Metastasis is a critical stage of prostate cancer, seriously impairing patient prognosis. In China, the percentage of newly diagnosed prostate cancer patients with metastatic prostate cancer is significantly higher at 51.4–54%, compared to only 7–8% in Europe and the United States16,17. Prostate cancer frequently spreads to the bones, with a bone metastasis rate of up to 90% in patients with metastatic prostate cancer1,6–8. Individuals with bone metastasis from prostate cancer experience a notable decline in their quality of life, and the mortality rate among these patients is considerably higher than that among those without bone metastasis3. The primary cause of death in such cases is predominantly attributed to severe harm caused by the spread of cancer to the bones2–4. In recent years, an increasing number of patients with prostate cancer have exhibited symptoms of bone metastasis upon visiting the hospital. Of the 208 individuals newly diagnosed with prostate cancer in this study, 41.3% (86 patients) exhibited bone metastasis. Hence, the timely identification and treatment of bone spread in these individuals can significantly enhance their prognosis and quality of life.
The occurrence and death rates of prostate cancer are influenced by age18,19, Nevertheless, there has been a debate regarding the connection between age and bone metastasis in individuals diagnosed with prostate cancer6,20. Some studies suggest that age is associated with bone metastasis in prostate cancer but is not an independent risk factor21,22. However, our study found no notable disparity in age between recently diagnosed prostate cancer patients with and without bone metastasis on univariate analysis. The inconsistent conclusions of the above studies may have resulted from differences in sample sizes, regions, and ethnicities.
PSAD can differentiate between benign prostatic hyperplasia and prostate cancer. Furthermore, it can assess the clinical extent of prostate cancer and exhibit a strong association with bone metastasis in individuals recently diagnosed with prostate cancer22–25. Similar to the findings of the aforementioned studies, this study revealed that PSAD was associated with bone metastasis in patients with prostate cancer. Moreover, multivariate regression analysis demonstrated that PSAD independently posed a risk for bone metastasis of prostate cancer (AUC: 0.822, 95%CI: 0.602–0.778, P < 0.001), with a sensitivity of 75.9%, specificity of 77.3%, and corresponding cutoff value of 1.693. This finding suggests that PSAD had a specific predictive value for bone metastasis in individuals initially diagnosed with prostate cancer. This study included a greater number of variables that were not influenced by external factors, thereby enhancing the predictive efficacy of PSAD.
In the last few years, there has been an increasing body of evidence from clinical and experimental data that CysC might play a role in the development of various diseases, such as cancer26–30. CysC controls the expression of androgen receptors in prostate cancer through the MAPK/ERK 1/2 signalling pathway, consequently hindering the invasion of tumour cells. The MAPK/ERK 1/2 signalling pathway is linked to tumour advancement, reliance on androgens, and unfavourable prognosis31. Serum CysC may have a major impact on the development of bone metastasis in individuals diagnosed with prostate cancer. This is achieved by suppressing the function of cysteine proteases and their natural ability to control cell growth, specialisation, movement, and bone restructuring. Consequently, elevated serum CysC levels in patients with prostate cancer may be strongly correlated with the severity of the disease and its invasive nature. In this study, CysC and other potentially relevant risk factors were analysed using univariate and multivariate analyses. These findings indicated that CysC exhibited a significant correlation with bone metastasis in individuals recently diagnosed with prostate cancer and was independently identified as a risk factor for bone metastasis in patients newly diagnosed with prostate cancer. CysC had an AUC of 0.690 (95%CI: 0.753–0.892, P < 0.001), sensitivity and specificity of 69.0% and 63.6%, respectively, and the corresponding cutoff value of 0.945. Using CysC to predict prostate cancer bone metastasis, we recommend incorporating additional indicators to exclude confounders. This suggestion stems from the susceptibility of CysC levels to intervention26,32–36.
SII integrates the lymphocyte, neutrophil, and platelet counts (SII = P × N/L). The spread of prostate cancer to the bones is associated with inflammatory reactions. Additionally, the SII has been identified as a separate factor that increases the risk of bone metastasis in individuals diagnosed with prostate cancer37,38. Moreover, as a marker of inflammation, the influence of LMR on the prognosis of urinary system tumours has been reported for many years 39,40. Under the action of certain cytokines (such as CSF-1 or IL-10) secreted by tumour cells, M2-like macrophages proliferate and promote tumour invasion and metastasis via angiogenesis39,40. Herein, univariate analysis revealed a correlation between bone metastasis in patients initially diagnosed with prostate cancer and both SII and LMR (P < 0.05). In the multivariate logistic regression analysis, SII emerged as a separate risk factor for bone metastasis in individuals initially diagnosed with prostate cancer. The AUC for SII was 0.716 (95%CI: 0.630–0.802, P < 0.001), with a sensitivity of 62.1%, specificity of 72.7%, and a cutoff value of 507.187. However, LMR was not an independent risk factor (P > 0.05).
There is growing evidence regarding the poor prognosis of tumour patients with elevated FIB levels, including those with prostate cancer41–43. In a study by Xie et al., FIB increased the risk of bone metastasis in patients newly diagnosed with prostate cancer, and the cutoff value for FIB was 3.08 g/l, with a sensitivity of 0.684 and a specificity of 0.760 (AUC, 0.739; 95%CI: 0.644–0.833, P < 0.001)44. In this study, the results of FIB analysis included in our study are consistent with those of the abovementioned studies. The AUC (95%CI: 0.623–0.797, P < 0.001) was 0.710, with a sensitivity of 65.5%, specificity of 70.5%, and cutoff value of 3.790.
If the GLS is > 7, it is crucial to consider the potential for bone metastasis in individuals diagnosed with prostate cancer, as stated in the European Association of Urology45,46. According to the guidelines of the American Urological Association, if GLS exceeds 8, individuals diagnosed with prostate cancer have a higher probability of experiencing bone metastasis46. In order to determine the significance of the GLS in predicting bone metastasis in patients recently diagnosed with prostate cancer, we transformed the quantitative data of the GLS into qualitative data for statistical analysis. The grading standard was: GLS ≤ 6 points, defined as GLS ① group; GLS = 7 points, defined as GLS ② group; and GLS ≥ 8 points, defined as GLS ③ group. The findings demonstrated a significant correlation between bone metastasis and GLS in individuals initially diagnosed with prostate cancer, with a GLS threshold of 8. The AUC value for the ROC curve was 0.731 (95%CI: 0.649–0.812; P < 0.001), indicating a sensitivity of 75.9% and a specificity of 65.9%.
Lymph node metastasis is closely associated with bone metastasis in patients initially diagnosed with prostate cancer47. Guo et al. obtained the clinical information of 249331 individuals diagnosed with prostate cancer from the SEER database, and statistical analysis revealed that lymph node metastasis was an independent risk factor for bone metastasis in patients initially diagnosed with prostate cancer48. In the present study, pelvic lymph node metastasis was significantly associated with bone metastasis in patients newly diagnosed with prostate cancer. It was an independent risk factor, as evidenced by an AUC of 0.694 (95%CI: 0.605–0.783; P < 0.001), with a sensitivity and specificity of 63.8% and 75.0%, respectively.
This nomogram model was constructed according to the weight of the influence coefficient of each risk factor, and the internal influence between the research factors was excluded through the interaction between the research factors and the multicollinearity test. External validation was carried out using the validation group data. After excluding the interaction between different factors and multicollinearity, our constructed nomogram prediction model accurately assessed the risk of bone metastasis with a high level of sensitivity (81.0%) and specificity (87.5%), as indicated by the findings of both univariate and multivariate logistic regression analyses. This study validated and incorporated new reliable indicators, namely, PSAD, CysC, and SII, in combination with several other related factors. In clinical practice, it would be convenient to obtain the variable indicators of the aforementioned model. Clinicians can easily comprehend and apply this nomogram, thereby enhancing their ability to assess the risk of bone metastasis in patients with newly diagnosed prostate cancer, especially under constrained conditions in actual clinical practice. The nomogram’s image was intuitive and illustrative, while the prediction results were particularly objective and reliable.
The primary objective of this study was to assess the risk of bone metastases in patients newly diagnosed with prostate cancer. The study is currently limited by its single-centre sample size; however, future efforts will involve collaboration with multiple centres to expand the sample size and incorporate additional research variables, including the clinical stage of patients diagnosed for the first time. Notably, our study introduced three novel variables—SII, CysC level, and PSAD—that have not been previously explored in this area. Our aim was to encourage more researchers to investigate and validate the risk factors associated with bone metastasis in patients newly diagnosed with prostate cancer and establish a more precise and reliable predictive model. Ultimately, this will enhance the diagnostic capabilities of frontline medical personnel in regions with limited healthcare resources, aiding in the early detection of prostate cancer bone metastasis.