Distribution of metastatic sites in patients with prostate cancer: A population‐based analysis

Metastatic Burden in Hormone-Naive Prostate Cancer: A Tale of Two Subgroups

BackgroundWe aimed to evaluate the prognostic value of site-specific metastases in patients with metastatic bladder cancer and analyze the roles that surgeries play in the treatment of this malignancy.Materials and methodsA population-based retrospective study using Surveillance, Epidemiology and End Results dataset was performed and metastatic bladder cancer patients were classified according to the sites of metastases (bone, brain, liver, lung and distant lymph nodes). Kaplan–Meier analysis with log-rank test was used for survival comparisons. Multivariate Cox regression model was employed to analyze the effect of distant metastatic sites on overall survival (OS) and cancer-specific survival (CSS).ResultsA total of 1862 patients with metastatic bladder cancer from 2010 to 2014 were identified. Bone, lung and distant lymph nodes were the most common metastatic sites. Patients with bone, brain, liver and lung involvement had worse OS and CSS compared to patients without the corresponding sites of metastases. Multivariate analysis showed that bone, brain, liver and lung metastases were independent prognostic factors for both OS and CSS, while distant node metastasis was not. Moreover, patients with a single metastatic site had more favorable OS (p<0.001) and CSS (p<0.001) than patients with multisite metastases. Among single-site metastatic patients, distant nodes and liver metastases represented the best and the worst prognosis, respectively. Moreover, radical cystectomy was an independent predictor for better OS and CSS, while in patients with liver metastasis and multiple metastatic sites, RC did not bring benefits. Besides, in patients with a single metastatic site, metastasectomy seemed to be associated with favorable OS (p=0.042), especially for patients with age <65 years (p=0.006) and for muscle-invasive bladder cancer patients (p=0.031).ConclusionDistant metastatic sites have differential impact on survival outcomes in patients with metastatic bladder cancer. Surgeries, including radical cystectomy and metastasectomy, might still lead to survival benefits for highly selected patients.

e17109 Background: Endometrial carcinoma is the most common gynecology malignancies in the worldwide. The clinical outcome of endometrial carcinoma is excellent, with disease specific survival rate over 90% in early stages. However, the prognosis of metastatic endometrial carcinoma is poor and the pattern of distant metastases has not been well characterized. In the present study, we sought to assess the incidence and prognosis of different distant metastatic sites in endometrial carcinoma. Methods: Patients who were diagnosed with endometrial carcinoma between 2010 and 2015 were identified according to the following criteria in the Surveillance, Epidemiology, and End Results (SEER) database: (1) confirmed age and older than 18 years old; (2) enrolled patients should have confirmed distant visceral metastatic status information. Kaplan-Meier analysis and log-rank tests were used to estimate the overall survival (OS) between difference groups. Data were analyzed with GraphPad Prism (version 7.01, GraphPad Software, USA), and R (version 4.3.1, R Development Core Team). Results: A total of 73328 patients with endometrial carcinoma were included. Median age of diagnosis was 62 years and 80.3% of patients were white. 92.8% of patents have received surgery. 4.2% of patients (3053/73328) suffered at least one site of distant metastases. The most common metastasis site was lung (1331/73328, 1.82%), followed by distant lymph nodes (1191/72703, 1.6%), liver (661/73328, 0.9%), bone (475/73328, 0.65%) and brain (133/73328, 0.18%). Median OS was 15 months, 4 months, 7 months, 9 months and 8 months for pure distant lymph node, brain, bone, lung and liver metastases, respectively. Furthermore, metastatic sites showed significant impact on OS in univariate analysis. Multivariate analysis with COX proportional regression model showed that distant metastatic sites were independent prognostic factors of OS. Conclusions: Lung is the most common distant metastatic site of endometrial carcinoma. Patients with pure distant lymph node metastasis exhibited the best overall survival, while patients with brain metastases had worst clinical prognosis compared with other metastatic sites.

The bone represents the most common site of metastases in patients with prostate cancer (PCa). However, the proportion of men experiencing atypical metastatic sites, defined as the metastases localizing to sites other than bones or lymph nodes outside the pelvis or abdomen, is significant. For example, 10.6%, 10.2% and 9.1% of patients with metastatic PCa experience distant lymph nodes, liver, and thorax involvement, respectively. The knowledge of the distribution of metastatic sites can help provide physicians with better staging strategies, as well as follow-up protocols aimed at a prompt diagnosis of tumor recurrence after primary treatment. The involvement of atypical sites of metastases might also have a prognostic value, where individuals with visceral metastases experience shorter survival compared to their counterparts with exclusive bone involvement. Consequently, this parameter should be taken in account during the decision-making process in the treatment of PCa patients.

Efficacy of Enzalutamide plus Androgen Deprivation Therapy in Metastatic Hormone-Sensitive Prostate Cancer by Pattern of Metastatic Spread: ARCHES Post Hoc Analyses.

To determine the prognostic importance of the metastatic site in metastatic renal cell cancer (mRCC) patients in the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) intermediate-risk. Observational study. Department of Medical Oncology, Dr Abdurrahman Yurtaslan Oncology Training and Research Hospital, Ankara, Turkey, from January 2010 to November 2018. Records of 113 mRCC patients, determined to be in the intermediate-risk group according to IMDC criteria, were reviewed retrospectively. All patients used a tyrosine kinase inhibitor - sunitinib or pazopanib - for metastatic disease. Patients' records included age, gender, metastatic site, number of metastases and treatment regimen. The Kaplan-Meier method was used for survival analysis, and a Cox regression model was formed. The median age of the patients was 58 years (Q1 - Q3: 44 - 66 years) and 87.6% of the patients had ≥2 metastatic sites. The most common metastatic sites were the lung (51.3%), lymph nodes (26.5%), bone (26.5%) and brain (17.7%). Median overall survival (OS) was shorter in the patients with bone and brain metastasis than in those without (15.0 months vs. 21.0 months, p = .026 and 14.0 months vs. 21.0 months, p = .009, respectively). Multivariate analysis showed that brain and bone metastasis were independent prognostic risk factors (HR: 2.43, p = .017 and HR: 2.10, p = .042, respectively). Bone and brain metastasis had a negative effect on OS in IMDC intermediate-risk group mRCC patients. Key Words: Metastatic site, Brain metastasis, Bone metastasis, Renal cell carcinoma, Prognosis.

The Impact of Race and Age on Distribution of Metastases in Patients with Prostate Cancer.

Metastatic disease of prostate cancer (PCa) is currently incurable. Bone is the most common tissue site for prostate cancer metastasis and progression in bone is largely dictated by tumor-stromal interactions in the bone microenvironment. We showed previously that bone marrow neutrophils inhibit bone metastatic PCa growth, however metastatic PCa becomes resistant to neutrophil response and progresses within the bone compartment. It is unclear how these findings translate to a clinical setting. Further, the mechanisms associated with tumor resistance to neutrophil immune response remain unknown and presents a new avenue for therapeutic intervention. Thus, the goals of this study were: 1) to define the impact of metastatic PCa on neutrophil function throughout prostate cancer progression and 2) to determine the potential of neutrophils as predictive biomarkers of PCa disease progression. To do this, peripheral blood polymorphonuclear neutrophils (PMNs) were collected from 4 patient cohorts (localized PCa, metastatic hormone-sensitive PCa (mHSPC), metastatic castration-resistant (mCRPC) and healthy men) and PMN molecular and functional properties assessed, including: cancer cell cytotoxicity and cell surface markers. There was a significant decrease with disease progression in PMN expression of CD10, a marker for differentiation, while in tandem, there was an increase in pro-inflammatory marker, CD88 (complement receptor) in mCRPC men compared to mHSPC. PMNs from all disease stages were equally cytotoxic to human PCa cell lines (LNCaP, C42B, and PC3). However, second generation androgen deprivation therapy (ADT) suppressed patient PMN cytotoxicity against mCRPC cells (C42B, PC3). This suppression was due to androgen receptor (AR)-mediated regulation of the pleotropic and immune suppressant cytokine, transforming growth factor beta receptor I (TβRI). PMNs from mCRPC patients who received 2nd generation ADT, expressed significantly more TβRI than patients who only received 1st line ADT. Further, we found that PMNs in CRPC patient bone metastases express more TβRI than PMNs in matched liver metastases, which express little to no TβRI. Treatment of mouse bone marrow neutrophils with enzalutamide, increased neutrophil TβRI expression in a dose dependent manner and blocked cytotoxicity against PCa cells. Exogenous testosterone treatment in vivo, pharmacologic inhibition (using Repsox, a small molecule kinase inhibitor of TβRI) or genetic deletion (using conditional TβRI knockout mice) rescued enzalutamide-mediated neutrophil suppression and restored neutrophil cytotoxicity. These data collectively suggest that AR inhibition suppresses anti-tumor neutrophil responses via TβRI however, this study highlights the ability to leverage standard-care ADT to generate neutrophil anti-tumor responses against bone metastatic PCa. Citation Format: Leah M Cook. Deciphering the mechanisms of neutrophil immune response in bone metastatic prostate cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr IA020.

Metastatic extraskeletal myxoid chondrosarcoma presenting as a forehead mass

Metastases rather than primary tumors are responsible for the lion’s share of the morbidity and mortality arising from malignant disease. Patients with advanced breast or prostate cancers usually develop bone metastases and usually harbor the bulk of their tumor burden in the bone at the time of death. Although it is difficult to quantify the prevalence of bone metastases, natural history and autopsy studies give an indication of the scope of the problem. In breast cancer, the skeleton is the most common site for metastasis and first distant relapse, and median survival following detection is more than 20 mo (1). At their presentation with prostate cancer, 8% of white American males and 14% of African-American males have bone metastases (2), whereas the mean incidence of bone metastasis in an analysis of autopsy studies of prostate cancer is 70% (3). It is clear, therefore, that bone metastases are both a common manifestation in patients with breast and prostate cancer and often a prolonged one. Given these considerations and the fact that bone metastases are not usually clinically silent, their importance in the context of the overall suffering and management associated with these malignancies is evident. Clinically, the lesions behave somewhat differently in the two cancers, with pathological fractures being relatively more common in breast cancer and severe, often intractable pain a classic feature of metastases in patients with advanced prostate cancer (4). Spinal cord compression as a result of vertebral metastasis is perhaps the most devastating complication of skeletal involvement with hypercalcemia and leukoerythroblastic anemia being the commonest systemic sequelae.KeywordsBreast CancerProstate CancerBone MetastasisZoledronic AcidMetastatic Bone DiseaseThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Objective: To explore the distant metastatic characteristics of metastatic hormone-sensitive prostate cancer (mHSPC) and metastatic castration-resistant prostate cancer (mCRPC) based on prostate-specific membrane antigen (PSMA) PET-CT. Methods: This is a retrospective cohort study. Ultimately, data from 227 patients with metastatic prostate cancer who underwent PSMA PET-CT examinations at Xiangya Hospital, Central South University between March 2016 and May 2025 were retrospectively reviewed, including 117 mHSPC patients with an age of (68.8±7.6) years (range:53 to 89 years) and 110 mCRPC patients with an age of (69.4±7.5) years (range: 49 to 88 years). Clinical and pathological data, along with metastatic characteristics identified via PSMA PET-CT, were collected and compared. Intergroup comparisons were performed using χ2 tests. Results: The incidence rates of lymph node metastasis, bone metastasis, and visceral metastasis in the mHSPC group were 71.8% (84/117), 89.7% (105/117), and 11.1% (13/117), respectively, while those in the mCRPC group were 52.7% (58/110), 91.8% (101/110), and 15.5% (17/110), respectively. The incidence of lymph node metastasis in the mHSPC group was significantly higher than that in the mCRPC group (χ2=8.800,P=0.003). Among patients with bone metastasis, the rates of osteoblastic metastasis, osteolytic metastasis, and mixed metastasis in the mHSPC group were 76.2% (80/105), 8.6% (9/105), and 15.2% (16/105), respectively, while the corresponding rates in the mCRPC group were 74.3% (75/101), 7.3% (8/101), and 16.4% (18/101), respectively, all indicating a relatively high probability of osteolytic and mixed bone metastases (χ2=0.260,P=0.878). Among patients with mHSPC and mCRPC who tested positive for visceral metastasis, lung metastasis (9/13 and 8/17) and liver metastasis (4/13 and 9/17) were the most common sites of metastasis, but there was no significant difference in the composition of visceral metastasis between the two groups (χ2=0.933,P=0.564). In this study, among 20 patients who progressed from mHSPC to mCRPC, 35.0% (7/20) had persistent or progressive activity at the original metastatic site, 35.0% (7/20) developed new metastatic lesions, and 30.0% (6/20) showed inhibitory changes in the original metastatic lesions. Among patients with imaging progression, 1/14 of patients with osteoblastic metastatic lesions at the mHSPC stage exhibited osteolytic changes upon progression to mCRPC. Conclusion: Compared with the mCRPC group, the mHSPC group has a higher lymph node metastasis rate,and both groups have common rates of osteolytic and mixed bone metastases and visceral metastasis.

Introduction/Objective Accurate immunohistochemical identification of prostatic origin in metastatic tumors is essential for guiding treatment decisions. While PSA remains the most widely used marker, PSAP and PSMA are increasingly employed in challenging or dedifferentiated cases. This study evaluates the expression patterns of these markers across various metastatic sites to inform their diagnostic utility. Methods/Case Report A retrospective analysis of 22 metastatic prostate cancer cases diagnosed at our institution from 2021 to 2024 was performed. Formalin-fixed, paraffin-embedded tissue sections from metastatic sites — including bone, liver, lung, lymph node, pleura, skin, and bladder — were subjected to immunohistochemical staining for PSA, PSAP, and PSMA. Each was scored using an immunoreactive score (IRS): 0 (negative), 1 (1–10%), 2 (11–50%), 3 (51–80%), and 4 (&amp;gt;80%). Marker distributions were visualized using box plots. Pearson correlation analysis assessed inter-marker relationships, and site-specific trends were qualitatively evaluated. Results All three markers were expressed across all metastatic sites. Bone and liver metastases demonstrated diffuse (IRS 2–4) expression of PSA, PSAP, and PSMA in over 80% of cases. Lung and lymph node sites exhibited more variability, with one lymph node case negative for PSMA and one lung case showing low PSMA expression (IRS 1). Bladder, pleura, and skin cases (n = 1 each) showed uniformly high expression across all markers. PSA and PSAP demonstrated more consistent expression than PSMA. Correlation analysis revealed moderate co-expression between PSA and PSAP (r = 0.49) and between PSAP and PSMA (r = 0.50), while PSA and PSMA showed a weaker correlation (r = 0.25). Conclusion PSA, PSAP, and PSMA are robust markers across metastatic prostate cancer sites. While all three are diagnostically valuable, PSAP and PSA showed the most consistent, site-independent expression. PSMA adds complementary value, particularly in cases with discordant staining or in sites such as lymph nodes and lungs, where expression may be more variable. These findings support the routine use of all three markers in immunohistochemical panels to improve diagnostic accuracy in metastatic prostate cancer.

Previous studies suggested that bone metastasis has a significant effect on the time of progression to metastatic castration-resistant prostate cancer (CRPC) for newly diagnosed de novo bone metastatic hormone-sensitive prostate cancer (mHSPC). Nevertheless, the effect of different bone metastasis sites was not fully evaluated. This study aimed to develop and validate a novel bone metastatic risk model. We enrolled 122 patients who were newly diagnosed with de novo bone metastatic prostate cancer following primary androgen deprivation based therapy at our institution from January 2008 to June 2021. The metastatic bone sites were classified into six sites: skull; cervical, thoracic, and lumbar vertebrae; chest (ribs and sternum); pelvis; upper limbs; and lower limbs. We calculated the bone metastatic score (BMS) for each site: 0 points were assigned for non-metastasis and 1 point was assigned for metastasis. The X-tile was adopted to acquire optimal cutoff points of BMS. We defined high-risk group (HRG) as BMS ≥ 3 and low-risk group (LRG) as BMS < 3. The new bone risk stratification was validated by calculating the area under the receiver operating characteristic curve (AUC). Subsequently, the relevant clinical prognostic variables were added to construct a predictive nomogram for predicting CRPC. The median patient age was 73 years. Most patients had Gleason score ≤8 (93 cases, 76.2%). The median follow-up duration was 11.5 months (range: 2-92 months). Eighty-six patients progressed to CRPC during the follow-up. The most common bone metastatic site was the pelvis (90.2%). The median BMS was 4. Seventy-six patients had HRG, while forty-six had LRG. The 1-, 2-, and 3-year AUCs for H/LRG were 0.620, 0.754, and 0.793, respectively. The HRG was associated with earlier time to CRPC. A nomogram based on four parameters (Gleason score, H/LRG, prostate-specific antigen [PSA] nadir, and time to PSA nadir) was developed to predict CRPC. Internal validation using bootstrapping demonstrated good accuracy for predicting the CRPC (C-index: 0.727). The calibration analysis demonstrated that the model performed well. We established a novel H/LRG risk model for newly diagnosed de novo bone metastatic prostate cancer, which provided evidence to support clinical decision-making.

Urothelial carcinoma of the urinary bladder (UCUB) is the most common malignancy of the urinary tract. We examined the distribution of site-specific metastases in patients with UCUB according to age and we assessed contemporary recommendations proposed by guidelines with regard to distant metastases. Patients with metastatic UCUB (mUCUB) were abstracted from the Nationwide Inpatient Sample (1998-2007). Age was stratified into quartiles: ≤63, 64-72, 73-79 and ≥80 years. Cochran-Armitage trend test and multivariable logistic regression analysis tested the relationship between age and the rate of metastases. Finally, we identified patients at high risk of brain or bone metastases. Within 7543 patients with mUCUB, 25%, 24%, 23%, 19%, 18% and 3% had lymph node, bone, urinary, lung and liver metastases, respectively. Overall, the rate of concomitant metastases was 29%. The rate of multiple metastatic sites decreased with increasing age (p < 0.001). This was confirmed in patients with lung, bone, liver, urinary system and brain metastases (all p ≤ 0.04). The rate of bone metastases was 15.0% in patients with exclusive abdominal metastases and 40.0% in patients with abdominal, thoracic and brain metastases. The rate of brain metastases was 1% in patients with exclusive abdominal metastases and 7% in patients with thoracic and bone metastases. Our findings are limited by the retrospective nature of the analyses. We report a higher number of concomitant metastatic sites in young UCUB patients. Bone metastases are frequent in all patient groups, whereas brain metastases are common in UCUB patients with thoracic and/or bone metastases.

Despite surgical treatment, chemotherapy, and/or radiotherapy, the vast majority of patients with anaplastic thyroid carcinoma (ATC) have a dismal prognosis. Better knowledge of the frequency of metastases to different sites might help us to perform the appropriate diagnostic tests before treatment and during the course of the disease. The aim of this study was to determine the frequency of metastases from ATC in different sites as found at autopsy. Altogether, 205 patients were treated for ATC at our institute during the years 1972-2008. Autopsy was performed in 45 cases (30 females, 15 males; median age 66 years). The relative frequencies of metastases in different sites were analyzed using descriptive statistics. Altogether, 41 cases (91%) had metastases at autopsy. The most common sites of metastases were the lungs (78%), intrathoracic lymph nodes (58%), neck lymph nodes (51%), pleura (29%), adrenal glands (24%), liver (20%), brain (18%), heart (18%), and retroperitoneal lymph nodes (18%). Less common sites of distant metastases were the pericardium (13%), bones (13%), kidneys (13%), mesentery or peritoneum (13%), skin (9%), pancreas (4%), stomach (4%), diaphragm (4%), pituitary gland (2%), ovary (2%), jejunum (2%), axillary lymph nodes (2%), and gingival mucosa (2%). Both distant and regional metastases were present in 23 cases, while only distant metastases were present in 18 cases. An extensive local infiltration of the primary tumor was found in 76% of the cases. The total number of the involved organs and lymph node basins were 123 and 58, respectively. The mean number of metastatic sites was 4.02±2.75. Lung metastases were present in 34 of 38 (89%) of our patients who had distant metastases found at autopsy. Of these 34 patients, 27 were known to have lung metastases when they were alive. Two or more metastatic sites were found at autopsy in 84% of cases. The most common metastatic sites are lungs, followed by the intrathoracic and neck lymph nodes.