A retrospective analysis of nearly 200 patients treated with local consolidative therapy for oligometastatic non–small cell lung cancer (NSCLC) has found improved overall survival associated with aggressive consolidation.1 According to data presented at the 2019 Multidisciplinary Thoracic Cancers Symposium, consolidative therapy, consisting of radiation therapy or surgery, extended the median survival by 6 months compared with no such intensive treatment (P = .026). Comprehensive local consolidation was also associated with durable long-term survival, with 1- and 5-year-survival rates approximating those historically observed in earlier stages of disease, the authors of the study reported.
We speculate that patients with adenocarcinoma, low intrathoracic disease burden, and absence of bone metastases constitute those patients most likely to derive a durable survival benefit from aggressive consolidation.— Erin M. Corsini, MD
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“Given our findings, we speculate that patients with adenocarcinoma, low intrathoracic disease burden, and absence of bone metastases constitute those patients most likely to derive a durable survival benefit from aggressive consolidation,” said Erin M. Corsini, MD, a clinical research fellow in thoracic and cardiovascular surgery at The University of Texas MD Anderson Cancer Center, Houston. “We also submit that the observed rates of systemic failure in this cohort highlight the need to further examine whether the benefits associated with this novel treatment paradigm can be enhanced by the use of contemporary systemic agents.”
As Dr. Corsini reported, advanced NSCLC is frequently present at the time of diagnosis and the presence of distant metastases has been historically associated with a dismal prognosis. The concept of the oligometastatic state of disease associated with a relatively indolent tumor biology first emerged several decades ago. Oligometastatic disease has been further suggested to represent a continuum, said Dr. Corsini, who noted that patients with metachronous lesions or oligorecurrent disease tend to have the best outcome, whereas those with a large number of synchronous metastases tend to have poorer outcomes; those with a limited burden of synchronous metastases represent an intermediate group.
A recent phase II trial demonstrated improvements in both progression-free and overall survival among patients treated with local therapy to all sites of disease when compared with those undergoing maintenance or observation.2 What remain unknown, said Dr. Corsini, are whether the use of comprehensive local therapy is associated with improved overall survival when compared with the use of local therapy to some but not all of the lesions, and also which patient groups can be expected to have the most durable, long-term survival after comprehensive local therapy.
Comprehensive local consolidative therapy was defined as local therapy regardless of treatment modality or radiation dose delivered to all sites of disease present at the time of diagnosis. Subcomprehensive local therapy was defined as local therapy to some but not all of the lesions, and patients who received no local therapy constituted the final group.
6-Month Increase in Overall Survival
As Dr. Corsini reported, patients with three or fewer synchronous metastases were included in the retrospective analysis (n = 194), most of whom had adenocarcinoma and advanced intrathoracic disease burden. Additionally, most patients had two or more sites of metastatic disease, and the most frequently observed metastatic sites were the brain, bone, and adrenal. Of the patients analyzed, 62% received comprehensive local consolidative therapy to all sites, whereas 38% of patients received either subcomprehensive or no local consolidative therapy to metastases.
After a median follow-up of 52 months, 128 patients had died. Patients who received comprehensive local therapy (n = 121) had a median survival of 29 months vs 23 months for patients receiving subcomprehensive or no local therapy. In patients who received comprehensive local therapy, the rates of 1-, 3-, and 5-year overall survival were 85%, 43%, and 32%, respectively.
On propensity-adjusted multivariable analysis, receipt of comprehensive local therapy was independently associated with improved overall survival, with an adjusted hazard ratio of 0.67, said Dr. Corsini.
To further define survival outcomes, researchers then analyzed the patients following an aggressive strategy of comprehensive local therapy. On a multivariable analysis, higher intrathoracic disease burden, squamous histology, and the presence of bone metastases were associated with an increased hazard of death.
Patterns of Disease Relapse or Progression
Finally, Dr. Corsini and colleagues sought to characterize the patterns of disease relapse or progression following comprehensive local consolidation. Whereas disease progression at the site of the primary lesion and known sites of metastatic disease was infrequent, development of new metastases was the most commonly observed pattern of disease progression. Among patients who had systemic failure, the overwhelming majority suffered isolated systemic disease progression without failure at the primary lesion or oligometastases, suggesting that improved systemic control with novel therapies could further enhance the benefit associated with comprehensive local therapy.
For more on new systemic treatments for non–small cell lung cancer, see an interview with Jyoti D. Patel, MD, on The ASCO Post Newsreels at www.ascopost.com/videos.
Although this study is limited by its retrospective nature, said Dr. Corsini, an attempt was made to account for selection, survivorship, and other biases by deliberate methodologic choices. Additionally, the effect of this therapeutic approach within the context of contemporary targeted agents and immune checkpoint inhibitors remains to be defined. Lastly, whether a specific local therapeutic modality or a threshold dose of radiation is associated with optimal disease control requires further study, Dr. Corsini concluded. ■
DISCLOSURE: Dr. Corsini reported no conflicts of interest.
1. Mitchell KG, Farooqui A, Ludmir EB, et al: Improved overall survival with local consolidative therapy in oligometastatic non-small cell lung cancer: Results from a cohort of 194 patients with synchronous disease. 2019 Multidisciplinary Thoracic Cancers Symposium. Abstract 1. Presented March 14, 2019.
2. Gomez DR, Tang C, Zhang J, et al: Local consolidative therapy improves overall survival compared to maintenance therapy/observation in oligometastatic non-small cell lung cancer: Final results of a multicenter, randomized, controlled phase 2 trial. 2018 ASTRO Annual Meeting. Abstract LBA3. Presented October 21, 2018.
Charles B. Simone II, MD
In a press briefing that preceded the 2019 Multidisciplinary Thoracic Cancers Symposium, Charles B. Simone II, MD, a radiation oncologist and Chief Medical Officer at the New York Proton Center, noted that this study should help clinicians better understand the impact ...