemic tumor biology demonstrated in the alternate scenarios increases the importance of chemotherapy and reduces the relative benefit of PORT, and, in turn, diminishes the justification for regular travel to a radiation therapy facility. This could explain the travel differences noted in this article: perhaps the enthusiasm of the disease management team (including the surgeon responsible for passing the baton to the radiation oncologist) for PORT was reduced in situations of aggressive, systemic tumor biology. Regarding the importance of PORT in the context of positive nodes, the authors show a declining use of PORT for nodal disease and higher nodal ratios, perhaps reflecting the need to focus on chemotherapy for the compelling systemic disease noted. Another interesting finding was the relatively better incremental survival curve for PORT in patients with N2 disease (Figs 2C and 2D) compared with that for the patients with N1 disease. Given that most surgeons do not operate immediately on patients with known N2 disease, this does raise the question of the adequate use of mediastinoscopy or endobronchial ultrasound. That being said, one can easily imagine that the N1 margin-positive group may have comprised many patients with large, bulky tumors with many hilar nodes who underwent resection attempts. Perhaps this represents a biology that is difficult to encompass in a focused treatment volume and is less likely to respond to PORT. Conversely, many patients in the N2 group may have had surgeons JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 33 NUMBER 25 SEPTEMBER 1 2015