Construction and validation of online nomograms for the detection and prognosis of prostate adenocarcinoma with bone metastases

Advanced PA is dominated by BM, which are usually osteogenic lesions, causing structurally disrupted and unstable osteogenic changes25. The pathogenesis of prostate cancer bone metastasis is now thought 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, PA affected approximately 1.41 million men worldwide, accounting for 30.7% of all cancers diagnosed1. The most common location of distant PA metastases is to bone. The incidence of BM has been reported to be around 3% to 10% in patients initially diagnosed with OA in developed countries, while it can be as high as 27% in developing countries.26.27. This study found that the probability of BM in patients with PA was 3.1% (4,147/132,601), which is comparable to results from previous research. 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 only BM have a better prognosis than those with multiple sites. However, until patients have MB, their OS will decline rapidly, with 1- and 5-year survival rates of 47% and 3%, respectively.12. Patients with BM are often incurable with standard treatments (surgery, radiotherapy, and chemotherapy) and may experience a succession of skeletal-related events that diminish their quality of life.23. Therefore, we need to discover the effective risk and prognostic factors for BM in patients with PA for early diagnosis, to facilitate early prevention, and to assess the prognosis of BM in patients with PA. In this study, we constructed a diagnostic nomogram to predict MB in newly diagnosed PA patients and a prognostic nomogram for MB patients. By obtaining data on several key variables accessible on the nomogram, diagnostic and prognostic scores can be calculated, facilitating further clinical assessment and management.

Based on the seed-soil theory, PA diffuses into bone via the hematogenous route, and the bone microenvironment provides a particularly fertile environment for tumor cell proliferation and progression.28. PA cells have a subtle tendency to bone, and in an autopsy study, 90.1% of people who died from PA were diagnosed with metastatic bone cancer.29. However, bone metastasis from PA is a complicated progression and its exact mechanisms remain unknown. Bone-derived chemokines have been shown to function as chemoattractants for circulating PA cells, which upon arriving in bone are exposed to elements of the bone microenvironment that promote the establishment of metastases. Release of growth factors by tumor cells can directly promote osteoblast activity, leading to elevation of NF-activating receptor(kappa)Expression of B ligands (RANK). This overproduction of RANK ligand then induces a vicious circle of tumor growth and bone destruction by promoting the formation, function and survival of osteoclasts, which leads to excessive bone reabsorption and the release of bone matrix growth factors, which which can perpetuate the tumor. activity30.31. Additionally, with respect to clinical characteristics, research has found that BM in PA patients has a substantial correlation with PSA.32T-stage33and ISUP groups34. When PSA 20 ng/ml, the probability of bone metastases was more than 70%32. According to the European Urological, the risk of newly diagnosed AP patients was stratified into low risk (Gleason score (the )7, T1–T3 and PSA (the )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 to guide treatment decisions. The scoring system has been extensively researched, which has influenced its use in clinical practice. Subsequently, ISUP convened several consensuses to change both the grading standards and the way grades were presented in accordance with the Gleason score.36.37. Ultimately, to more effectively communicate the prognostic importance of PA, the ISUP consensus conference established a five-level scoring system, with levels 1-5 based on Gleason scores. (the )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 classification, N grade, brain metastases, liver metastases and lung metastases. The association between PSA value, T grade and ISUP grade and BM in PA patients has been confirmed in previous research. Surprisingly, however, T3-stage PA patients had the lowest risk of BM. We hypothesize that it may be related to the PSA value; when PSA

Currently, there is no cure for AP patients with BM, and SER is widespread; therefore, early detection of BM is crucial for patients to receive proper treatment to reduce the inconvenience and pain caused by various complications, enabling them to live with tumors for an extended period. To date, the majority of research has focused only on independent risk variables, and only one realistic model has been developed to predict the risk of BM in AP patients.38. In the previous model, practitioners needed 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 DCA, which may improve the current state. risk assessment and enable more accurate personalized clinical decision-making.

Most AP patients with BM did not have overt clinical symptoms in the early stages, and some individuals might not be identified until they present with impaired limb movement, bone pain, and limb pain. pathological fractures.39. The spine is the most typical location of BM, which can induce spinal discomfort, radiating pain, limb paralysis, and even paraplegia in extreme cases. Patients with extensive BM may also present with systemic symptoms, including lassitude, emaciation, anemia, and possibly multi-organ system failure. Additionally, hypercalcemia can affect many physiological systems, such as the neurological system, cardiovascular system, digestive system, urinary system, and even tumor cachexia. Although SREs are commonly used to describe specific symptoms of BM in current clinical practice, the concept of SRE originated from early clinical studies of bone-modifying drugs and has only been used as a clinical endpoint. to assess the effectiveness of drug therapy, including four types of pathologic fractures, spinal cord compression, bone surgery, and radiotherapy to bone40. Although there is a correlation between SREs and clinical symptoms, the subjective assessment procedure and the fact that it can be changed in the short term makes it unsuitable as an endpoint in clinical trials. Therefore, OS was chosen as the outcome measure for BM patients. At present, the main goals of treatment of PA patients with BM are to prevent and minimize the incidence of ERS, to relieve pain caused by BM, and to improve the quality of life of patients. Our research found that OS in PA patients was associated with five factors: age, marital status, PSA value, ISUP group, and liver metastases, rather than treatment methods such as surgery. , chemotherapy or radiotherapy. Additionally, using ROC curves, calibration curves, and DCA validation, it has been shown that the nogram can provide new opportunities for individualized assessment and clinical decision-making. This finding 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 higher OS than grade 2, which is unexpected. This may be because both have comparable Gleason scores and largely intact prostate tissue. Nevertheless, ISUP grade 3 had higher OS than grade 2, which may be because both grades have comparable Gleason scores and partially intact prostate tissue. Additionally, Hu et al.42 established the prognostic nomogram of AP patients with BM using six genetic signatures, which is more expensive and cumbersome than our model.

Our study has a significant advantage over previous similar studies. First, the subject of our study is not consistent with previous research. The majority of previous research has focused on the risk and prognosis of AP patients with BM38,39,41. However, since PA is a heterogeneous disease with diverse biological traits for different disease subtypes, we chose PA as the subject of study. Second, our study had a considerable sample size, and to our knowledge was the largest sample size focusing on AP patients with BM. Third, we have developed two practical web tools to help clinicians in their daily work by enabling more efficient and easier prediction of risk and prognosis of BM in AP patients.

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