Simple Blood Formula Could Predict Survival in Colorectal Cancer That Spreads to the Lungs

When colorectal cancer spreads to the lungs, the outlook for patients can vary dramatically from one person to the next, even among those with seemingly similar disease. Some patients live for years after pulmonary metastases are detected, while others deteriorate rapidly despite aggressive treatment. Clinicians have long lacked a reliable, inexpensive way to sort these patients into meaningful risk groups at the moment the lung spread is discovered. A new retrospective study from Osaka Metropolitan University in Japan suggests that the answer may already be sitting in routine blood work, in the form of a single calculated number that combines two well-known markers of inflammation and nutrition.

The marker, called the N-CALLY index, is elegantly simple in its construction. It is calculated by multiplying the neutrophil-to-lymphocyte ratio, a standard gauge of systemic inflammation derived from a complete blood count, by the C-reactive protein-to-albumin ratio, which pairs an acute-phase inflammatory protein with a measure of nutritional reserve. Both components have individually been linked to cancer outcomes in previous research, but the Osaka team, led by Iguru Omori and Hiroaki Kasashima, reasoned that multiplying them together might capture something that neither could alone: the combined burden of inflammation and nutritional decline that often accompanies advancing disease.

The study, published in BMC Cancer, analyzed 76 patients who developed pulmonary metastasis after undergoing curative resection of their primary colorectal cancer between January 2008 and December 2022. One outlier case was excluded from the initial cohort of 77 consecutive patients. The researchers measured the N-CALLY index and a battery of competing inflammatory, nutritional, and skeletal muscle indices at the exact moment each patient’s lung metastasis was diagnosed, then tracked overall survival using the statistical tools that underpin modern prognostic research: receiver operating characteristic analysis to find the best cut-off, Kaplan-Meier curves to visualize survival differences, and Cox proportional hazards regression to test whether the index held up after accounting for other clinical factors.

The results were striking for a marker that costs nothing beyond tests already performed in routine care. Among all the systemic inflammatory and nutritional indices examined, the N-CALLY index showed the highest area under the receiver operating characteristic curve, at 0.628, with a cohort-derived cut-off value of 0.03. Patients whose index was at or above that threshold faced significantly worse overall survival. In univariate analysis, an elevated index carried a hazard ratio of 3.524, with a 95 percent confidence interval of 1.536 to 8.084 and a p-value of 0.003. Crucially, the association survived multivariable adjustment, with an adjusted hazard ratio of 3.014 and a confidence interval of 1.285 to 7.068, meaning the index predicted survival independently of established clinicopathological factors.

Perhaps the most clinically relevant finding came when the researchers tested whether adding the N-CALLY index to a conventional prognostic model actually improved that model’s performance. Using time-dependent receiver operating characteristic analysis, they found that the model including the index achieved higher area under the curve values for predicting one-, three-, and five-year overall survival than the model without it: 0.730 versus 0.619 at one year, 0.771 versus 0.705 at three years, and 0.758 versus 0.721 at five years. The apparent concordance index, a standard measure of a model’s ability to rank patients correctly by risk, rose from 0.662 to 0.708, and after bootstrap correction for optimism, from 0.645 to 0.686. In plain terms, the blood-based formula made the risk predictions measurably sharper across every time horizon tested.

The biology behind the index is grounded in a growing body of research on the systemic inflammatory response in cancer. Neutrophils, the abundant white blood cells that mount the first line of defense against infection, can be recruited by tumors and can actively promote invasion, angiogenesis, and metastatic seeding. Lymphocytes, by contrast, are the immune system’s primary anti-tumor warriors, and their depletion signals an immunosuppressed, tumor-tolerant state. A high neutrophil-to-lymphocyte ratio therefore reflects an immune environment tilted in the cancer’s favor. C-reactive protein, produced by the liver under inflammatory stimulation, rises when tumors drive chronic systemic inflammation, while albumin falls as inflammation suppresses appetite and accelerates protein breakdown. By multiplying the two ratios, the N-CALLY index effectively asks whether a patient is simultaneously inflamed and nutritionally depleted, a combination that previous work has repeatedly associated with poor outcomes across many cancer types.

Why does this matter specifically for lung metastases from colorectal cancer? Pulmonary metastasectomy, the surgical removal of lung lesions, remains a mainstay of treatment for selected patients, but deciding who truly benefits from an operation is one of the most debated questions in gastrointestinal oncology. Current selection relies heavily on the number, size, and resectability of lesions, the disease-free interval, and the status of lymph nodes, yet these criteria leave considerable uncertainty. A blood test that adds independent prognostic information could, in principle, help clinicians and patients weigh the risks and benefits of surgery versus systemic therapy, or help identify patients whose disease biology warrants closer surveillance or earlier escalation of treatment.

The authors are careful, and appropriately so, about the limits of their work. This was a retrospective, single-center study of a modest 76 patients, and the cut-off of 0.03 was derived from the same cohort in which it was tested, a practice that tends to inflate apparent performance. The area under the curve of 0.628, while the best among the indices compared, indicates only moderate discriminatory power on its own. The researchers explicitly state that the N-CALLY index should serve as an adjunctive marker to complement established clinicopathological factors, not as a stand-alone criterion for deciding who undergoes pulmonary metastasectomy or any other treatment. They call for validation in independent external cohorts before any clinical application, a caution that reflects the well-documented tendency of prognostic markers to perform less impressively when tested outside their birthplace.

Still, the appeal of the approach is hard to overstate. Unlike genomic assays or advanced imaging, the N-CALLY index requires only a complete blood count, a C-reactive protein measurement, and an albumin level, tests that are already ordered for virtually every cancer patient at every major hospital. It costs pennies, can be computed on a napkin, and delivers a single number that quantifies the intersection of two of the most powerful forces shaping cancer outcomes: the body’s inflammatory state and its nutritional reserve. If larger, multi-center studies confirm the Osaka findings, this humble formula could find its way into the risk stratification schemes that guide care for the growing population of patients living with colorectal cancer that has reached the lungs, offering a faster, cheaper complement to the clinical judgment on which oncologists have long had to rely.

Subject of Research: Prognostic value of a composite inflammatory–nutritional blood index for risk stratification in colorectal cancer patients with pulmonary metastasis

Article Title: Risk stratification in patients with pulmonary metastasis from colorectal cancer: prognostic utility of a composite inflammatory–nutritional index (N-CALLY index) — a retrospective cohort study

Article References: Omori, I., Kasashima, H., Fukuoka, T., Wang, Z., Naito, N., Tanaka, A., Yonemitsu, K., Fukui, Y., Seki, Y., Kuroda, K., Miki, Y., Yoshii, M., Tamura, T., Shibutani, M., Toyokawa, T., & Maeda, K. (2026). Risk stratification in patients with pulmonary metastasis from colorectal cancer: prognostic utility of a composite inflammatory–nutritional index (N-CALLY index) — a retrospective cohort study. BMC Cancer. https://doi.org/10.1186/s12885-026-17055-2

Image Credits: AI Generated

DOI: 10.1186/s12885-026-17055-2

Keywords: colorectal cancer, pulmonary metastasis, N-CALLY index, prognostic marker, systemic inflammation, neutrophil-to-lymphocyte ratio, C-reactive protein, albumin, overall survival, risk stratification, pulmonary metastasectomy, retrospective cohort study