Are Calculated Immune Markers with or Without Comorbidities Good Predictors of Colorectal Cancer Survival? The Results of a Longitudinal Study

Abstract

Background/objectives: Although numerous prognostic biomarkers have been proposed for colorectal cancer (CRC), their longitudinal evaluation remains limited. The aim of this study was to investigate longitudinal changes in biomarkers calculated from routinely used laboratory markers and their relationships to common chronic diseases (comorbidities).

Methods: A retrospective longitudinal observational study was completed with the inclusion of 817 CRC patients and a total of 4542 measurement points. Pan-immune inflammation value (PIV), prognostic nutritional index (PNI), and systemic immune-inflammation index (SII) were calculated based on complete blood count and albumin measurement data.

Results: Longitudinal data analyses confirmed the different values and slopes of the parameters tested at the different endpoints. Survivors had the lowest and most constant PIVs and SII values, and the highest and most slowly decreasing PNI values. Those patients with non-cancerous death had similar values to the previous cohort, but an increase/decrease occurred towards the death event. Patients with CRC-related death had significantly higher PIVs and SII values and significantly lower PNI values (p < 0.0001), and a significant increase/decrease was observed at the early observational periods. The presence of lymph node and/or distant metastases, adjuvant chemotherapy, and hypertension significantly affected PIVs and SII and/or PNI values. The changes in PIVs and SII and PNI values toward pathological values are poor prognostic signs (p < 0.0001).

Conclusions: Each of the three calculated markers demonstrates suitability for longitudinal patient follow-up, and their pathological alterations over time serve as valuable prognostic indicators. They may also be useful to detect certain clinicopathological parameters early.

Keywords: colorectal neoplasms; longitudinal analysis; pan-immune inflammation value; prognostic nutritional index; systemic immune-inflammation index.

Figure 1

After the removal of ineligible patients, a total of 817 colorectal cancer patients were identified, of whom 771 and 591 patients had at least one pan-immune inflammation (PIV) and systemic immune-inflammation index (SII) value, and prognostic nutritional index (PNI) value, respectively.

Figure 2

Longitudinal changes in the pan-immune inflammation (PIV; (A)), the systemic immune-inflammation index (SII; (B)), and the prognostic nutritional index (PNI; (C)) values throughout the observational period of the study. Higher PIVs and SII values and lower PNI values are associated with worse clinical outcomes. Those patients who died due to colorectal cancer (CRC) had significantly higher PIVs and SII values and lower PNI values throughout the entire study. Those patients who died due to other reasons or were still alive at the end of the observational period had more constant and similar values, compared to those who died due to CRC.

Figure 3

Cumulative incidences of two competing events throughout the observational period of this study. It was found that death due to colorectal cancer (CRC) occurred more frequently in the earlier part of the study, while death due to other causes was more frequent in the later period of the study.

Figure 4

Throughout the whole observation period of the study, there was a significant difference between the pan-immune inflammation (A) and the prognostic nutritional index (B) values of the two sexes and those patients with and without hypertension, respectively.

Figure 5

Overall survival curves for (A) patients with different SII values and (B) patients in the four PNI categories. No group number could be given for the PNI categories because dynamic group switching between the four groups was allowed in the model. The SII values shown in the figure are hypothetical values only.