Treatment Of Prostate Adenocarcinoma Research Articles

Identification and validation of obesity related genes signature based on microenvironment phenotypes in prostate adenocarcinoma.

The role of obesity related genes (ORGs) in the immune checkpoint inhibitors (ICIs) treatment of prostate adenocarcinoma (PRAD) has not yet been proved by research. We comprehensively evaluated the ORGs patterns in PRAD based on tumor microenvironment (TME) phenotypes and immunotherapy efficacies. Then we constructed a ORGs risk score for prognosis and a ORGs signature for accurate prediction of TME phenotype and immunotherapy efficacy in order to evaluate individual patients. Two distinct ORGs patterns were generated. The two ORGs patterns were consistent with inflammatory and non-inflammatory TME phenotypes. ORGs patterns had an important role for predicting immunotherapy efficacies. Next, we constructed a ORGs risk score for predicting each patient's prognosis with high performance in TCGA-PRAD. The ORGs risk score could be well verified in the external cohorts including GSE70769 and GSE21034. Then, we developed a ORGs signature and found it was significantly positively correlated with tumor-infiltrating lymphocytes in TCGA-PRAD. We found that each patient in the high-risk ORGs signature group represented a non-inflamed TME phenotype on the single cell level. The patients with high ORGs signature had more sensitivity to immunotherapy. And those ORGs were verified. ORGs pattern depicts different TME phenotypes in PRAD. The ORGs risk score and ORGs signature have an important role for predicting prognosis and immunotherapy efficacies.

MEDICINAL BIOMAGNETISMO IN THE TREATMENT OF PROSTATE CANCER

Prostate cancer (PC) is reported as an important neoplasm worldwide, caused by the uncontrolled multiplication of cells in the prostate. The main risk factors are age over 50 years, family history, genetic susceptibility, hormonal disorders, obesity and environmental factors. Active surveillance of low-risk PC defers aggressive treatment until disease progression and is an increasingly recommended treatment strategy. This strategy aims to reduce costs and decrease treatment-related morbidity without affecting survival. Medicinal Biomagnetism (BM) is based on the distortion of the limit of homeostasis towards hyperacidity and hyperalkalinity of two specific points for each pathogenic microorganism or glandular dysfunction. The induction of loads that are in a vibrational and energetic relationship, by means of medium intensity magnets, greater than 1000 Gauss, corrects or prevents the distortion of the pH of the organs or tissues of the human body. In this way, the neutralization of pathogenic bioenergetic distortions promotes health. The aim of this study was to evaluate the effect of BM in the treatment of prostatic adenocarcinoma, prognostic group 1. After three sessions of BM, the levels of prostate-specific antigen (PSA) decreased and the prostate adenocarcinoma regressed to discrete chronic inflammation. This study represents the first in the evaluation of BM for the treatment of CP and may stimulate further studies in this field that are likely to yield important discoveries.

Ectopic adrenocorticotrophic hormone syndrome secondary to treatment-related neuroendocrine differentiation of metastatic castrate-resistant prostate cancer.

A 64-year-old man with progressive metastatic castrate-resistant prostate adenocarcinoma presented with recurrent fluid overload, severe hypokalaemia with metabolic alkalosis and loss of glycaemic control. Clinical features were facial plethora, skin bruising and proximal myopathy. Plasma adrenocorticotrophic hormone (ACTH), serum cortisol and 24-h urinary cortisol levels were elevated. Low-dose dexamethasone failed to suppress cortisol. Pituitary MRI was normal and 68Gallium-DOTATATE PET-CT scan showed only features of metastatic prostate cancer. He was diagnosed with ectopic ACTH syndrome secondary to treatment-related neuroendocrine prostate cancer differentiation. Medical management was limited by clinical deterioration, accessibility of medications and cancer progression. Ketoconazole and cabergoline were utilised, but cortisol remained uncontrolled. He succumbed 5 months following diagnosis. Treatment-related neuroendocrine differentiation of prostate adenocarcinoma is a rare cause of ectopic ACTH syndrome. Neuroendocrine differentiation following prostate adenocarcinoma treatment with androgen deprivation has been described. Ectopic adrenocorticotrophic hormone (ACTH) syndrome should be considered where patients with metastatic prostate cancer develop acute electrolyte disturbance or fluid overload. Ketoconazole interferes with adrenal and gonadal steroidogenesis and can be used in ectopic ACTH syndrome, but the impact may be insufficient. Inhibition of gonadal steroidogenesis is favourable in prostate cancer. More data are required to evaluate the use of cabergoline in ectopic ACTH syndrome. Ectopic ACTH syndrome requires prompt management and is challenging in the face of metastatic cancer.

EARLY DIAGNOSIS AND TREATMENT IN TWO CASES OF MICROINVASIVE SQUAMOUS CELL CARCINOMA ON THE PALATE

Squamous cell carcinoma (SCC) is the most common malignancy that affects the oral cavity. It is related to smoking and drinking, which can increase the carcinogenic effect. The objective of the work is to report 2 cases of microinvasive SCC, presenting their clinical characteristics and emphasizing early diagnosis and clinical management. Case 1: A 65-year-old male smoker undergoing treatment for prostate adenocarcinoma with bone metastasis and use of alendronate complained of bilateral white plaques on the palate without painful symptoms. Case 2: A 43-year-old female smoker with no comorbidities presented with a shallow ulcer in the palate region. The diagnostic hypotheses were mild dysplasia and SCC. Incisional biopsies were performed and histopathologic reports revealed microinvasive SCC. The patients were referred for treatment. It was concluded that the dentist must be attentive to the diagnosis of oral lesions for a favorable prognosis and patient survival. Squamous cell carcinoma (SCC) is the most common malignancy that affects the oral cavity. It is related to smoking and drinking, which can increase the carcinogenic effect. The objective of the work is to report 2 cases of microinvasive SCC, presenting their clinical characteristics and emphasizing early diagnosis and clinical management. Case 1: A 65-year-old male smoker undergoing treatment for prostate adenocarcinoma with bone metastasis and use of alendronate complained of bilateral white plaques on the palate without painful symptoms. Case 2: A 43-year-old female smoker with no comorbidities presented with a shallow ulcer in the palate region. The diagnostic hypotheses were mild dysplasia and SCC. Incisional biopsies were performed and histopathologic reports revealed microinvasive SCC. The patients were referred for treatment. It was concluded that the dentist must be attentive to the diagnosis of oral lesions for a favorable prognosis and patient survival.

Case Report of Mesorectal Failure in the Treatment of Prostate Adenocarcinoma

Prostate cancer afflicts a substantial portion of the male population with increasing incidence each decade after the age of 40. Standard of care for localized disease at presentation includes prostatectomy and/or radiation therapy which can include management of pelvic lymph nodes. However, the selection of lymph nodes treated by radiotherapy remains variable among practitioners including individual practitioners in the same institution. We present a patient with prostate adenocarcinoma who underwent radical prostatectomy with adjuvant radiotherapy for lymph node involvement and developed mesorectal failure secondary to metastatic spread to untreated tissue.

A STUDY TO CORRELATE HISTOPATHOLOGY, SERUM PSA LEVEL AND IMMUNOHISTOCHEMICAL EXPRESSION OF ER & PR IN PROSTATIC GROWTH

Objectives- Prostate is a bromusculoglandular structure situated at the neck of urinary bladder. It enlarges due to benign hyperplasia of prostate (BHP), prostatic intraepithelial neoplasia (PIN) or adenocarcinoma. Enlargement of prostate is associated with raised serum level of prostate-specic antigen (PSA) and altered expression of estrogen receptor (ER) and progesterone receptor (PR). The aim of our study is to correlate the histopathology, PSA levels and altered expression of ER and PR by immunohistochemistry in different prostatic growth lesions. Methodology- Patients diagnosed as having prostatic growth were enrolled and their serum PSA levels were noted. Histopathological examination and immunohistochemical analysis of prostatic tissues for ER and PR were carried out to nd out correlation of different type of growth with serum PSA level and expression of ER and PR. Results- A total 96 cases studied of them 61(63.54%) patients presented with BHP, 20(20.83%) patients with BHP with chronic prostatitis, 3 patients presented with metaplastic changes, 5 cases with of PIN and 6 patients presented with adenocarcinoma with different Gleason score. PR expression positivity in epithelial cells and stromal cells of BHP cases were 51(83.6%) and 53(86.88%) respectively. Patients presented with adenocarcinoma showed only 33.33 %( 2cases) positivity in epithelial cells and 50% (3cases) positivity in stromal cells. Serum PSA level were signicantly higher in adenocarcinoma patients as compare to BHP patients. Conclusion- By observing these ndings it can be suggested that and antiprogesterone therapy may be helpful in the treatment of prostatic adenocarcinoma.

Abstract 3056: Alpha particle radiobiology and the treatment of prostate adenocarcinoma

Abstract Background: Castration-resistant prostate cancer (CRPC) is treated with the androgen receptor (AR) antagonist Enzalutamide (ENZA). However, early positive outcomes are later reversed by acquired resistance, ultimately leading to lethal AR-independent disease progression. High linear energy transfer (LET) alpha particle emitting drugs targeting Prostate Specific Membrane Antigen (e.g., [Actinium-225]-PSMA617) are potent and specific, yielding radiological and biomarker disease regression, but are not curative. DNA damage responses (DDR) in irradiated cells repair double strand breaks (DSB) allowing CRPC to escape. We are exploring the pharmacological effect of AR signaling on alpha particle therapy. AR signaling has a significant role in DDR and a better understanding of the alpha radiobiology is necessary to better deploy these potent drugs in combination. Methods: Alpha particle-induced DDR was investigated using readouts of clonogenic survival, cell cycle, apoptosis, and gene expression in AR-positive LNCaP-AR and AR-negative DU145 cells that were also treated with ENZA and an ATM inhibitor (ATMi, KU59403). Briefly, cells were seeded on mylar, treated with ENZA and ATMi and subsequently irradiated with alpha particles. Clonogenic survival was quantified at 10 days post alpha-irradiation. DNA damage was confirmed by imaging gamma-H2AX foci. Flow cytometry was used to analyze cell cycle arrest and apoptosis. Relative gene expression was quantified from RNA extracted immediately after and 10 days post-irradiation via RT-qPCR. Results: We observed the formation of increased DNA DSB (gamma-H2AX foci) versus controls after irradiation. ENZA radiosensitized LNCaP-AR versus untreated cells as evidenced by the D0 values obtained from clonogenic assays. However, combination of ENZA and alpha particles also upregulated expression of DDR genes. LNCaP-AR were in G2 arrest with increased apoptosis following irradiation. An ATMi was added to the regimen to address the upregulated DDR and increased apoptosis was observed. Altogether, these results indicate that cells are radiosensitized by ENZA but concomitant activation of DDR requires ATMi to improve therapy. Conclusion: DNA damage caused by alpha particles alone does not eradicate CRPC because some cells can repair DSB. Cell control from ENZA treatment alone is transient, leading to development of acquired resistance and disease relapse. Combining alpha particles and ENZA radiosensitizes AR-dependent prostate cancer cells, but DDR rescues a fraction of cells. Inhibiting the ATM pathway in AR-antagonized cells, in combination with high LET alpha irradiation, is a better approach to overcome prostate cancer cell resistance mechanisms. Combination ENZA/ATMi/alpha particles is a strategy designed to address the radioresistant subpopulation and could avoid CRPC progression to the more lethal, non-treatable stage of this disease. Citation Format: Barbara P. Mello, Ekaterina Revskaya, David A. Scheinberg, Michael R. McDevitt. Alpha particle radiobiology and the treatment of prostate adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3056.

Reprogramming of the FOXA1 cistrome in treatment-emergent neuroendocrine prostate cancer

Lineage plasticity, the ability of a cell to alter its identity, is an increasingly common mechanism of adaptive resistance to targeted therapy in cancer. An archetypal example is the development of neuroendocrine prostate cancer (NEPC) after treatment of prostate adenocarcinoma (PRAD) with inhibitors of androgen signaling. NEPC is an aggressive variant of prostate cancer that aberrantly expresses genes characteristic of neuroendocrine (NE) tissues and no longer depends on androgens. Here, we investigate the epigenomic basis of this resistance mechanism by profiling histone modifications in NEPC and PRAD patient-derived xenografts (PDXs) using chromatin immunoprecipitation and sequencing (ChIP-seq). We identify a vast network of cis-regulatory elements (N~15,000) that are recurrently activated in NEPC. The FOXA1 transcription factor (TF), which pioneers androgen receptor (AR) chromatin binding in the prostate epithelium, is reprogrammed to NE-specific regulatory elements in NEPC. Despite loss of dependence upon AR, NEPC maintains FOXA1 expression and requires FOXA1 for proliferation and expression of NE lineage-defining genes. Ectopic expression of the NE lineage TFs ASCL1 and NKX2-1 in PRAD cells reprograms FOXA1 to bind to NE regulatory elements and induces enhancer activity as evidenced by histone modifications at these sites. Our data establish the importance of FOXA1 in NEPC and provide a principled approach to identifying cancer dependencies through epigenomic profiling.

TRPM8 protein expression in hormone naïve local and lymph node metastatic prostate cancer.

SummaryObjectiveProstate cancer (PCa) is the second most common malignancy in men. Radiotherapy and surgery successfully control organ-confined tumors, although, locally advanced/high-risk PCa frequently progress to the metastatic stage of the disease, which is uncurable. Identification of novel strategies to improve the efficacy of standard clinical protocols is a primary need. Among the molecular targets of potential clinical interest recently highlighted by accurate preclinical studies, the TRPM8 cation channel is particularly promising. In this study, we aim at establishing a standardized immunohistochemistry protocol to evaluate TRPM8 expression in normal and pathological prostate tissues.MethodsThe specificity and sensitivity of TRPM8 antibody ACC-049 was validated in different human prostate cell lines by western blot and immunocytochemistry analyses. Expression of the TRPM8 channel in normal and pathological prostate tissue was evaluated by immunohistochemistry using a tissue microarray containing 58 cases of prostate adenocarcinomas and in primary and lymph nodes metastatic human PCa matched specimens.ResultsTRPM8 expression marks luminal epithelial cells in benign prostate tissue. In malignant lesions of the prostate, TRPM8 expression is frequently more abundant in advanced stages of the disease (PCa stage III/IV). Finally, lymph node metastases and matched primary tumors show similar amounts of the channel.ConclusionsCollectively, our results reinforce the importance of TRPM8 as prostate biomarker and emphasize the value of the channel as promising novel molecular target for the treatment of prostate adenocarcinoma.

Prognostic value of FUS immunoexpression for Gleason patterns and prostatic adenocarcinoma progression

BackgroundRisk assessment is important when planning treatment for prostatic adenocarcinoma. Gleason score is a strong predictor of disease progression, despite the possibility of mismatches between biopsy and prostatectomy. In order to increase the accuracy of Gleason scores, several markers have been proposed. One of these, FUS (fused in sarcoma), plays a role in RNA processing, chromosome stability and gene transcription. Patients and methodsNon-neoplastic tissue and Gleason pattern 3, 4 and 5 adenocarcinoma samples were submitted to tissue microarrays. Gleason pattern 3 and 4 were compared to the final Gleason score. We also conducted univariate and multivariate tests to probe the association between FUS expression in adenocarcinoma samples and outcome: biochemical persistence and biochemical recurrence (separately or pooled as biochemical progression), biochemical failure after salvage radiotherapy, and systemic progression. ResultsOur cohort consisted of 636 patients. Non-neoplastic tissue stained less frequently (36.5%) than neoplastic tissue (47.4%), with expression increasing from Gleason pattern 3 towards pattern 5. FUS-positive Gleason pattern 3 was significantly associated with final Gleason scores >6 (HR = 1.765 [1.203–2.589]; p = 0.004). Likewise, FUS-positive Gleason pattern 4 was significantly associated with final Gleason scores ≥7 (4 + 3). The association between FUS positivity and biochemical persistence and recurrence observed in the univariate analysis was not maintained in the multivariate analysis (HR = 1.147 [0.878–1.499]; p = 0.313). ConclusionNon-neoplastic tissue was less frequently FUS-positive than neoplastic tissue. FUS positivity in Gleason pattern 3 and 4 increased the risk of high grade adenocarcinoma and was associated with clinical/laboratory progression in the univariate, but not in multivariate analysis.

Disparities in Refusal of Locoregional Treatment for Prostate Adenocarcinoma.

We assessed sociodemographic factors associated with and survival implications of refusal of potentially survival-prolonging locoregional treatment (LT, including radiotherapy and surgery) despite provider recommendation among men with localized prostate adenocarcinoma. The National Cancer Database (2004-2015) identified men with TxN0M0 prostate cancer who either received or refused LT despite provider recommendation. Multivariable logistic regression defined adjusted odds ratios (AORs) with 95% CI of refusing LT, with sociodemographic and clinical covariates. Models were stratified by low-risk and intermediate- or high-risk (IR or HR) disease, with a separate interaction analysis between race and risk group. Multivariable Cox proportional hazard ratios compared overall survival (OS) among men who received versus refused LT. Of 887,839 men (median age 64 years, median follow-up 6.14 years), 2,487 (0.28%) refused LT. Among men with IR or HR disease (n = 651,345), Black and Asian patients were more likely to refuse LT than White patients (0.35% v 0.29% v 0.17%; Black v White AOR, 1.75; 95% CI, 1.52 to 2.01; P < .001; Asian v White AOR, 1.47; 95% CI, 1.05 to 2.06; P = .027, race * risk group interaction P < .001). Later year of diagnosis, community facility type, noninsurance or Medicaid, and older age were also associated with increased odds of LT refusal, overall and when stratifying by risk group. For men with IR or HR disease, LT refusal was associated with worse OS (5-year OS 80.1% v 91.5%, HR, 1.65, P < .001). LT refusal has increased over time; racial disparities were greater in higher-risk disease. Refusal despite provider recommendation highlights populations that may benefit from efforts to assess and reduce barriers to care.

Zinc finger C3H1 domain-containing protein (ZFC3H1) evaluates the prognosis and treatment of prostate adenocarcinoma (PRAD): A study based on TCGA data

ABSTRACT The present study was aimed to evaluate the expression profile of Zinc finger C3H1 domain-containing protein (ZFC3H1) using bioinformatic analysis of public datasets from The Cancer Genome Atlas database (TCGA). The results showed that the expression levels of ZFC3H1 were notably lower than the corresponding non-cancerous tissues in prostate adenocarcinoma (PRAD), and patients in the high ZFC3H1-expression group showed poor survival. We hypothesized that the low expression of ZFC3H1 in tumor tissue might have be an inhibitory effect on the autoimmune system. We predicted the regulatory target and protein interaction partner network of ZFC3H1, and identified a PPI network composed of 26 node genes in PRAD. Furthermore, we found that the expression levels of MPHOSPH6 (encoding M-phase phosphoprotein 6) and MRPS31 (encoding mitochondrial ribosomal protein S31) were lower in PRAD tissues than in non-cancerous tissues, and the survival time of patients with high MPHOSPH6 and MRPS31 expression was poor. To further demonstrate the role of ZC3H1 in PRAD, we knocked-down the ZFC3H1 expression and found that the inhibition of ZFC3H1 significantly inhibited PRAD cell migration and invasion. Furthermore, ZFC3H1 siRNA treatment could reduce cell viability and increase the number of apoptotic cells in PRAD cells. Taken together, ZFC3H1 could represent a new marker for PRAD prognosis and provide a reference for the development of new therapies to treat PRAD.

Novel therapeutic compounds for prostate adenocarcinoma treatment: An analysis using bioinformatic approaches and the CMap database.

Introduction:Prostate adenocarcinoma is the most frequently diagnosed malignancy, particularly for people >70 years old. The main challenge in the treatment of advanced neoplasm is bone metastasis and therapeutic resistance for known oncology drugs. Novel treatment methods to prolong the survival time and improve the life quality of these specific patients are required. The present study attempted to screen potential therapeutic compounds for the tumor through bioinformatics approaches, in order to provide conceptual treatment for this malignant disease.Methods:Differentially expressed genes were obtained from the Gene Expression Omnibus database and submitted into the Connectivity Map database for the detection of potentially associated compounds. Target genes were extracted from the search results. Functional annotation and pathway enrichment were performed for the confirmation. Survival analysis was used to measure potential therapeutic effects.Results:It was revealed that 3 compounds (vanoxerine, tolnaftate, and gabexate) may help to prolong the disease-free survival time from tumor metastasis of patients with the tumor. A total of 6 genes [also-keto reductase family 1 member C3 (AKR1C3), collagen type III α 1 chain (COL3A1), lipoprotein lipase (LPL), glucuronidase, β pseudogene 11 (GUSBP11), apolipoprotein E (APOE), and collagen type I α 1 chain (COL1A1)] were identified to be the potential therapeutic targets for the aforementioned compounds.Conclusion:In the present study, it was speculated that 3 compounds may function as the potential therapeutic drugs of bone metastatic prostate adenocarcinoma; however, further studies verifying vitro and in vivo are necessary.

Subsequent Anal Malignancies In Patients With Prostate Adenocarcinoma Treated With Brachytherapy Or External Beam Radiotherapy Compared With Surgery

It is important to understand the potential long-term sequelae of treatment of prostate adenocarcinoma, as patients are being diagnosed at a younger age and surviving longer. The risk of subsequent malignancies after brachytherapy (BT) has been reported to be low due to the limited exposure of normal tissue to radiation given the rapid dose fall off. However, our clinical experience suggested an increased risk of subsequent anal malignancy in patients receiving prostate BT. This risk may have implications for post-treatment surveillance. Therefore, we sought to compare the risk of subsequent anal malignancy after BT or external beam radiotherapy (EBRT) compared to surgery for prostate adenocarcinoma. Data regarding the rate of incidence from the Surveillance, Epidemiology, and End Results Program cancer registry (1988–2016) were used to directly compare subsequent anal malignancy risk in men with prostate adenocarcinoma treated with BT or EBRT versus surgery alone using two-sided Poisson exact rate ratio tests. We also compared risks in patients whose follow up time since prostate cancer diagnosis was ≥ 5 years. The year 1988 represents the first year in which radiotherapy modality (EBRT versus BT) was reported. Directly comparing the risks in each radiotherapy group with the surgery group helps to avoid problems associated with underreporting subsequent malignancies. Subsequent anal malignancies developed in 12 of 25,011 men with prostate adenocarcinoma who received BT, 28 of 65,353 who underwent EBRT, and 10 of 85,868 men who underwent surgery. BT was associated with a statistically significant increase in the risk of subsequent anal cancer (rate ratio (RR) 3.83 [95% confidence interval (CI): 1.52, 9.90] relative to surgery; P = 0.004). EBRT for prostate adenocarcinoma was also associated with a statistically significant increase in the risk of subsequent anal cancer (RR 3.39 [95 % CI: 1.60, 7.81] relative to surgery; P < 0.001). Among patients whose follow up time since prostate cancer diagnosis was ≥ 5 years, EBRT was not associated with an increased risk of subsequent anal cancer (RR 2.66 [95% CI: 0.87, 9.64] relative to surgery; P = 0.09); however, BT was associated with a statistically significant increase in the risk of subsequent anal cancer (RR 5.03 (95% CI: 1.45 – 19.53) relative to surgery; P = 0.009). Both BT and EBRT for prostate adenocarcinoma were associated with a statistically significant enhancement in the risk of subsequent anal cancers. While subsequent anal cancers occurred rarely, the increased risk of subsequent anal cancers after prostate BT, especially in those with follow up ≥ 5 years after prostate cancer diagnosis, may have implications for surveillance after treatment.

Magnet-Assisted Robotic Prostatectomy Using the da Vinci SP Robot: An Initial Case Series.

Introduction: Tissue retraction during minimally invasive surgery has been achieved to date with patient positioning or additional instrumentation. The Levita™ Magnetic Surgical System (San Mateo, CA), a novel, noninvasive, magnetic retraction device for minimally invasive surgery, has been used to facilitate reduced-port robotic prostatectomy using a multiport robotic platform. With the release of the da Vinci SP robotic system (Intuitive, Sunnyvale, CA), we now report a multi-institutional initial case series of magnet-assisted robotic prostatectomy using the single-port robotic platform. Materials and Methods: An IRB-approved, retrospective chart review was performed of all patients undergoing robot-assisted radical prostatectomy using the da Vinci SP surgical system and a single Levita magnetic retractor in treatment of prostatic adenocarcinoma at two institutions from November 2018 to January 2019. Preoperative, intraoperative, and postoperative data were collected for descriptive analysis. Results: A total of 15 men, median age 62 years (range 57-71), with mean PSA 7.0 ± 2.3 underwent surgery. The robotic cannula and a single 12-mm assistant port were utilized in all cases, the latter for suction, suture passage, and clip placement; the magnetic retractor aided with posterior dissection, dorsal venous complex stitch placement, bladder neck dissection, and lymphadenectomy. No cases required conversion to a multiport robotic platform, laparoscopy, or open surgery, nor placement of additional assistant ports. No intraoperative or postoperative complications occurred. Average operative time was 224 ± 43 minutes and blood loss was 198 ± 115 mL. All patients were discharged home within 2 days of surgery. Conclusions: Robotic prostatectomy utilizing the da Vinci SP system is feasible, safe, and effective. Use of the magnetic retractor facilitates tissue exposure and improves procedure ergonomics, mimicking the conventional multiport technique. Further exploration of magnet utilization in robotic surgery and optimization of assistant port placement for true single-site surgery is warranted.

Salvage cryoablation for local recurrence of prostatic cancer after curative therapy

PurposeThe purpose of this study was to determine the efficacy of salvage cryotherapy for intra-prostatic and local extraprostatic recurrences after curative treatment of prostate adenocarcinoma. Material and methodTwenty-eight men (mean age, 69±6 [SD] years; range: 51–82 years) treated with cryoablation for prostatic (N=21) or extraprostatic (N=7) recurrent prostate cancer after radiotherapy with or without associated prostatectomy were included. Technical success, complication and recurrences were reported. Biological recurrence was defined as an elevation ≥2ng/mL of prostate specific antigen (PSA) serum level after the treatment. ResultsThe mean follow-up was 18 months. Among the 21 patients with intraprostatic recurrence, 14 had successful cryotherapy with a mean decrease in serum prostate-specific antigen (PSA) levels of −5.7±2.6 (SD) ng/mL (range: −2.1 to −16.9ng/mL). Four patients (19%) had early progression and three patients (14%) had delayed biological recurrence (mean time: 15 months). Among the 7 patients with extraprostatic recurrence, 2/7 (291%) had successful cryotherapy with a decrease in PSA serum level of −2.7±1.6 (SD) ng/mL (range: −0.5–−5.5ng/mL) and 4/7 (57%) had early biological recurrence after cryotherapy that required androgen deprivation therapy, whereas 1/7 (4%) was lost to follow-up. No major complications were observed for both intra- and extraprostatic recurrence. ConclusionSalvage cryoablation of locally recurrent prostate cancer after curative treatment is feasible and safe when the half prostate is treated. It could delay initiation of androgen deprivation therapy in these patients.

Abstract 4713: Extraction, purification and evaluation of prmt5-inhibitory phytochemical compounds for the treatment of prostate adenocarcinoma

Abstract The development and advancement of prostate cancer is supported by a plethora of genetic and proteomic abnormalities, including events of post-translational modifications. The protein arginine methyltransferase 5 (PRMT5) enzyme regulates epigenetic events of histone modifications and of post-translational modifications within protein signaling pathways. Under abnormal conditions of overexpression and/or upregulation, PRMT5 functions by constitutively driving the growth and/or proliferation of dysregulated cells. Overexpression and/or upregulation of PRMT5 correlates with disease progression as observed among numerous cancer types, including breast, colorectal, leukemia, lung, melanoma and prostate cancers. We demonstrated previously that PRMT5 localized to the cytoplasm, functions to drive both growth and proliferation of prostatic tumors. Plants naturally produce chemical toxins as mechanisms of defense against microbial and other biological threats. Human exploitation, consumption and/or application of agents isolated from plants for therapeutic intervention dates back throughout the millennia. In this study, we extracted, purified and evaluated natural, small, chemical compounds from plant products that antagonize PRMT5 activity in prostate cancer cells. We found that crude and purified extracts of Dendrobium, Fennel Seed and Magnolia plants attenuated prostate tumor growth and proliferation by selective inhibition of PRMT5 methyltransferase activity. These findings establish the first set of natural PRMT5-specific inhibitors reported. Citation Format: Oliver H. Richmond, Zhengxin Wang. Extraction, purification and evaluation of prmt5-inhibitory phytochemical compounds for the treatment of prostate adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4713.

Prenatal exposure to finasteride promotes sex-specific changes in gerbil prostate development.

Finasteride is a drug that is widely used in the treatment of benign prostatic hyperplasia, hair loss and even as a chemotherapeutic agent in the treatment of prostatic adenocarcinoma. However, its use is known to cause several side effects in adults and it can also cause changes in the embryonic development of the male prostate, which is a cause for concern given the possibility of the accumulation of finasteride in the environment. Nevertheless, no studies have investigated the effects of finasteride on the development of the prostate in females, which occurs in several species of mammals. To evaluate the effects of intrauterine exposure to finasteride (500μgkg-1 day-1) on postnatal prostate development in the Mongolian gerbil in the present study, we used immunohistochemistry, immunofluorescence, serological analysis and three-dimensional reconstruction techniques. Differences were observed in the effects of finasteride on periductal smooth muscle and cell proliferation between the sexes, as well as intersex differences in the presence of the androgen receptor, which was elevated in males, and the oestrogen receptor ERα, which was increased in females. Together, the data indicate that the female prostate has its own hormone dynamics and that there are sex-specific differences in the way in which the female prostate reacts to prenatal exposure to finasteride.

Magnetic-assisted robotic surgery: initial case series of reduced-port robotic prostatectomy

Minimally invasive radical prostatectomy has rapidly been adopted as the primary means of surgical intervention for prostate cancer. Intraoperative tissue retraction relies on either gravity (via positioning) or use of additional ports and instrumentation. We report the use of a novel trocar-less magnetic retractor system to aid with tissue retraction. Three patients underwent robotic-assisted radical prostatectomy in the treatment of prostatic adenocarcinoma at a single tertiary care institution. All surgeries utilized the Levita™ Magnetic Surgical System (San Mateo, CA) without the use of a fourth robotic arm. The magnetic grasper was used to manipulate the bowel, peritoneum, seminal vesicles, and prostatic capsule. Demographic, pre-operative, and perioperative information were collected. No cases required placement of any additional ports. No intraoperative or immediate post-operative complications occurred. No tissue tearing or subjective tissue damage was noted by placement or removal of the magnetic retractor. Mean operative time was 216 ± 17min and mean blood loss was 333 ± 57mL. All patients were discharged to home on post-operative day 1. Robotic prostatectomy utilizing a magnetically anchored tissue grasper appears to be safe and effective while reducing the number of ports (fourth robotic arm) needed. Further investigation is warranted.

Morphological changes in tumor and nontumor tissue in the treatment of prostate adenocarcinoma with high-intensity focused ultrasound in combination with androgen deprivation

To investigate structural changes in the tumor and nontumor tissues of the prostate in patients with its cancer (PC) after treatment with high-intensity focused ultrasound (HIFU) in combination with androgen deprivation to clarify criteria for evaluating the efficiency of treatment. Comparative morphological, immunohistochemical, and morphometric analyses were carried out to examine 253 pre- and postoperative biopsy specimens, as well as transurethral resection specimens from 32 patients with localized PC and with or without a local recurrence within 3 years after a HIFU session. HIFU ablation was accompanied by coagulation necrosis and progressive pancreatic fibrosis with complete tumor regression or by a reduction in the number of positive columns (by an average of 58%) in cases with recurrence. An inverse relationship was found between the degree of a reduction in the nontumor parenchyma in the control specimens and the probability of a recurrence - a less than 20% reduction in the non-tumor glands corresponded to a 3.4-fold increased risk of tumor progression. The development of recurrence was associated with less differentiated PC (GS ≥4+3) and the presence of cribriform structures in the pretreatment samples. Combined androgen deprivation as the maximum blockade was associated with the most pronounced signs of therapeutic pathomorphism, with a reduction of the microcirculatory bed in the focus of residual tumor, and a decrease in the frequency of local progression. Neoadjuvant hormone therapy contributes to the enhanced efficiency of HIFU treatment for PC. A less than 20% reduction in nontumor parenchyma volumes in the control biopsy specimens may indicate insufficient ablation in pancreatic tissue and serve as a marker for increased risk of local progression.