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Prostate Cancer

Prostate cancer accounts for over a quarter of all cancers in men. The prostate is a small male sex gland located below the bladder, it produces fluid that becomes semen. Prostate cancer occurs mostly in older men, it is rare before the age of 50, and the risk increases with age. There has been an increase in the incidence of prostate cancer since the early 1980's, most likely due to an increased use of screening using the prostate-specific antigen (PSA) test. However, the role as screening for prostate cancer remains controversial. World-wide about 395,000 men are diagnosed with prostate cancer each year.

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Molecular Biology of Prostate Cancer
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    MeSH term: Prostatic Neoplasms
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Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Bravaccini S, Fonzi E, Tebaldi M, et al.
Estrogen and Androgen Receptor Inhibitors: Unexpected Allies in the Fight Against COVID-19.
Cell Transplant. 2021 Jan-Dec; 30:963689721991477 [PubMed] Related Publications
TRANSLATIONAL RELEVANCE: No prophylactic treatments for COVID-19 have been clearly proven and found. In this pandemic context, cancer patients constitute a particularly fragile population that would benefit the best from such treatments, a present unmet need. TMPRSS2 is essential for COVID-19 replication cycle and it is under androgen control. Estrogen and androgen receptor dependent cues converge on TMPRSS2 regulation through different mechanisms of action that can be blocked by the use of hormonal therapies. We believe that there is enough body of evidence to foresee a prophylactic use of hormonal therapies against COVID-19 and this hypothesis can be easily tested on cohorts of breast and prostate cancer patients who follow those regimens. In case of pandemic, if the protective effect of hormonal therapies will be proven on cancer patients, the use of specific hormonal therapies could be extended to other oncological groups and to healthy individuals to decrease the overall risk of infection by SARS-CoV-2.
Given the COVID-19 coronavirus emergency, a special focus is needed on the impact of this rapidly spreading viral infection on cancer patients. Androgen receptor (AR) signaling in the transmembrane protease serine 2 (TMPRSS2) regulation is emerging as an important determinant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) susceptibility. In our study, we analyzed AR and TMPRSS2 expression in 17,352 normal and 9,556 cancer tissues from public repositories and stratified data according to sex and age. The emerging picture is that some patient groups may be particularly susceptible to SARS-CoV-2 infection and may benefit from antiandrogen- or tamoxifen-based therapies. These findings are relevant to choose proper treatments in order to protect cancer patients from concomitant SARS-CoV-2 contagion and related symptoms and put forward the idea that hormonal therapies could be used as prophylactic agents against COVID-19.

Grewal K, Grewal K, Tabbara IA
PARP Inhibitors in Prostate Cancer.
Anticancer Res. 2021; 41(2):551-556 [PubMed] Related Publications
Treatment of metastatic prostate cancer has evolved significantly over the past decade. Palliative therapy has, historically, consisted of androgen deprivation, chemotherapy and different radiation therapy approaches. More recently, breakthrough therapy with the use of poly-ADP-ribose polymerase (PARP) inhibitors has led to significant improvement in the outcome of patients with metastatic prostate cancer who harbor certain genetic mutations. This concise review focuses on the 3 PARP inhibitors that have shown activity in metastatic prostate cancer.

Liu X, Shi D, Guo L, et al.
Echogenic, Ultrasound-Sensitive Chitosan Nanodroplets for Spatiotemporally Controlled
Int J Nanomedicine. 2021; 16:421-432 [PubMed] Free Access to Full Article Related Publications
Purpose: To synthesize echogenic chitosan/perfluorohexane nanodroplets (CNDs) for DKK-2 gene delivering in a spatiotemporally controlled manner in vitro.
Methods: The characteristics, contrast-enhanced ultrasound imaging, DNA binding and DNase protection capacity, DKK-2 gene transfection and effects on LNCaP cells of these CNDs were investigated.
Results: The obtained CNDs showed positive surface charges and could attract the genetic cargo with negative surface charges to form nanocomplexes. Agarose gel electrophoresis confirmed binding of the CNDs and pDNA. DKK-2 pDNA-loaded CNDs, in combination with ultrasound, ruptured and released DKK-2 pDNA, entering LNCaP cells through nano-scale pores in the cell membrane, which further reduced the proliferation of LNCaP cells.
Conclusion: These stable and safe CNDs may be a promising choice to achieve efficient ultrasound-mediated gene delivery to specific tissues in a spatiotemporally controlled manner.

Choksi P, Gay BL, Reyes-Gastelum D, et al.
Understanding Osteoporosis Screening Practices in Men: A Nationwide Physician Survey.
Endocr Pract. 2020; 26(11):1237-1243 [PubMed] Related Publications
OBJECTIVE: To understand osteoporosis screening practices, particularly in men, by a diverse cohort of physicians, including primary care physicians, endocrinologists, and geriatricians.
METHODS: We surveyed randomly selected members of the American Academy of Family Practice, Endocrine Society, and American Geriatrics Society. Respondents were asked to rate how often they would screen for osteoporosis in four different clinical scenarios by ordering a bone density scan. Multivariable logistic regression analyses were conducted to determine factors associated with offering osteoporosis screening in men in each clinical scenario. Physicians were also asked to note factors that would lead to osteoporosis screening in men.
RESULTS: Response rate was 63% (359/566). While 90% respondents reported that they would always or frequently screen for osteoporosis in a 65-year-old post-menopausal woman, only 22% reported they would screen a 74-year-old man with no significant past medical history. Endocrinologists were more likely to screen a 74-year-old man compared to primary care physicians (odds ratio, 2.32; 95% confidence interval, 1.10 to 4.88). In addition to chronic steroid use (94%), history of nontraumatic fractures (88%), and androgen-deprivation therapy for prostate cancer (82%), more than half the physicians reported suppressive doses of thyroid hormone (64%) and history of falls (52%) as factors leading to screening for osteoporosis in men.
CONCLUSIONS: Our survey results highlight heterogeneity in osteoporosis screening in men, with underscreening in some scenarios compared to women, and identify factors that lead to screening in men. These findings can help design interventions to improve osteoporosis screening in men.

Zhang Y, Chen B, Xu N, et al.
Exosomes Promote the Transition of Androgen-Dependent Prostate Cancer Cells into Androgen-Independent Manner Through Up-Regulating the Heme Oxygenase-1.
Int J Nanomedicine. 2021; 16:315-327 [PubMed] Free Access to Full Article Related Publications
Background: Castration-resistant prostate cancer (CRPC) is still considered incurable, even though the mechanisms of CRPC had been extensively researched. Studies have demonstrated that exosomes in the tumor microenvironment contribute to prostate cancer development and progression. However, the role of exosomes in the process of CRPC progression has not yet been determined.
Methods: Co-culturing and exosome treatment assays combined with in vitro and in vivo assays were performed to determine the function of exosomes in the transformation of androgen-dependent prostate cancer (ADPC) cells into androgen-independent cells. Then, the mRNA expression profiles of ADPC cells and ADPC cells co-cultured with androgen-independent prostate cancer (AIPC) cell-derived exosomes were studied using microarrays. After silencing the expression of heme oxygenase-1 (HMOX1), Western blotting, quantitative real-time PCR, immunohistochemistry (IHC) studies, and MTS assay were used to confirm the mechanisms of exosome participation in CRPC progression.
Results: The results showed that ADPC cells acquired tolerance for androgen deprivation due to the exosome-mediated communication between cells. AIPC cell-derived exosomes promoted the transformation of ADPC cells into androgen-independent cells in vivo and in vitro. Microarray analysis revealed that HMOX1 in ADPC cells was up-regulated after treatment with AIPC cell-derived exosomes. Further results showed that HMOX1 is overexpressed in human AIPC specimens and protects ADPC cells from androgen deprivation.
Conclusions: Our findings revealed that exosomes contribute to CRPC progression via promoting the transition of prostate cancer cells into an androgen-independent growth stage by activating HMOX1.

Wu G, Sun R, Hong H, et al.
Contrast-enhanced ultrasound diagnosis of prostatic sarcoma: Two case reports.
Medicine (Baltimore). 2021; 100(2):e24038 [PubMed] Free Access to Full Article Related Publications
RATIONALE: Prostatic sarcoma (PS) is a very rare malignant tumor that accounts for <0.1% of prostate malignancies, and Ewing's sarcoma is an extremely rare form of PS.
PATIENT CONCERNS: We reported on a 64-year-old patient with PS and a 36-year-old patient with Ewing's sarcoma, both of whom were examined by contrast-enhanced ultrasonography (CEUS) before surgery.
DIAGNOSES: The 2 cases were proven to be prostatic stromal sarcoma, which was confirmed by imaging manifestations and histopathological findings.
INTERVENTIONS: The 64-year-old patient underwent radical prostatectomy, and the 36-year-old patient underwent chemotherapy combined with local radiotherapy.
OUTCOMES: PS showed diffuse enlargement of the prostate on sonography, and the necrotic liquefying area within the large vessels could be clearly displayed by CEUS. CEUS can be advocated as a valuable noninvasive and safe imaging diagnosis method for PS.

Shafi AA, McNair CM, McCann JJ, et al.
The circadian cryptochrome, CRY1, is a pro-tumorigenic factor that rhythmically modulates DNA repair.
Nat Commun. 2021; 12(1):401 [PubMed] Free Access to Full Article Related Publications
Mechanisms regulating DNA repair processes remain incompletely defined. Here, the circadian factor CRY1, an evolutionally conserved transcriptional coregulator, is identified as a tumor specific regulator of DNA repair. Key findings demonstrate that CRY1 expression is androgen-responsive and associates with poor outcome in prostate cancer. Functional studies and first-in-field mapping of the CRY1 cistrome and transcriptome reveal that CRY1 regulates DNA repair and the G2/M transition. DNA damage stabilizes CRY1 in cancer (in vitro, in vivo, and human tumors ex vivo), which proves critical for efficient DNA repair. Further mechanistic investigation shows that stabilized CRY1 temporally regulates expression of genes required for homologous recombination. Collectively, these findings reveal that CRY1 is hormone-induced in tumors, is further stabilized by genomic insult, and promotes DNA repair and cell survival through temporal transcriptional regulation. These studies identify the circadian factor CRY1 as pro-tumorigenic and nominate CRY1 as a new therapeutic target.

Abrahams HJG, Knoop H, Schreurs M, et al.
Moderators of the effect of psychosocial interventions on fatigue in women with breast cancer and men with prostate cancer: Individual patient data meta-analyses.
Psychooncology. 2020; 29(11):1772-1785 [PubMed] Related Publications
OBJECTIVE: Psychosocial interventions can reduce cancer-related fatigue effectively. However, it is still unclear if intervention effects differ across subgroups of patients. These meta-analyses aimed at evaluating moderator effects of (a) sociodemographic characteristics, (b) clinical characteristics, (c) baseline levels of fatigue and other symptoms, and (d) intervention-related characteristics on the effect of psychosocial interventions on cancer-related fatigue in patients with non-metastatic breast and prostate cancer.
METHODS: Data were retrieved from the Predicting OptimaL cAncer RehabIlitation and Supportive care (POLARIS) consortium. Potential moderators were studied with meta-analyses of pooled individual patient data from 14 randomized controlled trials through linear mixed-effects models with interaction tests. The analyses were conducted separately in patients with breast (n = 1091) and prostate cancer (n = 1008).
RESULTS: Statistically significant, small overall effects of psychosocial interventions on fatigue were found (breast cancer: β = -0.19 [95% confidence interval (95%CI) = -0.30; -0.08]; prostate cancer: β = -0.11 [95%CI = -0.21; -0.00]). In both patient groups, intervention effects did not differ significantly by sociodemographic or clinical characteristics, nor by baseline levels of fatigue or pain. For intervention-related moderators (only tested among women with breast cancer), statistically significant larger effects were found for cognitive behavioral therapy as intervention strategy (β = -0.27 [95%CI = -0.40; -0.15]), fatigue-specific interventions (β = -0.48 [95%CI = -0.79; -0.18]), and interventions that only targeted patients with clinically relevant fatigue (β = -0.85 [95%CI = -1.40; -0.30]).
CONCLUSIONS: Our findings did not provide evidence that any selected demographic or clinical characteristic, or baseline levels of fatigue or pain, moderated effects of psychosocial interventions on fatigue. A specific focus on decreasing fatigue seems beneficial for patients with breast cancer with clinically relevant fatigue.

Reva BA, Omelchenko T, Nair SS, Tewari AK
Immune Escape in Prostate Cancer: Known and Predicted Mechanisms and Targets.
Urol Clin North Am. 2020; 47(4S):e9-e16 [PubMed] Related Publications
Complex immune evasion mechanisms and lack of biomarkers predicting responsiveness to immune checkpoint blockade therapies compromise immunotherapy's therapeutic efficacy for patients with prostate cancer. The authors review established and nominated immune evasion mechanisms in prostate cancer and discuss how the precise treatment strategies can be developed to improve efficacy of immunotherapy.

Nair SS, Weil R, Dovey Z, et al.
The Tumor Microenvironment and Immunotherapy in Prostate and Bladder Cancer.
Urol Clin North Am. 2020; 47(4S):e17-e54 [PubMed] Related Publications
Bladder cancer has been successfully treated with immunotherapy, whereas prostate cancer is a cold tumor with inadequate immune-related treatment response. A greater understanding of the tumor microenvironment and methods for harnessing the immune system to address tumor growth will be needed to improve immunotherapies for both prostate and bladder cancer. Here, we provide an overview of prostate and bladder cancer, including fundamental aspects of the disease and treatment, the elaborate cellular makeup of the tumor microenvironment, and methods for exploiting relevant pathways to develop more effective treatments.

Salazar AM, Celis E
Double-Stranded RNA Immunomodulators in Prostate Cancer.
Urol Clin North Am. 2020; 47(4S):e1-e8 [PubMed] Related Publications
Relatively simple, synthetic, double-stranded RNAs can be powerful viral pathogen-associated molecular pattern (PAMP) mimics, inducing a panoply of antiviral and antitumor responses that act at multiple stages of host defense. Their mechanisms of action and uses are beginning to be understood, alone, in combination with other therapeutics, or as novel PAMP-adjuvants providing the critical danger signal that has been missing from most cancer and other modern vaccines. Dose, timing, route of administration combinations, and other clinical variables can have a critical impact on immunogenicity. This article reviews advances in the use of polyinosinic-polycytidylic acid and derivatives, in particular poly-ICLC.

Braga SFM, Silva RPD, Guerra Junior AA, Cherchiglia ML
Prostate Cancer Survival and Mortality according to a 13-year retrospective cohort study in Brazil: Competing-Risk Analysis.
Rev Bras Epidemiol. 2021; 24:e210006 [PubMed] Related Publications
OBJECTIVE: To analyze cancer-specific mortality (CSM) and other-cause mortality (OCM) among patients with prostate cancer that initiated treatment in the Brazilian Unified Health System (SUS), between 2002 and 2010, in Brazil.
METHODS: Retrospective observational study that used the National Oncological Database, which was developed by record-linkage techniques used to integrate data from SUS Information Systems, namely: Outpatient (SIA-SUS), Hospital (SIH-SUS), and Mortality (SIM-SUS). Cancer-specific and other-cause survival probabilities were estimated by the time elapsed between the date of the first treatment until the patients' deaths or the end of the study, from 2002 until 2015. The Fine-Gray model for competing risk was used to estimate factors associated with patients' risk of death.
RESULTS: Of the 112,856 studied patients, the average age was 70.5 years, 21% died due to prostate cancer, and 25% due to other causes. Specific survival in 160 months was 75%, and other-cause survival was 67%. For CSM, the main factors associated with patients' risk of death were: stage IV (AHR = 2.91; 95%CI 2.73 - 3.11), systemic treatment (AHR = 2.10; 95%CI 2.00 - 2.22), and combined surgery (AHR = 2.30, 95%CI 2.18 - 2.42). As for OCM, the main factors associated with patients' risk of death were age and comorbidities.
CONCLUSION: The analyzed patients with prostate cancer were older and died mainly from other causes, probably due to the presence of comorbidities associated with the tumor.

Vėželis A, Platkevičius G, Kinčius M, et al.
Systematic and MRI-Cognitive Targeted Transperineal Prostate Biopsy Accuracy in Detecting Clinically Significant Prostate Cancer after Previous Negative Biopsy and Persisting Suspicion of Malignancy.
Medicina (Kaunas). 2021; 57(1) [PubMed] Free Access to Full Article Related Publications

Singh VK, Pal R, Srivastava P, et al.
Exposure of androgen mimicking environmental chemicals enhances proliferation of prostate cancer (LNCaP) cells by inducing AR expression and epigenetic modifications.
Environ Pollut. 2021; 272:116397 [PubMed] Related Publications
Exposure to environmental endocrine disrupting chemicals (EDCs) is highly suspected in prostate carcinogenesis. Though, estrogenicity is the most studied behavior of EDCs, the androgenic potential of most of the EDCs remains elusive. This study investigates the androgen mimicking potential of some common EDCs and their effect in androgen-dependent prostate cancer (LNCaP) cells. Based on the In silico interaction study, all the 8 EDCs tested were found to interact with androgen receptor with different binding energies. Further, the luciferase reporter activity confirmed the androgen mimicking potential of 4 EDCs namely benzo[a]pyrene, dichlorvos, genistein and β-endosulfan. Whereas, aldrin, malathion, tebuconazole and DDT were reported as antiandrogenic in luciferase reporter activity assay. Next, the nanomolar concentration of androgen mimicking EDCs (benzo[a]pyrene, dichlorvos, genistein and β-endosulfan) significantly enhanced the expression of AR protein and subsequent nuclear translocation in LNCaP cells. Our In silico studies further demonstrated that androgenic EDCs also bind with epigenetic regulatory enzymes namely DNMT1 and HDAC1. Moreover, exposure to these EDCs enhanced the protein expression of DNMT1 and HDAC1 in LNCaP cells. These observations suggest that EDCs may regulate proliferation in androgen sensitive LNCaP cells by acting as androgen mimicking ligands for AR signaling as well as by regulating epigenetic machinery. Both androgenic potential and epigenetic modulatory effects of EDCs may underlie the development and growth of prostate cancer.

Kano H, Kadono Y, Kadomoto S, et al.
Similar Recurrence Rate Between Gleason Score of Six at Positive Margin and Negative Margin After Radical Prostatectomy.
Anticancer Res. 2021; 41(1):509-516 [PubMed] Related Publications
BACKGROUND/AIM: To investigate whether surgical margin (SM) status would affect the biochemical recurrence (BCR) after robot-associated RP (RARP).
PATIENTS AND METHODS: We evaluated BCR after RARP and the association between pre- and postoperative predictive factors and BCR.
RESULTS: Positive SM (PSM) was observed in 97 out of 365 enrolled patients. On multivariate analysis, preoperative prostate specific antigen, biopsy Gleason score (GS), clinical stage, GS ≥7 at the PSM and pathological GS ≥7 were predictive factors for BCR. The 5-year BCR-free survival rate was 84.1% in the negative SM (NSM), 87.4% when GS=6 at the PSM, and 47.6% when GS ≥7 at the PSM. There was no statistically significant difference in BCR-free survival between the NSM group and GS=6 at the PSM group (p=0.966).
CONCLUSION: It would be desirable to evaluate GS at PSM when PSM is present in a specimen removed by RP.

KÖditz B, Stog A, GÖbel H, et al.
Vimentin 3 Expression in Prostate Cancer Cells.
Anticancer Res. 2021; 41(1):169-174 [PubMed] Related Publications
BACKGROUND/AIM: Vimentin3 (Vim3) was recently described as a tumour marker for the direct discrimination between benign and malignant kidney tumours. Here, we examined its expression in prostate cancer (PCa) cell lines and the regulation of its expression by endothelin receptors.
MATERIALS AND METHODS: Prostate cancer cell lines (PC3, DU145, LNCap) were incubated with endothelin 1 (ET-1), BQ123 [endothelin A receptor (ETAR) antagonist], BQ788 [endothelin B receptor (ETBR) antagonist], BQ123+ET-1, BQ788+ET-1 for 24 h and a scratch assay was performed. Cell extracts were analysed by western blotting and qRT-PCR.
RESULTS: ET-1 induced Vim3 overexpression. Blocking the ETBR in the different prostate cancer cell lines yielded a higher migration rate, whereby Vim3 expression was significantly increased.
CONCLUSION: Vim3 concentration increases in cell lines without a functional ETBR and may be used as a marker for PCas where ETBR is frequently methylated.

Conti DV, Darst BF, Moss LC, et al.
Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction.
Nat Genet. 2021; 53(1):65-75 [PubMed] Related Publications
Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.

Tai Z, Ma J, Ding J, et al.
Aptamer-Functionalized Dendrimer Delivery of Plasmid-Encoding lncRNA
Int J Nanomedicine. 2020; 15:10305-10320 [PubMed] Free Access to Full Article Related Publications
Purpose: The clinical management of patients with castration-resistant prostate cancer (CRPC) is difficult. However, novel treatment methods are gradually being introduced. Considering the adverse effects of traditional treatments, recent studies have investigated gene therapy as a method to combat CRPC; but, the application of long non-coding (lnc) RNA in gene therapy remains scarce, despite their promise. Therefore, it is imperative to develop a system that can efficiently deliver lncRNA for the treatment of CRPC. Here, we investigated the efficacy of a delivery system by introducing the plasmid-encoding tumor suppressor lncRNA
Materials and Methods: An EpDT3 aptamer-linked poly(amidoamine) (PAMAM) dendrimer targeting EpCAM was used to deliver pMEG3 in CRPC cells. The PAMAM-PEG-EpDT3/pMEG3 nanoparticles (NPs) were tested using in vitro cellular assays including cellular uptake, entry, and CCK-8 measurement, and tumor growth inhibition, histological assessment, and safety evaluations in in vivo animal models.
Results: The EpDT3 aptamer promoted endocytosis of PAMAM and PAMAM-PEG-EpDT3/pMEG3 NPs in CRPC cells. PAMAM-PEG-EpDT3/pMEG3 NPs exhibited a significant anti-CRPC effect, both in vivo and in vitro, when compared to that of unfunctionalized PAMAM-PEG/pMEG3 NPs.
Conclusion: PAMAM-PEG-EpDT3/pMEG3 NPs can potentially improve gene therapy in CRPC cells.

Li K, Fan J, Qin X, Wei Q
Novel therapeutic compounds for prostate adenocarcinoma treatment: An analysis using bioinformatic approaches and the CMap database.
Medicine (Baltimore). 2020; 99(51):e23768 [PubMed] Free Access to Full Article Related Publications
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.

Luo HC, Fu ZC, Wang XP, et al.
Treating the primary in low burden metastatic prostate cancer: Where do we stand?
Medicine (Baltimore). 2020; 99(51):e23715 [PubMed] Free Access to Full Article Related Publications
ABSTRACT: On the basis of endocrine therapy for patients with low burden metastatic prostate cancer (LBMP), the clinical efficacy and quality of life were compared between prostate-only directed radiotherapy (PODT) and prostate and metastasis radiotherapy (PMRT).From November 2009 to November 2015, total 91 patients newly diagnosed with LBMP were retrospectively analyzed, of which 52 patients received PODT and 39 patients received PMRT. The biochemical failure free interval (IBF), prostate specific survival (PCSS), and overall survival (OS) time were compared between the 2 groups, and expanded prostate cancer index composite (EPIC) scale was used to evaluate the difference in quality of life between the 2 groups.The median IBF of the PODT group was 31 months, which was significantly lower than the 39 months of the PMRT group (P < .05); the 5-year OS and PCSS were 58.9%, 65.3% in PODT group, and 58.9%, 71.79% in PMRT group, respectively. There was no significant between the 2 groups (P > .05); the side effects of acute radiotherapy in PMRT group were significantly higher than PODT group (P < .05), especially in bone marrow suppression and gastrointestinal reactions; The scores of urinary system function and intestinal system function in PMRT group were significantly higher than PODT group at the end of radiotherapy, 3 months after radiotherapy, and 6 months after radiotherapy (P < .05). The score of sexual function in PMRT group was significantly lower than that in PODT group after radiotherapy (P < .05), and higher than that in PORT group at other follow-up time points (P < .05). The hormone function was decreased at each follow-up time point in 2 groups, and there was no significant difference between the 2 groups (P > .05).Patients with LBMP receiving PMRT can improve IBF, but cannot increase PCSS and OS, and increase the incidence of acute radiation injury.

Wang C, Tao Y
Superb microvascular imaging in guiding targeted biopsy of prostate cancer: A protocol for systematic review and meta analysis.
Medicine (Baltimore). 2020; 99(51):e23604 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Studies suggested superb microvascular imaging technology to guide prostate cancer biopsy could improve the positive rate of draw materials. The present meta-analysis aimed at determining the accuracy of SMI in the location diagnosis for prostate cancer.
METHODS: We will search PubMed, Web of Science, Cochrane Library, and Chinese biomedical databases from their inceptions to the October 31st, 2020. Two authors will independently carry out searching literature records, scanning titles and abstracts, full texts, collecting data, and assessing risk of bias. Review Manager 5.2 and Stata14.0 software will be used for data analysis.
RESULTS: This systematic review will determine the accuracy of superb microvascular imaging in guiding targeted biopsy of prostate cancer.
CONCLUSION: Its findings will provide helpful evidence for the accuracy of superb microvascular imaging in guiding targeted biopsy of prostate cancer.

Washington SL, Jeong CW, Lonergan PE, et al.
Regional Variation in Active Surveillance for Low-Risk Prostate Cancer in the US.
JAMA Netw Open. 2020; 3(12):e2031349 [PubMed] Free Access to Full Article Related Publications
Importance: Active surveillance (AS) is now recognized as the preferred management option for most low-risk prostate cancers to minimize risks of overtreatment. Despite increasing use of AS in the US, wide regional variability has been observed, and these regional variations in contemporary practice have not been well described.
Objective: To explore variations between county and Surveillance, Epidemiology, and End Results (SEER) regions in AS in the US.
Design, Setting, and Participants: A cohort study using the SEER Prostate with Watchful Waiting (WW) database linked to the County Area Health Resource File for detailed county-level demographics and physician distribution data was conducted from January 2010 to December 2015. Analysis was performed in October 2020. A total of 79 825 men with clinically localized, low-risk prostate cancer eligible for AS or WW were included.
Exposures: Multiple patient-, county-, and SEER region-level factors, including age, year of diagnosis, county-level densities of urologists, radiation oncologists, primary care physicians, and SEER registry region.
Main Outcomes and Measures: Use of AS or WW as the initial reported treatment strategy were noted. Hierarchical mixed-effect logistic regression models were used to evaluate clustered random regional variation on use of AS or WW. Temporal trends by year in proportions of initial treatment type, as well as county-level local variation, were also estimated.
Results: Of 79 825 men (mean [SD] age, 62.8 [7.6] years, 11 292 [14.1%] non-Hispanic Black, 7506 [9.4%] Hispanic) with low-risk prostate cancer, the mean annualized percent increase in AS rates from 2010 to 2015 ranged from 6.3% in New Mexico to 81.0% in New Jersey. Differences across SEER regions accounted for 17% of the total variation in AS. Increasing age (51-60 years: odds ratio [OR], 1.33; 95% CI, 1.21-1.46; 61-70 years: OR, 1.86; 95% CI, 1.70-2.04; 71-80 years: OR, 2.26; 95% CI, 2.05-2.50) was associated with greater odds of AS. Hispanic ethnicity (OR, 0.79; 95% CI, 0.74-0.85), T category (OR, 0.79; 95% CI, 0.73-0.84), and Medicaid enrollment (OR, 0.73; 95% CI, 0.66-0.81) were associated with lower odds of AS. Black race, county-level socioeconomic factors (household income, educational level, and city type), and specialist densities were not associated with AS use.
Conclusions and Relevance: In this US cohort study based on the SEER-WW database, although the use of AS increased, considerable practice variation appeared to be associated with geographic location, but use of AS was not associated with Black race, specialty professional density, or socioeconomic factors. This small area variation underlies the broader national trends in AS practice and may inform policies aimed at continuing to affect risk-appropriate care for men throughout the US.

Pang B, Zhu Y, Ni J, et al.
Quality Assessment and Comparison of Plasma-Derived Extracellular Vesicles Separated by Three Commercial Kits for Prostate Cancer Diagnosis.
Int J Nanomedicine. 2020; 15:10241-10256 [PubMed] Free Access to Full Article Related Publications
Introduction: Current standard biomarkers in clinic are not specific enough for prostate cancer (PCa) diagnosis. Extracellular vesicles (EVs) are nano-scale vesicles released by most mammalian cells. EVs are promising biomarker source for PCa liquid biopsy due to its minimal invasive approach, rich information and improved accuracy compared to the clinical standard prostate-specific antigen (PSA). However, current EV separation methods cannot separate pure EVs and the quality characteristics from these methods remain largely unknown. In this study, we evaluated the quality characteristics of human plasma-derived EVs by comparing three clinical suitable separation kits.
Methods: We combined EV separation by commercial kits with magnetic beads capture and flow cytometry analysis, and compared three kits including ExoQuick Ultra based on precipitation and qEV35 and qEV70 based on size exclusion chromatography (SEC).
Results: Our results indicated that two SEC kits provided higher EV purity and lower protein contamination compared to ExoQuick Ultra precipitation and that qEV35 demonstrated a higher EV yield but lower EV purity compared to qEV70. Particle number correlated very well particularly with CD9/81/63 positive EVs for all three kits, which confirms that particle number can be used as the estimate for EV amount. At last, we found that several EV metrics including total EVs and PSA-specific EVs could not differentiate PCa patients from health controls.
Conclusion: We provided a systematic workflow for the comparison of three separation kits as well as a general analysis process in clinical laboratories for EV-based cancer diagnosis. Better EV-associated cancer biomarkers need to be explored in the future study with a larger cohort.

Hüttl AB, Korda DÁ, Lénárd MZ, et al.
Our initial experiences with mpMRI-ultrasound fusion-guided prostate biopsy
Orv Hetil. 2020; 161(52):2188-2194 [PubMed] Related Publications
Összefoglaló. Bevezetés: A prosztatarák diagnosztikájában az utóbbi években paradigmaváltás történt. Az MR-vizsgálat fejlődése lehetővé tette a prosztatatumor gyanús elváltozásainak célzott mintavételét. Az mpMR fúziós biopszia pontos és költséghatékony módszer. Célkitűzés: Célkitűzésünk az volt, hogy összegezzük az mpMR fúziós biopsziák terén szerzett tapasztalatainkat. Módszer: A Semmelweis Egyetem Urológiai Klinikáján 2017 és 2019 között 40, mpMR fúziós biopsziát végeztünk a BioJet-program segítségével, transperinealis behatolásból. Az MR-vizsgálatok kiértékelése a PI-RADS v2 ajánlása szerint történt. Megvizsgáltuk, hogy a laesiók PI-RADS-besorolása, elhelyezkedése, mérete, az extraprosztatikus terjedés jeleinek megléte, a páciensek PSA-, illetve PSAD-értékei, valamint a prosztata volumene befolyásolja-e a mintavételek kimenetelét. Eredmények: A célzott mintavételek során pácienseink 80%-ánál igazolódott malignitás. PI-RADS 5. és 4. besorolású laesiók esetén a detektációs ráta 91%, illetve 85%, míg PI-RADS 3. laesióknál 20% volt. A perifériás zóna elváltozásainál szignifikánsan magasabb volt a pozitív eredmény valószínűsége, mint a tranzicionális zóna laesióinál (khi2(1) = 6,555, p = 0,010, Fisher-féle egzakt p = 0,017, V = 0,355). Az extraprosztatikus terjedés jelei és a magasabb PSAD-értékek növelték a pozitív minták valószínűségét (khi2(1) = 7,704, p = 0,006, Fisher-féle egzakt p = 0,004, V = 0,355; illetve 0,47 ± 0,50 ng/ml2 vs. 0,18 ± 0,17 ng/ml2; Z = 3,447, p<0,001), míg az elváltozások mérete nem befolyásolta a kimenetelt. A prosztatavolumen szignifikánsan magasabb volt azoknál, akiknél nem igazolódott malignitás (50,9 ± 18,8 ml vs. 119,6 ± 91,6 ml; Z = -3,505, p<0,001). Következtetések: Az elvégzett fúziós biopsziák detektációs rátája magasabb volt az irodalmi átlagnál. Eredményeink alapján a mintavételek kimenetelét befolyásolhatja az elváltozások PI-RADS-besorolása, elhelyezkedése, az extraprosztatikus terjedés, a PSAD-értékek, valamint a prosztatatérfogat. A fenti szempontok figyelembevételével kiválaszthatók azok a páciensek, akik a legtöbbet profitálhatnak a beavatkozásból. Orv Hetil. 2020; 161(52): 2188-2194.

Kane T
Early vs. Late Androgen Suppression Therapy for Advanced Prostate Cancer.
Am J Nurs. 2021; 121(1):25 [PubMed] Related Publications
Editor's note: The mission of Cochrane Nursing is to provide an international evidence base for nurses involved in delivering, leading, or researching nursing care. Cochrane Corner provides summaries of recent systematic reviews from the Cochrane Library. For more information, see https://nursing.cochrane.org.

Pisano C, Tucci M, Di Stefano RF, et al.
Interactions between androgen receptor signaling and other molecular pathways in prostate cancer progression: Current and future clinical implications.
Crit Rev Oncol Hematol. 2021; 157:103185 [PubMed] Related Publications
In last years several improvements have been made in the management of prostate cancer (PCa). Androgen receptor (AR) is considered the main driver in PCa growth and progression and most drugs are directed against AR pathway. Once PCa spreads outside the prostate, androgen deprivation therapy (ADT) represents the cornerstone of treatment in hormone-sensitive prostate cancer (HSPC). Unfortunately, the response is only transient and most patients eventually develop castration-resistant prostate cancer (CRPC). Most resistance mechanisms depend on maintenance of AR signalling in castration environment. Recent discoveries of multiple growth-promoting and survival pathways in PCa suggest the importance of alternative mechanisms involved in disease progression, such as DNA damage response pathway, PTEN/PI3K/AKT/mTOR pathway, cell cycle pathway, WNT pathway, TMPRSS2/ETS fusion, neuroendocrine pattern and immune system response. In this review, we discuss the interplay between AR signaling and other molecular pathways involved in PCa pathogenesis and their therapeutic implication in advanced disease.

Brady L, Hayes B, Sheill G, et al.
Platelet cloaking of circulating tumour cells in patients with metastatic prostate cancer: Results from ExPeCT, a randomised controlled trial.
PLoS One. 2020; 15(12):e0243928 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Circulating tumour cells (CTCs) represent a morphologically distinct subset of cancer cells, which aid the metastatic spread. The ExPeCT trial aimed to examine the effectiveness of a structured exercise programme in modulating levels of CTCs and platelet cloaking in patients with metastatic prostate cancer.
METHODS: Participants (n = 61) were randomised into either standard care (control) or exercise arms. Whole blood was collected for all participants at baseline (T0), three months (T3) and six months (T6), and analysed for the presence of CTCs, CTC clusters and platelet cloaking. CTC data was correlated with clinico-pathological information.
RESULTS: Changes in CTC number were observed within group over time, however no significant difference in CTC number was observed between groups over time. Platelet cloaking was identified in 29.5% of participants. A positive correlation between CTC number and white cell count (WCC) was observed (p = 0.0001), in addition to a positive relationship between CTC clusters and PSA levels (p = 0.0393).
CONCLUSION: The presence of platelet cloaking has been observed in this patient population for the first time, in addition to a significant correlation between CTC number and WCC.
TRIAL REGISTRATION: ClincalTrials.gov identifier NCT02453139.

Yan F, Chen L, Chen W, et al.
Protective effect of procyanidin A-type dimers against H
Life Sci. 2021; 266:118908 [PubMed] Related Publications
It has been reported that B-type procyanidins can alleviate oxidative damage of prostatic cells, but there has been limited information on the similar role of A-type procyanidins. This study investigated the protective effect of procyanidin A-type dimers from peanut skin against H

Pantanowitz L, Quiroga-Garza GM, Bien L, et al.
An artificial intelligence algorithm for prostate cancer diagnosis in whole slide images of core needle biopsies: a blinded clinical validation and deployment study.
Lancet Digit Health. 2020; 2(8):e407-e416 [PubMed] Related Publications
BACKGROUND: There is high demand to develop computer-assisted diagnostic tools to evaluate prostate core needle biopsies (CNBs), but little clinical validation and a lack of clinical deployment of such tools. We report here on a blinded clinical validation study and deployment of an artificial intelligence (AI)-based algorithm in a pathology laboratory for routine clinical use to aid prostate diagnosis.
METHODS: An AI-based algorithm was developed using haematoxylin and eosin (H&E)-stained slides of prostate CNBs digitised with a Philips scanner, which were divided into training (1 357 480 image patches from 549 H&E-stained slides) and internal test (2501 H&E-stained slides) datasets. The algorithm provided slide-level scores for probability of cancer, Gleason score 7-10 (vs Gleason score 6 or atypical small acinar proliferation [ASAP]), Gleason pattern 5, and perineural invasion and calculation of cancer percentage present in CNB material. The algorithm was subsequently validated on an external dataset of 100 consecutive cases (1627 H&E-stained slides) digitised on an Aperio AT2 scanner. In addition, the AI tool was implemented in a pathology laboratory within routine clinical workflow as a second read system to review all prostate CNBs. Algorithm performance was assessed with area under the receiver operating characteristic curve (AUC), specificity, and sensitivity, as well as Pearson's correlation coefficient (Pearson's r) for cancer percentage.
FINDINGS: The algorithm achieved an AUC of 0·997 (95% CI 0·995 to 0·998) for cancer detection in the internal test set and 0·991 (0·979 to 1·00) in the external validation set. The AUC for distinguishing between a low-grade (Gleason score 6 or ASAP) and high-grade (Gleason score 7-10) cancer diagnosis was 0·941 (0·905 to 0·977) and the AUC for detecting Gleason pattern 5 was 0·971 (0·943 to 0·998) in the external validation set. Cancer percentage calculated by pathologists and the algorithm showed good agreement (r=0·882, 95% CI 0·834 to 0·915; p<0·0001) with a mean bias of -4·14% (-6·36 to -1·91). The algorithm achieved an AUC of 0·957 (0·930 to 0·985) for perineural invasion. In routine practice, the algorithm was used to assess 11 429 H&E-stained slides pertaining to 941 cases leading to 90 Gleason score 7-10 alerts and 560 cancer alerts. 51 (9%) cancer alerts led to additional cuts or stains being ordered, two (4%) of which led to a third opinion request. We report on the first case of missed cancer that was detected by the algorithm.
INTERPRETATION: This study reports the successful development, external clinical validation, and deployment in clinical practice of an AI-based algorithm to accurately detect, grade, and evaluate clinically relevant findings in digitised slides of prostate CNBs.
FUNDING: Ibex Medical Analytics.

Liao KM, Wang YL, Chen CY
Medication utilization evaluation of androgen deprivation therapy for prostate cancer in Taiwan.
Medicine (Baltimore). 2020; 99(50):e23644 [PubMed] Free Access to Full Article Related Publications
Prostate cancer is one of the most common cancer in males. Both the incidence and the mortality rates of prostate cancer show an increasing trend. Androgen deprivation therapy (ADT) is the standard treatment for metastatic prostate cancer. The aim of our study was to show the epidemiology of prostate cancer and the proportion of patients utilizing ADT.This study used Taiwan's National Health Insurance Research Database (NHIRD) and identified the patients who had been diagnosed with prostate cancer (International Classification of Disease (ICD)-10: C61) and followed up between Jan 1, 2008 and Dec 31, 2015. The ADT drugs used by prostate cancer patients were recorded: Gonadotropin-releasing hormone (GnRH) agonists; GnRH antagonist; estrogen analogs and androgen receptor antagonist.A total of 25,233 patients with newly diagnosed prostate cancer in 2008-2014 were enrolled. The utilization of ADT increased from more than 7,000 person-time in 2008 to more than 50,000 person-time in 2014. Cyproterone acetate was the most commonly used drug in 2008-2015, but its proportion of utilization, which was the highest in stage 2 cancer, dropped from 43% in 2008 to 15% in 2015. Bicalutamide was the second most used drug from 2008 to 2015, but its utilization was not different for different stages.The incidence rate of prostate cancer increased in the study period and medical expenditure also increased in ADT treatment. Health insurance benefits for various ADT drugs should be further evaluated.

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