Abstract
Objective
This study investigated whether the postoperative advanced lung cancer inflammation index (ALI) has prognostic significance in patients with prostate cancer who underwent radical prostatectomy. It also explored the potential role of ALI as a biomarker for assessing postoperative recurrence risk.
Patients and Methods
This retrospective, single-center study included 425 patients with localized or selected locally advanced prostate cancer who underwent radical prostatectomy at the First Affiliated Hospital of Chengdu Medical College. Postoperative ALI was calculated using clinical and laboratory data obtained at the first follow-up visit, approximately three months after surgery. Patients were categorized into low- and high-ALI groups according to the optimal ALI cut-off value. Associations between postoperative ALI and overall survival and biochemical recurrence-free survival were evaluated using Kaplan–Meier analysis, Cox proportional hazards regression, and propensity score matching. The median follow-up duration was 56 months, 38 patients dead, and 156 patients had biochemical recurrences at the end of follow-up.
Results
A low postoperative ALI was significantly associated with a lower body mass index (p = 0.001), higher Gleason scores (p = 0.0036), elevated preoperative prostate-specific antigen levels (p < 0.0001), more advanced pathological T stage (p < 0.0001), and a greater frequency of lymph-node metastasis (p = 0.002). Kaplan–Meier survival curves demonstrated that patients in the low-ALI group experienced worse survival outcomes, including reduced overall survival (HR = 3.32; 95% CI, 2.41–5.87; p = 0.012) and shorter biochemical recurrence-free survival (HR = 2.57; 95% CI, 1.58–3.65; p = 0.002), compared with those in the high-ALI group. In multivariable Cox regression models, ALI remained an independent predictor of both overall survival (p < 0.0001) and biochemical recurrence-free survival (p < 0.0001) after adjustment of confounding factors.
Conclusion
Among patients with prostate cancer undergoing radical prostatectomy, a low postoperative ALI was associated with shorter overall survival and biochemical recurrence-free survival compared with a high postoperative ALI. These findings suggest that postoperative ALI may provide prognostic information in patients undergoing radical prostatectomy; however, its clinical utility requires confirmation through prospective, multicenter studies and external validation.
Keywords: advanced lung cancer inflammation index, biochemical recurrence, overall survival, prostate cancer, radical prostatectomy
Introduction
Prostate cancer is among the most frequently diagnosed cancers in men and continues to contribute substantially to cancer-related deaths worldwide.1 Radical prostatectomy is commonly used as a potentially curative option for patients with localized disease and selected cases of locally advanced prostate cancer. Nevertheless, some patients develop biochemical recurrence or further disease progression after surgery.2,3 Postoperative risk assessment is typically based on established clinicopathological parameters, such as prostate-specific antigen (PSA), Gleason score or Grade Group, pathological tumor stage, seminal vesicle invasion, lymph-node involvement, and surgical margin status.4–6 However, these clinicopathological parameters may not fully capture interindividual differences in tumor biology and host systemic condition, highlighting the need for more comprehensive prognostic assessment tools.
Systemic inflammatory responses and nutritional condition are now considered key factors that may influence tumor progression and postoperative prognosis.5,7,8 In prostate cancer, several immune-inflammatory biomarkers, such as the neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII), have been investigated as convenient blood-based indicators for predicting recurrence and survival outcomes after radical prostatectomy.9–12 A recent study reported that the combined assessment of preoperative SII and Ki-67 improved prognostic prediction in patients undergoing laparoscopic radical prostatectomy, supporting the clinical relevance of integrating host inflammatory status with tumor aggressiveness.13 Chronic systemic inflammation has been implicated in tumor invasion, angiogenesis, immune evasion, and metastatic progression, whereas malnutrition and hypoalbuminemia may reflect impaired physiological reserve and compromised postoperative recovery.14,15 Therefore, biomarkers that combine indicators of inflammation and nutritional status may offer prognostic insights that extend beyond those provided by traditional pathological characteristics.
The advanced lung cancer inflammation index (ALI), calculated as body mass index × serum albumin/neutrophil-to-lymphocyte ratio, is a composite biomarker that reflects both nutritional reserve and systemic inflammatory status.16 Although ALI was originally developed for patients with advanced lung cancer, accumulating evidence has demonstrated its prognostic value across various malignancies.16–19 In gastric cancer, low ALI was found to be associated with poorer survival outcomes and remained an independent prognostic factor after adjustment for confounding variables.17,18 Moreover, ALI has shown prognostic performance comparable to or superior to other commonly used inflammatory biomarkers, including NLR, lymphocyte-to-monocyte ratio, and platelet-to-lymphocyte ratio.20
A recent study using NHANES data reported an association between preoperative ALI and prostate cancer prevalence and included an exploratory prognostic analysis.21 However, evidence regarding the prognostic significance of ALI in prostate cancer remains limited, particularly in the postoperative setting following radical prostatectomy. Preoperative ALI reflects baseline tumor-related inflammation and nutritional status, whereas postoperative ALI may additionally capture changes associated with tumor removal, surgical stress, and early recovery. Surgery can alter neutrophil, and lymphocyte counts and serum albumin through tissue injury, anesthesia, blood loss, fluid shifts, and wound healing. Consequently, measurements obtained immediately after surgery may predominantly reflect the acute surgical response rather than a stable host condition. We therefore investigated the prognostic significance of postoperative ALI assessed approximately three months after radical prostatectomy.
Patients and Methods
Study Population
This study initially screened 657 patients with localized or selected locally advanced prostate cancer who received radical prostatectomy at The First Affiliated Hospital of Chengdu Medical College from January 2019 to December 2022. Written informed consent was obtained from all participants before enrollment. The study complied with the principles of the Declaration of Helsinki and was approved by the Ethics Committee of The First Affiliated Hospital of Chengdu Medical College (No. 2238CDM321).
Inclusion and Exclusion Criteria
Patients were eligible for inclusion when they satisfied all of the following criteria: (1) age of 18 years or older; (2) primary prostate cancer confirmed by postoperative pathological examination; (3) localized or selected locally advanced disease managed with radical prostatectomy; (4) absence of distant metastasis at the time of surgery; (5) complete postoperative clinicopathological information, including PSA level, Gleason score or Grade Group, pathological T stage, lymph-node status, seminal vesicle invasion, and surgical margin status; (6) available postoperative laboratory indicators needed to calculate ALI, including serum albumin, absolute neutrophil count, body mass index, and absolute lymphocyte count; and (7) complete follow-up records.
Patients were excluded if they had any of the following: (1) incomplete clinicopathological, laboratory, or follow-up data; (2) history of other malignant tumors; (3) evidence of distant metastasis at initial treatment; (4) active infection, acute or chronic inflammatory disorder, autoimmune disease, or hematological disease during the perioperative period; or (5) loss to follow-up. After applying these criteria, 425 patients were included for the final analysis. The patient selection procedure is illustrated in Figure 1.
Figure 1.
The flowchart of the patient screening process.
Data Collection
Clinicopathological information was extracted from the cancer database of the study hospital. The collected variables included age at the time of surgery, BMI, preoperative PSA levels, surgical approach, surgical margin status, pathological Gleason score, pathological T stage, lymph-node status, seminal vesicle invasion, and postoperative treatment. Prostate cancer was staged according to eighth edition of the American Joint Committee on Cancer/Union for International Cancer Control TNM classification system. Postoperative laboratory and clinical data were recorded at the first follow-up appointment, which was scheduled approximately three months after radical prostatectomy. This interval was chosen to reduce the potential impact of acute inflammatory changes related to surgery. The NLR was calculated as the absolute neutrophil count divided by the absolute lymphocyte count. Postoperative ALI was then computed as follows: ALI = BMI (kg/m2) × serum albumin (g/dL)/NLR.17,18
Follow-Up
Patients were followed every three months during the first two years after surgery, every six months from years three to five, and annually thereafter. Follow-up information was collected through outpatient medical records, telephone contact, and the hospital follow-up system. The recorded follow-up data included postoperative PSA values, imaging examinations when clinically required, biochemical recurrence, disease progression, survival status, and the date of the final follow-up or death. The median follow-up duration was 56 months, 38 patients dead, and 156 patients had biochemical recurrences at the end of follow-up.
Overall survival was calculated from the date of radical prostatectomy to death from any cause or the last available follow-up. Biochemical recurrence was defined as a serum PSA level of ≥0.2 ng/mL after radical prostatectomy, confirmed by a second consecutive PSA measurement during follow-up, in accordance with American Urological Association guidelines.22 Biochemical recurrence-free survival was measured from radical prostatectomy to biochemical recurrence or the most recent follow-up.
Propensity Score Matching Analysis
Variables considered clinically relevant or potentially related to prognosis were incorporated into the propensity score model. These included age, preoperative PSA level, pathological Gleason score, lymph-node metastasis, pathological T stage, surgical margin, radiotherapy, androgen deprivation therapy, and total prostate volume. Patients in the low-ALI and high-ALI groups were matched at a 1:1 ratio using nearest-neighbor matching without replacement. To minimize remaining baseline differences between groups, a caliper of 0.1 standard deviations of the logit-transformed propensity score was applied. Propensity score matching was performed using the “MatchIt” package in R software.
Survival analyses were then repeated in the matched cohort. In the matched population, univariate and multivariate Cox proportional hazards models were further applied to determine whether ALI remained independently associated with overall survival and biochemical recurrence-free survival after baseline clinicopathological variables had been balanced. Findings from the matched cohort were regarded as sensitivity analyses to evaluate the stability of the association between postoperative ALI and prognosis.
Statistical Analysis
Statistical analyses were conducted with SPSS (IBM Corp., Armonk, NY, USA). Continuous variables with a normal distribution were reported as mean ± standard deviation and analyzed using Student’s t-test. Variables that were not normally distributed were summarized as medians with interquartile ranges (IQRs) and compared using the Mann–Whitney U-test. Categorical data were described as counts and percentages, and group comparisons were performed using the chi-square test or Fisher’s exact test, when appropriate.
The optimal postoperative ALI threshold was identified by receiver operating characteristic (ROC) curve analysis according to biochemical recurrence status. The Youden index was applied to determine the best cut-off point, after which patients were classified into low- and high-ALI groups. The discriminative ability of ALI was assessed using the area under the ROC curve (AUC). The Youden index was calculated as follows: sensitivity + specificity − 1.
Overall survival and biochemical recurrence-free survival were assessed using the Kaplan–Meier method, with between-group differences tested by the Log rank test. Univariate Cox proportional hazards regression was used to screen variables associated with overall survival and biochemical recurrence-free survival. Factors with P < 0.05 in univariate analysis were subsequently included in multivariate Cox proportional hazards models. Hazard ratios (HRs) and 95% confidence intervals (CIs) were reported. The proportional hazards assumption was tested for each Cox model using scaled Schoenfeld residuals for individual covariates and a global test. No significant violation was identified for the overall survival model or the biochemical recurrence-free survival model. Statistical significance was defined as P < 0.05.
Results
Patient Characteristics of the Study Population
A total of 425 prostate cancer patients treated with radical prostatectomy were included in the final analysis. Table 1 presents a summary of the patients’ baseline clinicopathological characteristics. The median age of the patients was 63 years (IQR: 54–77 years). The median BMI was 23.21 kg/m2 (IQR: 19.16–26.18 kg/m2), and the median preoperative PSA level was 15.74 ng/mL (IQR: 12.36–18.28 ng/mL). The median total prostate volume was 36.83 mL (IQR: 30.28–43.72 mL). The median postoperative ALI was 48.47 (IQR: 31.24–64.32).
Table 1.
Patient Characteristics of the Study Population
| Characteristics | Median | IQR or % |
|---|---|---|
| Total | 425 | 100 |
| Age (years) | 63 | 54 - 77 |
| BMI (kg/m2) | 23.21 | 19.16–26.18 |
| Preoperative PSA (ng/mL) | 15.74 | 12.36–18.28 |
| Total prostate volume (mL) | 36.83 | 30.28–43.72 |
| ALI | 48.47 | 31.24–64.32 |
| Gleason Score | ||
| ≤6 | 23 | 5.41 |
| = 7 | 210 | 49.41 |
| ≥8 | 192 | 45.18 |
| T stage | ||
| T1 | 165 | 38.82 |
| T2 | 228 | 53.65 |
| T3 | 32 | 7.53 |
| Lymph-node metastasis | ||
| No | 377 | 88.71 |
| Yes | 48 | 11.29 |
| Surgical margin | ||
| Negative | 366 | 86.12 |
| Positive | 59 | 13.88 |
| Radiotherapy | ||
| No | 353 | 83.06 |
| Yes | 72 | 16.94 |
| Androgen deprivation therapy | ||
| No | 342 | 80.47 |
| Yes | 83 | 19.53 |
Notes: Continuous variables were expressed as the median and interquartile range. Categorical variables were presented as frequencies and percentages.
Abbreviations: ALI, advanced lung cancer inflammation index; BMI, body mass index; PSA, prostate-specific antigen; IQR, interquartile range.
Regarding pathological Gleason Score distribution, 23 patients (5.41%) had score six or lower, 210 patients (49.41%) had score seven, and 192 patients (45.18%) had score eight or higher. With respect to pathological T stage, 165 patients (38.82%) had T1 disease, 228 patients (53.65%) had T2 disease, and 32 patients (7.53%) had T3 disease. Lymph-node metastasis was absent in 377 patients (88.71%) and present in 48 patients (11.29%). 59 patients (13.88%) had positive surgical margin, 72 patients (16.94%) received radiotherapy, and 83 patients (19.53%) received androgen deprivation therapy.
Determination of the Optimal ALI Cut-off Value
A receiver operating characteristic (ROC) curve analysis was performed to determine the optimal ALI cut-off value (Figure 2). The AUC for ALI was 0.813. The optimal ALI cut-off value was determined to be 43.7, with a sensitivity of 82.61%, a specificity of 75.45%, and a Youden index of 0.581. Based on this threshold, patients were divided into two groups: a low-ALI group, consisting of 229 patients with ALI values less than 43.7, and a high-ALI group, consisting of 196 patients with ALI values greater than 43.7.
Figure 2.
Receiver operating characteristic analysis was performed to identify the most appropriate cut-off value of ALI. The red dashed line represents the reference line of no discriminative ability, while the blue curve represents the receiver operating characteristic curve of postoperative ALI for predicting biochemical recurrence status. The area under the curve for ALI was 0.813. The optimal cut-off value was 43.7, with a sensitivity of 82.61%, a specificity of 75.45%, and a Youden index of 0.581.
Abbreviations: ALI, Advanced Lung Cancer Inflammation Index; AUC, area under the curve.
Association Between Clinicopathological Characteristics and the ALI
The associations between ALI status and clinicopathological characteristics are presented in Table 2. No significant difference in age was observed between the low- and high-ALI groups (p = 0.131). Similarly, the total prostate volume was not significantly different between the two groups (p = 0.271). Patients in the low-ALI group had a significantly lower BMI than those in the high-ALI group (p = 0.001). However, patients in the low-ALI group had a significantly higher preoperative PSA levels than those in the high-ALI group (p < 0.0001).
Table 2.
Association Between Patient Clinicopathological Characteristics and the ALI
| Characteristics | Low-ALI (n = 229) | High-ALI (n = 196) | p-values |
|---|---|---|---|
| Age (years) | 63 (56–78) | 62 (52–74) | 0.131 |
| BMI (kg/m2) | 21.13 (17.24–23.21) | 24.32 (19.16–26.18) | 0.001 |
| Preoperative PSA (ng/mL) | 16.14 (10.27–19.16) | 9.32 (6.13–15.35) | < 0.0001 |
| TPV (mL) | 36.12 (29.32–42.39) | 37.48 (31.45–44.76) | 0.271 |
| Gleason Score | 0.0036 | ||
| ≤6 | 5 | 18 | |
| = 7 | 122 | 88 | |
| ≥8 | 102 | 90 | |
| T stage | < 0.0001 | ||
| T1 | 62 | 103 | |
| T2 | 140 | 88 | |
| T3 | 27 | 5 | |
| Lymph-node metastasis | 0.0002 | ||
| No | 191 | 186 | |
| Yes | 38 | 10 | |
| Surgical margin | 0.004 | ||
| Negative | 187 | 179 | |
| Positive | 42 | 17 | |
| Radiotherapy | < 0.0001 | ||
| No | 171 | 182 | |
| Yes | 58 | 14 | |
| Androgen deprivation therapy | 0.0002 | ||
| No | 169 | 173 | |
| Yes | 60 | 23 |
Notes: Continuous variables were expressed as the median and interquartile range and compared using the Mann–Whitney U-test. Categorical variables were presented as frequencies and compared using the chi-square test or Fisher’s exact test. A p <0.05 was considered statistical significance and was highlighted in bold text.
Pathological Gleason Score was significantly associated with ALI status (p = 0.0036). Compared with patients in the high-ALI group, those in the low-ALI group showed a significantly greater frequency of higher Gleason scores. Specifically, score seven and score eight or higher disease were observed in 122 and 102 patients in the low-ALI group, respectively, compared with 88 and 90 patients in the high-ALI group. Pathological T stage was also significantly associated with ALI status (p < 0.0001). The low-ALI group had a greater proportion of patients with advanced pathological T stage than the high-ALI group. Specifically, T2 and T3 disease were observed in 140 and 27 patients in the low-ALI group, respectively, compared with 88 and 5 patients in the high-ALI group. Lymph node metastasis (p = 0.0002), surgical margin (p = 0.004), radiotherapy (p < 0.0001), androgen deprivation therapy (p = 0.0002) were all significantly associated with ALI status.
Association Between ALI and Prognosis
Kaplan–Meier survival curves were generated to assess the association between ALI and patient prognosis. Prognostic outcomes were assessed using overall survival and biochemical recurrence-free survival. Patients in the low-ALI group experienced significantly worse prognostic outcomes than those in the high-ALI group, as reflected by shorter overall survival (HR = 3.32; 95% CI, 2.41–5.87; p=0.012) (Figure 3A) and biochemical recurrence-free survival (HR = 2.57; 95% CI, 1.58–3.65; p = 0.002) (Figure 3B).
Figure 3.
Association Between ALI and prognosis. Kaplan–Meier survival analysis was performed to evaluate the association between ALI and prognosis. (A) Patients with low ALI had shorter overall survival than those with high ALI (HR = 3.32; 95% CI, 2.41–5.87; p = 0.012). (B) Patients with low ALI had shorter biochemical recurrence-free survival than those with high ALI (HR = 2.57; 95% CI, 1.58–3.65; p = 0.002).
Abbreviations: ALI, Advanced Lung Cancer Inflammation Index; CI, confidence interval; HR, hazard ratio.
Identification of Risk Factors for Overall Survival and Biochemical Recurrence-Free Survival
Univariable and multivariable Cox proportional hazards regression models were applied to determine risk factors for overall survival and biochemical recurrence-free survival. Continuous variables were categorized into two groups based on their respective median values. On univariable analysis, age (p = 0.001), BMI (p = 0.002), preoperative PSA level (p = 0.005), Gleason Score (p < 0.0001), tumor T stage (p = 0.001), lymph node metastasis (p = 0.003), surgical margin (p = 0.002), radiotherapy (p = 0.012), androgen deprivation therapy (p = 0.007) and ALI score (p < 0.0001) were all significantly associated with overall survival (Table 3). These variables were analyzed in the multivariable model and adjusted for potential confounding factors. Multivariable analysis identified lymph node metastasis (p = 0.001), tumor T stage (p = 0.002), surgical margin (p = 0.004), and ALI score (p < 0.0001) as independent risk factors for overall survival (Table 3). Similarly, multivariable analysis for biochemical recurrence-free survival demonstrated that lymph node metastasis (p = 0.004), preoperative PSA level (p = 0.005), surgical margin (p = 0.001), and ALI score (p < 0.0001) were independent risk factors for biochemical recurrence-free survival (Table 4).
Table 3.
Univariate and Multivariate Cox Proportional Hazards Regression Analyses of Risk Factors for Overall Survival
| Variables | Univariate Analysis HR (95% CI) |
p-value | Multivariate Analysis HR (95% CI) |
Adjusted p-value |
|---|---|---|---|---|
| Age | ||||
| < 63 | 1.00 (Reference) | 1.00 (Reference) | ||
| ≥ 63 | 2.48 (1.22–4.67) | 0.001 | 1.03 (1.01–1.14) | 0.124 |
| BMI (kg/m2) | ||||
| < 23.21 | 1.00 (Reference) | 1.00 (Reference) | ||
| ≥ 23.21 | 3.65 (1.87–5.72) | 0.002 | 1.06 (1.02–1.11) | 0.218 |
| Preoperative PSA (ng/mL) | ||||
| < 15.74 | 1.00 (Reference) | 1.00 (Reference) | ||
| ≥ 15.74 | 3.47 (2.04–5.68) | 0.005 | 1.07 (1.03–1.19) | 0.415 |
| TPV (mL) | ||||
| < 36.83 | 1.00 (Reference) | 1.00 (Reference) | ||
| ≥ 36.83 | 1.18 (1.01–1.26) | 0.217 | 1.09 (1.02–1.35) | 0.358 |
| Gleason Score | ||||
| ≤6 | 1.00 (Reference) | 1.00 (Reference) | ||
| = 7 | 3.34 (1.81–5.18) | < 0.0001 | 1.12 (1.02–1.54) | 0.514 |
| ≥8 | 4.01 (2.31–6.42) | < 0.0001 | 1.09 (1.01–1.43) | 0.514 |
| T stage | ||||
| T1 | 1.00 (Reference) | 1.00 (Reference) | ||
| T2 | 2.34 (1.52–4.27) | 0.001 | 2.21 (1.22–4.57) | 0.002 |
| T3 | 3.52 (2.17–5.14) | 0.001 | 2.05 (1.87–3.87) | 0.002 |
| Lymph-node metastasis | ||||
| No | 1.00 (Reference) | 1.00 (Reference) | ||
| Yes | 3.15 (2.07–5.04) | 0.003 | 2.81 (1.67–4.09) | 0.001 |
| Surgical margin | ||||
| Negative | 1.00 (Reference) | 1.00 (Reference) | ||
| Positive | 2.63 (1.24–4.36) | 0.002 | 2.38 (1.41–4.52) | 0.004 |
| Radiotherapy | ||||
| No | 1.00 (Reference) | 1.00 (Reference) | ||
| Yes | 0.87 (0.82–0.94) | 0.012 | 0.92 (0.86–0.97) | 0.125 |
| Androgen deprivation therapy | ||||
| No | 1.00 (Reference) | 1.00 (Reference) | ||
| Yes | 0.83 (0.80–0.95) | 0.007 | 0.94 (0.86–0.98) | 0.227 |
| ALI score | ||||
| High | 1.00 (Reference) | 1.00 (Reference) | ||
| Low | 3.17 (1.05–5.42) | < 0.0001 | 3.12 (2.17–5.38) | < 0.0001 |
Notes: Multivariate analysis adjusted for potential confounding factors, including age, BMI, Preoperative PSA, TPV, tumor stage, and lymph-node metastasis, surgical margin, radiotherapy, and androgen deprivation therapy. A p < 0.05 was considered statistical significance and highlighted in bold text.
Abbreviations: ALI, advanced lung cancer inflammation index; BMI, body mass index; CI, Confidence interval; HR, hazard ratio; PSA, prostate-specific antigen; TPV, total prostate volume.
Table 4.
Univariate and Multivariate Cox Proportional Hazards Regression Analyses of Risk Factors for Biochemical Recurrence-Free Survival
| Variables | Univariate Analysis HR (95% CI) |
p-value | Multivariate Analysis HR (95% CI) |
Adjusted p-value |
|---|---|---|---|---|
| Age | ||||
| < 63 | 1.00 (Reference) | 1.00 (Reference) | ||
| ≥ 63 | 1.03 (1.01–1.18) | 0.421 | 1.02 (1.01 −1.09) | 0.326 |
| BMI (kg/m2) | ||||
| < 23.21 | 1.00 (Reference) | 1.00 (Reference) | ||
| ≥ 23.21 | 1.04 (1.02–1.15) | 0.331 | 1.03 (1.01–1.12) | 0.414 |
| Preoperative PSA (ng/mL) | ||||
| < 15.74 | 1.00 (Reference) | 1.00 (Reference) | ||
| ≥ 15.74 | 3.83 (2.23–5.79) | 0.001 | 3.28 (1.39–5.72) | 0.005 |
| TPV (mL) | ||||
| < 36.83 | 1.00 (Reference) | 1.00 (Reference) | ||
| ≥ 36.83 | 1.03 (1.01–1.14) | 0.128 | 1.02 (1.01–1.24) | 0.231 |
| Gleason Score | ||||
| ≤6 | 1.00 (Reference) | 1.00 (Reference) | ||
| = 7 | 2.25 (1.69–4.67) | 0.003 | 1.12 (1.02–1.54) | 0.514 |
| ≥8 | 3.29 (2.08–5.32) | 0.003 | 1.08 (1.01–1.32) | 0.514 |
| T stage | ||||
| T1 | 1.00 (Reference) | 1.00 (Reference) | ||
| T2 | 2.48 (1.89–4.78) | 0.001 | 1.12 (1.02–1.48) | 0.104 |
| T3 | 3.49 (2.26–4.82) | 0.001 | 1.15 (1.08–1.32) | 0.104 |
| Lymph-node metastasis | ||||
| No | 1.00 (Reference) | 1.00 (Reference) | ||
| Yes | 3.42 (2.15–5.27) | 0.002 | 2.47 (1.62–4.38) | 0.004 |
| Surgical margin | ||||
| Negative | 1.00 (Reference) | 1.00 (Reference) | ||
| Positive | 2.43 (1.38–4.18) | 0.005 | 2.27 (1.47–4.32) | 0.001 |
| Radiotherapy | ||||
| No | 1.00 (Reference) | 1.00 (Reference) | ||
| Yes | 0.93 (0.89–0.95) | 0.341 | 0.95 (0.91–0.98) | 0.273 |
| Androgen deprivation therapy | ||||
| No | 1.00 (Reference) | 1.00 (Reference) | ||
| Yes | 0.95 (0.93–0.99) | 0.142 | 0.92 (0.88–0.95) | 0.431 |
| ALI score | ||||
| High | 1.00 (Reference) | 1.00 (Reference) | ||
| Low | 3.25 (2.18–5.71) | < 0.0001 | 3.01 (2.02–4.43) | < 0.0001 |
Notes: Multivariate analysis adjusted for potential confounding factors, including age, BMI, Preoperative PSA, TPV, tumor stage, and lymph-node metastasis, surgical margin, radiotherapy, and androgen deprivation therapy. A p < 0.05 was considered statistical significance and highlighted in bold text.
Abbreviations: ALI, advanced lung cancer inflammation index; BMI, body mass index; CI, Confidence interval; HR, hazard ratio; PSA, prostate-specific antigen; TPV, total prostate volume.
Sensitivity Analysis According to Propensity Score Matching Analysis
Propensity score matching was used to minimize potential selection bias and improve the comparability of survival outcomes between the low-ALI and high-ALI groups. After propensity score matching, the matched cohort consisted of 196 patients for each group. The propensity score matching analysis of patient characteristics was showed in Supplementary Table 1. Kaplan–Meier survival analysis showed that patients in the low-ALI group continued to have significantly poorer survival outcomes than those in the high-ALI group, with shorter overall survival (HR = 2.16; 95% CI, 1.28–4.26; p = 0.001) (Figure 4A) and biochemical recurrence-free survival (HR = 2.85; 95% CI, 1.82–3.92; p = 0.004) (Figure 4B). Multivariable Cox proportional hazards regression analysis in the matched cohort further demonstrated that lymph node metastasis (p = 0.003), pathological tumor T stage (p = 0.001), surgical margin (p = 0.005), and ALI (p < 0.0001) remained independent risk factors for overall survival (Table 5); lymph node metastasis (p = 0.001), preoperative PSA level (p = 0.003), surgical margin (p = 0.002), and ALI score (p < 0.0001) remained independent risk factors for biochemical recurrence-free survival (Table 6).
Figure 4.
Association Between ALI and prognosis in the propensity score–matched cohort was assessed by Kaplan–Meier survival analysis. (A) Patients in the low-ALI group have shorter overall survival than those in the high-ALI group (HR = 2.16; 95% CI, 1.28–4.26; p = 0.001). (B) Patients in the low-ALI group have shorter biochemical recurrence-free survival than those in the high-ALI group (HR = 2.85; 95% CI, 1.82–3.92; p = 0.004).
Abbreviations: ALI, Advanced Lung Cancer Inflammation Index; CI, confidence interval; HR, hazard ratio.
Table 5.
Univariate and Multivariate Cox Proportional Hazards Regression Analyses of Risk Factors for Overall Survival in Propensity-Score Matched Cohort
| Variables | Univariate Analysis HR (95% CI) |
p-value | Multivariate Analysis HR (95% CI) |
Adjusted p-value |
|---|---|---|---|---|
| Age | ||||
| < 63 | 1.00 (Reference) | 1.00 (Reference) | ||
| ≥ 63 | 2.52 (1.68–4.82) | 0.002 | 1.05 (1.02–1.32) | 0.331 |
| BMI (kg/m2) | ||||
| < 23.21 | 1.00 (Reference) | 1.00 (Reference) | ||
| ≥ 23.21 | 2.39 (1.26–5.72) | 0.003 | 1.04 (1.01–1.27) | 0.326 |
| Preoperative PSA (ng/mL) | ||||
| < 15.74 | 1.00 (Reference) | 1.00 (Reference) | ||
| ≥ 15.74 | 2.87 (1.76–4.23) | 0.001 | 1.14 (1.03–1.32) | 0.113 |
| TPV (mL) | ||||
| < 36.83 | 1.00 (Reference) | 1.00 (Reference) | ||
| ≥ 36.83 | 1.03 (1.01–1.18) | 0.132 | 1.02 (1.01–1.14) | 0.153 |
| Gleason Score | ||||
| ≤6 | 1.00 (Reference) | 1.00 (Reference) | ||
| = 7 | 2.87 (1.39–4.26) | 0.001 | 1.07 (1.03–1.47) | 0.429 |
| ≥8 | 3.14 (2.02–5.32) | 0.001 | 1.03 (1.01–1.21) | 0.429 |
| T stage | ||||
| T1 | 1.00 (Reference) | 1.00 (Reference) | ||
| T2 | 2.53 (1.31–4.27) | 0.005 | 2.32 (1.47–4.35) | 0.001 |
| T3 | 3.27 (1.42–5.63) | 0.005 | 2.14 (1.39–3.62) | 0.001 |
| Lymph-node metastasis | ||||
| No | 1.00 (Reference) | 1.00 (Reference) | ||
| Yes | 2.82 (1.62–5.35) | 0.002 | 2.54 (1.45–4.21) | 0.003 |
| Surgical margin | ||||
| Negative | 1.00 (Reference) | 1.00 (Reference) | ||
| Positive | 2.84 (1.47–4.67) | 0.001 | 2.41 (1.53–3.98) | 0.005 |
| Radiotherapy | ||||
| No | 1.00 (Reference) | 1.00 (Reference) | ||
| Yes | 0.85 (0.81–0.96) | 0.003 | 0.94 (0.82–0.98) | 0.334 |
| Androgen deprivation therapy | ||||
| No | 1.00 (Reference) | 1.00 (Reference) | ||
| Yes | 0.87 (0.82–0.97) | 0.005 | 0.95 (0.91–0.99) | 0.375 |
| ALI score | ||||
| High | 1.00 (Reference) | 1.00 (Reference) | ||
| Low | 3.16 (2.12–6.09) | < 0.0001 | 2.98 (1.31–4.33) | < 0.0001 |
Notes: Multivariate analysis adjusted for potential confounding factors, including age, BMI, Preoperative PSA, TPV, tumor stage, and lymph-node metastasis, surgical margin, radiotherapy, and androgen deprivation therapy. A p < 0.05 was considered statistical significance and highlighted in bold text.
Abbreviations: ALI, advanced lung cancer inflammation index; BMI, body mass index; CI, Confidence interval; HR, hazard ratio; PSA, prostate-specific antigen; TPV, total prostate volume.
Table 6.
Univariate and Multivariate Cox Proportional Hazards Regression Analyses of Risk Factors for Biochemical Recurrence-Free Survival in Propensity-Score Matched Cohort
| Variables | Univariate Analysis HR (95% CI) |
p-value | Multivariate Analysis HR (95% CI) |
Adjusted p-value |
|---|---|---|---|---|
| Age | ||||
| < 63 | 1.00 (Reference) | 1.00 (Reference) | ||
| ≥ 63 | 1.08 (1.02–0.15) | 0.265 | 1.02 (1.01 −1.09) | 0.224 |
| BMI (kg/m2) | ||||
| < 23.21 | 1.00 (Reference) | 1.00 (Reference) | ||
| ≥ 23.21 | 1.02 (1.01–1.12) | 0.224 | 1.05 (1.02–1.23) | 0.331 |
| Preoperative PSA (ng/mL) | ||||
| < 15.74 | 1.00 (Reference) | 1.00 (Reference) | ||
| ≥ 15.74 | 3.41 (2.17–5.28) | 0.002 | 3.15 (1.24–5.45) | 0.003 |
| TPV (mL) | ||||
| < 36.83 | 1.00 (Reference) | 1.00 (Reference) | ||
| ≥ 36.83 | 1.03 (1.01–0.99) | 0.257 | 1.04 (1.02–1.18) | 0.187 |
| Gleason Score | ||||
| ≤6 | 1.00 (Reference) | 1.00 (Reference) | ||
| = 7 | 1.85 (1.41–3.17) | 0.004 | 1.04 (1.01–1.43) | 0.427 |
| 8≥ | 2.47 (2.31–4.05) | 0.004 | 1.03 (1.01–1.29) | 0.427 |
| T stage | ||||
| T1 | 1.00 (Reference) | 1.00 (Reference) | ||
| T2 | 2.23 (1.43–3.92) | 0.002 | 1.32 (1.14–1.89) | 0.289 |
| T3 | 3.08 (2.14–4.69) | 0.002 | 1.27 (1.06–1.34) | 0.289 |
| Lymph-node metastasis | ||||
| No | 1.00 (Reference) | 1.00 (Reference) | ||
| Yes | 2.98 (2.01–4.18) | 0.001 | 2.32 (1.12–3.42) | 0.001 |
| Surgical margin | ||||
| Negative | 1.00 (Reference) | 1.00 (Reference) | ||
| Positive | 2.83 (1.65–4.37) | 0.004 | 2.51 (1.58–4.01) | 0.002 |
| Radiotherapy | ||||
| No | 1.00 (Reference) | 1.00 (Reference) | ||
| Yes | 0.96 (0.91–0.98) | 0.521 | 0.94 (0.90–0.97) | 0.362 |
| Androgen deprivation therapy | ||||
| No | 1.00 (Reference) | 1.00 (Reference) | ||
| Yes | 0.91 (0.89–0.95) | 0.317 | 0.95 (0.92–0.99) | 0.267 |
| ALI score | ||||
| High | 1.00 (Reference) | 1.00 (Reference) | ||
| Low | 2.81 (1.42–5.02) | < 0.0001 | 2.27 (1.13–4.65) | < 0.0001 |
Notes: Multivariate analysis adjusted for potential confounding factors, including age, BMI, Preoperative PSA, TPV, tumor stage, and lymph-node metastasis, surgical margin, radiotherapy, and androgen deprivation therapy. A p < 0.05 was considered statistical significance and highlighted in bold text.
Abbreviations: ALI, advanced lung cancer inflammation index; BMI, body mass index; CI, Confidence interval; HR, hazard ratio; PSA, prostate-specific antigen; TPV, total prostate volume.
Discussion
This study examined the prognostic significance of postoperative ALI in patients with prostate cancer who underwent radical prostatectomy. Several findings were observed. First, low postoperative ALI was significantly associated with adverse clinicopathological characteristics, including lower BMI, higher preoperative PSA levels, higher Gleason score, more advanced pathological T stage, and increased lymph node metastasis. Second, Kaplan–Meier analysis demonstrated that patients in the low-ALI group experienced significantly poorer survival outcomes, as shown by shorter overall survival and biochemical recurrence-free survival compared with those in the high-ALI group. Third, after adjustment for potential confounders, multivariable Cox regression and propensity score matching analyses showed that ALI remained independently associated with prognosis. Collectively, these results indicate that postoperative ALI may represent a practical and clinically relevant biomarker for risk assessment after radical prostatectomy.
ALI is a composite index calculated using BMI, serum albumin level, and NLR.23,24 Compared with single inflammatory or nutritional markers, ALI simultaneously reflects nutritional reserve, systemic inflammatory burden, and immune balance. Jafri et al first proposed ALI as a prognostic marker in metastatic non-small cell lung cancer, emphasizing its value as a simple index integrating body weight, albumin, and NLR to estimate systemic inflammation and host condition.25 Subsequent studies have extended its application to other malignancies. In patients with gastric cancer undergoing radical resection, low ALI has been associated with worse overall survival and cancer-specific survival and remained an independent prognostic factor after multivariable adjustment and propensity score matching.18 Similarly, recent studies in skin cancer and lung cancer have suggested that ALI may serve as a comprehensive indicator of inflammatory and nutritional status and may have prognostic value across different tumor types.16,26 Our findings extend this concept to prostate cancer after radical prostatectomy and indicate that postoperative ALI may provide prognostic information beyond conventional pathological variables.
The association between low ALI and poor outcomes may be explained by several biological mechanisms. A low ALI may result from decreased BMI, hypoalbuminemia, elevated NLR, or a combination of these factors.27 Low BMI and reduced albumin levels may indicate malnutrition, decreased physiological reserve, impaired immune function, and insufficient recovery capacity after surgery.28–30 Albumin is not only a marker of nutritional status but also a negative acute-phase reactant; therefore, hypoalbuminemia may reflect ongoing systemic inflammation.31 In contrast, elevated NLR reflects neutrophil predominance and relative lymphocyte depletion. Neutrophils may promote tumor progression by secreting cytokines, growth factors, proteases, and proangiogenic mediators, whereas lymphocytes play a central role in antitumor immune surveillance.8,32,33 Therefore, a low ALI may represent a systemic condition characterized by malnutrition, persistent inflammation, and impaired antitumor immunity, which may facilitate micrometastatic progression and biochemical recurrence after radical prostatectomy.
An important feature of the present study is that ALI was assessed approximately three months after surgery rather than during the immediate perioperative period. Immediate postoperative inflammatory responses may be strongly influenced by surgical trauma, anesthesia, blood loss, infection, and early wound healing. By selecting the first postoperative follow-up visit for ALI assessment about three months after surgery, our study attempted to capture a more stable host inflammatory and nutritional status during early postoperative recovery. This timing may be clinically relevant because patients are commonly reassessed at this stage for PSA monitoring, functional recovery, and decisions regarding additional treatment or intensified surveillance. Therefore, postoperative ALI may be easily incorporated into routine follow-up without additional cost or invasive procedures.
The results of propensity score matching further support the robustness of our findings. Because patients with low ALI had more unfavorable baseline features, including higher Gleason score, more advanced pathological T stage, and more frequent lymph node metastasis, confounding by disease severity was a potential concern. After matching for clinically relevant variables, low ALI remained significantly associated with worse overall survival and biochemical recurrence-free survival. Multivariable Cox regression analysis in the matched cohort further confirmed ALI as an independent prognostic factor. These findings suggest that the prognostic role of ALI is not merely a reflection of adverse pathological stage but may represent an additional dimension of host–tumor interaction.
This study has several limitations. First, because it was conducted retrospectively at a single institution, the possibility of selection bias could not be fully excluded, even though propensity score matching was applied. Second, the optimal ALI cut-off value was determined using the present cohort, and external validation in multicenter studies is required. Third, ALI was measured at only one postoperative time point; dynamic changes in ALI during follow-up may provide additional prognostic information. Finally, this study demonstrated an association between ALI and prognosis, but it cannot establish a causal relationship. Prospective multicenter studies are needed to validate these findings and determine whether ALI-guided follow-up or intervention strategies can improve clinical outcomes.
Conclusion
Postoperative ALI was significantly associated with clinicopathological aggressiveness and survival outcomes in patients with prostate cancer undergoing radical prostatectomy. Low ALI predicted shorter overall survival and biochemical recurrence-free survival and remained an independent prognostic factor after multivariable adjustment and propensity score matching. As a simple, inexpensive, and routinely available biomarker integrating nutritional and inflammatory status, postoperative ALI may be useful for postoperative risk stratification and individualized follow-up planning. However, prospective multicenter studies and external validation are required before postoperative ALI can be incorporated into routine clinical practice.
Acknowledgment
This article used DeepSeek, version 4, for language improvement.
Funding Statement
This study received grants from the Chengdu Medical Scientific Research Project (No. 2023084).
Abbreviations
ALI, advanced lung cancer inflammation index; AUC, area under the curve; BMI, body mass index; CI, confidence interval; HR hazard ratio; IQR, interquartile range; NLR, neutrophil-to-lymphocyte ratio; PSA, prostate-specific antigen; ROC, receiver operating characteristic; SII, systemic immune-inflammation index.
Data Sharing Statement
The data supporting the results of this study were included within the article, and additional reasonable requests are available from the corresponding author of Fu Zhou.
Ethics Approval
The study complied with the principles of the Declaration of Helsinki and was approved by the Ethics Committee of The First Affiliated Hospital of Chengdu Medical College (No. 2238CDM321).
Author Contributions
GX and RK: Data curation, Formal analysis, Investigation, Methodology, Writing-original draft. DC: Methodology, Data curation, Investigation, Writing-original draft, Supervision, Software. FZ: Resources, Supervision, Investigation, Validation, Data analysis, Writing-original draft. All authors reviewed the manuscript. All authors gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.
Disclosure
The authors declare no conflict of interest.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data supporting the results of this study were included within the article, and additional reasonable requests are available from the corresponding author of Fu Zhou.