Construction and validation of web-based nomograms for detection and prognosis in prostate adenocarcinoma with bone metastases

Advanced AP is dominated by BM, which are generally osteogenic lesions, causing structurally altered and unstable osteogenic changes.25. The pathogenesis of bone metastases from prostate cancer is now believed to include two main mechanisms: metastasis to the spine via Baston’s spinal venous plexus and Paget’s seed and soil theory; however, the specific mode of action is still under investigation. In 2020, AP affected approximately 1.41 million men worldwide, representing 30.7% of all cancers diagnosed1. The most prevalent location of distant metastases from PA is bone. The incidence of BM was reported to be around 3% to 10% in patients who were initially diagnosed with PsA in developed countries, while it could reach 27% in developing countries.26.27. This study found that the probability of MO in patients with AP was 3.1% (4147/132601), which is comparable with the results of previous investigations. Since the early symptoms of PA are similar to those of benign prostatic hyperplasia, many people have BM when they are first diagnosed. Patients with OM alone have a better prognosis than those with multiple sites. However, until patients have BM, their OS will decline rapidly, with 1-year and 5-year survival rates of 47% and 3%, respectively.12. BM patients often cannot be treated with standard treatments (surgery, radiation, and chemotherapy) and may experience a succession of skeletal-related events that decrease their quality of life.23. Therefore, we need to discover the effective risk and prognostic factors for MB in PsA patients for early diagnosis, to facilitate early prevention, and to assess the prognosis of MB in PsA patients. In this study, we constructed a diagnostic nomogram to predict BM in newly diagnosed PA patients and a prognostic nomogram for BM patients. By obtaining data on several key variables accessible on the nomogram, scores related to diagnosis and prognosis can be calculated, facilitating further clinical evaluation and management.

Based on the seed and soil theory, PA spreads to bone hematogenously, and the bone microenvironment provides a particularly fertile environment for tumor cell proliferation and progression.28. PA cells have a subtle tendency to form bone, and in one autopsy study, 90.1% of people who died of PA were diagnosed with metastatic bone cancer.29. However, bone metastasis from PA is a complicated progression and its exact mechanisms are still unknown. Bone-derived chemokines have been shown to function as chemoattractants for circulating PA cells which, upon arrival in bone, are exposed to elements within the bone microenvironment that promote the establishment of metastases. The release of growth factors by tumor cells can directly promote the activity of osteoblasts, leading to an increase in the receptor activator of NF-\(\kappa \)Expression of B ligands (RANK). This overproduction of RANK ligand then mediates a vicious cycle of tumor growth and bone destruction by promoting osteoclast formation, function, and survival, resulting in excessive bone resorption and the release of growth factors from the bone matrix, which which can perpetuate the tumor. exercise30.31. Furthermore, in terms of clinical features, the investigation found that OM in PA patients had a substantial correlation with PSA.32T-stage33and ISUP groups3. 4. When PSA < 10 ng/ml, la frecuencia de metástasis óseas en pacientes con AP se encontró cercana a cero; cuando PSA > 20 ng/mL, the probability of bone metastases was reported to be greater than 70%32. According to the European Urological, the risk of newly diagnosed PsA patients was stratified into low risk (Gleason score \(\ you \)7, T1-T3 and PSA <10 ng/ml, considering low-risk T1 patients regardless of the PSA value), intermediate risk (Gleason score \(\ you \)7, T2/T3 and PSA >10 ng/mL) or high risk (Gleason score >7)35. The Gleason score has been used for half a century to estimate the prognosis of patients with PA and guide treatment decisions. The scoring system has been the subject of extensive research, which has influenced its use in clinical practice. Subsequently, ISUP convened several consensuses to modify both the grading standards and the way grades were presented according to the Gleason score.36.37. Ultimately, to more effectively communicate the prognostic significance of PA, the ISUP Consensus Conference established a five-grade grading system, with grades 1 through 5 based on Gleason scores. \(\ you \)6, \(3+4=7, 4+3=7, 8\), and 9–10, respectively. In this study, we used clinical data from the SEER database for analysis to identify eight predictors of BM in PA patients, namely age, PSA, T-grade, N-grade, brain metastases, liver metastases, and lung metastases. The association between PSA value, T grade and ISUP grade and OM in patients with PsA has been confirmed in previous investigations. Surprisingly, however, patients with stage T3 PA had the lowest risk of BM. We hypothesize that it may be related to the PSA value; when PSA <10 ng/mL, patients with stage T1-T3 belong to the low-risk group overall. Meanwhile, our research revealed that older people, stage N1, brain metastases, liver metastases, and lung metastases were more likely to develop BM. We speculate that this is due to the weakened immunity of elderly patients, making them susceptible to BM. Furthermore, we found that lymph nodes, brain metastasis, liver metastasis, and lung metastasis are risk factors for synchronous BM.

Currently, there is no curative therapy for PA patients with BM, and SERs are highly prevalent; therefore, early detection of BM is crucial for patients to receive proper treatment to reduce discomfort and pain caused by various complications, allowing them to live with tumors for an extended period of time. To date, most research has focused only on independent risk variables and only one realistic model has been developed to predict the risk of BM in PA patients.38. In the previous model, practitioners were required to accurately estimate prostate volume to predict BM, which was impractical for treatment. To address this shortcoming, we developed a new web-based nomogram based on eight independent predictors and demonstrated excellent performance with ROC curves, calibration curves, and DCAs, which can improve the current state of risk assessment and enable better decision-making. more accurate personalized clinical decisions.

Most patients with AP and BM did not exhibit overt clinical symptoms in the early stages, and some individuals may not be identified until they present with limb movement problems, bone pain, and pathologic fractures.39. The spine is the most typical location for BM, which can induce spinal discomfort, radiating pain, limb paralysis, and even paraplegia in extreme cases. Patients with extensive BM may also have systemic symptoms, including fatigue, wasting, anemia, and possibly multi-organ failure. In addition, hypercalcemia can affect numerous physiological systems, such as the neurological system, the cardiovascular system, the digestive system, the urinary system, and even tumor cachexia. Although SREs are commonly used to describe the specific symptoms of BM in current clinical practice, the SRE concept originated in early clinical studies of bone-modifying drugs and was only used as a clinical endpoint to assess the efficacy of drug therapy, including four types of pathologic fractures, spinal cord compression, bone surgery, and bone radiation therapy40. Although there is a correlation between SRE and clinical symptoms, the subjective assessment procedure and the fact that it may be altered in the short term make it unsuitable as an end point in clinical trials. Therefore, OS was chosen as the outcome measure for patients with BM. Currently, the main goals of treating PsA patients with BM are to prevent and minimize the incidence of SRE, relieve pain caused by BM, and improve the quality of life of patients. Our investigation found that OS in patients with AP was associated with five factors: age, marital status, PSA value, ISUP group, and liver metastases, rather than treatment methods such as surgery, chemotherapy, or radiation therapy. Furthermore, using ROC curves, calibration curves, and DCA validation, it was shown that the nogram can provide new opportunities for individualized assessment and clinical decision making. This conclusion is comparable to the metastatic PA model developed by Jiang et al.41. It appears that younger, married individuals with lower PSA levels, lower ISUP grades, and no liver metastases achieved better OS. However, ISUP grade 3 had a higher OS than grade 2, which is unexpected. This may be because they both have comparable Gleason scores and largely intact prostate tissue. However, ISUP grade 3 had a higher OS than grade 2, which may be due to the fact that both grades have comparable Gleason scores and partially intact prostate tissue. Furthermore, Hu et al.42 established the prognostic nomogram of PA patients with BM using six gene signatures, which is more expensive and cumbersome than our model.

Our study has a significant advantage compared to previous similar studies. First, the topic of our study is not made up of previous research. Most of the previous research has focused on the risk and prognosis of patients with PA and BM.38,39,41. However, since PA is a heterogeneous disease with various biological traits for different pathological subtypes, we selected PA as the subject of study. Second, our study had a sizable sample size and, to the best of our knowledge, was the largest sample size that focused on PsA patients with BM. Third, we developed two practical web-based tools to help clinicians in their daily work by enabling more efficient and easier prediction of BM risk and prognosis in PA patients.

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