Novel Early-Stage CRC Prognostic Features Uncovered

Low muscle mass and/or an above average neutrophil-to-lymphocyte ratio are significantly associated with poor survival among patients with a new diagnosis of early-stage colorectal cancer

medwireNews: The presence of sarcopenia and a high neutrophil-to-lymphocyte ratio (NLR) significantly predict the overall survival (OS) of patients with early-stage colorectal cancer (CRC), C SCANS Study investigators have found.

“If our findings are confirmed by additional studies, these 2 biomarkers are already collected in routine care and thus have high potential for use in clinical prognostication”, say Elizabeth Cespedes Feliciano, from Kaiser Permanente Northern California in Oakland, USA, and team.

The research included 2470 patients, aged an average of 63 years and diagnosed with stage I–III CRC between 2006 and 2011, of whom 656 died during a median of 6 years’ follow-up, including 357 deaths from CRC.

Using a mean of three NLR measurements taken in the 2 years before diagnosis, the researchers found that 46% of patients had an NLR of 3 or more, denoting the presence of inflammation.

In addition, computed tomography imaging allowed the researchers to calculate that 44% of patients had low muscle mass, or sarcopenia, at time of diagnosis, without the accompanying weight loss indicative of cachexia.

Sarcopenia was defined as skeletal muscle indices for normal or overweight men and women of 52 cm2/m2 and less than 38 cm2/m2, respectively. The values for obese men and women were less than 54 cm2/m2 and less than 47 cm2/m2, respectively, the authors explain.

Analysis showed that there was a significant dose–response relationship between rising NLR and the likelihood of sarcopenia. Compared with an NLR of below 3, the odds ratio of a patient having sarcopenia was 1.35 for an NLR of at least 3 and below 5, and 1.47 for an NLR of 5 or above.

An NLR of at least 3 was significantly associated with reduced OS and CRC-specific survival, with hazard ratios (HRs) for death of 1.64 and 1.71, respectively, compared with a lower NLR. Similarly, the presence of sarcopenia was significantly associated with OS and CRC-specific survival, with corresponding HRs of 1.28 and 1.42.

And patients with both an NLR above 3 and sarcopenia were twice as likely to die from any cause, and from CRC, than those with neither risk factor, with HRs of 2.12 and 2.43, respectively.

Moreover, Cox proportional hazards model analysis, adjusting for characteristics such as body mass index, race, cancer site and stage, gender and age at diagnosis, indicated that such factors did not influence the relationship between survival and elevated NLR and/or sarcopenia.

Indeed, even patients with positive prognostic markers, such as stage I disease (HR=1.81) or age less than 65 years (HR=1.65), had an almost two-fold increase in the risk of death from any cause if they had both an elevated NLR and sarcopenia than neither of these two risk factors.

Writing in JAMA Oncology, however, the researchers caution that “[c]ancer begins years before diagnosis, yet the appearance of sarcopenia was evaluated once, for the first time, at diagnosis; thus, we cannot determine how muscle mass changes in relation to cancer initiation or the onset of inflammation.”

“Furthermore, whereas sarcopenia and elevated NLR were independently associated with survival, we do not know to what extent inflammation or sarcopenia are consequences of a more aggressive tumor or a shared pathologic mechanism vs conditions that enhance tumor growth.”

Elizabeth Cespedes Feliciano et al therefore conclude: “[B]efore this information can be used to influence treatment decisions or tailor interventions, future research must clarify whether reducing systemic inflammation or increasing muscle mass can enhance progression-free survival and through what mechanisms.”

Reference

Cespedes Feliciano EM, Kroenke CH, Meyerhardt JA, et al. Association of systemic inflammation and sarcopenia with survival in nonmetastatic colorectal cancer. Results from the C SCANS Study. JAMA Oncol; Advance online publication 10 August 2017. doi:10.1001/jamaoncol.2017.2319

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