Poor-Performance Status Assessment of Patients with Non-small Cell Lung Cancer Remains Vague and Blurred in the Immunotherapy Era

In the latest decade, the introduction of immune-checkpoint inhibitors (ICIs) has dramatically improved the prognosis of patients with NSCLC. First-line ICIs or chemo-ICI trials have demonstrated OS advantages but the accrual was limited to Eastern Cooperative Oncology Group (ECOG) performance status (PS)0-1 patients. ICI studies have for the vast majority excluded patients with poor performance status. PS 2 particularly is known as a negative prognostic factor for survival and a predictive factor of adverse events and poor response to treatments. Data on the activity of ICIs in PS2 patients are limited and come from heterogeneous meta-analyses and small phase II or expanded access trials. Often, terms such as “unfit” or “frail” ascertain the eligibility of patients to undergo cytotoxic chemotherapy, without specifying PS.

Other tools exist to aid in decision-making, and one simple, rapid, and validated screening test for frailty is the FRAIL scale consisting of 5 straightforward questions that can be self-administered and may represent an efficient and cost-effective way to screen large groups of patients for frailty. The Comprehensive Geriatric Assessment (CGA) is a widely used method to determine the medical, psychological, and functional capabilities of older patients. However, CGA is time-consuming and this could represent a real barrier to its adoption in clinical practice. For this reason, a quick screening tool, the G8 questionnaire, has been developed and demonstrated validity also in a younger population. A complementary tool to assess patients’ frailty is Charlson comorbidity index (CCI) which has become the most widely used clinical index for a variety of disorders and cancers. Yet, none of these tools has been validated as predictive in ICI.

In conclusion, solid data regarding the benefit of ICIs in ECOG PS2 NSCLC patients are currently lacking and the role of immunotherapy remains uncertain for PS2 patients. Prospective randomized trials addressing this question are warranted or ongoing. However, we are concerned that without a more extensive and objective assessment of patients’ fitness and frailty by using and validating appropriate tools a clear answer may not come to light.