Our principal finding is that preoperative GNRI, as a nutritional status evaluation tool, is an independent prognostic factor for UTUC patients receiving RNU. Age, surgical margin positive and tumor stage also independently affect the overall survival under a long-term follow- up.
Malnutrition is a common problem in hospitalized elderly patients, and it is associated with their functional decline and higher mortality rate 26. Malnutrition may be characterized by loss of muscle or fat mass causing body weight loss, which is common for cancer patients as the result of cachexia and is responsible for 22% of deaths 27. Pretreatment serum albumin levels provide useful nutritional assessment and prognostic significance for cancer patients. Serum albumin levels may drop due to tumor progression, immune response to tumor and anticancer therapy 28. The nutritional risk index is first used to evaluate nutritional status and postoperative outcome which is calculated by albumin content, in terms of present body weight and usual body weight 29. However, this index is not widely used because most elderly patients do not remember their usual body weight, and their weight loss may require correcting multiple contributing factors 30. GNRI was proposed by Bouillanne et al., and with the usual body weight replaced by ideal body weight. It became a simplified and more convenient predictive tool 11. Although albumin is a well-known index of nutrition status affecting wound healing and postoperative complication, it will be altered by digestive function and systemic inflammation 31,32. In contrast, GNRI calculated by albumin, actual body weight and ideal body weight is more objective and easily determined and it was associated with risk of deaths in many human diseases such as diabetes mellitus, cardiovascular disease, end stage renal disease and cancers 33.
Several studies reported the value of GNRI in predicting oncologic outcome and comorbidity in cancer patients receiving curative surgical treatment. Kubo et al., found that low GNRI are associated with high incidences of preoperative dysphagia, postoperative lung complications and 5-year overall survival in esophagus cancer 13. Hirahara et al. and Sasaki et al. also reported that GNRI is an independent prognostic factor for OS in gastric patients underwent laparoscopic gastrectomy and in colorectal cancer patients after curative surgery 14,15. Malnutrition is relative less common in genitourinary tract malignancy, and it may present as a sequela of advanced disease or paraneoplastic syndrome 34. In a large-scale retrospective study, Kang et al. found that low values of GNRI are associated with aggressive pathologic characteristics and poor survival in patients with renal clear cell carcinoma who have nephrectomy 17. Riveros et al. found that in bladder cancer patients receiving radical cystectomy, GNRI independently predicts mortality, blood transfusion, pneumonia, extended length of stay and non-home discharge 16. They also suggest GNRI being part of Enhanced Recovery after Surgery (ERAS) protocols for nutritional risk screening before radical cystectomy 35.
Our present study is the first to investigate the relationship between GNRI and survival outcomes in UTUC patients receiving RNU, not only elderly but also young age populations. It could be the sequela of advanced tumor stage causing cancer cachexia or paraneoplastic syndrome and advanced malignant features were associated with low GNRI score. Additionally in multivariate analysis, we confirmed GNRI is the independent risk factor for OS, CSS and DFS.
Below are some limitations of our study. First, retrospective design had selection and information bias that had restricted the power of the prognostic role. Prospective cohort study is needed to overcome the limitations of the potential bias. Second, the surgical method is a possible confounder that impacts oncologic outcomes. For example, in the period starting from 2008, we routinely performed hilar lymph node dissection. This procedure was only performed given suspicious presence of lymph nodes before 2008. Third, reports in the literature suggested that the nutrition status is associated with physical performance and the quality of life [36]. However, the research approach using questionnaires was not feasible due to the retrospective nature of our study. Finally, we did not assess the impact of neoadjuvant or adjuvant therapy which may have systemic impacts leading to malnutrition. In the present era of using immune check-point inhibitors, further large scale prospective cohort studies are needed to verify the association between GNRI and malignance.