Background
Urinary cancers, as a term mainly consisting of prostate cancer (PC), bladder cancer (BC), renal cell cancer (RCC), are much more common in men than in women and the incidence of these tumors ranks the second, fifth and seventh most commonly diagnosed cancer in the United States, 2017 [
1]. Generally, the mainstay of therapy for localized urological tumors is surgical resection, while target therapy is mainly for metastatic cases. Due to the appearance of sipuleucel-T based immunotherapy and the development of molecular target drugs [
2,
3], survival of urinary cancer has been greatly improved [
4]. However, the prognosis of these tumors is still not satisfying. As for RCC, postoperative recurrence occurs in one-third of patients [
5]. Meanwhile, in terms of BC, its 5-year survival remains 77.9%, even only 5.4% for distant diseases [
6]. Therefore, exploring the prognostic factors for survival, death or recurrence may be of great value to better understand these and help physicians to develop the optimal treatment strategies for patients.
Prognostic nutritional index (PNI), as a predictor of cancer prognosis, was firstly introduced by Onodera et al. [
7] to investigate the potential prognostic role in gastrointestinal malignancy in 1984. Moreover, it had also been validated to be an independent prognostic factor in many other types of tumors, such as hepatocellular carcinoma [
8], pancreatic cancer [
9], and pleural mesothelioma [
10]. Recently, PNI as a prognostic factor in the case of urinary cancer, had gradually gained a lot of interest and accumulating researches considered it to be an independent prognostic factor in urinary tumors, associated with overall survival (OS), progression-free survival (PFS) or cancer specific survival (CSS). However, their results remained inconsistent. Hence, this meta-analysis was conducted systematically to shed light on the relationship between PNI and urinary cancer. Due to the absence of level I evidence guiding the application of PNI in urinary cancers, our results were also anticipated to provide some references for clinical work.
Discussion
Urinary cancers had accounted for a relatively large proportion of all tumors and the newly estimated cases of PC, RCC and BC were 161,360, 63,990 and 79,030 respectively in USA, 2017 [
1]. Metastases or postoperative recurrence were highly likely to occur in these tumors, for example, approximately 75% high-risk bladder cancer patients would recur, progress, or die within 10 years after their initial diagnosis [
29]. Moreover, up to 20% of all RCC patients would lead to local or distant disease recurrence ultimately [
30]. Once metastasized, the 5-year survival rate was less than 10% [
31]. Obviously, it was utmostly important to identify the prognostic factors in urinary tumors. To our best knowledge, it was the first meta-analysis to estimate the prognostic role of pre-treatment PNI in urinary cancers.
Accumulating data had been widely investigated for a long time on the prediction of tumor survival and recurrence. The host inflammatory response had already been proved to be a predictor of survival independent of stage and grade in many solid tumors [
32,
33]. Existing hypothesis claimed that this process was suitable for the tumor growth in their microenvironment, based on its provision of growth factors, proangiogenic factors or extracellular matrix enzymes [
34]. On the other hand, the cancer stem cell pathway could also be activated by inflammatory cytokines, which could promote the development and invasion of the tumor [
35]. In terms of these, the prognostic role of C-reactive protein in RCC had been confirmed [
36]. Furthermore, the host nutritional status was considered to be closely related to tumor prognosis. In 2009, Karl et al. [
37] made an evaluation in 897 urologic patients utilizing the Nutritional Risk Screening 2002 (NRS), claimed that 16% of patients were under the risk of malnutrition, which can contribute to malignant disease. Gregg et al. [
38] found a simple model, measured by body mass index (BMI), serum albumin and preoperative weight loss, that which can predict 90-day mortality and poor OS at 3 years in BC patients. Additionally, a study conducted by Lambert et al. [
39] demonstrated that the pre-treatment albumin levels had something to do with higher mortality. However, there is no unified and approved standard to reflect the nutritional status of preoperative patients.
Past researches had revealed that many factors could be investigated to predict the prognosis in urinary tumors. Pre-treatment neutrophil-to-lymphocyte (NLR) ratio and pre-treatment lymphocyte-monocyte ratio (LMR) had been proved to be an independent prognostic factor in various urinary cancers [
40‐
42]. Generally, high pre-treatment NLR or LMR was closely associated with poor survival. Santoni et al. [
43] thought pre-treatment NLR to be an independent prognostic factor for mRCC patients treated with second- or third-line everolimus. Yoshida et al. [
44] found that pre-treatment lower level LMR could predict poorer OS and CSS by analyzing 302 patients underwent radical cystectomy. Meanwhile, the potential role of LMR may superior to NLR to some extent. Similarly, the potential role of Glasgow prognostic score (GPS) [
45] and systemic immune-inflammation index (SII) [
46] had also been explored.
In this meta-analysis, conclusion could be drawn that a relatively lower pre-treatment PNI was tightly associated with a poorer OS, DFS/PFS/RFS and CSS/DSS. Subgroup analysis by cancer type or treatment type showed the similar results. PNI, calculated by serum albumin levels and lymphocyte count and its accurate value equals to 10 * serum albumin concentration (g/dL) + 0.005 * lymphocyte counts (number/mm
2), was first applied by Onodera et al. [
7] to assess the nutritional and immunological status of gastrointestinal surgical patients. Serum albumin, known as an indicator of host inflammatory and nutritional status, had been verified its prognostic role in various types of cancers [
47,
48]. In addition, the host immune response activated by lymphocytes can help clearance of the tumor cells or prevent them from developing [
34], the lower level of lymphocytes may represent a poorer survival or a higher mortality [
49]. Therefore, it was easy to explain that why the PNI level, determined by serum albumin and lymphocytes, played an important role in prognosis of urinary tumors. In our study, a lower level of PNI may indicate a poorer survival and higher possibility of recurrence in urinary tumors regardless of its tumor type and treatment.
During our selection process, only one article focused on the relationship between PNI and prostate cancer [
28]. In that research, Fan and his team assessed the prognostic role of PNI in prostate cancer treated with abiraterone (AA), a high baseline PNI level was tightly related to the initial response to AA treatment in metastatic castration-resistant prostate cancer patients (mCRPC), and the lower PNI level may predict poorer OS, radiographic PFS (rPFS), PSA-PFS. Furthermore, add PNI into the prediction model could increase the accuracy of a multivariate model for OS.
The strength of our study was mainly its strict inclusion criteria for eligible studies and the entire heterogeneity was relatively low. In addition, it was the first time for us to shed light on the prognostic role of pre-treatment PNI in urinary cancers. Nonetheless, several potential limitations should be paid attention to before fully understanding this study. Firstly, uncontrollable bias may exist because all of the included articles were retrospective studies rather than randomized controlled trials. Secondly, related articles were too few to obtain a reliable result in some specific endpoints (e.g. only five articles included in the analysis for CSS/DSS). Due to the relatively small sample size, unavoidable bias might also exist. Thirdly, most of the included articles were from Asia which may make the subgroup analysis hard to be performed. Last but not least, upcoming prospective RCTs were required to provide more available data and subsequent researches should resolve the aforementioned difficulties before pretreatment PNI was widely used in clinical practice.
Authors’ contributions
YJ, NHS: protocol/project development; YMW, YCW: data collection or management; RC, QJZ: data analysis; FQ, XZ, YW: manuscript writing/editing. All authors read and approved the final manuscript.