Prostate Cancer Status Research Articles

Beta thalassemia minor: a potential risk factor for osteopenia and osteoporosis

A 74-year-old male patient with beta thalassemia minor presented in 2022 for a follow-up of osteoporosis diagnosed prior to 2004. At the time of presentation, his medical history included: radiation exposure to his head and neck, goiter, prostate cancer status post resection in 2019 without a history of anti-androgen therapy, and atrial fibrillation, for which he had been prescribed apixaban since 2021. Treatment with risedronate occurred from approximately 2004 to about 2011, with improvement in bone density to osteopenia. He had also taken vitamin D and calcium supplementation and engaged in regular weight-bearing exercise. The patient had no other known risk factors for decreased bone mineral density preceding the onset of his osteoporosis, and a previous workup for secondary causes of his osteoporosis etiology proved negative. We propose that beta thalassemia minor is potentially a risk factor for osteopenia and osteoporosis, and that bisphosphonates can be considered for management when therapeutic intervention is indicated. Even in the absence of other known risk factors, clinicians should consider periodically screening beta thalassemia minor patients with DXA for evaluation of bone health.

Abstract A031: Methylomic Biomarkers Associated with Prostate Cancer in Black Men

Abstract Introduction: The prostate cancer (PCa) disparity remains the highest cancer disparity in the US, with Black men facing an estimated 78% higher incidence and 230% higher mortality than White men. However, current understanding of risk factors for PCa such as socioeconomic status (SES), diet, and genetics cannot fully explain these disparities. Our objective is to examine DNA methylation (DNAm) markers in a cohort of Black men and assess their associations with PCa status. Methods: We randomly selected 100 Black men for DNAm profiling (50 cases diagnosed with clinically significant (Gleason Grade 3+) prostate cancer and 50 age-matched controls) from two larger cohorts. The cohorts recruited 400 Black men who were newly diagnosed with sporadic PCa as well as 400 controls matched on age and race. All men were 40-79 at recruitment and were enrolled from urology clinics at five Chicago-area medical institutions. All PCa cases underwent a transrectal prostate biopsy for abnormal prostate-specific antigen (PSA) or digital rectal exam and had a histologically confirmed prostate cancer and were not previously diagnosed with PCa. All men in the control group had been recruited from community prostate cancer screening events or were referred to participating urology clinics and had a negative prostate biopsy for a PSA <10ng/ml and were not diagnosed with PCa for 2 years of follow-up. Men with prior PCa diagnosis or conditions known to affect PSA levels were excluded. After enrollment and informed consent, all men provided demographic and lifestyle data via three questionnaires, followed by venipuncture for DNA collection. These specimens were obtained using buffy coat extraction after red blood cell lysis, centrifugation, and pipetting off the overlying plasma and buffy coat for freezing followed by Illumina EPIC arrays for DNAm assays. We examined DNAm markers in gene promoter regions associated with PCa using logistic regression and adjusted for multiple testing using Bonferroni correction. All models controlled for age, BMI, smoking status, first degree family history of PCa, blood cell types, and technical control variables. Results: We found 2,180 CpG sites in gene promoter regions associated with any PCa in this population. The top ten strongest associations identified in our models include loci on genes that have already been associated with prostate cancer progression (MAFG, FAM65B, OSM, PRKAG2), risk (SLC11A1, LAT), and metastasis (S1PR4) as well as immune system functioning (RAP1GAP2). Conclusions: Our initial findings suggest that DNAm markers may be useful predictors of clinically significant PCa status among Black men. Additional research is currently ongoing to expand the sample size of the DNAm profiling and to explore links between these loci and social determinants of health, as well as associations with more advanced (i.e., higher Gleason Grade) PCa. Citation Format: Brian T. Joyce, Yishu Qu, Jun Wang, Kai Zhang, Zequn Sun, Lifang Hou, Adam B. Murphy. Methylomic Biomarkers Associated with Prostate Cancer in Black Men [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr A031.

A cross-species analysis of fecal microbiomes in humans and mice reveals similarities and dissimilarities associated with prostate cancer risk.

Prostate cancer is a complex disease that develops over time and is influenced by several lifestyle factors that also impact gut microbes. Gut dysbiosis is intricately linked to prostate carcinogenesis, but the precise mechanisms remain poorly understood. Mice are crucial for studying the relationships between gut microbes and prostate cancer, but discovering similarities between humans and mice may aid in elucidating new mechanisms. We used 16s rRNA sequencing data from stool samples of tumor-bearing prostate-specific conditional Pten-knockout mice, disease-free wildtype mice, and a human cohort suspected of having prostate cancer to conduct taxonomic and metagenomic profiling. Features were associated with prostate cancer status and low risk (a negative biopsy of Gleason grade <2) or high risk (Gleason grade ≥2) in humans. In both humans and mice, community composition differed between individuals with and without prostate cancer. Odoribacter spp. and Desulfovibrio spp. were taxa associated with prostate cancer in mice and humans. Metabolic pathways associated with cofactor and vitamin synthesis were common in mouse and human prostate cancer, including bacterial synthesis of folate (vitamin B9), ubiquinone (CoQ10), phylloquinone (vitamin K1), menaquinone (vitamin K2), and tocopherol (vitamin E). Our study provides valuable data that can help bridge the gap between human and mouse microbiomes. Our findings provide evidence to support the notion that certain bacterial-derived metabolites may promote prostate cancer, as well as a preclinical model that can be used to characterize biological mechanisms and develop preventive interventions.

Evaluation of homologous recombination repair (HRR) status in metastatic prostate cancer by next-generation sequencing and functional tissue-based immunofluorescence assays.

Evaluation of homologous recombination repair (HRR) status in metastatic prostate cancer by next-generation sequencing and functional tissue-based immunofluorescence assays.

Homologous Recombination Repair Deficiency in Metastatic Prostate Cancer: New Therapeutic Opportunities.

More than 20% of metastatic prostate cancer carries genomic defects involving DNA damage repair pathways, mainly in homologous recombination repair-related genes. The recent approval of olaparib has paved the way to precision medicine for the treatment of metastatic prostate cancer with PARP inhibitors in this subset of patients, especially in the case of BRCA1 or BRCA2 pathogenic/likely pathogenic variants. In face of this new therapeutic opportunity, many issues remain unsolved. This narrative review aims to describe the relationship between homologous recombination repair deficiency and prostate cancer, the techniques used to determine homologous recombination repair status in prostate cancer, the crosstalk between homologous recombination repair and the androgen receptor pathway, the current evidence on PARP inhibitors activity in metastatic prostate cancer also in homologous recombination repair-proficient tumors, as well as emerging mechanisms of resistance to PARP inhibitors. The possibility of combination therapies including a PARP inhibitor is an attractive option, and more robust data are awaited from ongoing phase II and phase III trials outlined in this manuscript.

Can we predict pathology without surgery? Weighing the added value of multiparametric MRI and whole prostate radiomics in integrative machine learning models.

To test the ability of high-performance machine learning (ML) models employing clinical, radiological, and radiomic variables to improve non-invasive prediction of the pathological status of prostate cancer (PCa) in a large, single-institution cohort. Patients who underwent multiparametric MRI and prostatectomy in our institution in 2015-2018 were considered; a total of 949 patients were included. Gradient-boosted decision tree models were separately trained using clinical features alone and in combination with radiological reporting and/or prostate radiomic features to predict pathological T, pathological N, ISUP score, and their change from preclinical assessment. Model behavior was analyzed in terms of performance, feature importance, Shapley additive explanation (SHAP) values, and mean absolute error (MAE). The best model was compared against a naïve model mimicking clinical workflow. The model including all variables was the best performing (AUC values ranging from 0.73 to 0.96 for the six endpoints). Radiomic features brought a small yet measurable boost in performance, with the SHAP values indicating that their contribution can be critical to successful prediction of endpoints for individual patients. MAEs were lower for low-risk patients, suggesting that the models find them easier to classify. The best model outperformed (p ≤ 0.0001) clinical baseline, resulting in significantly fewer false negative predictions and overall was less prone to under-staging. Our results highlight the potential benefit of integrative ML models for pathological status prediction in PCa. Additional studies regarding clinical integration of such models can provide valuable information for personalizing therapy offering a tool to improve non-invasive prediction of pathological status. The best machine learning model was less prone to under-staging of the disease. The improved accuracy of our pathological prediction models could constitute an asset to the clinical workflow by providing clinicians with accurate pathological predictions prior to treatment. • Currently, the most common strategies for pre-surgical stratification of prostate cancer (PCa) patients have shown to have suboptimal performances. • The addition of radiological features to the clinical features gave a considerable boost in model performance. Our best model outperforms the naïve model, avoiding under-staging and resulting in a critical advantage in the clinic. •Machine learning models incorporating clinical, radiological, and radiomics features significantly improved accuracy of pathological prediction in prostate cancer, possibly constituting an asset to the clinical workflow.

Real-World Overall Survival and Treatment Patterns by PTEN Status in Metastatic Castration-Resistant Prostate Cancer.

It is estimated that the PTEN tumor suppressor gene is functionally lost in 40%-50% of patients with metastatic castration-resistant prostate cancer (mCRPC). There is limited information on the prognostic significance of PTEN status identified with genomic testing. This real-world cohort study assessed PTEN as a genetic biomarker using data from US-based oncology practices. This retrospective real-world cohort study used a deidentified US-based metastatic prostate cancer clinicogenomic database linked to longitudinal clinical data derived from electronic health records. Patients were aged 18 years and older and diagnosed with mCRPC between January 1, 2018, and June 30, 2021. Comprehensive genomic profiling (CGP) of tumor specimens was performed using next-generation sequencing. First-line (1L) and second-line (2L) treatment patterns were assessed and stratified by PTEN status. Kaplan-Meier methods and a multivariable Cox model were used to compare the real-world overall survival by PTEN status among patients who received 1L novel hormone therapy or taxanes. In patients with mCRPC who underwent CGP, PTEN loss of function (LOF) was associated with decreased survival compared with intact PTEN (hazard ratio, 1.61 [95% CI, 1.07 to 2.42]; P = .024). The results were not influenced by 1L treatment type. 1L treatment patterns were similar between intact PTEN and PTEN LOF subgroups, with abiraterone and enzalutamide being the two most common treatments in both groups. Patients with PTEN LOF were less likely to receive 2L treatments than patients with intact PTEN. PTEN LOF, identified with genomic testing, was associated with decreased survival and negative prognoses in patients with mCRPC.

Individualized detection of TMPRSS2-ERG fusion status in prostate cancer: a rank-based qualitative transcriptome signature

BackgroundTMPRSS2-ERG (T2E) fusion is highly related to aggressive clinical features in prostate cancer (PC), which guides individual therapy. However, current fusion prediction tools lacked enough accuracy and biomarkers were unable to be applied to individuals across different platforms due to their quantitative nature. This study aims to identify a transcriptome signature to detect the T2E fusion status of PC at the individual level.MethodsBased on 272 high-throughput mRNA expression profiles from the Sboner dataset, we developed a rank-based algorithm to identify a qualitative signature to detect T2E fusion in PC. The signature was validated in 1223 samples from three external datasets (Setlur, Clarissa, and TCGA).ResultsA signature, composed of five mRNAs coupled to ERG (five ERG-mRNA pairs, 5-ERG-mRPs), was developed to distinguish T2E fusion status in PC. 5-ERG-mRPs reached 84.56% accuracy in Sboner dataset, which was verified in Setlur dataset (n = 455, accuracy = 82.20%) and Clarissa dataset (n = 118, accuracy = 81.36%). Besides, for 495 samples from TCGA, two subtypes classified by 5-ERG-mRPs showed a higher level of significance in various T2E fusion features than subtypes obtained through current fusion prediction tools, such as STAR-Fusion.ConclusionsOverall, 5-ERG-mRPs can robustly detect T2E fusion in PC at the individual level, which can be used on any gene measurement platform without specific normalization procedures. Hence, 5-ERG-mRPs may serve as an auxiliary tool for PC patient management.

Semi-Supervised, Attention-Based Deep Learning for Predicting TMPRSS2:ERG Fusion Status in Prostate Cancer Using Whole Slide Images.

Our study illuminates the potential of deep learning in effectively inferring key prostate cancer genetic alterations from the tissue morphology depicted in routinely available histology slides, offering a cost-effective method that could revolutionize diagnostic strategies in oncology.

Prostate cancer genetic risk and associated aggressive disease in men of African ancestry

African ancestry is a significant risk factor for prostate cancer and advanced disease. Yet, genetic studies have largely been conducted outside the context of Sub-Saharan Africa, identifying 278 common risk variants contributing to a multiethnic polygenic risk score, with rare variants focused on a panel of roughly 20 pathogenic genes. Based on this knowledge, we are unable to determine polygenic risk or differentiate prostate cancer status interrogating whole genome data for 113 Black South African men. To further assess for potentially functional common and rare variant associations, here we interrogate 247,780 exomic variants for 798 Black South African men using a case versus control or aggressive versus non-aggressive study design. Notable genes of interest include HCP5, RFX6 and H3C1 for risk, and MKI67 and KLF5 for aggressive disease. Our study highlights the need for further inclusion across the African diaspora to establish African-relevant risk models aimed at reducing prostate cancer health disparities.

FRI242 Primary And Secondary Adrenal Insufficiency Post Transsphenoidal Surgery In Patient On Abiraterone Therapy

Abstract Disclosure: R.O. Akande: None. J. Abramowitz: None. S. Mirfakhraee: None. Introduction: This case report describes the co-existence of primary and secondary adrenal insufficiency in a patient who received abiraterone therapy for metastatic prostate cancer and had transsphenoidal surgery for symptomatic pituitary adenoma. It sheds light on the presentation of the patient and explains the subsequent management. Clinical Case: A 67-year-old man with a history of metastatic prostate cancer (status post prostatectomy and radiation) and recent transsphenoidal surgery for pituitary adenoma presented with 3+ pedal edema. The patient had been discharged on hydrocortisone as per neurosurgery protocol and continued abiraterone after his transsphenoidal surgery. His pedal edema started two months after discharge. He denied fatigue, nausea, and dizziness. His vital signs and electrolytes, including serum potassium, were within normal limits. The patient was diagnosed with mineralocorticoid excess in the context of combined primary and secondary adrenal insufficiency. His hydrocortisone was changed to prednisone 5mg daily and his pedal edema subsequently resolved. Conclusion: Abiraterone, a hormonal therapy for the treatment of metastatic prostate cancer, is an irreversible inhibitor of CYP17, a microsomal enzyme with 17 alpha-hydroxylase and 17,20-lyase activities. This inhibition reduces cortisol and androgen concentrations while stimulating ACTH production. Thus, abiraterone use led to primary adrenal insufficiency in this patient. As a result of the 17 alpha-hydroxylase and 17,20-lyase pathway inhibition, there is increased production of deoxycorticosterone, which can lead to fluid retention. This patient was post pituitary surgery with partial secondary adrenal insufficiency and received hydrocortisone postoperatively as an appropriate glucocorticoid replacement in this setting. He developed pedal edema due to mineralocorticoid excess from abiraterone use while on hydrocortisone therapy. He was placed on prednisone, a more potent synthetic glucocorticoid than hydrocortisone, with subsequent rapid resolution of his edema. Presentation: Friday, June 16, 2023

THU451 Low Bone Mineral Density In A Patient With Thalassemia Minor

Abstract Disclosure: F. Woron: None. P. Madhavan: None. Osteoporosis is a known complication of thalassemia major and thalassemia intermedia, but is not typically considered in patients with thalassemia minor. Here, we present a 74-year-old Caucasian male patient with thalassemia minor who presented to us for follow-up of osteoporosis. The patient reports a history of osteoporosis that was diagnosed prior to 2004. Additionally, he has a history of radiation exposure to his head and neck, goiter, prostate cancer status post resection in 2019, and atrial fibrillation, for which he has been on apixaban since 2021. He was treated with risedronate for his osteoporosis from approximately 2004 to about 2011 by other providers, with improvement in bone density to osteopenia. Free testosterone, parathyroid hormone, calcium, and serum protein electrophoresis levels evaluated prior to his diagnosis of osteoporosis were all noted to be normal. He has not had a fracture as an adult. He is being monitored with conservative management and currently aims for a daily calcium intake of 1000-1200 mg, including diet and supplements, and a daily Vitamin D intake of 2000 IU. He engages in frequent weight-bearing exercise. As of September 2021, his bone mineral density was osteopenic in the lumbar spine (T score of −2) and left hip (total T score of the left hip −1.6, and −1.8 in the femoral neck). The patient had no other known risk factors for decreased bone mineral density preceding the onset of his osteoporosis, and a previous workup for secondary causes of his osteoporosis etiology proved negative. Adding to one existing case report in the literature, we propose that thalassemia minor may potentially be a risk factor for osteopenia and osteoporosis, and that we should consider screening thalassemia minor patients with DXA for evaluation of bone health. Presentation: Thursday, June 15, 2023

Germline Genetic Variants Associated with Somatic TMPRSS2:ERG Fusion Status in Prostate Cancer: A Genome-Wide Association Study.

The prostate cancer subtype defined by the presence of TMPRSS2:ERG has been shown to be molecularly and epidemiologically distinct. However, few studies have investigated germline genetic variants associating with TMPRSS2:ERG fusion status. We performed a genome-wide association study with 396 TMPRSS2:ERG(+) cases, 390 TMPRSS2:ERG(-) cases, and 2,386 cancer-free controls from the Physicians' Health Study (PHS), the Health Professionals Follow-up Study (HPFS), and a Seattle-based Fred Hutchinson (FH) Cancer Center Prostate Cancer Study. We applied logistic regression models to test the associations between ∼5 million SNPs with TMPRSS2:ERG fusion status accounting for population stratification. We did not identify genome-wide significant variants comparing the TMPRSS2:ERG(+) to the TMPRSS2:ERG(-) prostate cancer cases in the meta-analysis. When comparing TMPRSS2:ERG(+) prostate cancer cases with controls without prostate cancer, 10 genome-wide significant SNPs on chromosome 17q24.3 were observed in the meta-analysis. When comparing TMPRSS2:ERG(-) prostate cancer cases with controls without prostate cancer, two SNPs on chromosome 8q24.21 in the meta-analysis reached genome-wide significance. We observed SNPs at several known prostate cancer risk loci (17q24.3, 1q32.1, and 8q24.21) that were differentially and exclusively associated with the risk of developing prostate tumors either with or without the gene fusion. Our findings suggest that tumors with the TMPRSS2:ERG fusion exhibit a different germline genetic etiology compared with fusion negative cases.

Role of Race and Insurance Status in Prostate Cancer Diagnosis-to-Treatment Interval.

Numerous studies have shown that both race and insurance status may affect prostate cancer (PCa) workup and treatment. Preliminary investigations have shown that these factors may be associated with treatment delays, which may indicate inequitable care and increase risk of tumor progression. This investigation aimed to assess whether race and insurance impacted the interval between multiparametric MRI (mpMRI)-to-biopsy, and biopsy-to-prostatectomy. A single-institution analysis of 261 patients with recorded race and insurance data was performed using an Institutional Review Board-compliant database with information spanning from 2016 to 2022. Race was self-reported during intake, and insurance status was retrieved from the electronic medical record. Insurance was sub-divided into private, Medicare, and Medicaid. Diagnostic or treatment latency was defined as time between mpMRI-to-biopsy, or biopsy-to-surgery. Stratified by race, there was no difference in either latency period when comparing African American (AA) and white patients. Stratified by insurance status, there was no difference in time from mpMRI-to-biopsy (P = .50), but there was a significantly longer interval from biopsy-to-prostatectomy for patients with Medicaid insurance (P=.02). Patients with Medicaid waited on average 168 days to receive surgery, in contrast to 92 days for private and 87 for Medicare. Notably, 82% of Medicaid patients were AA. Insurance status, which is inherently linked to race and social determinants of health, portended a significantly increased interval between biopsy and surgery. Physicians should be aware of the relationship between insurance status and treatment delay, as well as its potential downstream consequences.

Differential Expression of miRNAs Contributes to Tumor Aggressiveness and Racial Disparity in African American Men with Prostate Cancer.

Prostate cancer is the leading cancer in incidence and second leading cause of cancer mortality in US men. African American men have significantly higher incidence and mortality rates from prostate cancer than European American men. Previous studies reported that the disparity in prostate cancer survival or mortality can be explained by different biological backgrounds. microRNAs (miRNAs) regulate gene expression of their cognate mRNAs in many cancers. Therefore, miRNAs may be a potentially promising diagnostic tool. The role of miRNAs in prostate cancer aggressiveness and racial disparity has not been fully established. The goal of this study is to identify miRNAs associated with aggressiveness and racial disparity in prostate cancer. Here we report miRNAs that are associated with tumor status and aggressiveness in prostate cancer using a profiling approach. Further, downregulated miRNAs in African American tissues were confirmed by qRT-PCR. These miRNAs have also been shown to negatively regulate the expression of the androgen receptor in prostate cancer cells. This report provides a novel insight into understanding tumor aggressiveness and racial disparities of prostate cancer.

Synchronous bladder and prostate cancer specimens obtained from radical cystoprostatectomy: A single‑center retrospective analysis.

The aim of the present study was to analyze incidence, histopathological features and clinical outcomes of patients undergoing radical cystoprostatectomy (RCP) for bladder cancer, in which incidental prostate cancer (PCa) was found. How these types of cancer impacted the patients' management and whether prostate-sparing cystectomy could be an option for these patients was determined. The current study retrospectively analyzed the data of a cohort of patients from 'Umberto I' Hospital of Nocera Inferiore who underwent RCP for bladder transitional cell carcinoma. Patients with a preoperative diagnosis or clinical suspicion of PCa were excluded. Patients affected by incidental PCa in the RCP specimens were identified, and then their demographic, histopathological and clinical outcome data were collected. Overall, it was revealed that of the 303 patients undergoing RCP for bladder cancer, 69 (22.7%) had incidental PCa, with a median age of 71.6 (age range, 54-89 years). In total, 23 (33.33%) of the 69 patients with incidental PCa were considered to have clinically significant prostate disease. In conclusion, it was relatively common to identify incidental PCa in RCP specimens but no preoperative predictive factors were identified that were able to determine 'non-aggressive' PCa status. Therefore, the present results demonstrate the need for a careful and complete prostate removal during RCP. Nevertheless, since organ-sparing surgeries are widely performed in young population, due to the impossibility of predicting aggressive prostate cancer, these patients require close monitoring through lifelong PSA surveillance, particularly focusing on the possible relapse of PCa after RCP.

Establishing a Proteomics-Based Signature of AKR1C3-Related Genes for Predicting the Prognosis of Prostate Cancer

Aldo-keto reductase family 1 member C3 (AKR1C3) plays an important role in prostate cancer (PCa) progression, particularly in castration-resistant prostate cancer (CRPC). It is necessary to establish a genetic signature associated with AKR1C3 that can be used to predict the prognosis of PCa patients and provide important information for clinical treatment decisions. AKR1C3-related genes were identified via label-free quantitative proteomics of the AKR1C3-overexpressing LNCaP cell line. A risk model was constructed through the analysis of clinical data, PPI, and Cox-selected risk genes. Cox regression analysis, Kaplan-Meier (K-M) curves, and receiver operating characteristic (ROC) curves were used to verify the accuracy of the model, and two external datasets were used to verify the reliability of the results. Subsequently, the tumor microenvironment and drug sensitivity were explored. Moreover, the roles of AKR1C3 in the progression of PCa were verified in LNCaP cells. MTT, colony formation, and EdU assays were conducted to explore cell proliferation and drug sensitivity to enzalutamide. Migration and invasion abilities were measured using wound-healing and transwell assays, and qPCR was used to assess the expression levels of AR target genes and EMT genes. CDC20, SRSF3, UQCRH, INCENP, TIMM10, TIMM13, POLR2L, and NDUFAB1 were identified as AKR1C3-associated risk genes. These risk genes, established using the prognostic model, can effectively predict the recurrence status, immune microenvironment, and drug sensitivity of PCa. Tumor-infiltrating lymphocytes and several immune checkpoints that promote cancer progression were higher in high-risk groups. Furthermore, there was a close correlation between the sensitivity of PCa patients to bicalutamide and docetaxel and the expression levels of the eight risk genes. Moreover, through in vitro experiments, Western blotting confirmed that AKR1C3 enhanced SRSF3, CDC20, and INCENP expression. We found that PCa cells with a high expression of AKR1C3 have high proliferation ability and high migration ability and were insensitive to enzalutamide. AKR1C3-associated genes had a significant role in the process of PCa, immune responses, and drug sensitivity and offer the potential for a novel model for prognostic prediction in PCa.

Stereotactic Ablative Radiation Therapy in 3 Fractions Induces a Favorable Systemic Immune Cell Profiling in Prostate Cancer Patients

ABSTRACT The impact of radiotherapy (RT) on immune cell status in prostate cancer (PCa) is only partially determined. The aim of this study was to assess the effect of different RT strategies on peripheral B, T, and Natural killer (NK) lymphocytes at precise longitudinal time-points in PCa. 18 patients treated with stereotactic body radiation therapy (SBRT) (40 Gy/3FRX), definitive moderate-hypofractionation (62 Gy/20FRX), or post-operative conventional-fractionation RT (66–69 Gy/30FRX) were prospectively evaluated for the immune cell profile in terms of immune cell composition, differentiation stage, cytokine production and inhibitory receptor (IR) expression. The immune-monitoring of the 18 patients revealed that RT affects the balance of systemic immune cells, with the main differences observed between SBRT and conventionally fractionated RT. SBRT favorably impacts immune response in term of increased B cells, central-memory and effector-memory CD8+ T cells, along with decreased Treg cells after treatment. On the contrary, conventional fractionated RT had a long-term negative effect on the systemic immune profile, including a decrease of total lymphocyte counts accompanied by an increase of neutrophils-to-lymphocytes ratio. Total B and T cells decreased and Treg-to-CD8+ ratio increased. Functionality of T lymphocytes were not affected by any of the 3-fractionation schedules. Interestingly, SBRT significantly up-regulates the expression of V-domain immunoglobulin suppressor of T-cell activation (VISTA) in CD8+ T cells in the absence of other IRs. Our results indicate the relevance of systematic immunomonitoring during RT to identify novel immune-related target to design trials of combined radio-immunotherapy as a promising strategy in the clinical management of PCa.

Assessment of oligometastasis status of prostate cancer following combined robot-assisted radical prostatectomy and androgen deprivation versus androgen deprivation therapy alone using PSA percentage decline rate.

To compare the tumor control in prostate cancer patients with oligo-metastasis following combined robot-assisted radical prostatectomy and androgen deprivation versus androgen deprivation therapy alone based on total prostate-specific antigen (tPSA) assessment. Medical data of a total of 18 prostate cancer patients with oligometastasis administered in The First Affiliated Hospital of Nanchang University from March 2017 to March 2018 were prospectively collected. 10 patients received a combined therapy of robot-assisted radical prostatectomy and pharmaceutical androgen deprivation (RARP+ADT group), while 8 patients received pharmaceutical androgen deprivation therapy alone (ADT group). Then demographic characteristics, prostate volume, tumor characteristics and tPSA data were analysised and compared. Statistical analysis was performed using t-test for continuous variables and Pearson chi-square test or Fisher's exact test for categorical variables. No significant difference was found in patients' age (p = 0.075), prostate volume (p = 0.134) and number of bone metastasis (p = 0.342). Pre-treatment Gleason score was significantly lower in RA group (p = 0.003). Patients in RARP+ADT group had significantly lower pre-treatment tPSA (p = 0.014), while no statistical difference was noted in reexamined tPSA (p = 0.140) on follow-up. No statistical difference was noted in tPSA decline rates (declined tPSA value per day) in RARP+ADT and ADT group (8.1 ± 4.7 verse 7.5 ± 8.0 ng/ml/d, p = 0.853). However, tPSA percentage decline rate (declined tPSA percentage per day) was significantly higher in RARP+ADT group (11.6 ± 1.5%/d verses 2.9 ± 2.2%/d, p< 0.001). Immediate urinary continence was achieved in 9 patients (90%) upon removal of urethral catheter on post-operative day 7 in RARP+ADT group. ADT alone and in combination with RARP both provide effective tumor control in patients suffering from prostate cancer with oligometastasis. ADT combined with RARP exhibited significant advantage in PSA percentage decline rate without compromising patients' urinary continence. Long-term tumor control requires further follow-up.

Role of Metabolism and Metabolic Pathways in Prostate Cancer

Prostate cancer (PCa) is the common cause of death in men. The pathophysiological factors contributing to PCa are not well known. PCa cells gain a protective mechanism via abnormal lipid signaling and metabolism. PCa cells modify their metabolism in response to an excessive intake of nutrients to facilitate advancement. Metabolic syndrome (MetS) is inextricably linked to the carcinogenic progression of PCa, which heightens the severity of the disease. It is hypothesized that changes in the metabolism of the mitochondria contribute to the onset of PCa. The studies of particular alterations in the progress of PCa are best accomplished by examining the metabolome of prostate tissue. Due to the inconsistent findings written initially, additional epidemiological research is required to identify whether or not MetS is an aspect of PCa. There is a correlation between several risk factors and the progression of PCa, one of which is MetS. The metabolic symbiosis between PCa cells and the tumor milieu and how this type of crosstalk may aid in the development of PCa is portrayed in this work. This review focuses on in-depth analysis and evaluation of the metabolic changes that occur within PCa, and also aims to assess the effect of metabolic abnormalities on the aggressiveness status and metabolism of PCa.