The Prognostic Value of Neutrophil-to-Lymphocyte Ratio in Metastatic Testicular Cancer

Abstract

We investigated the prognostic utility of pre-chemotherapy neutrophil-to-lymphocyte ratio (NLR) in patients with metastatic germ cell tumors (GCTs) undergoing first-line chemotherapy. We utilized two institutional databases to analyze the pretreatment-derived NLR (dNLR). Predictive accuracy was evaluated using the Cox proportional hazard model adjusted for the international germ cell cancer collaborative group (IGCCCG) risk classification. Discriminatory accuracy was evaluated by determining the area under the receiver operating characteristic curve (AUROC). In total, 569 of 690 patients had available dNLR (IGCCCG: good, 64%; intermediate, 21%; poor, 16%). The 5-year and 10-year overall survivals (OSs) for good, intermediate, and poor risk groups were 96.2%, 92.8%, and 62.7% and 93.9%, 90.3%, and 62.7%, respectively. A dNLR of 2 provided the best discriminatory accuracy with an AUROC of 0.58 (95% CI: 0.52–0.65, p = 0.01) for progression-free survival (PFS), whereas for OS, a dNLR of 3 provided the best discriminatory accuracy with an AUROC of 0.62 (95% CI: 0.53–0.70, p < 0.01). A dNLR > 2 was associated with a hazard ratio (HR) of 1.99 (95% CI: 1.27–3.12, p < 0.01) for PFS, which lost its effect after adjustment for IGCCCG (HR: 1.44, 95% CI: 0.90–2.30, p = 0.13). For OS, a dNLR >3 was associated with an HR of 3.00 (95% CI: 1.79–5.01, p < 0.01), but lost its effect after adjustment for IGCCCG. Systemic inflammation plays a role in metastatic GCT, but its prognostic utility beyond established algorithms is limited. The general prognostic value of NLR can be seen across a number of tumors, although the consistency and magnitude of the effect differ according to cancer type, disease stage, and treatment received. We identified that an elevated NLR was associated with an adverse PFS and OS, but not independent of the IGCCCG risk classification. dNLRs >2 and >3 were associated with an adverse PFS and OS, respectively, in patients with metastatic GCT receiving first-line chemotherapy, but not independent of the IGCCCG risk classification.

Comprehensive Assessment of Selected Immune Cell Subpopulations Changes in Chemotherapy-Naïve Germ Cell Tumor Patients

“…In addition, survival analyses revealed that the percentage of neutrophils and lymphocytes could be used as a prognostic factor for PFS and OS, but not independently of the IGCCCG classification, in an analyzed cohort of chemotherapy-naïve GCT patients. Similar findings were also presented by Ribnikar et al (27).…”

“…It is interesting to note that the increased levels of cytotoxic T cells were described in patients with poor prognosis according to the IGCCCG classification, and the presence of lung and non-pulmonary visceral metastases. These results also support the implication of the pro-inflammatory state noted in the tumor burden, which was supported by the interconnection between high neutrophil percentage and decreased percentage of lymphocytes and activated T cells ( 27 , 45 – 47 ). In addition, survival analyses revealed that the percentage of neutrophils and lymphocytes could be used as a prognostic factor for PFS and OS, but not independently of the IGCCCG classification, in an analyzed cohort of chemotherapy-naïve GCT patients.…”

“…Several systemic inflammatory markers that are easily obtained from routine blood tests, such as leukocyte, neutrophil and thrombocyte counts, have been proposed as potentially additional predictive and prognostic markers that can be used in various malignancies. In recent years, several reports established the prognostic and the predictive role of inflammatory indices, such as the neutrophil-to-lymphocyte ratio (23)(24)(25)(26)(27)(28), platelet-to-lymphocyte ratio (28,29) and the systemic immune-inflammation index (SII) (24,28,30) in testicular GCTs. All these data emphasized the important role of the immune response in GCTs (29).…”

The Prognostic Role of Neutrophil-to-Lymphocyte Ratio (NLR) in Testicular Germ Cell Tumor (GCT)

“…A similar finding also reported a correlation between high NLR value and low chemotherapy response rate (Karakaya et al 2021). Survival parameters were reported that NLR was associated with progression-free survival (PFS) and overall survival (OS) (Ribnikar et al 2021). Even though this study showed that NLR seemed to be higher in patients with stable and progressive disease than patients with partial and complete response, a definitive conclusion still could not be made until a prospective cohort prognostic study with larger sample size is performed.…”

The novel pretreatment immune prognostic index discriminates survival outcomes in locally advanced non-operative esophageal squamous cell carcinoma patients treated with definitive chemoradiotherapy: a 6-year retrospective study

“…Among these biomarkers, dNLR is a popular and novel biomarker that measures the immunity or inflammation ratio in cancers. Increasing evidence has shown that high dNLR is significantly associated with poor prognosis in several types of cancers, including ESCC, NSCLC, non-colorectal gastrointestinal cancer, prostate cancer, melanoma, testicular cancer, and ampullary cancer [ [15] , [16] , [17] , [18] , [32] , [33] , [34] ]. It is encouraging that these studies were consistent with our results.…”