The Prognostic Role of the Naples Prognostic Score in Testicular Germ Cell Tumors: A Retrospective Analysis

The Prognostic Role of the Naples Prognostic Score in Testicular Germ Cell Tumors: A Retrospective Analysis | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article The Prognostic Role of the Naples Prognostic Score in Testicular Germ Cell Tumors: A Retrospective Analysis Hakan Tekinaslan, Osman Köse, Serkan Özcan, Sacit Nuri Görgel, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6762404/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective: To evaluate the prognostic significance of the Naples Prognostic Score (NPS) in patients with testicular germ cell tumors (TGCT), including its association with tumor stage, histological subtype, and survival outcomes. Methods: In this retrospective study, 133 patients with TGCT treated at a single tertiary center between 2015 and 2023 were evaluated. The NPS was calculated for each patient based on pre-treatment albumin, cholesterol, neutrophil-to-lymphocyte ratio (NLR), and lymphocyte-to-monocyte ratio (LMR). Patients were stratified into low (0–2) and high (3–4) NPS groups. Clinicopathological characteristics were compared between NPS groups. Overall survival was analyzed using Kaplan–Meier estimates with log-rank tests, and Cox proportional hazards regression was performed to identify independent prognostic factors. Results: Patients with high NPS were significantly younger on average and more likely to have non-seminomatous histology, advanced clinical stage, elevated tumor markers, and metastatic disease compared to those with low NPS (all p < 0.01). Overall survival was markedly worse in the high NPS group ( p < 0.005). On multivariate analysis, NPS emerged as an independent predictor of poorer overall survival alongside clinical stage (hazard ratio for high NPS ≈8.4, p = 0.018). Conclusion: The NPS is a significant prognostic indicator in TGCT. A high NPS is associated with aggressive disease features and inferior survival outcomes, remaining an independent prognostic factor when controlling for stage. Incorporating NPS into clinical risk stratification may help identify TGCT patients at higher risk of treatment failure, though prospective studies are warranted to validate its utility. Testicular germ cell tumor Naples Prognostic Score Prognosis Survival Inflammation Nutrition Figures Figure 1 Figure 2 Introduction Testicular germ cell tumors (TGCT) are the most common solid malignancies in young adult males, and with appropriate treatment they generally have a good prognosis [ 1 ]. However, in some patients the disease can exhibit aggressive biological behavior and metastatic potential, making the identification of prognostic markers crucial for tailoring treatment strategies. In recent years, various systemic inflammatory markers and parameters of nutritional status have been investigated as prognostic tools in a range of solid tumors [ 2 – 4 ]. The Naples Prognostic Score (NPS) is a composite scoring system that integrates neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), serum albumin level, and total cholesterol level – thereby reflecting the systemic inflammatory response and nutritional condition of the patient. NPS has demonstrated prognostic value in several malignancies, including colorectal cancer, osteosarcoma, non-small cell lung cancer, endometrial cancer, and pancreatic cancer [ 5 , 6 ]. By contrast, the prognostic role of NPS in testicular germ cell tumors has not yet been clearly established. Given the potential for biologic aggressiveness and metastatic spread in TGCT, a readily accessible and objective scoring system like NPS could be particularly attractive in clinical practice. The aim of this study was to investigate the prognostic value of the Naples Prognostic Score in patients with testicular germ cell tumors. Additionally, we evaluated the relationship between the NPS and tumor stage, histopathological subtypes, and survival outcomes. Materials and Methods Study Design and Patients This retrospective study included a total of 133 patients who were diagnosed with testicular germ cell tumor (TGCT) and treated at the Urology Clinic of İzmir Katip Çelebi University Atatürk Training and Research Hospital between 2015 and 2023. Institutional ethics approval for the study was obtained from the İzmir Katip Çelebi University Non-Interventional Clinical Research Ethics Committee. Data Collection Patient data were collected from medical charts and electronic records. The variables obtained included age at diagnosis, tumor histology (seminoma vs. non-seminomatous germ cell tumor), pathological T stage of the primary tumor (pT stage), surgical margin status (negative or positive), clinical stage (I, II, or III according to standard staging criteria), serum tumor marker levels category (S0–S3, referred to as “S group”), presence of retroperitoneal lymph node involvement (lymphadenopathy) on imaging or pathology, presence of pulmonary metastasis, presence of extrapulmonary (non-pulmonary visceral) metastasis, administration of adjuvant therapy (chemotherapy and/or radiotherapy), and duration of follow-up. Calculation of Naples Prognostic Score The Naples Prognostic Score (NPS) was calculated for each patient using pre-treatment laboratory values, as follows Serum albumin < 4.0 g/dL: 1 point Total cholesterol 2.96: 1 point Lymphocyte-to-monocyte ratio (LMR) < 4.44: 1 point Each of these four adverse parameters contributes one point to the NPS. The total score thus ranges from 0 to 4. Patients were stratified into two groups based on NPS: 0–2 points (low NPS group) and 3–4 points (high NPS group). Statistical Analysis Survival outcomes were evaluated using Kaplan–Meier analysis to estimate overall survival, and differences between groups were compared with the log-rank test. Prognostic factors for survival were examined by univariate and multivariate Cox proportional hazards regression models. Variables that were significant in univariate analysis were entered into the multivariate Cox model to identify independent prognostic factors. All statistical analyses were performed using IBM SPSS software (version 25). A p-value < 0.05 was considered statistically significant. Results Patient Characteristics A total of 133 TGCT patients were included, with a mean age of 40.7 ± 25.0 years (range not specified). According to the Naples Prognostic Score stratification, 97 patients (72.9%) had an NPS of 0–2 (low score group) and 36 patients (27.1%) had an NPS of 3–4 (high score group). Key clinicopathological characteristics of the patients stratified by NPS group are summarized in Table 1 . Demographic and Clinical Features by NPS Group : The high NPS group was observed to be significantly younger on average than the low NPS group (29.90 ± 28.83 years vs. 45.00 ± 22.67 years, p = 0.031). In terms of tumor histology, non-seminomatous germ cell tumors were significantly more frequent in the high NPS group, whereas seminomas were more common in the low NPS group (p = 0.040). Patients in the high NPS group also presented with more advanced disease: higher pathological T stages, higher clinical stage distribution, and higher serum tumor marker categories (S groups) compared to the low NPS group (all p < 0.005). Moreover, the presence of retroperitoneal lymph node involvement was significantly greater in the high NPS group (83.3% of high NPS patients had retroperitoneal lymphadenopathy) compared to the low NPS group (18.6%, p < 0.005). Distant metastases were also more common in patients with high NPS: 44.4% had pulmonary metastases vs. only 2.1% in the low NPS group (p < 0.005), and 25.0% had extrapulmonary metastases (e.g., liver, brain or other sites) vs. 0% in the low NPS group (p < 0.005). The rate of undergoing a retroperitoneal lymph node dissection (RPLND) was higher in the high NPS group (16.7% vs. 3.1%, p = 0.012), presumably reflecting the greater burden of retroperitoneal disease in this group. With regard to treatment, a higher proportion of patients in the high NPS group received adjuvant chemotherapy compared to the low NPS group (80.6% vs. 62.9%), although this difference only approached statistical significance (p = 0.053). There was no significant difference in the use of adjuvant radiotherapy between the groups (19.4% in high NPS vs. 27.8% in low NPS, p = 0.324). The mean follow-up duration was significantly shorter for patients with high NPS, at 29.90 ± 28.84 months, compared to 45.00 ± 22.67 months in the low NPS group (p = 0.016). This difference likely reflects the poorer survival outcomes in the high NPS cohort. All above comparisons are detailed in Table 1 . Table 1 Comparison of Clinicopathological Characteristics Between Patients With Low (0–2) and High (3–4) NPS Characteristic NPS 0–2 (n = 97) NPS 3–4 (n = 36) p-value Age (years) 45.00 ± 22.67 29.90 ± 28.83 0.031* Histology Seminoma: 42 (31.6%) Non-seminomatous: 55 (44.4%) Seminoma: 6 (4.5%) Non-seminomatous: 30 (22.6%) 0.040** Pathological T stage (pT) pT1: 69 (51.9%) pT2: 23 (17.3%) pT3: 5 (3.8%) pT4: 0 (0%) pT1: 18 (13.5%) pT2: 11 (8.3%) pT3: 7 (5.3%) pT4: 0 (0%) 0.016** Surgical margin status Negative: 96 (72.2%) Positive: 1 (0.8%) Negative: 34 (25.5%) Positive: 2 (1.5%) 0.178*** Clinical stage Stage I: 79 (59.4%) Stage II: 17 (12.8%) Stage III: 1 (0.8%) Stage I: 3 (2.3%) Stage II: 16 (12.0%) Stage III: 17 (12.8%) < 0.005** Serum tumor marker category (S) S0 (Normal): 60 (45.1%) S1: 29 (21.8%) S2: 6 (4.5%) S3: 2 (1.5%) S0 (Normal): 8 (6.8%) S1: 13 (9.8%) S2: 4 (3.0%) S3: 11 (8.3%) < 0.005** Retroperitoneal LAP Absent: 79 (59.4%) Present: 18 (13.5%) Absent: 6 (4.5%) Present: 30 (22.6%) < 0.005** Pulmonary metastasis Absent: 95 (71.5%) Present: 2 (1.5%) Absent: 20 (15.0%) Present: 16 (12.0%) < 0.005*** Extrapulmonary metastasis Absent: 97 (72.9%) Present: 0 (0%) Absent: 27 (20.3%) Present: 9 (6.8%) < 0.005*** Adjuvant chemotherapy No: 36 (27.1%) Yes: 61 (45.9%) No: 7 (5.3%) Yes: 29 (21.8%) 0.053** Adjuvant radiotherapy No: 70 (52.6%) Yes: 27 (20.3%) No: 29 (22.8%) Yes: 7 (5.3%) 0.324** RPLND performed No: 94 (70.7%) Yes: 3 (2.3%) No: 30 (22.6%) Yes: 6 (4.5%) 0.012*** Follow-up duration (months) 45.00 ± 22.67 29.90 ± 28.84 0.016* *p < 0.05 by independent samples test; **p < 0.01 by chi-square test; ***p < 0.01 by Fisher’s exact test (two-tailed). LAP: lymphadenopathy; RPLND: retroperitoneal lymph node dissection. Survival Analyses : Kaplan–Meier survival analysis revealed a significant difference in overall survival between the NPS groups. Patients with high NPS (3–4) had markedly worse overall survival compared to those with low NPS (0–2) (log-rank test, p < 0.005) By approximately 5 years of follow-up, the survival probability remained high in the low NPS group but had declined substantially in the high NPS group (exact survival rates not provided in text). Figure 1 illustrates the divergence of the survival curves between the two NPS groups. Similarly, advanced clinical stage at presentation was associated with significantly inferior overall survival: patients with Stage II–III disease had significantly shorter survival than those with Stage I disease (log-rank test, p < 0.005). This effect of clinical stage on survival is shown in Fig. 2 . Univariate Cox proportional hazards regression identified several factors that significantly affected overall survival ( Table 2 ). Advanced clinical stage (Stage II–III vs I) was associated with a markedly increased risk of death (hazard ratio [HR] ~ 7.12, p < 0.005). Other significant univariate predictors included a higher serum tumor marker category (S2–S3 vs S0–S1; HR ~ 2.20, p < 0.005), presence of retroperitoneal lymphadenopathy (HR ~ 10.08, p < 0.005), presence of pulmonary metastasis (HR ~ 15.08, p < 0.005), presence of extrapulmonary metastasis (HR ~ 13.94, p < 0.005), and high NPS group (3–4 vs 0–2; HR ~ 28.44, p < 0.005). On multivariate analysis, only clinical stage and NPS remained in the final model as independent prognostic factors for overall survival (Stage II–III vs I: HR 3.09, p = 0.016; high NPS vs low: HR 8.43, p = 0.018). Table 2 Univariate and Multivariate Cox Regression Analysis of Factors Predicting Overall Survival in TGCT Patients Variable Univariate HR (95% CI) p (Univ) Multivariate HR (95% CI) p (Multi) Age at diagnosis (per year) 0.972 (0.926–1.020) 0.251 – – Histology (non-seminoma vs seminoma) 3.675 (1.059–12.756) 0.040 – – Pathologic T stage (pT) 1.170 (0.628–2.182) 0.621 – – Surgical margin (positive vs negative) 2.593 (0.342–19.663) 0.357 – – Clinical stage (Stage II–III vs I) 7.117 (3.395–14.922) < 0.005 3.091 (1.235–7.735) 0.016 Serum tumor markers (elevated vs normal) 2.201 (1.472–3.291) < 0.005 – – Retroperitoneal LAP (yes vs no) 10.083 (2.905–35.001) < 0.005 – – Pulmonary metastasis (yes vs no) 15.080 (5.553–40.950) < 0.005 – – Extrapulmonary metastasis (yes vs no) 13.937 (5.270–36.861) < 0.005 – – Adjuvant therapy (yes vs no) 0.550 (0.126–2.404) 0.427 – – Naples Prognostic Score (3–4 vs 0–2) 28.443 (6.537–123.753) < 0.005 8.428 (1.433–49.581) 0.018 *HR: hazard ratio; CI: confidence interval; LAP: lymphadenopathy; NPS: Naples Prognostic Score. Only clinical stage and NPS remained in the final multivariate model as independent prognostic factors. Discussion In our study, patients with a higher Naples Prognostic Score had significantly shorter overall survival, supporting the prognostic utility of NPS in testicular germ cell tumors. On multivariate analysis, NPS was identified as an independent prognostic factor alongside clinical stage. This finding suggests that NPS may serve as a complementary indicator reflecting the patient’s systemic biological status even in TGCT, a disease that predominantly affects a young population and is often curable. The ability of NPS to remain prognostically relevant in this context indicates its potential to capture aspects of tumor biology and host response not fully accounted for by traditional staging. The interplay between cancer progression, inflammation, and nutritional status has been recognized for well over a century [ 7 ]. Chronic inflammation in the tumor microenvironment can promote cancer development and progression, and it is estimated that infectious or inflammatory conditions are linked to around 15–20% of all cancer-related deaths [ 8 ]. In addition, recent studies have highlighted the prognostic relevance of composite indices combining inflammatory and nutritional parameters across several tumor types [ 9 , 10 ]. Likewise, nutritional status has a profound influence on cancer outcomes. Low serum albumin reflects a catabolic state and inadequate protein reserves and has been associated with poor prognosis in cancer patients [ 11 ]. Hypocholesterolemia, as an indicator of altered cellular energy balance and immune dysfunction, has been linked to worse survival in various solid tumors [ 12 ]. The NLR is a marker of systemic inflammation and immune suppression in the tumor milieu; an elevated NLR signifies a shift toward a pro-tumor inflammatory state and correlates with tumor progression [ 13 ]. Conversely, the LMR reflects the balance between lymphocyte-mediated anti-tumor immunity and monocyte/macrophage-mediated tumor-promoting processes; a low LMR indicates a dominance of the latter and is associated with unfavorable prognosis [ 14 ]. In this context, the Naples Prognostic Score, which jointly assesses systemic inflammation and nutritional status via NLR, LMR, albumin, and cholesterol, stands out as an integrative prognostic indicator [ 15 , 16 ]. Most studies on NPS to date have focused on patients with various oncologic diagnoses. In a large-scale study examining over 42,000 individuals, NPS was found to be strongly associated with both cancer incidence and outcomes [ 17 ]. NPS has demonstrated efficacy in predicting survival across a range of malignancies, including colorectal cancer, pancreatic cancer, osteosarcoma, and endometrial cancer [ 18 – 21 ]. However, data on NPS in testicular germ cell tumors have been very limited. Our analysis is among the first to show that NPS can provide prognostic information in TGCT, suggesting that this scoring system might contribute to outcome prediction in this unique patient population. We observed that a high NPS was significantly associated with several adverse clinicopathological features in TGCT. High NPS correlated with non-seminomatous histology, advanced disease stage, high tumor marker levels (poor prognostic “S” category), retroperitoneal lymph node involvement, and the presence of distant metastases (both pulmonary and extrapulmonary). These findings indicate that NPS is reflective of an aggressive tumor phenotype. Interestingly, patients in the high NPS group were, on average, significantly younger than those in the low NPS group. Although age itself was not a significant predictor of survival in our cohort (p = 0.251 in univariate analysis), the association of younger age with high NPS might suggest that more aggressive tumor biology can manifest even in younger patients. This is an intriguing observation, albeit one that must be interpreted cautiously; it may be that age is not a direct prognostic factor but rather that certain aggressive tumors occur in younger individuals. Consistent with known prognostic factors in testicular cancer, our univariate analysis found that classic indicators such as pathological stage, serum tumor marker elevation, and the presence of metastases (lung or other sites) were significantly associated with survival. We also found that patients who underwent RPLND had worse univariate survival, likely because the need for RPLND indicates more extensive disease; however, RPLND was not an independent prognostic factor in the multivariate model. Surgical margin positivity was very low in our series (observed in only 3 patients, 2.3%), and not surprisingly it did not show a significant impact on survival. These results align with the literature, which suggests that other inflammation- or nutrition-based scores have potential prognostic value in testicular cancer. For example, low levels of the Hemoglobin, Albumin, Lymphocyte, and Platelet (HALP) score and the Prognostic Nutritional Index (PNI) have been reported to distinguish early-stage from advanced-stage testicular tumors [ 22 ]. Additionally, a recent systematic review and meta-analysis examining the Systemic Immune-Inflammation Index (SII) in testicular cancer found that high SII values were associated with worse overall survival and progression-free survival [ 23 ]. Another study in patients with germ cell tumors reported that the pre-treatment Glasgow Prognostic Score (GPS) was the strongest inflammation-based predictor of overall and progression-free survival [ 24 ]. These findings underscore that multiple markers of systemic inflammation or nutritional status have been explored in TGCT, and among these, NPS is noteworthy for its comprehensive nature combining four different parameters. The strengths of our study include the comprehensive assessment of all NPS components for each patient, the use of both univariate and multivariate survival analyses, and data collection from a single high-volume center with TGCT expertise, enhancing internal validity. However, several limitations should be acknowledged. The retrospective design carries an inherent risk of selection bias and incomplete data. The follow-up period was limited for some patients, potentially affecting long-term outcome evaluation. Additionally, as a single-center study, the results may not be generalizable to broader populations. The relatively small number of high-NPS patients further limits statistical power, and larger multicenter studies are needed to confirm these findings. Conclusion In summary, the Naples Prognostic Score (NPS) was identified as a significant predictor of overall survival in patients with testicular germ cell tumors. High NPS scores were associated with markedly poorer outcomes, and NPS remained an independent prognostic factor even after adjusting for clinical stage. These findings support the integration of NPS into routine risk stratification for TGCT and may assist in tailoring treatment intensity. Nevertheless, validation through larger, prospective multicenter studies is necessary before widespread clinical adoption. Declarations Funding No specific funding was received for this study. Conflict of Interest The authors declare that they have no conflict of interest. Ethics Approval and Consent to Participate The study was approved by the İzmir Katip Çelebi University Non-Interventional Clinical Research Ethics Committee. References Batool A, Karimi N, Wu XN, Chen SR, Liu YX. Testicular germ cell tumor: a comprehensive review. 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Comparison of inflammation-based prognostic scores as predictors of survival outcomes in patients with germ cell tumors. Investig Clin Urol . 2021;62:47-55. doi:10.4111/icu.20200103 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6762404","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":462712921,"identity":"674c759b-6227-4017-ac11-3f1006a2a9f5","order_by":0,"name":"Hakan Tekinaslan","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABA0lEQVRIiWNgGAWjYBACAwY2CEOCgYHxAAODDZDJ2HiACC0GIC0MQJVpIC0NJGk5DBbFq8Wc/Vji5wKGP3KS7ccfHPi547zd2vbDQFtqbKJxabHsSTssPYPBwFiaJ8fgYO+Z28nbziQCtRxLy23A5bAD6Q3SPAwGifMYchgO8LbdTjY7ANTC2HAYt5bzz5t/A7XUz+N//uDg37ZzyWbnHxLQciPtGMiWBGmJBIPDvG0H7MxuELLlxrM0ax4DY8OZM94YHJZtS04wuwG0JQGfX86nGd/mqZCTlzif/vDh2zY7ezMg48GHGhucWqAaEcxEsMoEvMrRgD0pikfBKBgFo2BkAACfSGSmkcAISgAAAABJRU5ErkJggg==","orcid":"","institution":"Menderes Devlet Hastanesi","correspondingAuthor":true,"prefix":"","firstName":"Hakan","middleName":"","lastName":"Tekinaslan","suffix":""},{"id":462712922,"identity":"240f2e74-3763-4e42-a04b-da6fe282e831","order_by":1,"name":"Osman Köse","email":"","orcid":"","institution":"Izmir Kâtip Çelebi University","correspondingAuthor":false,"prefix":"","firstName":"Osman","middleName":"","lastName":"Köse","suffix":""},{"id":462712923,"identity":"3fd141f4-0806-4e79-aeb1-ce0cf80eae26","order_by":2,"name":"Serkan Özcan","email":"","orcid":"","institution":"Izmir Kâtip Çelebi University","correspondingAuthor":false,"prefix":"","firstName":"Serkan","middleName":"","lastName":"Özcan","suffix":""},{"id":462712924,"identity":"ac3da597-7244-435e-86c2-5dbf43a71786","order_by":3,"name":"Sacit Nuri Görgel","email":"","orcid":"","institution":"Izmir Kâtip Çelebi University","correspondingAuthor":false,"prefix":"","firstName":"Sacit","middleName":"Nuri","lastName":"Görgel","suffix":""},{"id":462712925,"identity":"0248073a-8718-4f33-8282-a7539c884550","order_by":4,"name":"Yiğit Akın","email":"","orcid":"","institution":"Izmir Kâtip Çelebi University","correspondingAuthor":false,"prefix":"","firstName":"Yiğit","middleName":"","lastName":"Akın","suffix":""}],"badges":[],"createdAt":"2025-05-27 20:23:16","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6762404/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6762404/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":83612705,"identity":"9d76a9be-6b73-4001-b6b6-6807eab03857","added_by":"auto","created_at":"2025-05-29 12:41:26","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":47433,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe Kaplan-Meier overall survival curves are stratified by clinical stage, with Stage I compared to Stage II-III. Patients with advanced-stage disease (Stage II–III) exhibited significantly worse survival outcomes in comparison with those with Stage I disease (log-rank test, p \u0026lt; 0.05).\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6762404/v1/238bf1aafcc8de1460ac5756.png"},{"id":83612109,"identity":"4524adf6-05e5-4d17-91b3-0c0cedb0b546","added_by":"auto","created_at":"2025-05-29 12:33:26","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":40690,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe Kaplan–Meier overall survival curves are stratified by Naples Prognostic Score group, which is categorized as low NPS (0–2) versus high NPS (3–4). The high NPS group exhibited a significantly shorter overall survival duration compared to the low NPS group (log-rank test, p \u0026lt; 0.05).\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-6762404/v1/9c3eefb34d9d8edd1fa70b2f.png"},{"id":83730114,"identity":"e7a279c9-b0ee-499d-9894-bb14d1cd8341","added_by":"auto","created_at":"2025-06-01 12:46:41","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1004363,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6762404/v1/e76b75a8-2762-4e7e-9def-6ac7b73bcff5.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"The Prognostic Role of the Naples Prognostic Score in Testicular Germ Cell Tumors: A Retrospective Analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eTesticular germ cell tumors (TGCT) are the most common solid malignancies in young adult males, and with appropriate treatment they generally have a good prognosis [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. However, in some patients the disease can exhibit aggressive biological behavior and metastatic potential, making the identification of prognostic markers crucial for tailoring treatment strategies.\u003c/p\u003e \u003cp\u003eIn recent years, various systemic inflammatory markers and parameters of nutritional status have been investigated as prognostic tools in a range of solid tumors [\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The Naples Prognostic Score (NPS) is a composite scoring system that integrates neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), serum albumin level, and total cholesterol level \u0026ndash; thereby reflecting the systemic inflammatory response and nutritional condition of the patient. NPS has demonstrated prognostic value in several malignancies, including colorectal cancer, osteosarcoma, non-small cell lung cancer, endometrial cancer, and pancreatic cancer [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eBy contrast, the prognostic role of NPS in testicular germ cell tumors has not yet been clearly established. Given the potential for biologic aggressiveness and metastatic spread in TGCT, a readily accessible and objective scoring system like NPS could be particularly attractive in clinical practice.\u003c/p\u003e \u003cp\u003eThe aim of this study was to investigate the prognostic value of the Naples Prognostic Score in patients with testicular germ cell tumors. Additionally, we evaluated the relationship between the NPS and tumor stage, histopathological subtypes, and survival outcomes.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003e \u003cstrong\u003eStudy Design and Patients\u003c/strong\u003e \u003cp\u003eThis retrospective study included a total of 133 patients who were diagnosed with testicular germ cell tumor (TGCT) and treated at the Urology Clinic of İzmir Katip \u0026Ccedil;elebi University Atat\u0026uuml;rk Training and Research Hospital between 2015 and 2023. Institutional ethics approval for the study was obtained from the İzmir Katip \u0026Ccedil;elebi University Non-Interventional Clinical Research Ethics Committee.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eData Collection\u003c/strong\u003e \u003cp\u003ePatient data were collected from medical charts and electronic records. The variables obtained included age at diagnosis, tumor histology (seminoma vs. non-seminomatous germ cell tumor), pathological T stage of the primary tumor (pT stage), surgical margin status (negative or positive), clinical stage (I, II, or III according to standard staging criteria), serum tumor marker levels category (S0\u0026ndash;S3, referred to as \u0026ldquo;S group\u0026rdquo;), presence of retroperitoneal lymph node involvement (lymphadenopathy) on imaging or pathology, presence of pulmonary metastasis, presence of extrapulmonary (non-pulmonary visceral) metastasis, administration of adjuvant therapy (chemotherapy and/or radiotherapy), and duration of follow-up.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eCalculation of Naples Prognostic Score\u003c/strong\u003e \u003cp\u003eThe Naples Prognostic Score (NPS) was calculated for each patient using pre-treatment laboratory values, as follows\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eSerum albumin\u0026thinsp;\u0026lt;\u0026thinsp;4.0 g/dL: 1 point\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eTotal cholesterol\u0026thinsp;\u0026lt;\u0026thinsp;180 mg/dL: 1 point\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eNeutrophil-to-lymphocyte ratio (NLR)\u0026thinsp;\u0026gt;\u0026thinsp;2.96: 1 point\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003eLymphocyte-to-monocyte ratio (LMR)\u0026thinsp;\u0026lt;\u0026thinsp;4.44: 1 point\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003cp\u003eEach of these four adverse parameters contributes one point to the NPS. The total score thus ranges from 0 to 4. Patients were stratified into two groups based on NPS: 0\u0026ndash;2 points (low NPS group) and 3\u0026ndash;4 points (high NPS group).\u003c/p\u003e \u003cp\u003e \u003cstrong\u003eStatistical Analysis\u003c/strong\u003e \u003cp\u003eSurvival outcomes were evaluated using Kaplan\u0026ndash;Meier analysis to estimate overall survival, and differences between groups were compared with the log-rank test. Prognostic factors for survival were examined by univariate and multivariate Cox proportional hazards regression models. Variables that were significant in univariate analysis were entered into the multivariate Cox model to identify independent prognostic factors. All statistical analyses were performed using IBM SPSS software (version 25). A p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e \u003cstrong\u003ePatient Characteristics\u003c/strong\u003e \u003cp\u003eA total of 133 TGCT patients were included, with a mean age of 40.7\u0026thinsp;\u0026plusmn;\u0026thinsp;25.0 years (range not specified). According to the Naples Prognostic Score stratification, 97 patients (72.9%) had an NPS of 0\u0026ndash;2 (low score group) and 36 patients (27.1%) had an NPS of 3\u0026ndash;4 (high score group). Key clinicopathological characteristics of the patients stratified by NPS group are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eDemographic and Clinical Features by NPS Group\u003c/b\u003e: The high NPS group was observed to be significantly younger on average than the low NPS group (29.90\u0026thinsp;\u0026plusmn;\u0026thinsp;28.83 years vs. 45.00\u0026thinsp;\u0026plusmn;\u0026thinsp;22.67 years, p\u0026thinsp;=\u0026thinsp;0.031). In terms of tumor histology, non-seminomatous germ cell tumors were significantly more frequent in the high NPS group, whereas seminomas were more common in the low NPS group (p\u0026thinsp;=\u0026thinsp;0.040). Patients in the high NPS group also presented with more advanced disease: higher pathological T stages, higher clinical stage distribution, and higher serum tumor marker categories (S groups) compared to the low NPS group (all p\u0026thinsp;\u0026lt;\u0026thinsp;0.005).\u003c/p\u003e \u003cp\u003eMoreover, the presence of retroperitoneal lymph node involvement was significantly greater in the high NPS group (83.3% of high NPS patients had retroperitoneal lymphadenopathy) compared to the low NPS group (18.6%, p\u0026thinsp;\u0026lt;\u0026thinsp;0.005). Distant metastases were also more common in patients with high NPS: 44.4% had pulmonary metastases vs. only 2.1% in the low NPS group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.005), and 25.0% had extrapulmonary metastases (e.g., liver, brain or other sites) vs. 0% in the low NPS group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.005). The rate of undergoing a retroperitoneal lymph node dissection (RPLND) was higher in the high NPS group (16.7% vs. 3.1%, p\u0026thinsp;=\u0026thinsp;0.012), presumably reflecting the greater burden of retroperitoneal disease in this group.\u003c/p\u003e \u003cp\u003eWith regard to treatment, a higher proportion of patients in the high NPS group received adjuvant chemotherapy compared to the low NPS group (80.6% vs. 62.9%), although this difference only approached statistical significance (p\u0026thinsp;=\u0026thinsp;0.053). There was no significant difference in the use of adjuvant radiotherapy between the groups (19.4% in high NPS vs. 27.8% in low NPS, p\u0026thinsp;=\u0026thinsp;0.324). The mean follow-up duration was significantly shorter for patients with high NPS, at 29.90\u0026thinsp;\u0026plusmn;\u0026thinsp;28.84 months, compared to 45.00\u0026thinsp;\u0026plusmn;\u0026thinsp;22.67 months in the low NPS group (p\u0026thinsp;=\u0026thinsp;0.016). This difference likely reflects the poorer survival outcomes in the high NPS cohort. All above comparisons are detailed in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of Clinicopathological Characteristics Between Patients With Low (0\u0026ndash;2) and High (3\u0026ndash;4) NPS\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacteristic\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNPS 0\u0026ndash;2 (n\u0026thinsp;=\u0026thinsp;97)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNPS 3\u0026ndash;4 (n\u0026thinsp;=\u0026thinsp;36)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge (years)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45.00\u0026thinsp;\u0026plusmn;\u0026thinsp;22.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29.90\u0026thinsp;\u0026plusmn;\u0026thinsp;28.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.031*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHistology\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSeminoma: 42 (31.6%)\u003c/p\u003e \u003cp\u003eNon-seminomatous: 55 (44.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSeminoma: 6 (4.5%)\u003c/p\u003e \u003cp\u003eNon-seminomatous: 30 (22.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.040**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePathological T stage (pT)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003epT1: 69 (51.9%)\u003c/p\u003e \u003cp\u003epT2: 23 (17.3%)\u003c/p\u003e \u003cp\u003epT3: 5 (3.8%)\u003c/p\u003e \u003cp\u003epT4: 0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003epT1: 18 (13.5%)\u003c/p\u003e \u003cp\u003epT2: 11 (8.3%)\u003c/p\u003e \u003cp\u003epT3: 7 (5.3%)\u003c/p\u003e \u003cp\u003epT4: 0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.016**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSurgical margin status\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNegative: 96 (72.2%)\u003c/p\u003e \u003cp\u003ePositive: 1 (0.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNegative: 34 (25.5%)\u003c/p\u003e \u003cp\u003ePositive: 2 (1.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.178***\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eClinical stage\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eStage I: 79 (59.4%)\u003c/p\u003e \u003cp\u003eStage II: 17 (12.8%)\u003c/p\u003e \u003cp\u003eStage III: 1 (0.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStage I: 3 (2.3%)\u003c/p\u003e \u003cp\u003eStage II: 16 (12.0%)\u003c/p\u003e \u003cp\u003eStage III: 17 (12.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.005**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSerum tumor marker category (S)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eS0 (Normal): 60 (45.1%)\u003c/p\u003e \u003cp\u003eS1: 29 (21.8%)\u003c/p\u003e \u003cp\u003eS2: 6 (4.5%)\u003c/p\u003e \u003cp\u003eS3: 2 (1.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eS0 (Normal): 8 (6.8%)\u003c/p\u003e \u003cp\u003eS1: 13 (9.8%)\u003c/p\u003e \u003cp\u003eS2: 4 (3.0%)\u003c/p\u003e \u003cp\u003eS3: 11 (8.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.005**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRetroperitoneal LAP\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAbsent: 79 (59.4%)\u003c/p\u003e \u003cp\u003ePresent: 18 (13.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAbsent: 6 (4.5%)\u003c/p\u003e \u003cp\u003ePresent: 30 (22.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.005**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePulmonary metastasis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAbsent: 95 (71.5%)\u003c/p\u003e \u003cp\u003ePresent: 2 (1.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAbsent: 20 (15.0%)\u003c/p\u003e \u003cp\u003ePresent: 16 (12.0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.005***\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eExtrapulmonary metastasis\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAbsent: 97 (72.9%)\u003c/p\u003e \u003cp\u003ePresent: 0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAbsent: 27 (20.3%)\u003c/p\u003e \u003cp\u003ePresent: 9 (6.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.005***\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAdjuvant chemotherapy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo: 36 (27.1%)\u003c/p\u003e \u003cp\u003eYes: 61 (45.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo: 7 (5.3%)\u003c/p\u003e \u003cp\u003eYes: 29 (21.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.053**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAdjuvant radiotherapy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo: 70 (52.6%)\u003c/p\u003e \u003cp\u003eYes: 27 (20.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo: 29 (22.8%)\u003c/p\u003e \u003cp\u003eYes: 7 (5.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.324**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRPLND performed\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo: 94 (70.7%)\u003c/p\u003e \u003cp\u003eYes: 3 (2.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNo: 30 (22.6%)\u003c/p\u003e \u003cp\u003eYes: 6 (4.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.012***\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eFollow-up duration (months)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45.00\u0026thinsp;\u0026plusmn;\u0026thinsp;22.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29.90\u0026thinsp;\u0026plusmn;\u0026thinsp;28.84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.016*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e*p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 by independent samples test; **p\u0026thinsp;\u0026lt;\u0026thinsp;0.01 by chi-square test; ***p\u0026thinsp;\u0026lt;\u0026thinsp;0.01 by Fisher\u0026rsquo;s exact test (two-tailed). LAP: lymphadenopathy; RPLND: retroperitoneal lymph node dissection.\u003c/p\u003e \u003cp\u003e \u003cb\u003eSurvival Analyses\u003c/b\u003e: Kaplan\u0026ndash;Meier survival analysis revealed a significant difference in overall survival between the NPS groups. Patients with high NPS (3\u0026ndash;4) had markedly worse overall survival compared to those with low NPS (0\u0026ndash;2) (log-rank test, p\u0026thinsp;\u0026lt;\u0026thinsp;0.005) By approximately 5 years of follow-up, the survival probability remained high in the low NPS group but had declined substantially in the high NPS group (exact survival rates not provided in text). Figure\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e illustrates the divergence of the survival curves between the two NPS groups. Similarly, advanced clinical stage at presentation was associated with significantly inferior overall survival: patients with Stage II\u0026ndash;III disease had significantly shorter survival than those with Stage I disease (log-rank test, p\u0026thinsp;\u0026lt;\u0026thinsp;0.005). This effect of clinical stage on survival is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eUnivariate Cox proportional hazards regression identified several factors that significantly affected overall survival \u003cb\u003e(\u003c/b\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u003cb\u003e).\u003c/b\u003e Advanced clinical stage (Stage II\u0026ndash;III vs I) was associated with a markedly increased risk of death (hazard ratio [HR]\u0026thinsp;~\u0026thinsp;7.12, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.005). Other significant univariate predictors included a higher serum tumor marker category (S2\u0026ndash;S3 vs S0\u0026ndash;S1; HR\u0026thinsp;~\u0026thinsp;2.20, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.005), presence of retroperitoneal lymphadenopathy (HR\u0026thinsp;~\u0026thinsp;10.08, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.005), presence of pulmonary metastasis (HR\u0026thinsp;~\u0026thinsp;15.08, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.005), presence of extrapulmonary metastasis (HR\u0026thinsp;~\u0026thinsp;13.94, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.005), and high NPS group (3\u0026ndash;4 vs 0\u0026ndash;2; HR\u0026thinsp;~\u0026thinsp;28.44, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.005). On multivariate analysis, only clinical stage and NPS remained in the final model as independent prognostic factors for overall survival (Stage II\u0026ndash;III vs I: HR 3.09, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.016; high NPS vs low: HR 8.43, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.018).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eUnivariate and Multivariate Cox Regression Analysis of Factors Predicting Overall Survival in TGCT Patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUnivariate HR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ep (Univ)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMultivariate HR (95% CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep (Multi)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge at diagnosis (per year)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.972 (0.926\u0026ndash;1.020)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.251\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHistology (non-seminoma vs seminoma)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3.675 (1.059\u0026ndash;12.756)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.040\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePathologic T stage (pT)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.170 (0.628\u0026ndash;2.182)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.621\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgical margin (positive vs negative)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.593 (0.342\u0026ndash;19.663)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.357\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical stage (Stage II\u0026ndash;III vs I)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7.117 (3.395\u0026ndash;14.922)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.091 (1.235\u0026ndash;7.735)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.016\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum tumor markers (elevated vs normal)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.201 (1.472\u0026ndash;3.291)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRetroperitoneal LAP (yes vs no)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10.083 (2.905\u0026ndash;35.001)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePulmonary metastasis (yes vs no)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15.080 (5.553\u0026ndash;40.950)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExtrapulmonary metastasis (yes vs no)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13.937 (5.270\u0026ndash;36.861)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdjuvant therapy (yes vs no)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.550 (0.126\u0026ndash;2.404)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.427\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u0026ndash;\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNaples Prognostic Score (3\u0026ndash;4 vs 0\u0026ndash;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e28.443 (6.537\u0026ndash;123.753)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.005\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.428 (1.433\u0026ndash;49.581)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.018\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e*HR: hazard ratio; CI: confidence interval; LAP: lymphadenopathy; NPS: Naples Prognostic Score. Only clinical stage and NPS remained in the final multivariate model as independent prognostic factors.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn our study, patients with a higher Naples Prognostic Score had significantly shorter overall survival, supporting the prognostic utility of NPS in testicular germ cell tumors. On multivariate analysis, NPS was identified as an independent prognostic factor alongside clinical stage. This finding suggests that NPS may serve as a complementary indicator reflecting the patient\u0026rsquo;s systemic biological status even in TGCT, a disease that predominantly affects a young population and is often curable. The ability of NPS to remain prognostically relevant in this context indicates its potential to capture aspects of tumor biology and host response not fully accounted for by traditional staging.\u003c/p\u003e \u003cp\u003eThe interplay between cancer progression, inflammation, and nutritional status has been recognized for well over a century [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Chronic inflammation in the tumor microenvironment can promote cancer development and progression, and it is estimated that infectious or inflammatory conditions are linked to around 15\u0026ndash;20% of all cancer-related deaths [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. In addition, recent studies have highlighted the prognostic relevance of composite indices combining inflammatory and nutritional parameters across several tumor types [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Likewise, nutritional status has a profound influence on cancer outcomes. Low serum albumin reflects a catabolic state and inadequate protein reserves and has been associated with poor prognosis in cancer patients [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Hypocholesterolemia, as an indicator of altered cellular energy balance and immune dysfunction, has been linked to worse survival in various solid tumors [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The NLR is a marker of systemic inflammation and immune suppression in the tumor milieu; an elevated NLR signifies a shift toward a pro-tumor inflammatory state and correlates with tumor progression [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Conversely, the LMR reflects the balance between lymphocyte-mediated anti-tumor immunity and monocyte/macrophage-mediated tumor-promoting processes; a low LMR indicates a dominance of the latter and is associated with unfavorable prognosis [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. In this context, the Naples Prognostic Score, which jointly assesses systemic inflammation and nutritional status via NLR, LMR, albumin, and cholesterol, stands out as an integrative prognostic indicator [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMost studies on NPS to date have focused on patients with various oncologic diagnoses. In a large-scale study examining over 42,000 individuals, NPS was found to be strongly associated with both cancer incidence and outcomes [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. NPS has demonstrated efficacy in predicting survival across a range of malignancies, including colorectal cancer, pancreatic cancer, osteosarcoma, and endometrial cancer [\u003cspan additionalcitationids=\"CR19 CR20\" citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. However, data on NPS in testicular germ cell tumors have been very limited. Our analysis is among the first to show that NPS can provide prognostic information in TGCT, suggesting that this scoring system might contribute to outcome prediction in this unique patient population.\u003c/p\u003e \u003cp\u003eWe observed that a high NPS was significantly associated with several adverse clinicopathological features in TGCT. High NPS correlated with non-seminomatous histology, advanced disease stage, high tumor marker levels (poor prognostic \u0026ldquo;S\u0026rdquo; category), retroperitoneal lymph node involvement, and the presence of distant metastases (both pulmonary and extrapulmonary). These findings indicate that NPS is reflective of an aggressive tumor phenotype. Interestingly, patients in the high NPS group were, on average, significantly younger than those in the low NPS group. Although age itself was not a significant predictor of survival in our cohort (p\u0026thinsp;=\u0026thinsp;0.251 in univariate analysis), the association of younger age with high NPS might suggest that more aggressive tumor biology can manifest even in younger patients. This is an intriguing observation, albeit one that must be interpreted cautiously; it may be that age is not a direct prognostic factor but rather that certain aggressive tumors occur in younger individuals.\u003c/p\u003e \u003cp\u003eConsistent with known prognostic factors in testicular cancer, our univariate analysis found that classic indicators such as pathological stage, serum tumor marker elevation, and the presence of metastases (lung or other sites) were significantly associated with survival. We also found that patients who underwent RPLND had worse univariate survival, likely because the need for RPLND indicates more extensive disease; however, RPLND was not an independent prognostic factor in the multivariate model. Surgical margin positivity was very low in our series (observed in only 3 patients, 2.3%), and not surprisingly it did not show a significant impact on survival. These results align with the literature, which suggests that other inflammation- or nutrition-based scores have potential prognostic value in testicular cancer. For example, low levels of the Hemoglobin, Albumin, Lymphocyte, and Platelet (HALP) score and the Prognostic Nutritional Index (PNI) have been reported to distinguish early-stage from advanced-stage testicular tumors [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Additionally, a recent systematic review and meta-analysis examining the Systemic Immune-Inflammation Index (SII) in testicular cancer found that high SII values were associated with worse overall survival and progression-free survival [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Another study in patients with germ cell tumors reported that the pre-treatment Glasgow Prognostic Score (GPS) was the strongest inflammation-based predictor of overall and progression-free survival [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. These findings underscore that multiple markers of systemic inflammation or nutritional status have been explored in TGCT, and among these, NPS is noteworthy for its comprehensive nature combining four different parameters.\u003c/p\u003e \u003cp\u003eThe strengths of our study include the comprehensive assessment of all NPS components for each patient, the use of both univariate and multivariate survival analyses, and data collection from a single high-volume center with TGCT expertise, enhancing internal validity. However, several limitations should be acknowledged. The retrospective design carries an inherent risk of selection bias and incomplete data. The follow-up period was limited for some patients, potentially affecting long-term outcome evaluation. Additionally, as a single-center study, the results may not be generalizable to broader populations. The relatively small number of high-NPS patients further limits statistical power, and larger multicenter studies are needed to confirm these findings.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn summary, the Naples Prognostic Score (NPS) was identified as a significant predictor of overall survival in patients with testicular germ cell tumors. High NPS scores were associated with markedly poorer outcomes, and NPS remained an independent prognostic factor even after adjusting for clinical stage. These findings support the integration of NPS into routine risk stratification for TGCT and may assist in tailoring treatment intensity. Nevertheless, validation through larger, prospective multicenter studies is necessary before widespread clinical adoption.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo specific funding was received for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Approval and Consent to Participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the İzmir Katip Çelebi University Non-Interventional Clinical Research Ethics Committee.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eBatool A, Karimi N, Wu XN, Chen SR, Liu YX. Testicular germ cell tumor: a comprehensive review. \u003cem\u003eCellular and Molecular Life Sciences\u003c/em\u003e. 2019;76:1713-1727. doi:10.1007/s00018-019-03022-7\u003c/li\u003e\n \u003cli\u003eCristofaro MG, Ferragina F, Tolino F, Barca I. Systemic Inflammatory Markers as Prognostic Factors in Oral Squamous Cell Carcinoma of the Tongue. \u003cem\u003eBiomedicines\u003c/em\u003e. 2025;13. doi:10.3390/biomedicines13030754\u003c/li\u003e\n \u003cli\u003eLu JN, Zhou LS, Zhang S, Li JX, Xu CJ. Performance of nutritional and inflammatory markers in patients with pancreatic cancer. \u003cem\u003eWorld J Clin Oncol\u003c/em\u003e. 2024;15:1021-1032. doi:10.5306/wjco.v15.i8.1021\u003c/li\u003e\n \u003cli\u003eNiu ZH, Lin L, Peng HY, et al. The prognostic value of systemic inflammation response index in digestive system carcinomas: a systematic review and meta-analysis. \u003cem\u003eBMC Gastroenterol\u003c/em\u003e. 2025;25:34. doi:10.1186/s12876-025-03635-2\u003c/li\u003e\n \u003cli\u003eChen S, Liu S, Xu S, et al. Naples Prognostic Score is an Independent Prognostic Factor in Patients with Small Cell Lung Cancer and Nomogram Predictive Model Established. \u003cem\u003eJ Inflamm Res\u003c/em\u003e. 2022;15. doi:10.2147/JIR.S371545\u003c/li\u003e\n \u003cli\u003eLi Q, Cong R, Wang Y, et al. Naples prognostic score is an independent prognostic factor in patients with operable endometrial cancer: Results from a retrospective cohort study. \u003cem\u003eGynecol Oncol\u003c/em\u003e. 2021;160:91-98. doi:10.1016/j.ygyno.2020.10.013\u003c/li\u003e\n \u003cli\u003eZhao H, Wu L, Yan G, et al. Inflammation and tumor progression: signaling pathways and targeted intervention. \u003cem\u003eSignal Transduct Target Ther\u003c/em\u003e. 2021;6. doi:10.1038/s41392-021-00658-5\u003c/li\u003e\n \u003cli\u003eBalkwill F, Mantovani A. Inflammation and cancer: Back to Virchow? \u003cem\u003eLancet\u003c/em\u003e. 2001;357:539-545. doi:10.1016/S0140-6736(00)04046-0\u003c/li\u003e\n \u003cli\u003eRuan GT, Xie HL, Gong YZ, et al. Prognostic importance of systemic inflammation and insulin resistance in patients with cancer: a prospective multicenter study. \u003cem\u003eBMC Cancer\u003c/em\u003e. 2022;22. doi:10.1186/s12885-022-09752-5\u003c/li\u003e\n \u003cli\u003eBai G, Zhou Y, Rong Q, Qiao S, Mao H, Liu P. Development of Nomogram Models Based on Peripheral Blood Score and Clinicopathological Parameters to Predict Preoperative Advanced Stage and Prognosis for Epithelial Ovarian Cancer Patients. \u003cem\u003eJ Inflamm Res\u003c/em\u003e. 2023;16:1227-1241. doi:10.2147/JIR.S401451\u003c/li\u003e\n \u003cli\u003eSoeters PB, Wolfe RR, Shenkin A. Hypoalbuminemia: Pathogenesis and Clinical Significance. \u003cem\u003eJournal of Parenteral and Enteral Nutrition\u003c/em\u003e. 2019;43:181-193. doi:10.1002/jpen.1451\u003c/li\u003e\n \u003cli\u003ePugliese L, Bernardini I, Pacifico N, et al. Severe hypocholesterolaemia is often neglected in haematological malignancies. \u003cem\u003eEur J Cancer\u003c/em\u003e. 2010;46:1735-1743. doi:10.1016/j.ejca.2010.03.041\u003c/li\u003e\n \u003cli\u003eFaria SS, Fernandes PC, Silva MJB, et al. The neutrophil-to-lymphocyte ratio: a narrative review. \u003cem\u003eEcancermedicalscience\u003c/em\u003e. 2016;10:702. doi:10.3332/ecancer.2016.702\u003c/li\u003e\n \u003cli\u003eGu L, Li H, Chen L, et al. Prognostic role of lymphocyte to monocyte ratio for patients with cancer: Evidence from a systematic review and meta-analysis. \u003cem\u003eOncotarget\u003c/em\u003e. 2016;7:31926-31942. doi:10.18632/oncotarget.7876\u003c/li\u003e\n \u003cli\u003eZhao J, Fan X, Li X, Luo Y, Liu S. The Naples prognostic score as a nutritional and inflammatory biomarkers of stroke prevalence and all-cause mortality: insights from NHANES. \u003cem\u003eJ Health Popul Nutr\u003c/em\u003e. 2025;44:85. doi:10.1186/s41043-025-00819-0\u003c/li\u003e\n \u003cli\u003eZhu N, Lin S, Yu H, Liu F, Huang W, Cao C. Naples prognostic score as a novel prognostic prediction indicator in adult asthma patients: A population-based study. \u003cem\u003eWorld Allergy Organization Journal\u003c/em\u003e. 2023;16(10). doi:10.1016/j.waojou.2023.100825\u003c/li\u003e\n \u003cli\u003eLiang C, Zhang C, Song J, et al. The Naples prognostic score serves as a predictor and prognostic indicator for cancer survivors in the community. \u003cem\u003eBMC Cancer\u003c/em\u003e. 2024;24. doi:10.1186/s12885-024-12448-7\u003c/li\u003e\n \u003cli\u003eXiu Y, Jiang C, Huang Q, et al. Naples score: a novel prognostic biomarker for breast cancer patients undergoing neoadjuvant chemotherapy. \u003cem\u003eJ Cancer Res Clin Oncol\u003c/em\u003e. 2023;149(17). doi:10.1007/s00432-023-05366-x\u003c/li\u003e\n \u003cli\u003eSugimoto A, Fukuoka T, Shibutani M, et al. Prognostic significance of the Naples prognostic score in colorectal cancer patients undergoing curative resection: a propensity score matching analysis. \u003cem\u003eBMC Gastroenterol\u003c/em\u003e. 2023;23(1). doi:10.1186/s12876-023-02722-6\u003c/li\u003e\n \u003cli\u003eLieto E, Auricchio A, Tirino G, et al. Naples prognostic score predicts tumor regression grade in resectable gastric cancer treated with preoperative chemotherapy. \u003cem\u003eCancers (Basel)\u003c/em\u003e. 2021;13. doi:10.3390/cancers13184676\u003c/li\u003e\n \u003cli\u003eYang Q, Chen T, Yao Z, Zhang X. Prognostic value of pre-treatment Naples prognostic score (NPS) in patients with osteosarcoma. \u003cem\u003eWorld J Surg Oncol\u003c/em\u003e. 2020;18. doi:10.1186/s12957-020-1789-z\u003c/li\u003e\n \u003cli\u003eBumbasirevic U, Petrovic M, Coric V, et al. The Utility of Immuno-Nutritional Scores in Patients with Testicular Germ Cell Tumors. \u003cem\u003eDiagnostics (Basel)\u003c/em\u003e. 2024;14. doi:10.3390/diagnostics14192196\u003c/li\u003e\n \u003cli\u003eSalazar-Valdivia FE, Valdez-Cornejo VA, Ulloque-Badaracco JR, et al. Systemic Immune-Inflammation Index and Mortality in Testicular Cancer: A Systematic Review and Meta-Analysis. \u003cem\u003eDiagnostics\u003c/em\u003e. 2023;13(5). doi:10.3390/diagnostics13050843\u003c/li\u003e\n \u003cli\u003eYoshinaga K, Sadahira T, Maruyama Y, et al. Comparison of inflammation-based prognostic scores as predictors of survival outcomes in patients with germ cell tumors. \u003cem\u003eInvestig Clin Urol\u003c/em\u003e. 2021;62:47-55. doi:10.4111/icu.20200103\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Testicular germ cell tumor, Naples Prognostic Score, Prognosis, Survival, Inflammation, Nutrition","lastPublishedDoi":"10.21203/rs.3.rs-6762404/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6762404/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective:\u003c/strong\u003e To evaluate the prognostic significance of the Naples Prognostic Score (NPS) in patients with testicular germ cell tumors (TGCT), including its association with tumor stage, histological subtype, and survival outcomes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e In this retrospective study, 133 patients with TGCT treated at a single tertiary center between 2015 and 2023 were evaluated. The NPS was calculated for each patient based on pre-treatment albumin, cholesterol, neutrophil-to-lymphocyte ratio (NLR), and lymphocyte-to-monocyte ratio (LMR). Patients were stratified into low (0–2) and high (3–4) NPS groups. Clinicopathological characteristics were compared between NPS groups. Overall survival was analyzed using Kaplan–Meier estimates with log-rank tests, and Cox proportional hazards regression was performed to identify independent prognostic factors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Patients with high NPS were significantly younger on average and more likely to have non-seminomatous histology, advanced clinical stage, elevated tumor markers, and metastatic disease compared to those with low NPS (all \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.01). Overall survival was markedly worse in the high NPS group (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.005). On multivariate analysis, NPS emerged as an independent predictor of poorer overall survival alongside clinical stage (hazard ratio for high NPS ≈8.4, \u003cem\u003ep\u003c/em\u003e = 0.018).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e The NPS is a significant prognostic indicator in TGCT. A high NPS is associated with aggressive disease features and inferior survival outcomes, remaining an independent prognostic factor when controlling for stage. Incorporating NPS into clinical risk stratification may help identify TGCT patients at higher risk of treatment failure, though prospective studies are warranted to validate its utility.\u003c/p\u003e","manuscriptTitle":"The Prognostic Role of the Naples Prognostic Score in Testicular Germ Cell Tumors: A Retrospective Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-29 12:33:22","doi":"10.21203/rs.3.rs-6762404/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"8e0d3479-1ea4-4e61-b9bd-96cde662984f","owner":[],"postedDate":"May 29th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-06-01T12:38:34+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-29 12:33:22","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6762404","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6762404","identity":"rs-6762404","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}