jbm Journal of Biosciences and Medicines 2327-5081 2327-509X Scientific Research Publishing 10.4236/jbm.2024.1210029 jbm-136797 Articles Biomedical Life Sciences Research Progress of Systemic Immune Inflammatory Index in Prostate Cancer Zhiwei Zhao Shaoping Cheng aUrology Department, The First Affiliated Hospital of Yangtze University, Jingzhou, China 27 09 2024 12 10 339 348 23, September 2024 21, September 2024 21, October 2024 © Copyright 2014 by authors and Scientific Research Publishing Inc. 2014 This work is licensed under the Creative Commons Attribution International License (CC BY). http://creativecommons.org/licenses/by/4.0/ Prostate cancer has gradually risen to become the second most common cancer threatening men’s health, and prostate-specific antigen (PSA), as the main screening indicator for prostate cancer, has the defects of low specificity and insufficient diagnostic efficacy. As a novel inflammatory index based on neutrophil, lymphocyte and platelet counts, the systemic immune-inflammation index (SII) has recently become a more powerful biomarker for predicting the occurrence and progression of various malignancies. SII reflects the systemic inflammatory response of prostate cancer patients in a more balanced manner, and has higher predictive value than neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). High SII values are often associated with cancer progression and poor prognosis. This article reviews the research progress of SII in prostate cancer, in order to provide guidance for clinical practice. Prostate Cancer Systemic Immune Inflammatory Index Prostate-Specific Antigen 1. Introduction

Prostate cancer primarily occurs in elderly males and is one of the most common malignancies among men [1] . The challenge of enhancing the detection rates of prostate cancer in individuals with PSA levels ranging from 4 to 10 ng/mL warrants further investigation [2] . Numerous expert consensus statements suggest that a PSA level above 4 ng/mL is typically classified as a positive result, while values between 4 and 10 ng/mL are referred to as the “gray zone,” necessitating further evaluation [3] . Various inflammation-based indicators, such as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and lymphocyte-C-reactive protein ratio (LCR), have been identified as potential predictors for certain cancers [4] . However, their predictive value for prostate cancer remains limited. The systemic immune-inflammation index (SII), a novel inflammatory marker derived from neutrophil, lymphocyte, and platelet counts, is considered to possess greater predictive value in assessing inflammation-related diseases compared to other inflammatory markers [5] . Future research should further explore the diagnostic efficacy of combining “gray zone” PSA values with SII in determining prostate cancer positivity rates, thereby enhancing clinical decision-making and improving the accuracy and effectiveness of prostate cancer screening.

 2. Overview of SII and Its Mechanisms

The systemic immune inflammatory index (SII), calculated as the product of neutrophils and platelets divided by lymphocyte count, plays an important role in the assessment of inflammatory response and immune status [6] . Studies have shown that inflammation is closely related to the onset, development, and prognosis of cancer. Neutrophils, lymphocytes, platelets, interleukin, and tumor necrosis factor run through the whole process of tumor cell proliferation and metastasis [7] , so the association between systemic inflammatory index and prostate cancer deserves further investigation. Some studies have shown that SII more evenly reflects the systemic inflammatory response of prostate cancer patients and has higher predictive value than PLR and NLR. Recently, it has emerged as a more powerful biomarker for predicting the occurrence and progression of various malignancies [8] . Clinical studies have shown that SII is closely related to the prognosis of various cancers such as lung cancer, liver cancer, gastric cancer, and colorectal cancer [9] - [11] . High SII values are often associated with cancer progression and poor prognosis [12] . In addition, SII can also be used as an indicator of early cancer screening [13] , which can be used as an adjunct to other imaging and biological detection methods.

 3. PSA Level “Gray Area” and Its Challenges

PSA is secreted by prostate epithelial cells and has organ specificity. Its concentration is positively correlated with the occurrence of prostate cancer [14] . PSA in the range of 4 to 10 ng/mL is defined as a “gray area”, and according to the consensus at home and abroad, imaging should be combined with imaging to assist in diagnosis, and ultrasound-guided prostate biopsy is recommended to be minimized as much as possible [3] . Studies have shown that only about 4% of patients with PSA levels < 20 ng/mL are diagnosed with PCa after needle biopsy. The diagnostic efficacy of PSA varies greatly at different PSA levels [15] . Secondly, the expression of PSA is often affected by the following factors: since PSA is an organ-specific antigen rather than a tumor-specific antigen, its expression level is positively correlated with the volume of benign prostatic hyperplasia, and the higher the stage of most prostate cancers, the higher the PSA, the higher the degree of acute infection, the positive correlation with age, and other non-malignant diseases; Maneuvers such as indwelling urinary catheter and prostate massage may result in varying degrees of elevation [16] , while the use of 5a-reductase inhibitors decreases PSA [17] . Different factors can cause PSA to leak into the lymphatic system and then into the bloodstream. Therefore, the use of PSA alone to diagnose PCa may lead to missed or misdiagnosed diagnoses.

 4. Research Progress of SII in Prostate Cancer 4.1. Overview of Prostate Cancer

According to the latest data from the World Health Organization, prostate cancer has jumped to one of the top cancers in the world for cancer incidence and mortality among men [18] . At present, the diagnosis of prostate cancer is based on PSA > 4 ng/mL, combined with prostate magnetic resonance, prostate needle biopsy, and postoperative pathology [19] . Chinese expert studies have shown that patients with significantly abnormally elevated PSA can be diagnosed with prostate cancer by Pet-CT without puncture, and patients without systemic metastasis can directly undergo radical prostatectomy. This will avoid related surgical complications such as infection, pain, etc., after prostate puncture [20] . At present, the treatment of prostate cancer is still based on radical surgery [21] , so early diagnosis of the prostate will be of great value for the recovery of the disease.

 4.2. Inflammatory Factors Contribute to the Development and Progression of Prostate Cancer

Studies have shown that PLR has the effect of influencing the growth and progression of cancer in the systemic circulation [22] . Platelets promote vascular growth and enhance tumor cell aggregation through the release of VEGF, which further promotes tumorigenesis and progression [23] . Platelets can not only enhance tumor growth and progression, but also respond to T cell-mediated immune responses in antibody circulation [24] . Tumor cells elevate platelet counts and cause activation by affecting the levels of various thrombocytopenic factors and platelet agonists [25] . There are two types of lymphocytes present in the systemic circulation, including T cells, which destroy cancer cells and viral host cells, and B cells, which produce antibodies. As the most important immune cells in the body, lymphocytes mainly induce target cell division and apoptosis, and exert anti-tumor effects [26] . Rulando et al. demonstrated that high NLR was associated with higher GS and higher rates of progression [27] . As the most important cancer-related systemic inflammatory factor, NLR has been proven to predict PCa and Gleason score escalation (GSU) in men undergoing prostate biopsy [28] . Baylan et al. believe that for patients with high NLR and PLR values, radical treatment options such as surgery or radiotherapy should be preferred [29] .

Hu et al. were the first to propose and use the systemic immune inflammation (SII) index, and through a retrospective analysis, it was concluded that a high SII value is a strong prognostic indicator of poor prognosis in patients with hepatocellular carcinoma [30] . The diagnostic value of SII for prostate cancer lies in the fact that it may provide a more objective measurement by capturing the complex interplay between host inflammation and immune response. Due to the influence of long-term inflammatory factors in chronic prostatitis, DNA damage is triggered, cell proliferation is promoted, and the apoptosis mechanism of cells is destroyed, which leads to the occurrence of cancer [31] . A high SII may correspond to an increased inflammatory response, which in turn increases the risk of prostate cancer. PSA is an important indicator of prostate cancer screening, but it is difficult to diagnose in the “gray area” of 4 - 10 ng/mL. A study of 148 patients with PSA in the “gray area” found a significant positive correlation between SII and PSA levels [13] . In addition, patients with high SII have a higher rate of positive prostate biopsy. This suggests that SII may be used as an adjunct indicator to help improve the diagnostic positivity rate of PSA in gray zone prostate cancer.

In the direction of PCa, SII was first applied to it in 2016 and is considered to be an important marker for predicting the prognosis of metastatic castration-resistant prostate cancer (mCRPC) [32] . In 2017, SII was first reported to be associated with the prognosis of a variety of solid tumors, including prostate cancer [33] . Massive neutrophil expansion in the tumor microenvironment and systemic circulation is associated with poor prognosis in cancer patients [12] . Neutrophils, while activating endothelial hyperplasia in vascular and parenchymal cells, increase the adhesion of tumor cells in the systemic circulation and lead to distant metastasis. The increase in platelets inhibits the cytolytic function of lymphocytes, activated T cells, and natural killer cells, thereby inhibiting tumor clearance by the immune system. Platelets protect circulating tumor cells (CTCs) from destruction by the immune system [34] . Platelets and endothelial cell adhesion proteins may facilitate spread by increasing tumor cell efflux. An increase in tumor-infiltrating lymphocytes (TILs) is associated with immunotherapy response and prognosis in cancer patients [35] . Many studies have found that SII is closely related to the clinical features and prognosis of prostate cancer. A study of 297 prostate cancer patients found that patients with prostate cancer with a higher SII had higher Gleason scores and a higher probability of metastasis of their cancer [28] . A meta-analysis of 8083 prostate cancer patients by Zhang et al. showed that in the PCa population, higher SII was significantly associated with poor overall survival (OS) and worse progression-free survival (PFS), while high SII was not significantly associated with T stage, lymph node metastasis, age, and Gleason score [36] . This conclusion is the same as that of the Chinese scholar Meng [37] . However, a meta-analysis of 7986 prostate cancer patients by Qi et al. showed that high SII was associated with advanced tumor stage of PCa (OR = 2.19. 95% CI: 1.11 - 4.33, P = 0.024), presence of lymph node involvement (OR = 2.72, 95% CI: 1.96 - 3.76, P < 0.001), Gleason score (OR = 1.27, 95% CI: 1.13 - 1.44, P < 0.001) [38] . SII and T stage, lymph node metastasis, and Gleason score remain controversial. An analysis of 291 pathologically confirmed prostate cancer patients after radical prostate cancer resection (RP) showed that high SII (HR, 4.521; 95% CI: 2.262 - 9.037, P < 0.001) and high NLR (HR, 4.787; 95% CI: 2.339 - 9.798, P < 0.001) were significant predictors of biochemical recurrence (BCR) after RP and were significantly associated with adverse clinicopathologic outcomes [39] . One study of 61 patients with mCRPC confirmed that SII was a strong independent prognostic indicator for predicting survival in patients with mCRPC treated with 177Lu-PSMA-617 [40] . One study of 519 patients with mCRPC treated with radium dichloride ([223Ra]RaCl2) showed that a high SII predicts worse OS [41] . Zapala et al. showed that SII can be used as a potential auxiliary marker to predict the survival of RP patients with non-metastatic prostate cancer, and suggested that the combination of CAPRA-S score and Charlson comorbidity index has higher value [42] . In summary, the studies concluded that SII may be an important indicator for predicting the prognosis of prostate cancer.

 5. Comparative Analysis of SII with Other Prostate Cancer Biomarkers

After PSA was used as a diagnostic criterion for prostate cancer, many PCa biomarkers have been developed one after another, such as the prostate health index (PHI) and the emergence of PCA3 (prostate cancer antigen 3) new prostate cancer biomarkers, which provide new tools for the diagnosis of prostate cancer [43] . PHI, an algorithm based on PSA and its subtypes ([−2] proPSA and fPSA), has been found to have higher diagnostic efficacy than PSA and fPSA in distinguishing PCa with and without PCa and PCa with Gleason score ≥ 7 [44] . However, PCA3 is a prostate-specific, non-coding RNA, and its levels in the urine of PCa patients are significantly increased [45] . The Prognostic Nutrient Index (PNI) is calculated using albumin levels that reflect nutritional status and lymphocyte counts that reflect immune status and can be used to show nutritional and immune status associated with survival and prognosis for many cancers [46] . Ellez et al. showed that cancer-specific survival (CSS) was significantly better in patients with high PNI (median: 65.60, 95% CI: 39.36 - 91.83) than in patients with low PNI (median: 34.93, 95% CI: 21.52 - 48.34) (P = 0.016) [47] . Sonmez et al. included 508 patients with PSA < 10 ng/mL and PI-RADS ≥ 3 who underwent transfusion prostate biopsies, and the results showed that SII plus PI-RADS score appeared to be an important diagnostic marker in patients with high-grade PCa neuropathological grade (ISUP grade 3 - 5). These values are higher compared to patients with benign pathology and patients with lower ISUP scores [48] . However, compared with these novel markers, SII has shown unique advantages as an indicator reflecting the state of immune inflammation, which can not only predict the occurrence of prostate cancer, but also predict the clinical diagnosis and prognosis of the disease. Due to the high cost of these experiments, they cannot be widely used in primary hospitals, which means that they cannot be used as a test for routine screening for PCa.

 6. Prospect

Early diagnosis of PCa is the main influencing factor affecting the treatment effect and quality of life of PCa. SII reflects the immune inflammatory status of the body and plays a key role in the development and progression of tumors, such as affecting the efficacy of immunotherapy. Therefore, SII may be used in individualized treatment decisions for prostate cancer, such as predicting the efficacy of immunotherapy and guiding the selection of treatment regimens. Although more studies are needed to verify its application value in prostate cancer, SII, as a novel biomarker, has great research potential and future application prospects. At present, many scholars have done a lot of research work on the early diagnosis of prostate cancer, but there is no direct use of SII combined with PSA for early prediction of prostate cancer and reduction of prostate needle biopsy. As an emerging biomarker, SII is still in the early stage of prostate cancer research, and there are many problems that need to be solved, such as its combination application with other biomarkers, and its role in the individualized treatment of prostate. With the deepening of research and the advancement of technology, the author believes that SII will play a greater role in the diagnosis and treatment of prostate cancer and bring new breakthroughs to the diagnosis and treatment of prostate cancer.

 NOTES

*Corresponding author.

 References Bergengren, O., Pekala, K.R., Matsoukas, K., Fainberg, J., Mungovan, S.F., Bratt, O., et al. (2023) 2022 Update on Prostate Cancer Epidemiology and Risk Factors—A Systematic Review. European Urology, 84, 191-206. >https://doi.org/10.1016/j.eururo.2023.04.021 Yang, J., Li, J., Xiao, L., Zhou, M., Fang, Z., Cai, Y., et al. (2023) 68Ga-PSMA PET/CT-Based Multivariate Model for Highly Accurate and Noninvasive Diagnosis of Clinically Significant Prostate Cancer in the PSA Gray Zone. Cancer Imaging, 23, Article No. 81. >https://doi.org/10.1186/s40644-023-00562-x Bostancı, C. and Demir, D.Ö. (2024) The Effect of the Combination of Prostate-Specific Antigen Derivatives with Multiparametric Prostate Magnetic Resonance Imaging Scores on the Negative Predictive Value of It in Grey Zone Patients. Actas Urológicas Españolas, 48, 238-245. >https://doi.org/10.1016/j.acuroe.2023.10.004 Ofner, H., Laukhtina, E., Hassler, M.R. and Shariat, S.F. (2023) Blood-Based Biomarkers as Prognostic Factors of Recurrent Disease after Radical Cystectomy: A Systematic Review and Meta-Analysis. International Journal of Molecular Sciences, 24, Article 5846. >https://doi.org/10.3390/ijms24065846 Zheng, J., Peng, L., Zhang, S., Liao, H., Hao, J., Wu, S., et al. (2023) Preoperative Systemic Immune-Inflammation Index as a Prognostic Indicator for Patients with Urothelial Carcinoma. Frontiers in Immunology, 14, Article 1275033. >https://doi.org/10.3389/fimmu.2023.1275033 Choucair, K., Nebhan, C., Cortellini, A., Hentzen, S., Wang, Y., Liu, C., et al. (2023) Characterization of Age-Associated, Neutrophil-To-Lymphocyte Ratio (NLR) and Systemic Immune-Inflammatory Index (SII) as Biomarkers of Inflammation in Geriatric Patients with Cancer Treated with Immune Checkpoint Inhibitors: Impact on Efficacy and Survival. Cancers, 15, Article 5052. >https://doi.org/10.3390/cancers15205052 Qadir, J., Wen, S., Yuan, H. and Yang, B.B. (2023) Circrnas Regulate the Crosstalk between Inflammation and Tumorigenesis: The Bilateral Association and Molecular Mechanisms. Molecular Therapy, 31, 1514-1532. >https://doi.org/10.1016/j.ymthe.2022.12.005 Luo, Z., Wang, W., Xiang, L. and Jin, T. (2023) Association between the Systemic Immune-Inflammation Index and Prostate Cancer. Nutrition and Cancer, 75, 1918-1925. >https://doi.org/10.1080/01635581.2023.2272800 Kou, J., Huang, J., Li, J., Wu, Z. and Ni, L. (2023) Systemic Immune-Inflammation Index Predicts Prognosis and Responsiveness to Immunotherapy in Cancer Patients: A Systematic Review and Meta-Analysis. Clinical and Experimental Medicine, 23, 3895-3905. >https://doi.org/10.1007/s10238-023-01035-y Xiang, S., Yang, Y., Pan, W., Li, Y., Zhang, J., Gao, Y., et al. (2023) Prognostic Value of Systemic Immune Inflammation Index and Geriatric Nutrition Risk Index in Early-Onset Colorectal Cancer. Frontiers in Nutrition, 10, Article 1134300. >https://doi.org/10.3389/fnut.2023.1134300 Zhang, J., Zhang, L., Duan, S., Li, Z., Li, G. and Yu, H. (2023) Single and Combined Use of the Platelet-Lymphocyte Ratio, Neutrophil-Lymphocyte Ratio, and Systemic Immune-Inflammation Index in Gastric Cancer Diagnosis. Frontiers in Oncology, 13, Article 1143154. >https://doi.org/10.3389/fonc.2023.1143154 Li, J., Cao, D., Huang, Y., Xiong, Q., Tan, D., Liu, L., et al. (2022) The Prognostic and Clinicopathological Significance of Systemic Immune-Inflammation Index in Bladder Cancer. Frontiers in Immunology, 13, Article 965643. >https://doi.org/10.3389/fimmu.2022.865643 Zhu, M., Zhou, Y., Liu, Z., Jiang, Z., Qi, W., Chen, S., et al. (2023) Diagnostic Efficiency of Pan-Immune-Inflammation Value to Predict Prostate Cancer in Patients with Prostate-Specific Antigen between 4 and 20 ng/mL. Journal of Clinical Medicine, 12, Article 820. >https://doi.org/10.3390/jcm12030820 Maeda-Minami, A., Nishikawa, T., Ishikawa, H., Mutoh, M., Akimoto, K., Matsuyama, Y., et al. (2023) Association of PSA Variability with Prostate Cancer Development Using Large-Scale Medical Information Data: A Retrospective Cohort Study. Genes and Environment, 45, Article No. 25. >https://doi.org/10.1186/s41021-023-00280-7 Zhang, Q., Li, H., Song, Z., Kong, S., Zhao, S., Fan, S., et al. (2023) Potential Diagnostic Value of Multiple Indicators Combined with Total Prostate-Specific Antigen in Prostate Cancer. Journal of International Medical Research, 51, Article 3000605231204429. >https://doi.org/10.1177/03000605231204429 Lee, J.H., Won Park, Y., Woo Lee, S., Duck Choi, J., Yoon Kang, J. and Yoo, T.K. (2022) Association between Predictors of Progression of Benign Prostatic Hyperplasia and Moderate-to-Severe Prostatitis-Like Symptoms: A Propensity Score-Matched Analysis. Prostate International, 10, 92-95. >https://doi.org/10.1016/j.prnil.2022.03.002 Busetto, G.M., del Giudice, F., D’Agostino, D., Romagnoli, D., Minervini, A., Rocco, B., et al. (2020) Efficacy and Safety of Finasteride (5 Alpha-Reductase Inhibitor) Monotherapy in Patients with Benign Prostatic Hyperplasia: A Critical Review of the Literature. Archivio Italiano di Urologia e Andrologia, 91, 205-210. >https://doi.org/10.4081/aiua.2019.4.205 Sekhoacha, M., Riet, K., Motloung, P., Gumenku, L., Adegoke, A. and Mashele, S. (2022) Prostate Cancer Review: Genetics, Diagnosis, Treatment Options, and Alternative Approaches. Molecules, 27, Article 5730. >https://doi.org/10.3390/molecules27175730 Wasim, S., Lee, S. and Kim, J. (2022) Complexities of Prostate Cancer. International Journal of Molecular Sciences, 23, Article 14257. >https://doi.org/10.3390/ijms232214257 Guo, S., Zhou, C., Zhang, Y., et al. (2023) Diagnostic Value of (18)F-PSMA-1007 PET/CT Combined with Prostate Specific Antigen Derived Indicators in Gray Area Prostate Cancer. Journal of Central South University Medical Sciences, 48, 1812-1819. Morgan, T.M., Boorjian, S.A., Buyyounouski, M.K., Chapin, B.F., Chen, D.Y.T., Cheng, H.H., et al. (2024) Salvage Therapy for Prostate Cancer: AUA/ASTRO/SUO Guideline Part III: Salvage Therapy after Radiotherapy or Focal Therapy, Pelvic Nodal Recurrence and Oligometastasis, and Future Directions. Journal of Urology, 211, 526-532. >https://doi.org/10.1097/ju.0000000000003890 Tuntinarawat, P., Tangmanomana, R. and Kittisiam, T. (2024) Association between Alteration of Neutrophil to Lymphocyte Ratio, Platelet to Lymphocyte Ratio, Cancer Antigen-125 and Surgical Outcomes in Advanced Stage Ovarian Cancer Patient Who Received Neoadjuvant Chemotherapy. Gynecologic Oncology Reports, 52, Article 101347. >https://doi.org/10.1016/j.gore.2024.101347 Yi, X., Pi, J., Liu, C., Xiong, Y., Liu, J., Fu, W., et al. (2023) The Relationship between Inflammatory Response Markers and the Prognosis of Non-Muscle Invasive Bladder Cancer and the Development of a Nomogram Model. Frontiers in Oncology, 13, Article 1189086. >https://doi.org/10.3389/fonc.2023.1189086 Asghar, M.S., Asghar, M.Z., Zahid, A., et al. (2022) Inflammatory Mediators as Surrogates of Malignancy. The Journal of the Pakistan Medical Association, 72, 2259-2263. Lei, X., Zhang, T., Deng, Z., Jiang, T., Hu, Y. and Yang, N. (2023) Coagulation Markers as Independent Predictors of Prostate Cancer Aggressiveness: A Retrospective Cohort Study. Scientific Reports, 13, Article No. 16073. >https://doi.org/10.1038/s41598-023-43427-w Li, X., Gu, L., Chen, Y., Chong, Y., Wang, X., Guo, P., et al. (2021) Systemic Immune-Inflammation Index Is a Promising Non-Invasive Biomarker for Predicting the Survival of Urinary System Cancers: A Systematic Review and Meta-Analysis. Annals of Medicine, 53, 1827-1838. >https://doi.org/10.1080/07853890.2021.1991591 Warli, S., Rulando, M. and Siregar, G. (2021) Correlation between Neutrophil-to-Lymphocyte Ratio with Gleason Score in Patients with Prostate Cancer at Adam Malik Hospital Medan 2013-2015. Urology Annals, 13, 53-55. >https://doi.org/10.4103/ua.ua_1_20 Wang, S., Ji, Y., Ma, J., Du, P., Cao, Y., Yang, X., et al. (2023) Role of Inflammatory Factors in Prediction of Gleason Score and Its Upgrading in Localized Prostate Cancer Patients after Radical Prostatectomy. Frontiers in Oncology, 12, Article 1079622. >https://doi.org/10.3389/fonc.2022.1079622 Baylan, B., Ulusoy, K., Ekenci, B. and Kartal, I.G. (2024) Can Systemic Immune-Inflammation Index and Hematologic Parameters Aid in Decision-Making for Active Surveillance or Curative Treatment in Low-Risk Prostate Cancer? Asian Journal of Surgery, 47, 1360-1365. >https://doi.org/10.1016/j.asjsur.2023.11.126 Hu, B., Yang, X., Xu, Y., Sun, Y., Sun, C., Guo, W., et al. (2014) Systemic Immune-Inflammation Index Predicts Prognosis of Patients after Curative Resection for Hepatocellular Carcinoma. Clinical Cancer Research, 20, 6212-6222. >https://doi.org/10.1158/1078-0432.ccr-14-0442 Liu, H., Gao, Y., Vafaei, S., Gu, X. and Zhong, X. (2021) The Prognostic Value of Plasma Cell-Free DNA Concentration in the Prostate Cancer: A Systematic Review and Meta-Analysis. Frontiers in Oncology, 11, Article 599602. >https://doi.org/10.3389/fonc.2021.599602 Lolli, C., Caffo, O., Scarpi, E., Aieta, M., Conteduca, V., Maines, F., et al. (2016) Systemic Immune-Inflammation Index Predicts the Clinical Outcome in Patients with mCRPC Treated with Abiraterone. Frontiers in Pharmacology, 7, Article 376. >https://doi.org/10.3389/fphar.2016.00376 Zhong, J., Huang, D. and Chen, Z. (2017) Prognostic Role of Systemic Immune-Inflammation Index in Solid Tumors: A Systematic Review and Meta-Analysis. Oncotarget, 8, 75381-75388. >https://doi.org/10.18632/oncotarget.18856 Yu, Z., Yuan, M. and Chen, G. (2023) The Clinical Association between Coagulation Indexes, Platelet-Related Parameters, and Bone Metastasis of Newly Diagnosed Prostate Cancer. European Journal of Medical Research, 28, Article No. 587. >https://doi.org/10.1186/s40001-023-01562-0 Zhou, M., Zhang, Z., Bao, S., Hou, P., Yan, C., Su, J., et al. (2020) Computational Recognition of Lncrna Signature of Tumor-Infiltrating B Lymphocytes with Potential Implications in Prognosis and Immunotherapy of Bladder Cancer. Briefings in Bioinformatics, 22, bbaa047. >https://doi.org/10.1093/bib/bbaa047 Zhang, B. and Xu, T. (2023) Prognostic Significance of Pretreatment Systemic Immune-Inflammation Index in Patients with Prostate Cancer: A Meta-Analysis. World Journal of Surgical Oncology, 21, Article No. 2. >https://doi.org/10.1186/s12957-022-02878-7 Meng, L., Yang, Y., Hu, X., Zhang, R. and Li, X. (2023) Prognostic Value of the Pretreatment Systemic Immune-Inflammation Index in Patients with Prostate Cancer: A Systematic Review and Meta-Analysis. Journal of Translational Medicine, 21, Article No. 79. >https://doi.org/10.1186/s12967-023-03924-y Qi, W., Zhou, Y., Liu, Z., Wang, J., Lv, G., Zhong, M., et al. (2022) Revealing the Prognostic and Clinicopathological Significance of Systemic Immune-Inflammation Index in Patients with Different Stage Prostate Cancer: A Systematic Review and Meta-Analysis. Frontiers in Medicine, 9, Article 1052943. >https://doi.org/10.3389/fmed.2022.1052943 Wang, S., Yang, X., Yu, Z., Du, P., Sheng, X., Cao, Y., et al. (2022) The Values of Systemic Immune-Inflammation Index and Neutrophil-Lymphocyte Ratio in Predicting Biochemical Recurrence in Patients with Localized Prostate Cancer after Radical Prostatectomy. Frontiers in Oncology, 12, Article 907625. >https://doi.org/10.3389/fonc.2022.907625 Şahin, E., Kefeli, U., Zorlu, Ş., Seyyar, M., Ozkorkmaz Akdag, M., Can Sanci, P., et al. (2023) Prognostic Role of Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio, Systemic Immune-Inflammation Index, and Pan-Immune-Inflammation Value in Metastatic Castration-Resistant Prostate Cancer Patients Who Underwent 177Lu-PSMA-617. Medicine, 102, e35843. >https://doi.org/10.1097/md.0000000000035843 Bauckneht, M., Rebuzzi, S.E., Signori, A., Frantellizzi, V., Murianni, V., Lodi Rizzini, E., et al. (2021) The Prognostic Power of Inflammatory Indices and Clinical Factors in Metastatic Castration-Resistant Prostate Cancer Patients Treated with Radium-223 (BIO-Ra Study). European Journal of Nuclear Medicine and Molecular Imaging, 49, 1063-1074. >https://doi.org/10.1007/s00259-021-05550-6 Zapała, P., Garbas, K., Lewandowski, Z., Zapała, Ł., Ślusarczyk, A., Ślusarczyk, C., et al. (2022) The Clinical Utility of Systemic Immune-Inflammation Index Supporting Charlson Comorbidity Index and CAPRA-S Score in Determining Survival after Radical Prostatectomy—A Single Centre Study. Cancers, 14, Article 4135. >https://doi.org/10.3390/cancers14174135 Becerra, M.F., Atluri, V.S., Bhattu, A.S. and Punnen, S. (2021) Serum and Urine Biomarkers for Detecting Clinically Significant Prostate Cancer. Urologic Oncology: Seminars and Original Investigations, 39, 686-690. >https://doi.org/10.1016/j.urolonc.2020.02.018 Ferro, M., Crocetto, F., Bruzzese, D., Imbriaco, M., Fusco, F., Longo, N., et al. (2021) Prostate Health Index and Multiparametric MRI: Partners in Crime Fighting Overdiagnosis and Overtreatment in Prostate Cancer. Cancers, 13, Article 4723. >https://doi.org/10.3390/cancers13184723 Dall’Era, M. (2021) Liquid Biomarkers in Active Surveillance. World Journal of Urology, 40, 21-26. >https://doi.org/10.1007/s00345-021-03609-5 Yamada, Y., Sakamoto, S., Sato, K., Saito, S., Kanesaka, M., Rii, J., et al. (2023) Clinical Utility of the Prognostic Nutritional Index in Patients with Metastatic Hormone-Sensitive Prostate Cancer: A Retrospective, Multicenter, Cohort Study. The Prostate, 83, 1610-1618. >https://doi.org/10.1002/pros.24619 Ellez, H.I., Keskinkilic, M., Semiz, H.S., Arayici, M.E., Kısa, E. and Oztop, I. (2023) The Prognostic Nutritional Index (PNI): A New Biomarker for Determining Prognosis in Metastatic Castration-Sensitive Prostate Carcinoma. Journal of Clinical Medicine, 12, Article 5434. >https://doi.org/10.3390/jcm12175434 Sonmez, G., Demirtas, T., Tombul, S.T., Akgun, H. and Demirtas, A. (2021) Diagnostic Efficiency of Systemic Immune-Inflammation Index in Fusion Prostate Biopsy. Actas Urológicas Españolas, 45, 359-365. >https://doi.org/10.1016/j.acuroe.2021.04.006