Metastatic Prostate Carcinoma Research Articles

Expression of TRPS1 in Metastatic Tumors of the Skin: An Immunohistochemical Study of 72 Cases

TRPS1 (Tricho-rhino-phalangeal syndrome 1) is a GATA transcriptional activator gene encoding for a protein used as a sensitive immunohistochemical marker of breast carcinomas. In dermatopathology, TRPS1 is used as a marker of mammary and extramammary Paget’s disease and is also expressed by a variety of primary cutaneous tumors, mostly of adnexal origin. So far, very limited data exist on the expression of TRPS1 in metastatic skin tumors. We studied the immunohistochemical expression of TRPS1 in 72 cutaneous metastatic tumors from the breast (n: 19) and other origins (n: 53) in order to assess its diagnostic usefulness. The intensity of TRPS1 immunostaining was expressed as a histoscore: the product of the percentage of positive cells (scored semi-quantitatively 0–4) and the staining intensity (scored 0–3). In normal skin, nuclear TRPS1 expression was predominantly observed in cells of adnexal structures (pilosebaceous follicles and sweat glands). Eighteen (18/19, 94.7%) metastatic breast carcinomas showed diffuse and strong TRPS1 positivity (histoscore 12). Lower reactivity was found in some other metastases, including from the lung (11/22), the female genital tract (3/4), and the kidney (2/4), whereas most (20/22) metastases from the digestive system and peritoneum, along with a case of metastatic prostate carcinoma, were negative. These results suggest that a high histoscore for TRPS1 is in favor of the mammary origin of metastatic cutaneous carcinoma. Although TRPS1 is not absolutely specific or sensitive to a particular primary, we consider that it can be added to a panel of other markers when investigating the origin of a cutaneous metastasis, namely when this is the first manifestation of the neoplastic disease.

Pure Squamous Cell Carcinoma of the Prostate With a Complete Remission to Gemcitabine-Cisplatin: Case Presentation and Literature Review

Abstract Squamous cell carcinoma of prostate is a very rare condition and little is known regarding the appropriate managment. Here we reported our patient with pure squamous cell carcinoma of prostate who had complete remission with gemcitabine and cisplatin treatment which last 5 months. Based on his genomic study of prostate cancer, he enrolled to our clinical trial and now receiveing mTOR pathway inhibtor. We also briefly reviewed previous cases of metastatic squamous cell carcinoma of prostate and their managment.

Effectiveness of ChatGPT 4.0 in Telemedicine-Based Management of Metastatic Prostate Carcinoma.

The recent rise in telemedicine, notably during the COVID-19 pandemic, highlights the potential of integrating artificial intelligence tools in healthcare. This study assessed the effectiveness of ChatGPT versus medical oncologists in the telemedicine-based management of metastatic prostate cancer. In this retrospective study, 102 patients who met inclusion criteria were analyzed to compare the competencies of ChatGPT and oncologists in telemedicine consultations. ChatGPT's role in pre-charting and determining the need for in-person consultations was evaluated. The primary outcome was the concordance between ChatGPT and oncologists in treatment decisions. Results showed a moderate concordance (Cohen's Kappa = 0.43, p < 0.001). The number of diagnoses made by both parties was not significantly different (median number of diagnoses: 5 vs. 5, p = 0.12). In conclusion, ChatGPT exhibited moderate agreement with oncologists in management via telemedicine, indicating the need for further research to explore its healthcare applications.

Metastatic Prostate Carcinoma in an Early 18th-Century South German Abbot—Interdisciplinary Research Reveals Clues to His Final Disease History

This interdisciplinary investigation of the human remains of Balduin Helm, one of the most important abbots of the Fürstenfeld monastery, provides novel information on this historic individual. This is particularly interesting since Balduin, during the early 18th century, was involved in the renovation of this large Bavarian monastery. Metastatic prostate cancer was found as evidenced by multiple mixed osteolytic–osteoblastic bone lesions in all available vertebral bodies, fragments of both os coxae, and isolated metastases in skull bones. Distribution, radio- and histomorphology, and especially the immunohistochemical detection of prostate-specific antigens in those metastases definitively confirm this diagnosis. Further investigation, especially by stable isotope analysis, showed a balanced high-level diet with considerable contribution from animal protein and significant freshwater fish. These additional findings suggest a significant radiocarbon reservoir effect as an explanation for a “too old” radiocarbon date. Finally, the obviously high-level protein diet may have contributed to the tumorigenesis which caused the death of the abbot at an advanced age.

The effect of unusual presentation on delayed diagnosis of prostate cancer: a case series

BackgroundEarly diagnosis of prostate cancer is key to achieving a cure and its proper management leads to a good prognosis. In Ghana a large percentage of patients present with advanced disease and unusual presentations in these patients result in greater delay in the diagnosis thus worsening the outcomes.Case presentationWe present three African males with advanced prostate cancer who had delayed diagnosis. The first patient, a 64 year old male presented with ascites of 2 years duration with weight loss and no lower urinary tract symptoms, the second, a 69 year old man with end stage renal failure of 6 months duration and was receiving dialysis, the third case, an 87 year old man was managed for pulmonary tuberculosis after he presented with chronic cough and lower urinary tract symptoms. All patients eventually had a prostate specific antigen done which were elevated. Further investigations including prostate biopsies, abdominopelvic CT scans for case 1, abdominopelvic ultrasound, prostate biopsies and blood urea and electrolytes for case 2, prostate biopsies, chest and lumbosacral showed a diagnosis of metastatic prostate carcinoma, and all patients were managed with androgen deprivation. The second patient received additional radiotherapy.ConclusionA lack of knowledge of prostate cancer symptoms including unusual symptoms, can result in delayed diagnosis especially in regions of the world where a large number of patients present with advanced disease.

Incidental Detection of Second Primary Thyroid Malignancy in Patients of Metastatic Castration-Resistant Prostate Carcinoma: Documentation on 68 Ga-PSMA-11 and 64 CuCl 2 PET/CT.

Second primary tumors are being increasingly detected owing to and in proportion to the use of advanced imaging modalities including PET/CT. Patients suffering from prostate cancer have been reported to have increased second primary cancers of gastrointestinal tract, urinary bladder, and thyroid. We herein describe incidental detection of thyroid carcinoma, in 2 patients of mCRPC (metastatic castration-resistant prostate carcinoma) undergoing preradioligand therapy workup, on 68 Ga-prostate-specific membrane antigen PET/CT initially, subsequently also observed on multitracer PET/CT ( 64 CuCl 2 and 18 F-FDG). Thus, the potential of PET/CT for early in vivo second primary detection in mCRPC setting is illustrated in the aforementioned 2 patients.

Simultaneous assessment of renal function with hybrid SPECT/CT during whole-body bonescintigraphy (WbBS) in patients with prostate carcinoma (PC) and concomitant urological diseases with impaired renal drainage

Introduction: Whole-body bone scintigraphy (WbBS) is the „gold standard“ worldwide for early detection and evaluation of treatment of bone metastatic tumors, incl.PC.Due to the known renal excretion of the osteotropic RPh – 99mTc-methylene diphosphonate (99mTc-MDP), it is possible to perform an „early“ assessment of renal function, followed by a „late“ standard WbBS with SPECT/CT. Aim: The aim of the present study was to evaluate and indicate the diagnostic utility of a single administration of 99mTc-MDP with a dual protocol implemented in the CNM for sequential scintigraphic assessment of renal function and early detection, staging and evaluation of the treatment effect of bone metastases in patients with PCand concomitant urological diseases. Materials and methods: We present three patients with PC, referred for restaging of the oncological disease and performing WbBS in the CNM in USHATO, Sofia, Bulgaria. According to the indications and assessment of a nuclear medicine physician, a one-day protocol was carried out and introduced in the CNM, starting with dynamic renal scintigraphy (DRS) at the time of bo-lus i.v.injection of 99mTc-MDP and subsequent after the 2nd hour planar WbBS with hybrid target or wholebody SPECT/CT scan. Results: The first patient is with metastatic PC after complex treatment.Due to elevated levels of creatinine, „early“ DRS and „late“ restaging WbBS were performed, with reported full therapeutic effect of bone-metastatic disease and isosthenuric changes in right kidney, but with altered secretory-excretory phases and reduced total GFR.The second case is a patient with high-risk CP, who underwent hormonal and definitive radiation therapy, with episodes of renal colic. DRS revealed a hydronephrotic type nephrogram on the right, and a subsequent CT scan showed osteoporotic compression fractures of two vertebrae, without bon metastasis. An additional SPECT/CT finding is a calcium-dense calculus as a probable cause of the hydronephrotic changes. The third patient, is with high-risk CP and undergonetreatment. Initial DRSshowed secretory-excretory dysfunction of the right kidney with retention in the pyelocaliceal system. SubsequentWbBSand SPECT/CT revealed a complete therapeutic effect of a solitary bony lesion in the 6th right rib and malrotation of the right kidney with a staghorn calculus in the pyelon. All patients are referred for urological control. Conclusion: DRS performed with hybrid SPECT/ CT, in the course of routine WbBS, for re-staging of patients with CP, gives along with bone metastatic follow-up, valuable functional information about the separated renal function, drainage and morphological guidance for pathological changes from concomitant urological diseases.

Abstract 1853: Prostate specific membrane antigen (PSMA) glycoforms and prostate cancer progression

Abstract Introduction: Prostate cancer (PCa) is the most common non-skin malignancy and the second leading cause of cancer related death in men. Prostate cancer is a heterogeneous disease with diverse clinical outcomes ranging from indolent asymptomatic cases to very aggressive and potentially lethal metastatic forms of the disease. Early detection of PCa is predominantly through determination of serum PSA levels and digital rectal examinations (DRE). Subsequently, biopsy based Gleason Grade Scores and TNM staging, tumor size or mpMRI are used to assess disease severity and progression. However, due to the low specificity of PSA concentration in diagnosis and prognosis, biopsy complications, and high mpMRI costs, there is still a critical need to identify and develop novel noninvasive biomarkers that discriminate indolent from aggressive PCa upon diagnosis. Our long-term objective is to discover biomarkers for aggressive PCa, develop and to implement them into robust clinical testing minimally invasive assays for PCa risk stratification at diagnosis. The current focus is on Prostate-Specific Membrane Antigen (PSMA), a membrane bound glycoprotein, that is significantly over-expressed in aggressive and metastatic prostate carcinomas and with poor patient prognosis. The role of its glycosylation status and composition in disease progression and its glycoforms on biomarker development and therapeutics is unknown. Aberrant glycosylation of glycoproteins occurs in many cancers, and it influences disease progression. We rationalize that differential glycosylation of PSMA correlate with progression to aggressive PCa and that PSMA glycopeptides and glycoforms can be used as diagnostics and prognosticators for aggressive disease. Methods/Results: PSMA was isolated from risk Grade Group stratified post-DRE urines, seminal plasma and prostate cancer cell lines with different metastatic phenotypes cell line lysates. Intact glycopeptides were isolated, purified and analyzed by qualitative and quantitative mass spectrometry to identify site specific glycoforms. Our data demonstrate differential expression of unique PSMA glycoforms that correlate with disease risk and severity. Conclusions: Differential glycosylation of PSMA correlates with PCa disease progression to aggressive phenotypes and may have utility in disease stratification. Ongoing studies focus on determining if these qualitative and quantitative changes have diagnostic/prognostic value and if these be integrated with other PCa biomarkers to improve their prognostic power in discriminating aggressive PCa. Acknowledgements: This work was supported by the DOD, USAMRAA, through the Prostate Cancer Research Program under Award No. W81XWH18-1-0228. Opinions, interpretations, and conclusions are those of the author and are not necessarily endorsed by the USAMRAA. Citation Format: Stephen Mackay, Ian O. Oduor, Tanya Burch, Dean A. Troyer, Oliver J. Semmes, Julius O. Nyalwidhe. Prostate specific membrane antigen (PSMA) glycoforms and prostate cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1853.

A Comparison of 68Ga-PSMA PET/CT-Based Split Renal Function with 99mTc-MAG3 Renography in Patients with Metastatic Castration-Resistant Prostate Carcinoma Treated with 177Lu-PSMA.

Physiological PSMA expression in the cells of the proximal renal tubules and consecutive radiopharmaceutical binding and retention could potentially lead to radioligand-therapy-induced nephrotoxicity. Thus, patients with metastatic castration-resistant prostate cancer undergo 99mTc-Mercaptoacetyltriglycine (MAG3) renal scintigraphy to assess kidney function and to exclude renal obstruction as part of their workup for PSMA-targeted radioligand therapy (RLT). 99mTc-MAG-3 renal scintigraphy often requires an additional visit to the nuclear medicine department and patients spend 30-90 min in the department, which is inconvenient and takes up camera time. In addition, the patients are subjected to a baseline 68Ga-PSMA PET/CT to assess for PSMA-positive disease prior to targeted radioligand therapy. The aim of this retrospective cross-sectional study was to compare 99mTc-MAG-3-based split renal function (SRF) with 68Ga-PSMA-derived SRF. This retrospective cross-sectional study included 28 patients with histologically proven metastatic castration-resistant prostate cancer (mCRPC) who received 177Lu-PSMA617. A comparison between the split renal function using 68Ga-PSMA PET/CT and the 99mTc-MAG-3-derived split renal function was carried out in 56 kidneys (n = 56). The SRF on 68Ga-PSMA was calculated using the volume and the average standard uptake value (SUVmean) within each VOI calculated as previously described by Roser et al.: SRF = (VOLUMEright) ∗ SUVmeanright/(VOLUMEright ∗ SUVmeanright + VOLUMEleft ∗ SUVmeanleft). Paired tests and correlation coefficients were used to compare 68Ga-PSMA and 99mTc-MAG-3. A visual comparison of kidney morphology on both studies was also performed. The median SRF of the right kidney was 49.9% (range: 3-91%) using 68Ga-PSMA PET/CT and 50.5% (range: 0-94%) with 99mTc-MAG3 scintigraphy. Notably, there was a strong correlation between SRF measurements obtained from PSMA and 99mTcMAG3, with a Pearson correlation coefficient of 0.957 (p < 0.001). Both 99mTc-MAG3 and 68Ga-PSMA PET/CT studies identified morphological renal abnormalities; there were nine hydronephrotic kidneys, four shrunken kidneys and one obstructed kidney, and there was a strong positive correlation between 68Ga-PSMA kidney morphology and 99mTcMAG3 renal scintigraphy kidney morphology, with a correlation coefficient of 0.93. PSMA-derived split function demonstrated a high correlation with renal function assessed on diuretic 99mTc-MAG3 renograms. PET-derived split renal function may, therefore, be considered an alternative to diuretic renogram-based split function. Furthermore, both 99mTc-MAG3 and 68Ga-PSMA PET/CT studies identified morphological renal abnormalities such as hydronephrosis, shrunken and obstructed kidneys. This correlation underscores the potential utility of 68Ga-PSMA imaging as a valuable tool for assessing kidney morphology as an alternative to renogram split function in clinical practice.

Comparative effectiveness of ChatGPT 4.0 and medical oncologists in telemedicine-based management of metastatic prostate carcinoma (mPC).

226 Background: The advent of telemedicine, accentuated during the COVID-19 pandemic, offers a prospective modality, especially when synergized with artificial intelligence (AI) tools such as ChatGPT 4.0. In this investigation, we sought to investigate the proficiency of ChatGPT vs. medical oncologists in the telemedicine-centric management of mPC. Methods: This IRB-approved retrospective study compared the competencies of ChatGPT and oncologists in conducting telemedicine consultations for patients with mPC. Out of 975 patients screened between April 1, 2022, and March 30, 2023, 102 met the inclusion criteria of having a diagnosis of mPC, attending at least one telemedicine consultation during the specified period, and having documentation available for two consecutive visits to enable the analysis of treatment decisions and outcomes. ChatGPT was asked to pre-chart and determine if a face-to-face consultation is needed. Its clinical competence was assessed using miniCEX, and medical decision-making (MDM). The Cohen's kappa test was used to measure the level of agreement between ChatGPT and oncologists in treatment decisions, and the Mann-Whitney U test was used to compare miniCEX and MDM. Results: The majority of patients were White (97.06%), with a median age of 75 years (range:53 to 99). Nearly all patients were diagnosed with adenocarcinoma (96.08%), with a median Gleason score of 7 (range: 6 to 10). The prevalent metastatic sites were bone (47.4%) and lymph nodes (44.16%). 26.88% had an ECOG score of 0, 54.84% had a score of 1, and 18.28% had a score greater than 1. Common coexisting conditions included diabetes mellitus (11.11%), hypertension (29.82%), hyperlipidemia (24.56%), and depression (7.6%). The primary outcome measured the concordance between ChatGPT and oncologists on whether to continue or cease the current treatment There was a statistical significance in sensitivity and specificity between clinicians and ChatGPT (Chi-squared=5.1, p=0.02). Cohen's Kappa showed a moderate concordance (Kappa = 0.43, p&lt;0.001). There was no difference in the number of diagnoses made by the two parties (p=0.13 and 0.06, respectively). ChatGPT's median miniCEX score was 8 (SD=0.59), and its median MDM length was 41 words (SD=6.06). The average time saved by ChatGPT in pre-charting was 41 minutes (SD=6). Conclusions: ChatGPT showed moderate concordance with oncologists for the management of mPC in telemedicine. Subsequent investigations are needed to explore its potential in healthcare.

Bilateral Subcapsular Orchidectomy as Surgical Castration: A Reasonable Aesthetic Alternative to Bilateral Total Orchidectomy in Patients with Metastatic Hormone-sensitive Prostate Cancer

Background: The study highlights the historical significance of bilateral orchidectomy as the traditional 'gold standard' for surgical androgen deprivation in treating advanced prostate cancer. The study presented aims to compare total orchidectomy and subcapsular orchidectomy, considering factors such as androgen ablation, disease progression control, and patient satisfaction. Objective: This study aims to compare the effectiveness and patient satisfaction of bilateral subcapsular orchidectomy and bilateral total orchidectomy treatment in managing hormone-sensitive metastatic prostate cancer. Methods and materials: In this prospective study of 18 months at North East Medical College Hospital, 40 participants with Metastatic Carcinoma of Prostate underwent bilateral orchidectomy, among them 20 subcapsular and 20 total orchidectomy. The research focused on evaluating the impact of these treatments on serum testosterone levels, serum PSA levels, employing as outpatient procedures and a 3-month follow-up, utilizing a satisfaction scoring scale. Data, including age, Gleason Grade Group, PSA, and testosterone levels at diagnosis &amp; at 3-month follow-up were recorded and analyzed using IBM SPSS-21 software. Result: The study compared Bilateral Subcapsular Orchidectomy and Bilateral Simple Orchidectomy for Hormone-Sensitive Metastatic Carcinoma of Prostate in 40 patients. The highest frequency was in the 71-75 age group (30%), with a mean age of 66.67 ± 2.21 years. Gleason grade group 3 dominated (40%), followed by 2 (25%). Pre-operative PSA levels were 31.14±1.27 ng/ml for Subcapsular and 35.21±1.70 ng/ml for Total Orchidectomy, decreasing post-operatively to 8.25±0.41 ng/ml and 7.32±0.80 ng/ml, respectively. Pre-operative testosterone levels were 513.21±3.01 ng/dl for Subcapsular and 498.40±2.10 ng/dl for Total Orchidectomy, decreasing post-operatively to 21.14±2.84 ng/dl and 16.90±1.08 ng/dl, respectively, with non-significant p-values. Surgery related Satisfaction scores in the Follow-Up phase were significantly higher for Subcapsular Orchidectomy, 2.91±0.31 comparing with Total Orchidectomy, 2.05±0.45. The results emphasize better patient satisfaction after subcapsular orchidectomy, while maintaining similar cancer control in the form of PSA and testosterone level changes. Conclusion: In conclusion, our study advocates for the reconsideration of bilateral subcapsular orchidectomy as a preferred method for surgical androgen ablation in metastatic prostatic carcinoma, offering comparable efficacy to traditional total orchidectomy approach while prioritizing patient satisfaction and psychological well-being. This suggests a potential paradigm shift in the landscape of cost-effective androgen deprivation therapy within the urological field.

Incidental diagnosis of microfilariae in urine in a case of prostatic carcinoma: A case report with a cytohistological correlation

Filariasis is an endemic parasitic infection commonly found in the tropics and subtropics, such as India. Microfilariae have been reported in various cytological samples, but they are rare to find in urine samples. The presence of microfilariae in urine can be incidental or associated with other malignancies. The cytological examination can help diagnose such cases. Clinically, it may present unusually as achylous hematuria and a urinary bladder mass lesion, mimicking bladder cancer. There have been a few reported cases of microfilariae in urine along with prostatic malignancy, and the present case highlights the same. Here, we report a treated case of metastatic prostatic carcinoma presenting as a bladder mass in a 61-year-old male, who was diagnosed with microfilariasis in urine cytology. This case is presented not only for its dual pathology or rare occurrence but also to emphasize that an incidental finding can help in treating it medically with no surgical intervention.

Effects of docetaxel on metastatic prostate (DU-145) carcinoma cells cultured as 2D monolayers and 3D multicellular tumor spheroids

ABSTRACT Docetaxel (DTX) is one of the chemotherapeutic drugs indicated as a first-line treatment against metastatic prostate cancer (mPCa). This study aimed to compare the impact of DTX on mPCa (DU-145) tumor cells cultured as 2D monolayers and 3D multicellular tumor spheroids (MCTS) in vitro. The cells were treated with DTX (1–96 µM) at 24, 48, or 72 hr in cell viability assays (resazurin, phosphatase acid, and lactate dehydrogenase). Cell death was assessed with fluorescent markers and proliferation by clonogenic assay (2D) and morphology, volume, and integrity assay (3D). The cell invasion was determined using transwell (2D) and extracellular matrix (ECM) (3D). Results showed that DTX decreased cell viability in both culture models. In 2D, the IC50 (72 hr) values were 11.06 μM and 14.23 μM for resazurin and phosphatase assays, respectively. In MCTS, the IC50 values for the same assays were 114.9 μM and 163.7 μM, approximately 10-fold higher than in the 2D model. The % of viable cells decreased, while the apoptotic cell number was elevated compared to the control in 2D. In 3D spheroids, only DTX 24 μM induced apoptosis. DTX (≥24 μM at 216 hr) lowered the volume, and DTX 96 μM completely disintegrated the MCTS. DTX reduced the invasion of mPCa cells to matrigel (2D) and migration from MCTS to the ECM. Data demonstrated significant differences in drug response between 2D and 3D cell culture models using mPCa DU-145 tumor cells. MCTS resembles the early stages of solid tumors in vivo and needs to be considered in conjunction with 2D cultures when searching for new therapeutic targets.

Ethnic Incidence of Metastatic Prostate Carcinoma in a Veteran Affairs Medical Center’s (VAMC) And Early Surveillance Guided by Sites of Metastases

Abstract Introduction/Objective Ethnic difference in incidence, mortality, and prognosis for prostate adenocarcinoma is well known with disparities between African American (AA), Caucasian and Asian origin population reported by tumor heterogeneity and increased number of gene mutations in genomic profiling. Early metastasis of prostate cancer with younger age at the presentation in AA ethnicity has been noted. Earlier screening, biopsy and tumor molecular profiling may lead to a decrease in morbidity and mortality related to metastatic prostate cancer. While there are known differences in the incidence of prostate cancer between different ethnic groups and differences in ethnic access to care and diagnosis varies widely between distinct medical practices, the ethnic incidence of diagnoses of metastatic prostatic adenocarcinoma and distribution of sites particularly in a Veteran population has not been well studied. Methods/Case Report A retrospective search was performed from December 2019 to October 2022 for metastatic prostatic carcinoma specimens at regional Veteran Affairs Medical Center (VAMC). Both H &amp; E and immunohistochemical antibodies for prostate were reviewed and used in the diagnosis of metastatic carcinoma of prostate origin. Results (if a Case Study enter NA) A total of 21 cases with metastatic prostatic adenocarcinoma were found from which 9 were metastases to bone, 5 were metastases to lymph node and 7 were metastatic to other organ sites. Majority of the cases were of ethnic African American veterans (12/21, 57%), followed by Caucasian Americans (7/21, 33%), and 2 of unknown ethnicity (2/21, 10%). On examination, most frequent site of metastases by ethnic African Americans was lymph node in 4 out of the 5 (80%) total cases metastatic to lymph node, and 5 out of 6 total cases (83%) with metastases to different organ sites together. On the other hand, ethnic Caucasian Americans the most common metastatic site was bone with 6 out of 10 total cases (60%) metastatic to bone. Conclusion African American Veteran patients have a higher incidence of metastatic prostate carcinoma and a higher incidence of earlier metastases. A similar trend was seen in the study population with African Americans making up most of the study population and also suggestively having more cases of lymph node and other organ metastases. The increased proportion of African Americans in the study population with lymph node metastases suggests targeting lymph nodes for biopsy for early detection of the metastatic prostatic carcinoma.

Liquid Biopsy as a Powerful Therapeutic Tool in Veteran Patients with Prostate Carcinoma

Abstract Introduction/Objective The National Comprehensive Cancer Network (NCCN) guidelines currently recommend somatic tumor molecular testing for alterations in homologous recombination (HR) DNA repair genes in patients with metastatic prostate cancer, which can be performed on either the sampled tumor tissue itself or by liquid biopsy. Particularly when the sampled tumor tissue may be limited, liquid biopsy with next generation sequencing is a recently available attractive alternative that is minimally invasive (requiring just phlebotomy). Based on the information gathered from circulating tumor cells (CTC), a tumor molecular profile can be obtained that can impact treatment, particularly if a HR DNA repair mutation is found as that may predict response to a poly (ADP-ribose) polymerase (PARP) enzyme inhibitor such as Olaparib. However, the literature of metastatic prostate cancers targeted by liquid biopsies and the mutations found is sparse, particularly for the veteran population. Methods/Case Report A retrospective review was performed of all patients with a submitted liquid biopsy specimen at a Veteran Affairs Medical Center (VAMC) October 23rd, 2019, to March 3rd, 2023 to examine those patients with metastatic prostate cancer. Information on mutations detected was collected. Results (if a Case Study enter NA) There were a total of 64 patient specimens with a history of metastatic prostate cancer, from which 56 had an available liquid biopsy report with the first liquid biopsy collection occurring on October 23rd, 2019. HR DNA repair mutations found included CHEK2 (6/56), ATM (4/56), and BRCA1 (1/56). Outside of HR DNA repair genes, relatively common detected mutations were found in TP53 (25/56), PTEN (6/56), BRAF (4/56), and an AR amplification (4/56). 7 of the 56 reports had no reportable genomic alterations detected. Conclusion Liquid biopsies continues to be a minimally invasive, highly useful powerful therapeutic tool in veteran patients with metastatic prostate carcinoma for molecular profiling. Not uncommonly in the Veteran population, these molecular findings include mutations in HR DNA repair genes that as noted by the NCCN may predict response to PARP inhibitor chemotherapy.

Acute spinal cord compression under systemic therapy - radiotherapy or surgery?

Vertebral bodies are one of the most common metastasis sites found in advanced prostate cancer and have a significant impact on patients' quality of life. Spinal metastases frequently cause severe back pain and in some occasions can lead to secondary complications, with serious neurological deficits and loss of function. The main treatment goals include adequate pain management, controlling tumour growth and restoring spinal stability. Publications on the role of surgery - both conventional and stereotactic radiotherapy, and either as an individual modality or in combination - have been inconclusive. The NOMS score has proven to be useful in making treatment decisions. Existing data show better outcomes in patients with surgical therapy, both when performed in isolation and also combined with radiotherapy, in which some of the cohorts studied including patients with primary cancer other than prostate cancer. Comparative studies that specifically investigate the superiority of specific therapy modalities for metastatic prostate carcinoma are scarce. Similarly, there are limited data on microsurgical interventions for spinal metastases. Radiotherapy alone is crucial in the setting of palliation, especially for pain relief, and its effectiveness has been shown in many studies. The patient's life expectancy plays a crucial role in deciding the most appropriate treatment approach. Given the complexity of the patient population, a multimodal therapy approach is necessary. Current trends in therapy favour greater use of surgical interventions, particularly in the early detection of spinal metastases.

Differentiation of Discordant Lesions on Dual-Tracer PET/CT (68Ga-PSMA-11 and 18F-FDG) in Prostate Carcinoma: Diagnosis of Second Primary Malignancies.

We present 2 cases of metastatic castration-resistant prostate carcinoma with discordant lesions on dual-tracer PET/CT (68Ga-PSMA-11 and 18F-FDG PET/CT), which on subsequent histopathologic evaluation revealed second primary malignancies of combined hepatocellular carcinoma and cholangiocarcinoma and poorly differentiated squamous cell carcinoma. These case illustrations emphasize the need to evaluate discordant lesions on dual-tracer PET/CT, which can lead to early diagnosis of second primary malignancies and thereby can provide better management in these patients.

Curcuphenol possesses an unusual histone deacetylase enhancing activity that counters immune escape in metastatic tumours.

Curcuphenol, a common component of the culinary spices, naturally found in marine invertebrates and plants, has been identified as a novel candidate for reversing immune escape by restoring expression of the antigen presentation machinery (APM) in invasive cancers, thereby resurrecting the immune recognition of metastatic tumours. Two synthetic curcuphenol analogues, were prepared by informed design that demonstrated consistent induction of APM expression in metastatic prostate and lung carcinoma cells. Both analogues were subsequently found to possess a previously undescribed histone deacetylase (HDAC)-enhancing activity. Remarkably, the H3K27ac ChIPseq analysis of curcuphenol-treated cells reveals that the induced epigenomic marks closely resemble the changes in genome-wide pattern observed with interferon-γ, a cytokine instrumental for orchestrating innate and adaptive immunity. These observations link dietary components to modifying epigenetic programs that modulate gene expression guiding poised immunity.

Comparison of Metabolic and Cardiovascular Impact between Gonadotropin-Releasing Hormone Agonists and Orchidectomy for Androgen Deprivation Therapy in Metastatic Carcinoma Prostate

Background: Metastatic prostate cancer is a global health challenge and requires a balanced approach to preserve the quality of life and extend survival. Current treatment is to offer monotherapy either orchidectomy or GnRH agonists or antagonists to hormone-sensitive metastatic prostate cancer patients. Androgen deprivation therapy increases the risk of obesity, diabetes, dyslipidemia and osteoporosis. Objectives: This study was done to compare the metabolic and cardiovascular impact of GnRH agonist and orchidectomy for androgendeprivation therapy in metastatic carcinoma prostate. Methods: This Quasi-experimental study was conducted at the Department of Urology, Dhaka Medical College Hospital, Dhaka during the period from July 2019 to December 2020. A total of 28 patients diagnosed with metastatic prostate cancer were included in the study as per inclusion and exclusion criteria. After counselling, patients were allocated to orchidectomy (Group- A) or GnRH agonist (group-B) as per the patient’s choice. After undergoing orchidectomy or receiving GnRH agonists, patients were advised to follow up at 1, 3 and 6 months. Two patients were lost to follow-up. Result: The mean age of patients in group-A was 66.55(range 58-74) years and in group B was67.8 (62-73) years. There was a significant increase in RBS, triglyceride and a decrease in HDL and bone mineral density at 6 months of group B compared to Group-A. After 6 months, 9.09% of patients in group-A compared to 26.6% of patients in group B had RBS above 11.1 mmol/L. In group-A, 45.45% of patients had triglyceride levels&gt;150 mg/dL compared to 80% in group B. HDL level decreased &lt;40 mg/dL in 45.45% of patients in group-A but 60% in group B. Bone mineral density decreased below -2.5 in 9.09% of patients in group- A compared to 46.66% in group B. Mean S.PSA was around 2 ng/ml in both groups during the follow-up period. The cardiovascular and metabolic impact of orchidectomy was less compared to GnRH agonists. .......

Unveiling the uncommon: Disseminated intravascular coagulation as an unusual presentation of metastatic carcinoma prostate

We present a rare case of disseminated intravascular coagulation (DIC) as the initial manifestation of metastatic carcinoma of the prostate. DIC is a life-threatening condition characterized by systemic activation of coagulation and widespread microvascular thrombosis, leading to organ dysfunction. Although DIC is commonly associated with hematological malignancies and sepsis, its occurrence as a paraneoplastic syndrome in solid tumors is extremely rare. Our case highlights the importance of considering DIC as a potential complication in patients with advanced prostate cancer, even in the absence of typical symptoms.