How I will treat my next patient

Long-term survival in stage IV NSCLC


Local consolidation

Johannes Uhlig, MD, and colleagues analyzed 6 years of National Cancer Database records, identifying 34,887 stage IV NSCLC patients who had fewer than two distant metastatic lesions in the liver, lung, brain, or bone (JAMA Netw Open. 2019 Aug 21. doi: 10.1001/jamanetworkopen.2019.9702). Treatment groups were divided into patients who received systemic therapy alone (70.3% of the total patients), had surgical resection of the primary site plus systemic therapy (2.4%), or received external beam radiation therapy or thermal ablation (EBRT/TA) of the primary site plus systemic therapy (27.3%). Multivariable Cox proportional hazards models, incorporating a number of clinical variables, were used to compare overall survival between the three groups at a median follow-up of approximately 39 months.

They found that patients treated with surgical consolidation had a 41% lower mortality, in comparison with systemic therapy alone. EBRT/TA was also associated with lower mortality (by 5%), in comparison with systemic therapy alone, but the benefit was more nuanced. For instance, patients with squamous cell histology with low tumor bulk, low nodal burden, and fewer distant sites of disease benefited, but patients with adenocarcinoma and bulkier disease or more than two distant sites did not benefit.

The discussion emphasized all of the caveats that would be appropriate for a retrospective, telescopic record review – patient selection factors; lack of detail about systemic therapy; small numbers of patients in various subsets; exclusion of patients who had consolidative treatment of metastatic sites; and the potential for unbalanced allocation of patients with various actionable, prognostically relevant mutations. Further research, including ongoing trials such as NRG-LU002, was encouraged.

How these results influence clinical practice

Ralph R. Weichselbaum, MD, in his Karnofsky lecture at the 2018 annual meeting of the American Society of Clinical Oncology highlighted the hypothesis that metastatic tumors are enriched differentially for oligometastatic or polymetastatic miRNAs and that these miRNAs could influence future clinical behavior (J Clin Oncol. 2018;36[32]:3240-50). This work, coupled with clinical features (number of sites of disease, pace of progression) could elucidate which oligometastatic NSCLC patients might benefit from aggressive local treatment and achieve long-term, disease-free survival.

As previously reported, Daniel R. Gomez, MD, and colleagues found improved median progression-free survival (14.2 vs. 4.4 months; P = .022) and overall survival (41.2 vs. 17.0 months; P = .017) among patients with oligometastatic NSCLC who were randomized to local consolidation versus standard maintenance therapy/observation (J Clin Oncol. 8 May 2019. doi: 10. 1200/JCO.19.00201). Joshua M. Bauml and colleagues reported impressive results for systemically treated stage IV NSCLC patients who received local consolidation and checkpoint inhibitors for “oligo-remnant disease” (JAMA Oncol. 2019 Jul 11. doi: 10.1001/jamaoncol.2019.1449).

At the present time, clinical practice should remain governed by the general tendency to discourage aggressive local treatment except in highly selected cases with poorly resolved or impending life-altering symptoms. The publication by Dr. Uhlig and colleagues and the previously reported phase 2 trials, support phase 3 randomized trials of local treatment of isolated sites in oligometastatic NSCLC patients, particularly in an era of immune-based systemic treatment that offers finite potential for long-term survival.

Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.

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