Monitoring Of Prostate Cancer Research Articles

B-332 Use of urinary volatile organic compounds in monitoring prostate cancer after radical prostatectomy

Abstract Background Prostate cancer (PCa) is the most commonly diagnosed non-cutaneous cancer among males and the second cause of cancer-related deaths. PCa treatment involves different methods, and most common is radical prostatectomy (RP), which entails removal of prostate-gland from men who have been diagnosed with PCa. Prostatic-specific-antigen (PSA) has been used for detection of recurrent disease for years. After its introduction as biochemical recurrence (BCR) marker, men with distinct diseases were treated similarly. Overtime, it has been observed that PSA relapse presents several meanings according to clinicopathological features, like Gleason score, PSA-doubling-time, clinical stage, surgical margin status. Despite this, PSA remains main tool to assess disease progression after RP. RP remains primary treatment for localized PCa and has been performed for years with excellent oncologic control. However, approximately 20-40% of patients with clinically localized PCa will present biochemical-recurrence (BCR) after RP, while some with recurrent-metastasis. The study aims to investigate potential volatile organic compounds (VOCs) associated with men who have undergone RP but still abhor the disease. Methods Urine samples were collected from 110 male adults with biopsy-proven PCa-positive results before and after RP. VOCs in urine were extracted by stir-bar-sorptive-extraction and analyzed using thermal-desorption with gas chromatography-mass spectrometry. Metabolomics and machine-learning tools used to develop and evaluate models for PCa diagnosis before and after RP. Results PLS-DA and VIP loading plots identified potential VOC panels that could be used to differentiate PCa patients before and after RP and those with BCR and recurrent metastasis. Furthermore, logistic-regression results with validation provide a promising diagnostic model for PCa diagnosis after RP. Conclusions This novel method using urinary VOCs was developed to fill gaps in PCa monitoring after RP. These research findings could aid and fast-track the provision of rapid point of care to the treated PCa patients who still abhor the disease.

B-348 Performance of the Atellica IM Analyzer’s HighSensitivity PSA Assay as an Aid for Monitoring Prostate Cancer Recurrence

Abstract Background Prostate specific antigen (PSA) is a suitable marker for monitoring men with prostate cancer (PC), and for detecting recurrence after therapy in conjunction with other diagnostic measures. Studies were performed to evaluate performance of the Atellica® IM High-Sensitivity PSA assay (hsPSA)* versus the Atellica® IM PSA assay in patients undergoing management (monitoring) of PC. Methods A total of 868 serum samples from 170 subjects with PC (92 [54%] subjects had a radical prostatectomy (RP) before enrollment) were collected at 7 sites across the United States. Subjects had baseline and >2 follow-up visits during treatment (average 5.106 visits, SD=1.414). Samples were tested using the Atellica IM hsPSA assay and the commercially available Atellica IM PSA assay (comparative method). For RP and non-RP combined, 644 paired samples for each assay were tested. Subjects were designated “No Progression” (responding, stable, and no evidence of disease subjects) or “Progression” at each visit based on clinical classification. Results In this study the Atellica IM hsPSA assay demonstrated equivalent performance as commercial Atellica IM PSA in predicting disease status (table). The PPA between the assays was 95.5% and the NPA was 98.9%. Concordance to clinician classification was similar for both assays (∼80% PPA and 90% NPA). Conclusions Preliminary results demonstrated equivalent performance of the Atellica IM hsPSA assay as the commercially available Atellica IM PSA assay in terms of predicting disease status. This hsPSA assay can detect very low levels of PSA, which is particularly important for the monitoring of RP patients. *CAUTION: Investigational Device. Not available for sale. Future availability cannot be guaranteed. The results are preliminary and were achieved in unique setting with no expected timeline for completion.

MRI and active surveillance: thoughts from across the pond.

In the United States (US), urological guidelines recommend active surveillance (AS) for patients with low-risk prostate cancer (PCa) and endorse it as an option for those with favorable intermediate-risk PCa with a > 10-year life expectancy. Multiparametric magnetic resonance imaging (mpMRI) is being increasingly used in the screening, monitoring, and staging of PCa and involves the combination of T2-weighted, diffusion-weighted, and dynamic contrast-enhanced T1-weighted imaging. The American Urological Association (AUA) guidelines provide recommendations about the use of mpMRI in the confirmatory setting for AS patients but do not discuss the timing of follow-up mpMRI in AS. The National Comprehensive Cancer Network (NCCN) discourages using it more frequently than every 12 months. Finally, guidelines state that mpMRI can be used to augment risk stratification but should not replace periodic surveillance biopsy. In this review, we discuss the current literature regarding the use of mpMRI for patients with AS, with a particular focus on the approach in the US. Although AS shows a benefit to the addition of mpMRI to diagnostic, confirmatory, and follow-up biopsy, there is no strong evidence to suggest that mpMRI can safely replace biopsy for most patients and thus it must be incorporated into a multimodal approach. CLINICAL RELEVANCE STATEMENT: According to the US guidelines, regular follow-ups are important for men with prostate cancer on active surveillance, and prostate MRI is a valuable tool that should be utilized, in combination with PSA kinetics and biopsies, for monitoring prostate cancer. KEY POINTS: According to the US guidelines, the addition of MRI improves the detection of clinically significant prostate cancer. Timing interval imaging of patients on active surveillance remains unclear and has not been specifically addressed. MRI should trigger further work-ups, but not replace periodic follow-up biopsies, in men on active surveillance.

Monitoring prostate cancer after low-dose-rate hemigland brachytherapy with delta-radiomics of diffusion-weighted magnetic resonance imaging.

Monitoring prostate cancer after low-dose-rate hemigland brachytherapy with delta-radiomics of diffusion-weighted magnetic resonance imaging.

Optimising Extracellular Vesicle Metabolomic Methodology for Prostate Cancer Biomarker Discovery.

Conventional diagnostic tools for prostate cancer (PCa), such as prostate-specific antigen (PSA), transrectal ultrasound (TRUS), digital rectal examination (DRE), and tissue biopsy face, limitations in individual risk stratification due to invasiveness or reliability issues. Liquid biopsy is a less invasive and more accurate alternative. Metabolomic analysis of extracellular vesicles (EVs) holds a promise for detecting non-genetic alterations and biomarkers in PCa diagnosis and risk assessment. The current research gap in PCa lies in the lack of accurate biomarkers for early diagnosis and real-time monitoring of cancer progression or metastasis. Establishing a suitable approach for observing dynamic EV metabolic alterations that often occur earlier than being detectable by other omics technologies makes metabolomics valuable for early diagnosis and monitoring of PCa. Using four distinct metabolite extraction approaches, the metabolite cargo of PC3-derived large extracellular vesicles (lEVs) was evaluated using a combination of methanol, cell shearing using microbeads, and size exclusion filtration, as well as two fractionation chemistries (pHILIC and C18 chromatography) that are also examined. The unfiltered methanol-microbeads approach (MB-UF), followed by pHILIC LC-MS/MS for EV metabolite extraction and analysis, is effective. Identified metabolites such as L-glutamic acid, pyruvic acid, lactic acid, and methylmalonic acid have important links to PCa and are discussed. Our study, for the first time, has comprehensively evaluated the extraction and separation methods with a view to downstream sample integrity across omics platforms, and it presents an optimised protocol for EV metabolomics in PCa biomarker discovery.

Phage Display's Prospects for Early Diagnosis of Prostate Cancer.

Prostate cancer (PC) is the second most diagnosed cancer among men. It was observed that early diagnosis of disease is highly beneficial for the survival of cancer patients. Therefore, the extension and increasing quality of life of PC patients can be achieved by broadening the cancer screening programs that are aimed at the identification of cancer manifestation in patients at earlier stages, before they demonstrate well-understood signs of the disease. Therefore, there is an urgent need for standard, sensitive, robust, and commonly available screening and diagnosis tools for the identification of early signs of cancer pathologies. In this respect, the "Holy Grail" of cancer researchers and bioengineers for decades has been molecular sensing probes that would allow for the diagnosis, prognosis, and monitoring of cancer diseases via their interaction with cell-secreted and cell-associated PC biomarkers, e.g., PSA and PSMA, respectively. At present, most PSA tests are performed at centralized laboratories using high-throughput total PSA immune analyzers, which are suitable for dedicated laboratories and are not readily available for broad health screenings. Therefore, the current trend in the detection of PC is the development of portable biosensors for mobile laboratories and individual use. Phage display, since its conception by George Smith in 1985, has emerged as a premier tool in molecular biology with widespread application. This review describes the role of the molecular evolution and phage display paradigm in revolutionizing the methods for the early diagnosis and monitoring of PC.

Long-term Prostate Cancer–specific Mortality After Prostatectomy, Brachytherapy, External Beam Radiation Therapy, Hormonal Therapy, or Monitoring for Localized Prostate Cancer

BackgroundThe optimal treatment of localized prostate cancer (PCa) remains controversial. ObjectiveTo compare long-term survival among men who underwent radical prostatectomy (RP), brachytherapy (BT), external beam radiation therapy (EBRT), primary androgen deprivation therapy (PADT), or monitoring (active surveillance [AS]/watchful waiting [WW]) for PCa. Design, setting, and participantsThis is a cohort study with long-term follow-up from the multicenter, prospective, largely community-based Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry. Men with biopsy-proven, clinical T1–3aN0M0, localized PCa were consecutively accrued within 6 mo of diagnosis and had clinical risk data and at least 12 mo of follow-up after diagnosis available. Outcome measurements and statistical analysisPCa risk was assessed, and multivariable analyses were performed to compare PCa-specific mortality (PCSM) and all-cause mortality by primary treatment, with extensive adjustment for age and case mix using the Cancer of the Prostate Risk Assessment (CAPRA) score and a well-validated nomogram. Results and limitationsAmong 11 864 men, 6227 (53%) underwent RP, 1645 (14%) received BT, 1462 (12%) received EBRT, 1510 (13%) received PADT, and 1020 (9%) were managed with AS/WW. At a median of 9.4 yr (interquartile range 5.8–13.7) after treatment, 764 men had died from PCa. After adjusting for CAPRA score, the hazard ratios for PCSM with RP as the reference were 1.57 (95% confidence interval [CI] 1.24–1.98; p < 0.001) for BT, 1.55 (95% CI 1.26–1.91; p < 0.001) for EBRT, 2.36 (95% CI 1.94–2.87; p < 0.001) for PADT, and 1.76 (95% CI 1.30–2.40; p < 0.001) for AS/WW. In models for long-term outcomes, PCSM differences were negligible for low-risk disease and increased progressively with risk. Limitations include the evolution of diagnostic and therapeutic strategies for PCa over time. In this nonrandomized study, the possibility of residual confounding remains salient. ConclusionsIn a large, prospective cohort of men with localized PCa, after adjustment for age and comorbidity, PCSM was lower after local therapy for those with higher-risk disease, and in particular after RP. Confirmation of these results via long-term follow-up of ongoing trials is awaited. Patient summaryWe evaluated different treatment options for localized prostate cancer in a large group of patients who were treated mostly in nonacademic medical centers. Results from nonrandomized trials should be interpret with caution, but even after careful risk adjustment, survival rates for men with higher-risk cancer appeared to be highest for patients whose first treatment was surgery rather than radiotherapy, hormones, or monitoring.

Picture Perfect: The Status of Image Quality in Prostate MRI.

Magnetic resonance imaging is the gold standard imaging modality for the diagnosis of prostate cancer (PCa). Image quality is a fundamental prerequisite for the ability to detect clinically significant disease. In this critical review, we separate the issue of image quality into quality improvement and quality assessment. Beginning with the evolution of technical recommendations for scan acquisition, we investigate the role of patient preparation, scanner factors, and more advanced sequences, including those featuring Artificial Intelligence (AI), in determining image quality. As means of quality appraisal, the published literature on scoring systems (including the Prostate Imaging Quality score), is evaluated. Finally, the application of AI and teaching courses as ways to facilitate quality assessment are discussed, encouraging the implementation of future image quality initiatives along the PCa diagnostic and monitoring pathway. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

Up-to-Date Imaging and Diagnostic Techniques for Prostate Cancer: A Literature Review

Prostate cancer (PCa) faces great challenges in early diagnosis, which often leads not only to unnecessary, invasive procedures, but to over-diagnosis and treatment as well, thus highlighting the need for modern PCa diagnostic techniques. The review aims to provide an up-to-date summary of chronologically existing diagnostic approaches for PCa, as well as their potential to improve clinically significant PCa (csPCa) diagnosis and to reduce the proliferation and monitoring of PCa. Our review demonstrates the primary outcomes of the most significant studies and makes comparisons across the diagnostic efficacies of different PCa tests. Since prostate biopsy, the current mainstream PCa diagnosis, is an invasive procedure with a high risk of post-biopsy complications, it is vital we dig out specific, sensitive, and accurate diagnostic approaches in PCa and conduct more studies with milestone findings and comparable sample sizes to validate and corroborate the findings.

Abstract B044: Exosomal cancer-type SLCO1B3 and ABCC3 as potential biomarkers of castration resistant prostate cancer

Abstract Extracellular vesicles (EVs) provide a minimally invasive source of tumor-specific markers for liquid biopsy that can be utilized for cancer detection, diagnosis, or monitoring progression. Our laboratory has previously demonstrated the endogenous expression of all transporter systems in the common prostate cancer cell lines (LNCaP, 22Rv1, PC3, DU-145) using a medium throughput TaqMan-based qRT-PCR assay. We identified the two most differentially expressed transporter genes in castration-resistant prostate cancer cells (CRPC) as the cancer-type solute carrier organic anion transporter family 1B3 (ct-SLCO1B3) and the ATP Binding Cassette Subfamily Member C (ABBC3). Both transporters have been investigated as EV-derived tumor markers; however, their detection in prostate cancer-derived EVs remains to be determined. This study aims to investigate whether ct-SLCO1B31B3 and ABCC3 mRNA exists in prostate cancer-derived EVs and can be further detected using plasma specimens. We isolated EVs from prostate cancer (LNCaP, 22Rv1, PC3, DU-145) cell line supernatant and extracted exosomal RNA for qPCR analyses. Both ct-SLCO1B3 and ABBC3 transcripts were only detected in CRPC-derived EV cells vs androgen-responsive prostate cancer cells. To explore the possibility that both transcripts in CRPC-derived EVs can be detected in plasma, we isolated plasma EVs derived from human prostate cancer xenograft mice, and then performed digital droplet PCR analysis. We demonstrated that ct-SLCO1B3 and ABBC3 are detectable in the DU-145 xenograft mouse model, both in tissues and in plasma-derived EVs. Our results provide evidence that ct-SLCO1B3 and ABCC3 exist in EVs and can be detected (at least) in mouse plasma, potentially supporting their roles as novel, plasma-based biomarkers for monitoring prostate cancer progression. Citation Format: Erica L. Beatson, Kristi Y. Lee, Martina A. Knechel, Elijah R. Sommer, Roger Depaz, Emily N. Risdon, Andres F. Leon, Jonathan D. Strope, Douglas K. Price, Cindy H. Chau, William D. Figg. Exosomal cancer-type SLCO1B3 and ABCC3 as potential biomarkers of castration resistant prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr B044.

Diagnosis of Prostate Cancer through the Multi-Ligand Binding of Prostate-Derived Extracellular Vesicles and miRNA Analysis.

The development of new non-invasive markers for prostate cancer (PC) diagnosis, prognosis, and management is an important issue that needs to be addressed to decrease PC mortality. Small extracellular vesicles (SEVs) secreted by prostate gland or prostate cancer cells into the plasma are considered next-generation diagnostic tools because their chemical composition might reflect the PC development. The population of plasma vesicles is extremely heterogeneous. The study aimed to explore a new approach for prostate-derived SEV isolation followed by vesicular miRNA analysis. We used superparamagnetic particles functionalized by five types of DNA-aptamers binding the surface markers of prostate cells. Specificity of binding was assayed by AuNP-aptasensor. Prostate-derived SEVs were isolated from the plasma of 36 PC patients and 18 healthy donors and used for the assessment of twelve PC-associated miRNAs. The amplification ratio (amp-ratio) value was obtained for all pairs of miRNAs, and the diagnostic significance of these parameters was evaluated. The multi-ligand binding approach doubled the efficiency of prostate-derived SEVs' isolation and made it possible to purify a sufficient amount of vesicular RNA. The neighbor clusterization, using three pairs of microRNAs (miR-205/miR-375, miR-26b/miR375, and miR-20a/miR-375), allowed us to distinguish PC patients and donors with sensitivity-94%, specificity-76%, and accuracy-87%. Moreover, the amp-ratios of other miRNAs pairs reflected such parameters as plasma PSA level, prostate volume, and Gleason score of PC. Multi-ligand isolation of prostate-derived vesicles followed by vesicular miRNA analysis is a promising method for PC diagnosis and monitoring.

Inherited risk for prostate cancer (PCa): Following the natural history of men with high-risk genetics using multiparametric MRI (mpMRI).

390 Background: PCa has inherited risk factors including high genetic risk variants such as BRCA1/2, HOXB13, and DNA mismatch repair genes. mpMRI has been shown to be effective for detection and staging of localized PCa. This study follows participants (prts), born biologically male, without a diagnosis of PCa with known germline pathogenic or likely pathogenic variants (PV) in BRCA1/2, MLH1, MSH2, MSH6, PMS2, EPCAM, HOXB13, ATM, NBN, TP53, CHEK2, PALB2, RAD51C/D, BRIP1, or FANCA-FANCM (NCT03805919). Methods: Up to 500 eligible prts 30-75 years old (yo) with a documented germline PV will enroll. Prts undergo biennial clinical exam and mpMRI, and annual PSA monitoring and are followed at 12-month intervals to determine PSA, prostate cancer diagnosis, and/or disease/survival status until death. Indication for prostate biopsy includes clinical or imaging findings. Biopsy specimens undergo molecular analyses. Results: To date, 175 prts have been enrolled: 169 (97%) White, 3 Hispanic (2%), 1 African American (1%), 1 Asian (1%), and 1 biethnic (1%). Median age is 47 yo. The most common monoallelic PV are: 48.6% BRCA2, 25.1% BRCA1, 6.3% CHEK2 and 5.7% MSH2. PVs in ATM, PALB2, HOXB13, PMS2, MLH1, MSH6, BRIP1, EPCAM and RAD51D are ≤4%. One subject carries three distinct PVs ( BRCA2, CHEK2, BRIP1). Indication for biopsy was found in 26.3% of prts with 22/46 (47.8%) with a PIRADS 4 lesion, 6/46 (13.0%) PIRADS 3 lesion, 12/46 (26.1%) elevated PSA (median=2.8 ng/mL) or 6/46 (13.0%) due to clinical discretion. Adenocarcinoma was diagnosed on 13/39 (33.3%) biopsies with median age at diagnosis=59 yo. 9/13 (69%) prts had a PSA &lt;3 ng/ml at diagnosis. Nine prts were diagnosed with ISUP Grade Group (GG) 1, 3 with GG2, and 1 with GG3. Eight prts opted for active surveillance (AS), 2 for radiation therapy (RT), and 3 for prostatectomy (RP). Two prts on AS converted to definitive treatment (one RP and one RT) due to progression in GG on the year 1 AS biopsy. Conclusions: mpMRI screening in men with germline PV can be used for diagnosis and monitoring of PCa and facilitates detection below conventional PSA thresholds in a high genetic risk setting. Access to genetic testing and other variables need to be addressed in underrepresented minorities. Correlative studies, including cfDNA and PBMCs, are ongoing. Clinical trial information: NCT03805919 . [Table: see text]

PSMA-PET Detection of Unusual Metastases in Castrate-Sensitive Prostate Carcinoma.

Prostate cancer (PCa) is a multifaceted, heterogeneous disease (with 7 molecular subtypes), which can metastasize to common sites, such as bone, lymph nodes, liver, and lungs. However, with PSMA PET imaging, rare sites of metastasis are increasingly discovered. We report 5 cases of unusual metastases in patients with castrate-sensitive PCa: solitary right inguinal nodal metastasis, solitary abdominal wall metastasis, penile shaft metastases, solitary perineum metastasis, and pleural metastases. These cases further support the use of PSMA-PET imaging in PCa monitoring, with the ability to detect solitary, small volume, and rare sites of metastases, which may not be apparent on conventional imaging.

An extracellular vesicle-based assay for noninvasive detection of metastases and monitoring prostate cancer.

e17004 Background: Optimizing outcomes in prostate cancer (PCa) requires timely detect of metastatic progression of prostate cancer patients. We aim to optimize an extracellular vesicle (EV)-based Digital Scoring Assay for detecting PCa metastasis and noninvasive monitoring disease progression. Methods: PCa EV Digital Scoring Assay was developed by combining EV Click Chip, a nanotechnology-enabled microfluidic device for purifying PCa-derived EV and reverse-transcription droplet digital PCR for profiling disease-relevant mRNAs. A panel of 11 PCa-relevant mRNA markers were selected from The Tissue Atlas and a blood-based biomarker study. Plasma samples from 20 localized, 20 metastatic PCa patients, and serial plasma from three PCa patients were used to assess the performance of PCa EV Digital Scoring Assay with the 11-gene panel. mRNA expression of the panel was computed using weighted Z score method. ROC analysis was applied to discriminate localized from metastatic PCa. Results: After optimization, the capability of EV Click Chips (92.5 ± 5.4%) for capturing PCa-derived EVs from artificial plasma samples spiked with EVs outperformed ultracentrifugation (41.0 ± 3.2%) or precipitation methods (34.9± 2.2%; P&lt; 0.001). Strong signals of the 11-gene panel, i.e., ACP3, FOLH1, HOXB13, KLK2, KLK3, KLK4, MSMB, RLN1, SLC45A3, STEAP2, and TMPRSS2, were detected from three PCa cells (LNCaP, C4-2B, and 22Rv1) and their derived EVs, while rare signals were detected in either WBCs or EVs purified from male healthy donor. In the clinical study, the Z scores calculated from the 11-gene panel were significantly higher in metastatic than localized PCa with an area under the ROC curve of 0.88 (95% CI: 0.78-0.98). Finally, longitudinal analyses of three PCa patients with clinical progression, response, and stable diseases, respectively, showed the Z scores can precisely reflect the disease status even when it is undetectable by imaging. Conclusions: We demonstrate a sensitive PCa EV Digital Scoring Assay to identify metastatic PCa and dynamically monitor disease states in a noninvasive manner. This assay may augment current imaging tools for timely detection of PCa progression and provide a means to better personalized care.

Upregulation of COPB2 Promotes Prostate Cancer Proliferation and Invasion Through the MAPK/TGF-β Signaling Pathway.

There is increasing evidence that coatomer protein complex subunit beta 2 (COPB2) plays an important role in various cancer types. This study explored the role and the downstream mediators of COPB2 in prostate cancer (PCa). The expression of COPB2 was determined by the Cancer Genome Atlas database and enzyme-linked immunosorbent assay. COPB2 expression was upregulated in PCa tissues and correlated with Gleason score, biochemical recurrence, and poor prognosis. The functional roles of COPB2 in PCa were verified through a series of experiments. Knocking down COPB2 expression inhibited the growth and clonogenesis of PCa cells, promoted cell apoptosis, and inhibited the ability of scratch repair, invasion of PCa cells, and tumor growth in Nude mice. To analyze downstream signaling pathways, ingenuity pathway analysis, GSEA, and whole-genome expression spectrum GeneChip analysis were used. Western blot revealed that COPB2 expression promoted the proliferation and invasion of PCa cells by regulating the MAPK/TGF-β signaling pathway. The interacting protein (nuclear protein 1, NUPR1) was identified via Co-IP, real-time PCR, Western blot, and TCGA database in sampled tissues. The expressions of the interaction proteins NUPR1 and COPB2 were negatively regulated by each other. COPB2 could be a new biomarker for PCa diagnosis and monitoring and to provide a theoretical basis for identifying effective drug intervention targets through in-depth mechanistic studies.

Signs and symptoms in relation to progression, experiences of an uncertain illness situation in men with metastatic castration-resistant prostate cancer-A qualitative study.

ObjectiveSigns and symptoms are important in monitoring prostate cancer, but there is a lack of understanding about the men's interpretation of signs and symptoms in relation to disease progression in advanced phases of the disease. The aim was to illuminate the experience of signs and symptoms in relation to disease progression in men with metastatic castration‐resistant prostate cancer (mCRPC).MethodThirty longitudinal interviews were conducted with 11 men undergoing life‐prolonging treatment for mCRPC. Conventional content analysis was used.ResultsThe results illuminate an uncertainty that the men experience when interpreting signs and symptoms. The overarching theme was The experience of an uncertain illness situation within the framework of progression, with four subthemes: Symptoms triggering thoughts about disease progression; Making sense of signs, also in the absence of symptoms; Making sense of symptoms during treatment; Progression triggering thoughts about the remainder of life.ConclusionIn the uncertain illness situation, the men strive to make sense of signs and symptoms based on previous experiences and in relation to disease progression. Understanding the men's perspectives on signs and symptoms in this late phase may help health care professionals communicate about disease progression considering the balance between treatment outcome and quality of life.

High resolution magic angle spinning MRS in prostate cancer.

Prostate cancer (PCa) is one of the leading causes of death among men worldwide. The current methods utilized to screen for prostate cancer may not have sufficient sensitivity in distinguishing aggressive from indolent diseases, which affect the quality of life of patients in the short and long term. The overdiagnosis of cases and overtreatment are prevalent due to the heterogeneity of the disease in terms of latent and progressive variants, as well as in the tissue types present in biopsy samples. The purpose of this review is to discuss the potential clinical benefits of incorporating high-resolution magic angle spinning (HRMAS) magnetic resonance spectroscopy (MRS) modalities to overcome the current challenges in the diagnosis, prognostication, and monitoring of PCa.

The waiting time for prostate cancer treatment in Italy: analysis from the PROS-IT CNR Study.

Prostate cancer (PCa) is the second most common neoplasm in male patients. To date, there's no certain indication about the maximum waiting time (WT) acceptable for treatment beginning and the impact on oncological and functional outcomes has not been well established. Data from the National Research Council PCa monitoring multicenter project in Italy (Pros-IT CNR) were prospectively collected and analyzed. WT was defined as the time from the bioptical diagnosis of PCa to the first treatment received. Patients were divided in two groups, using a time frame of 90 days. Quality of life was measured through the Italian version of the University of California Los Angeles-Prostate Cancer Index (UCLA-PCI) and of the Short-Form Health Survey (SF-12). The occurrence of upgrading, upstaging, presence of lymph node metastasis and positive surgical margins at the final histopathological diagnosis, and PSA at 12 months follow-up were evaluated. The overall median WT was 93 days. The logistic multivariable model confirmed that age, being resident in Southern regions of Italy and T staging at diagnosis were significantly associated with a WT>90 days. At 6 months from diagnosis the mean SF-12 score for the emotional-psychological component was significantly lower in WT≥90 days group (P=0.0428). Among patients treated with surgical approach, no significant differences in oncological outcomes were found in the two groups. In our study age, clinical T stage and provenance from Southern regions of Italy are associated with a WT>90 days. WT might have no impact on functional and oncological outcome.

Role of miRNA-145, 148, and 185 and Stem Cells in Prostate Cancer.

MicroRNAs (miRNAs) are small non-coding RNA molecules that play a role in cancer linked to the regulation of important cellular processes and pathways involving tumorigenesis, cell proliferation, differentiation, and apoptosis. A lot of human miRNA sequences have been identified which are linked to cancer pathogenesis. MicroRNAs, in prostate cancer (PC), play a relevant role as biomarkers, show a specific profile, and have been used as therapeutic targets. Prostate cancer (PC) is the most frequently diagnosed cancer in men. Clinical diagnoses among the gold standards for PC diagnosis and monitoring are prostate-specific antigen (PSA) testing, digital rectal examination, and prostate needle biopsies. PSA screening still has a large grey area of patients, which leads to overdiagnosis. Therefore, new biomarkers are needed to improve existing diagnostic tools. The miRNA expression profiles from tumour versus normal tissues are helpful and exhibit significant differences not only between cancerous and non-cancerous tissues, but also between different cancer types and subtypes. In this review, we focus on the role of miRNAs-145, 148, and 185 and their correlation with stem cells in prostate cancer pathogenesis. MiR-145, by modulating multiple oncogenes, regulates different cellular processes in PC, which are involved in the transition from localised to metastatic disease. MiR-148 is downregulated in high-grade tumours, suggesting that the miR-148-3 family might act as tumour suppressors in PC as a potential biomarker for detecting this disease. MiR-185 regulation is still unclear in being able to regulate tumour processes in PC. Nevertheless, other authors confirm the role of this miRNA as a tumour suppressor, suggesting its potential use as a suitable biomarker in disease prognosis. These three miRNAs are all involved in the regulation of prostate cancer stem cell behaviour (PCSCs). Within this contest, PCSCs are often involved in the onset of chemo-resistance in PC, therefore strategies for targeting this subset of cells are strongly required to control the disease. Hence, the relationship between these two players is interesting and important in prostate cancer pathogenesis and in PCSC stemness regulation, in the attempt to pave the way for novel therapeutic targets in prostate cancer.

Relevance of emerging metabolomics-based biomarkers of prostate cancer: a systematic review.

Prostate cancer (PC) presents great challenges in early diagnosis and often leads to unnecessary invasive procedures as well as over diagnosis and treatment, thus highlighting the need for promising early diagnostic biomarkers. The aim of this review is to provide an up-to-date summary of chronologically existing metabolomics PC biomarkers, their potential to improve clinical PC diagnosis and to reduce the proliferation and monitoring of PC. The systematic research was conducted on PubMed in accordance with PRISMA guidelines to report PC biomarkers. The majority of the studies distinguished malignant from benign prostate and few explored the biomarkers associated with the progression of PC. The present review summarises the primary outcomes of most significant studies to extend our knowledge of PC metabolomics biomarkers. We observed divergent inter-laboratory technical procedures employing different statistical approaches produced abundant information regarding PC metabolites perturbation. Since PC metabolomics is still in its early phase, it is vital that we dig out the most specific, sensitive and accurate metabolic signatures and conduct more studies with milestone findings with comparable sample sizes to validate and corroborate the findings.