High-grade Prostate Cancer Research Articles

Molecular Alterations in Intraductal Carcinoma of the Prostate

Intraductal carcinoma of the prostate is most commonly associated with high-grade invasive prostate cancer. However, isolated IDC-P without adjacent cancer or high-grade cancer is also well known. Common genetic alterations present in IDC-P with adjacent high-grade prostate cancer are those described in high-grade tumors, such as PTEN loss (69–84%). In addition, the rate of LOH involving TP53 and RB1 is significantly higher. IDC-P is common in the TCGA molecular subset of SPOP mutant cancers, and the presence of SPOP mutations are more likely in IDC-P bearing tumors. IDC-P without adjacent high-grade cancers are by far less common. They are less likely to have PTEN loss (47%) and rarely harbor an ERG fusion (7%). Molecular alterations that may predispose a person to the development of IDC-P include the loss of BRCA2 and PTEN as well as mutations in SPOP. However, the causative nature of these genetic alterations is yet to be validated.

Role of psa levels and pathological stadiation before radiation therapy in predicting mp-MRI results in patients with prostate cancer recurrence after radical prostatectomy

ObjectiveTo evaluate PSA value in mp-MRI results prediction, analyzing patients with high (GS≥8, pT≥3, pN1) and low grade (GS<8, pT<3, pN0) Prostate Cancer (PCa). Materials and methodsOne hundred eighty-eight patients underwent 1.5-Tmp-MRI after Radical Prostatectomy (RP) and before Radiotherapy (RT). They were divided into 2 groups: A and B, for patients with biochemical recurrence (BCR) and without BCR but with high local recurrence risk. Considering Gleason Score (GS), pT and pN as independent grouping variables, ROC analyses of PSA levels at primary PCa diagnosis and PSA before RT were performed in order to identify the optimal cut-off to predict mp-MRI result. ResultsGroup A and B showed higher AUC for PSA before RT than PSA at PCa diagnosis, in low and high grade tumors. For low grade tumors the best AUC was 0.646 and 0.685 in group A and B; for high grade the best AUC was 0.705 and 1 in group A and B, respectively. For low grade tumors the best PSA cut-off was 0.565−0.58ng/mL in group A (sensitivity, specificity: 70.5%, 66%), and 0.11−0.13ng/mL in B (sensitivity, specificity: 62.5%, 84.6%). For high grade tumors, the best PSA cut-off obtained was 0.265−0.305ng/mL in group A (sensitivity, specificity: 95%, 42.1%), and 0.13−0.15ng/mL in B (sensitivity, specificity: 100%). ConclusionMp-MRI should be performed as added diagnostic tool always when a BCR is detected, especially in high grade PCa. In patients without BCR, mp-MRI results, although poorly related to pathological stadiation, still have a good diagnostic performance, mostly when PSA>0.1−0.15ng/mL.

Aberrant expression of GATA3 in metastatic adenocarcinoma of the prostate: an important pitfall.

The distinction of high-grade prostate cancer (PCa) from poorly differentiated urothelial carcinoma (UC) can be somewhat challenging on clinical and morphological grounds alone, yet it is of great importance for prognostication and choice of treatment. GATA3 is a useful immunohistochemical marker to confirm urothelial origin. However, recent works report strong GATA3 immunoexpression in primary high-grade PCa. The aim of this study was to explore GATA3 expression specifically in metastatic PCa. The pathology databases of four tertiary institutions were queried for cases of metastatic PCa. Available slides and clinical records were reviewed by experienced genitourinary pathologists. Prostatic markers (PSA, PSAP, NKX3.1) and GATA3 immunohistochemistry were performed. A total of 163 metastatic PCa cases were included. At least one prostate marker was positive in each case of non-regional distant metastasis, confirming prostatic origin. GATA3 strong staining was found in four (2.5%) cases: two liver, one bone and one non-regional lymph-node metastases. All four patients had Grade Group 5 PCa at the initial diagnosis. The metastatic prostatic adenocarcinomas were solid, either with no gland formation (n = 3) or with only focal cribriforming (n = 1). To our knowledge, this is the first study exploring GATA3 expression specifically in metastatic PCa. Despite being infrequent, GATA3 positivity in high-grade PCa may lead to misdiagnosis, with clinical implications. We recommend a panel of immunohistochemical markers, both prostatic and urothelial, for ruling out UC, either in primary tumour samples or in the event of metastases of unknown primary, when a genitourinary origin is suspected.

The grade of individual prostate cancer lesions predicted by magnetic resonance imaging and positron emission tomography

BackgroundMultiparametric magnetic resonance imaging (mpMRI) and positron emission tomography (PET) are widely used for the management of prostate cancer (PCa). However, how these modalities complement each other in PCa risk stratification is still largely unknown. We aim to provide insights into the potential of mpMRI and PET for PCa risk stratification.MethodsWe analyzed data from 55 consecutive patients with elevated prostate-specific antigen and biopsy-proven PCa enrolled in a prospective study between December 2016 and December 2019. [68Ga]PSMA-11 PET (PSMA-PET), [11C]Acetate PET (Acetate-PET) and mpMRI were co-registered with whole-mount histopathology. Lower- and higher-grade lesions were defined by International Society of Urological Pathology (ISUP) grade groups (IGG). We used PET and mpMRI data to differentiate between grades in two cases: IGG 3 vs. IGG 2 (case 1) and IGG ≥ 3 vs. IGG ≤ 2 (case 2). The performance was evaluated by receiver operating characteristic (ROC) analysis.ResultsWe find that the maximum standardized uptake value (SUVmax) for PSMA-PET achieves the highest area under the ROC curve (AUC), with AUCs of 0.72 (case 1) and 0.79 (case 2). Combining the volume transfer constant, apparent diffusion coefficient and T2-weighted images (each normalized to non-malignant prostatic tissue) results in AUCs of 0.70 (case 1) and 0.70 (case 2). Adding PSMA-SUVmax increases the AUCs by 0.09 (p < 0.01) and 0.12 (p < 0.01), respectively.ConclusionsBy co-registering whole-mount histopathology and in-vivo imaging we show that mpMRI and PET can distinguish between lower- and higher-grade prostate cancer, using partially discriminative cut-off values.

Membrane-derived particles shed by PSMA-positive cells function as pro-angiogenic stimuli in tumors

Cell membrane-derived particles (Mp) are rounded membrane-enclosed particles that are shed from tumor cells. Mp are formed from tumor membranes and are capable of tumor targeting and immunotherapeutic agents because they share membrane homology with parental cells; thus, they are under consideration as a drug delivery vehicle. Prostate-specific membrane antigen (PSMA), a transmembrane glycoprotein with enzymatic functionality, is highly expressed in Mp and extracellular vesicles (EV) from prostate cancer (PCa) with poor clinical prognosis. Although PSMA expression was previously shown in EV and Mp isolated from cell lines and from the blood of patients with high-grade PCa, no pathophysiological effects have been linked to PCa-derived Mp. Here, we compared Mp from PSMA-expressing (PSMA-Mp) and PSMA-non-expressing (WT-Mp) cells side by side in vitro and in vivo. PSMA-Mp can transfer PSMA and new phenotypic characteristics to the tumor microenvironment. The consequence of PSMA transfer to cells and increased secretion of vascular endothelial growth factor-A (VEGF-A), pro-angiogenic and pro-lymphangiogenic mediators, with increased 4E binding protein 1 (4EBP-1) phosphorylation.

Mortality Risk for Docetaxel-Treated, High-Grade Prostate Cancer With Low PSA Levels

Patients with high-grade prostate cancer with low levels of prostate-specific antigen (PSA; <4 ng/mL) are at high risk of mortality, necessitating an improved treatment paradigm. To assess for these patients whether adding docetaxel to standard of care (SOC) treatment is associated with decreased prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM). PubMed search from 2000 to 2022. Five prospective randomized clinical trials (RCTs) performed in the US, France, and the United Kingdom evaluating SOC treatment with radiotherapy and androgen deprivation therapy (ADT) or with radical prostatectomy vs SOC plus docetaxel. Individual data were included from patients with nonmetastatic prostate cancer, a PSA level of less than 4 ng/mL, and a Gleason score of 8 to 10. Patients initiated treatment between February 21, 2006, and December 31, 2015 (median follow-up, 7.1 [IQR, 5.4-9.9] years). Data were analyzed on December 16, 2022. Hazard ratio (HR) of ACM and subdistribution HR (sHR) of PCSM adjusted for performance status (1 vs 0 or good health), Gleason score (9 or 10 vs 8), tumor category (T3-T4 vs T1-T2 or TX), and duration of ADT (2 years vs 4-6 months). From a cohort of 2184 patients, 145 patients (6.6%) in 4 RCTs were eligible (median age, 63 [IQR, 46-67] years). Thirty-one patients died, and of these deaths, 22 were due to prostate cancer. Performance status was 0 for 139 patients (95.9%) and 1 for 6 patients (4.1%). A reduced but nonsignificant risk of ACM (HR, 0.51 [95% CI, 0.24-1.09]) and PCSM (sHR, 0.42 [95% CI, 0.17-1.02]) was associated with patients randomized to SOC plus docetaxel compared with SOC. The risk reduction in ACM (HR, 0.46 [95% CI, 0.21-1.02]) was more pronounced among patients with a performance status of 0 and was significant for PCSM (sHR, 0.30 [95% CI, 0.11-0.86]). Adding docetaxel to SOC treatment for patients who are in otherwise good health with a PSA level of less than 4 ng/mL and a Gleason score of 8 to 10 was associated with a significant reduction in PCSM and therefore has the potential to improve prognosis.

Is There Any Relation Between High-Grade Prostate Cancer and Central Obesity, Hyperinsulinemia and Dyslipidemia?

Background: Prostate Cancer (PCa) is the sixth leading cause of cancer death in men, worldwide. Incidence of prostate cancer in India is on the rise. Most studies suggest that obesity has a positive correlation with a higher risk of developing high-grade PCa and dying of PCa. Central obesity and related biochemical alterations in terms of hyperinsulinemia and dyslipidemia are associated with severity of prostate cancer in terms of high Gleason score. Materials &amp; Methods: Central obesity was assessed using anthropometric measurements including waist hip ratio (WHR) and body mass index (BMI). Serum PSA, testosterone, and insulin levels were estimated. Serum levels of triglycerides (TG), cholesterol, low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL), high-density lipoprotein (HDL) were also measured. Standard staging procedures were followed and for histopathological evaluation of PCa, Gleason grading was done on core biopsy tissue. Results: In the present population-based study, persons with high Gleason score had significantly higher WHR supporting that central obesity may predispose to high-grade prostate cancer. Study has shown a significant relationship between high Gleason score and cholesterol, TG, VLDL, and low HDL levels; however no significant relation was found with LDL levels. Testosterone is a key prostate growth factor although PCa presents at an age when testosterone levels are declining. Conclusion: In this study, there was no significant difference in testosterone levels in patients with high and low Gleason scores. Keywords: Prostate, Cancer, High grade, Low grade

The relationship between methylation of tumor suppressor genes &lt;i&gt;APC&lt;/i&gt;, &lt;i&gt;GSTP1&lt;/i&gt;, &lt;i&gt;RASSF1A&lt;/i&gt; and content of prostate-specific antigen- associated markers in prostate cancer diagnosis

Despite the improvement of prostate cancer (PCa) diagnostic methods and the introduction of prostate-specific antigen (PSA) monitoring, the incidence of advanced PCa in Russia remains high. New more informative variables are needed for the effective diagnosis of early stage and high-grade PCa. In the field of epigenetics of special interest is the detection of DNA hypermethylation, which can serve as a PCa biomarker, since it is common to find and may induce a stable appropriate gene silencing, leading to significant cell changes. Aim of the study was to analyze the relationship between methylation of the APC, GSTP1 and RASSF1A genes and total PSA and prostate health index (PHI) in PCa. Material and methods. The present study included 54 patients with suspicion of PCa, up to 75-years old, who had an initial total PSA level from 2.5 to 10 ng/ml. To calculate PHI value the concentrations of total PSA, free PSA and pre-mature form of PSA ([–2]proPSA) in blood serum were measured by chemiluminescence immunoassay. Results and discussion. The study has revealed the statistically significant correlation between the degree of methylation in blood plasma samples and biopsy material of only the GSTP1 gene and PSA-associated markers. We found an increase of parameters contingency as Gleason score increased. Conclusions. As a result of this work, statistically significant direct correlations were identified between changes in methylation patterns of the promoter region of the GSTP1 gene and PHI, which allows us to consider them as potential candidates for inclusion in a diagnostic panel for more effective early detection of prostate cancer.

Sexually and Non-sexually Transmitted Infections and The risk of Prostate Cancer

Abstract Introduction Prostate cancer (PCa) is by far the most common type of cancer among men in western countries. However, relatively little is known about its etiology despite the high morbidity and mortality rates, where only advanced age, ethnicity, and family history of prostate cancer are well-established non-modifiable risk factors. It has been suggested that chronic inflammation may be involved in the development of prostate carcinogenesis. Therefore, our objective was to investigate the role of sexually and non-sexually transmitted infections in the occurrence of prostate cancer with a specific interest in the aggressive types based on data from EPICAP. Methods EPICAP is a population-based case-control study conducted in the département of Hérault, France, between 2012 and 2014. A total of 819 incident cases and 879 controls were interviewed face-to-face using a standardized questionnaire gathering information on known or suspected risk factors of prostate cancer and personal history of specific sexually and non-sexually transmitted infections: Gonorrhea, Syphilis, Trichomonas, Herpes, Mononucleosis, Epstein Barr, Varicella-zoster, and Dengue. Odds Ratios (OR) and their 95% confidence interval were estimated using multivariate unconditional logistic regression. Results No association emerged for the history of sexually transmitted infections (OR 1.04, 95%CI: 0.84-1.25) and non-sexually transmitted infections (OR1.09, 95%CI: 0.89-1.34) and the risk of prostate cancer. Even for all the infections studied separately, there was no association with the risk of low-grade or high-grade prostate cancer. Conclusions Our results showed that sexually or non-sexually transmitted infections do not seem to be risk factors for prostate cancer in the EPICAP study. Therefore, further investigation is needed to help advance our understanding of the role of chronic inflammation in the etiology of prostate cancer, with a particular focus on its most aggressive types.

El papel del antígeno prostático específico (PSA) y el estadio patológico antes de la radioterapia en la predicción de los resultados de la resonancia magnética multiparamétrica (RMmp) en pacientes con recidiva del cancer de próstata tras prostatectomía radical

ObjectiveTo evaluate prostate-specific antigen (PSA) value in multiparametric magnetic resonance imagin (mp-MRI) results prediction, analyzing patients with high (Gleason Score ≥8, pT≥3, pN1) and low grade (Gleason Score <8, pT<3, pN0) prostate cancer (PCa). Materials and methodsOne hundred eighty-eight patients underwent 1.5-T mp-MRI after radical prostatectomy and before radiotherapy. They were divided into 2 groups: A and B, for patients with biochemical recurrence (BCR) and without BCR but with high local recurrence risk. Considering Gleason Score, pT and pN as independent grouping variables, ROC analyses of PSA levels at primary PCa diagnosis and PSA before radiotherapy were performed in order to identify the optimal cut-off to predict mp-MRI result. ResultsGroup A and B showed higher area under the curve for PSA before radiotherapy than PSA at PCa diagnosis, in low and high grade tumors. For low grade tumors the best area under the curve was 0.646 and 0.685 in group A and B; for high grade the best area under the curve was 0.705 and 1 in group A and B, respectively. For low grade tumors the best PSA cut-off was 0.565-0.58ng/ml in group A (sensitivity, specificity: 70.5%, 66%), and 0.11-0.13ng/ml in B (sensitivity, specificity: 62.5%, 84.6%). For high grade tumors, the best PSA cut-off obtained was 0.265-0.305ng/ml in group A (sensitivity, specificity: 95%, 42.1%), and 0.13-0.15ng/ml in B (sensitivity, specificity: 100%). ConclusionMp-MRI should be performed as added diagnostic tool always when a BCR is detected, especially in high grade PCa. In patients without BCR, mp-MRI results, although poorly related to pathological stadiation, still have a good diagnostic performance, mostly when PSA>0.1-0.15ng/ml.

RAGE as a Novel Biomarker for Prostate Cancer: A Systematic Review and Meta-Analysis.

The receptor for advanced glycation end-products (RAGE) has been implicated in driving prostate cancer (PCa) growth, aggression, and metastasis through the fueling of chronic inflammation in the tumor microenvironment. This systematic review and meta-analysis summarizes and analyzes the current clinical and preclinical data to provide insight into the relationships among RAGE levels and PCa, cancer grade, and molecular effects. A multi-database search was used to identify original clinical and preclinical research articles examining RAGE expression in PCa. After screening and review, nine clinical and six preclinical articles were included. The associations of RAGE differentiating benign prostate hyperplasia (BPH) or normal prostate from PCa and between tumor grades were estimated using odds ratios (ORs) and associated 95% confidence intervals (CI). Pooled estimates were calculated using random-effect models due to study heterogeneity. The clinical meta-analysis found that RAGE expression was highly likely to be increased in PCa when compared to BPH or normal prostate (OR: 11.3; 95% CI: 4.4-29.1) and that RAGE was overexpressed in high-grade PCa when compared to low-grade PCa (OR: 2.5; 95% CI: 1.8-3.4). In addition, meta-analysis estimates of preclinical studies performed by albatross plot generation found robustly positive associations among RAGE expression/activation and PCa growth and metastatic potential. This review demonstrates that RAGE expression is strongly tied to PCa progression and can serve as an effective diagnostic target to differentiate between healthy prostate, low-grade PCa, and high-grade PCa, with potential theragnostic applications.

Association between Type 2 Diabetes Mellitus and Prostate Cancer Aggressiveness

Background: Type 2 diabetes mellitus (T2DM) and prostate cancer (Pca) are two different disease entities that occur frequently in the elderly populations. Researchers have identified some mechanisms that could link T2DM to the development, progression and prognosis of Pca. Although controversies surround this concept, T2DM has been reported to confer protection to the development of low grade Pca and to a lesser extent high grade Pca. Materials and Methods: One hundred and thirty-six (136) men with Pca were evaluated in this study. Information from their case-notes were retrospectively retrieved during their clinic visits including bio-data, history, physical examination findings, laboratory and radiological investigation results and reports of prostate biopsy. Patients were grouped as diabetic and non-diabetic based on the history and laboratory records. Age and prostate specific antigen (PSA) levels were also categorized. Collated data were analyzed using the Statistical Package for Social Sciences (SPSS) version 20.0 software. Results: One hundred and thirty six (136) men with a mean age of 69.10±8.40 years ranging from 48 to 91 years and diagnosed with Pca were evaluated. Diabetic men were older and had higher mean serum PSA and Gleason score (GS) than non-diabetic men (Table3i – iii). Conclusion: Diabetic men in this study had higher values of variables portraying more aggressive Pca than non-diabetic men. Therefore, in evaluating this group of patients presenting with symptoms suspicious of Pca, concerns of probably dealing with highly aggressive tumours should be held strong.

Coronary heart disease and the course of newly detected prostate cancer

Introduction. In recent years, the clinical and practical interest in malignant neoplasms and diseases of the cardiovascular system has been extremely high. These nosologies are the leading causes of hospitalisations and deaths worldwide.Objective. To assess the prevalence of coronary heart disease and risk factors among patients with newly diagnosed prostate cancer, as well as to identify their relationship with the severity of prostate cancer.Materials &amp; methods. The study included 140 newly diagnosed prostate cancer (PCa) patients with a median age of 65 [62; 70] years. All patients had the level of prostate-specific antigen, pelvic MRI, prostate biopsy with determination of Gleason score, all patients filled out the questionnaire of the International Index of Erectile Function (IIEF-5). Depending on the presence of coronary heart disease (CHD), all patients were divided into two groups: Group 1 — 94 (67%) PCa patients without CHD; Group 2 — 46 (33%) PCa patients with CHDResults. In a comparative analysis, the groups did not differ in indicators such as age, BMI, prostate volume, incidence of diabetes mellitus type 2, and lipid status level. However, in PCa patients with CHD, erectile dysfunction was statistically significantly more pronounced than in patients without CHD (10 vs 18 IIEF5 points, p = 0.03), respectively. In terms of PSA levels, it turned out that in Group 2, this indicator was significantly higher than in Group 1 (15.8 ng/ml vs 10.1 ng/ml, p = 0.03), respectively, which indicates possibly more high malignancy of the process. Furthermore, in Group 2, patients with a high grade PCa according to the classification of The International Society of Urological Pathology (ISUP) 4 / 5 were statistically significantly more common compared to patients of Group 1 (12 (26%) vs. 10 (11%), p = 0.01), respectively. In a comparative analysis of patients depending on the risk of a possible PCa recurrence of , which was taken into account by such parameters as PSA level, Gleason index + ISUP grade, it turned out that in Group 2 there were statistically significantly more patients with a higher risk of PCa progression compared to Group 1 (20 (44%) vs 26 (28%), p = 0.02), respectively.Conclusion. PCa patients with concomitant CHD are characterized by a higher waist circumference, they had lower indicators of erectile function, a more pronounced comorbid background, and more often had a history of stroke. In addition, PCa patients with CHD had a high grade PCa and a higher risk of PCa progression.

Diagnosis of prostate cancer with magnetic resonance imaging in men treated with 5-alpha-reductase inhibitors

PurposeThe primary aim of this study was to evaluate if exposure to 5-alpha-reductase inhibitors (5-ARIs) modifies the effect of MRI for the diagnosis of clinically significant Prostate Cancer (csPCa) (ISUP Gleason grade ≥ 2).MethodsThis study is a multicenter cohort study including patients undergoing prostate biopsy and MRI at 24 institutions between 2013 and 2022. Multivariable analysis predicting csPCa with an interaction term between 5-ARIs and PIRADS score was performed. Sensitivity, specificity, and negative (NPV) and positive (PPV) predictive values of MRI were compared in treated and untreated patients.Results705 patients (9%) were treated with 5-ARIs [median age 69 years, Interquartile range (IQR): 65, 73; median PSA 6.3 ng/ml, IQR 4.0, 9.0; median prostate volume 53 ml, IQR 40, 72] and 6913 were 5-ARIs naïve (age 66 years, IQR 60, 71; PSA 6.5 ng/ml, IQR 4.8, 9.0; prostate volume 50 ml, IQR 37, 65). MRI showed PIRADS 1–2, 3, 4, and 5 lesions in 141 (20%), 158 (22%), 258 (37%), and 148 (21%) patients treated with 5-ARIs, and 878 (13%), 1764 (25%), 2948 (43%), and 1323 (19%) of untreated patients (p < 0.0001). No difference was found in csPCa detection rates, but diagnosis of high-grade PCa (ISUP GG ≥ 3) was higher in treated patients (23% vs 19%, p = 0.013). We did not find any evidence of interaction between PIRADS score and 5-ARIs exposure in predicting csPCa. Sensitivity, specificity, PPV, and NPV of PIRADS ≥ 3 were 94%, 29%, 46%, and 88% in treated patients and 96%, 18%, 43%, and 88% in untreated patients, respectively.ConclusionsExposure to 5-ARIs does not affect the association of PIRADS score with csPCa. Higher rates of high-grade PCa were detected in treated patients, but most were clearly visible on MRI as PIRADS 4 and 5 lesions.Trial registrationThe present study was registered at ClinicalTrials.gov number: NCT05078359.

A urine extracellular vesicle lncRNA classifier for high-grade prostate cancer and increased risk of progression: A multi-center study

To construct a urine extracellular vesicle long non-coding RNA (lncRNA) classifier that can detect high-grade prostate cancer (PCa) of grade group 2 or greater and estimate the risk of progression during active surveillance, we identify high-grade PCa-specific lncRNAs by combined analyses of cohorts from TAHSY, TCGA, and the GEO database. We develop and validate a 3-lncRNA diagnostic model (Clnc, being made of AC015987.1, CTD-2589M5.4, RP11-363E6.3) that can detect high-grade PCa. Clnc shows higher accuracy than prostate cancer antigen 3 (PCA3), multiparametric magnetic resonance imaging (mpMRI), and two risk calculators (Prostate Cancer Prevention Trial [PCPT]-RC 2.0 and European Randomized Study of Screening for Prostate Cancer [ERSPC]-RC) in the training cohort (n= 350), two independent cohorts (n=232; n= 251), and TCGA cohort (n=499). In the prospective active surveillance cohort (n= 182), Clnc at diagnosis remains a powerful independent predictor for overall active surveillance progression. Thus, Clnc is a potential biomarker for high-grade PCa and can also serve as a biomarker for improved selection of candidates for active surveillance.

Isolated Castrate-resistant Prostate Cancer Metastasis to Both Adrenal Glands Detected on 68Ga PSMA PET/CT.

A 61-year-old male patient, who had undergone radical prostatectomy, underwent 68Ga labeled prostate-specific membrane antigen (PSMA) positron emission tomography/computerized tomography (PET/CT) for evaluation of suspected biochemical recurrence of prostate cancer (PCa). PET/CT scan showed increased 68Ga PSMA expressions in hypodense mass lesions in both adrenal gland localizations. An adrenal gland tru-cut biopsy was performed for the right side, which showed poor-differentiated carcinoma metastases associated with the patient's high-grade PCa. As far as we could determine based on an extensive literature search, this is the second case in which isolated adrenal metastasis was detected by 68Ga PSMA PET/CT study in a patient with PCa.

Association of Obesity with Prostate Cancer at Time of Biopsy: A MultiCentre 10-Year Retrospective Study

Background and Aim: The incidence of Prostate cancer (PCa) is on the rise in Cameroon, making it the most commonly diagnosed cancer amongst men. Factors, such as obesity, smoking, and the consumption of high fat diet have been reported to play a role in the aetiology and progression of cancers in general. However, the exact relationship between obesity and prostate cancer in Africans is still poorly described. The present study aimed to evaluate the association between obesity as measured by the body mass index (BMI) and high-grade prostate cancer in Cameroonians. Methods: This was a retrospective analyses of the clinical records of 300 consecutive men who underwent transrectal ultrasound-guided core needle prostate biopsy between January 2010 and January 2020. Patients were grouped as obese (BMI ≥30kg/m²) and non-obese (BMI &lt;30kg/m²) and binary logistic regression modelling was used to compare the association between obesity and patient characteristics, such as age, digital rectal examination (DRE) findings, prostate specific antigen (PSA) level, prostate volume, PSA density, and Gleason score (GS). Results: The mean age at diagnosis of PCa was 65.46 ± 8.54 years (Range: 34-89 years), the mean BMI was 28.93 ± 4.57 kg/m² (Range: 18.35-42.37 kg/m²), and the median total PSA level was 44.2 ng/ml. In total, 142 men (47.3%) were obese and biopsies detected high-grade prostate cancer in 160 men (63.3%). Obese men were significantly younger and had a higher risk (OR= 2.74, p &lt;0.001) of having high-grade PCa compared to nonobese men. Furthermore, 94 obese men (58.75%) had high-grade PCa. Obese men had higher age-adjusted PSA densities (P&lt;0.001), while there was no statistical difference in DRE findings (OR= 1.06, p= 0.225). Conclusion: This study demonstrated that obesity is associated with a higher risk of high-grade prostate cancer. This risk is more pronounced among younger patients and DRE findings are not influenced by BMI.

Prostate Cancer in New York City: Impact of Neighborhood Level Social Determinants of Care

Social determinants of health may impact stage and aggressiveness of cancer presentation. As neighborhoods may influence adjacent neighborhoods across often porous and arbitrary borders, an analysis that measures the spatial impact of these social determinants provides a more holistic evaluation than an analysis that treats each neighborhood as independent and unrelated units. In this paper, we study the impact of sociodemographic and environmental characteristics of neighborhoods on cancer presentation in New York City, using both patient-level analysis and spatial autoregression on the New York State Public Access Cancer Epidemiology Data (NYSPACED) and the NYC Open neighborhood-level dataset. Two outcomes of interest were chosen: Presentation with high grade prostate cancer and presentation with distant disease. We performed logistic regression on individual patient level analysis. We created generalized cross sectional autoregressive spatial regression models to assess direct and indirect (via adjacent neighborhoods) impact of neighborhood level independent variables. We analyzed the following neighborhood level variables: 1) Percent population that was Black, 2) Percent population living in poverty, 3) Percent population obese based on self-reported height and weight, 4) Percent who report being current smokers, 5) Percent who report eating one or more servings of fruits and/or vegetables in the last day, and 6) annual average micrograms of fine particulate matter per cubic meter of air. We identified 95,749 patients diagnosed with prostate adenocarcinoma in New York City from 2001-2018. With reported Black race as the referent value, White patients were less likely to present with high grade disease (OR 0.92 [95% CI 0.89-0.95]). Similarly, self-identified White patients were also less likely to present with distant disease (vs. Black, OR 0.76 [95% CI 0.72-0.81]). Spatial autoregression models revealed no neighborhood level variables associated with direct or indirect impacts on presentation with high grade disease. However, there were several variables initially associated with distant disease presentation, including race, poverty, obesity, fruit and vegetable consumption, and air pollution. However, only neighborhood poverty and obesity levels continued to have significant direct impact on presentation with distant disease when included in the regression model with percent Black residents. In conclusion, we discovered a strong association between Race and poverty with the likelihood of presenting with advanced prostate cancer, at both the individual and neighborhood levels. Geographically targeted outreach to improve prostate cancer screening and access to care should be focused on Black men and neighborhoods with high levels of poverty.

Economic evaluation of prostate cancer risk assessment methods: A cost-effectiveness analysis using population data.

The current prostate cancer (PCa) screening standard of care (SOC) leads to unnecessary biopsies and overtreatment because decisions are guided by prostate-specific antigen (PSA) levels, which have low specificity in the gray zone (3-10 ng/mL). New risk assessment tools (RATs) aim to improve biopsy decision-making. We constructed a modeling framework to assess new RATs in men with gray zone PSA from the British Columbia healthcare system's perspective. We evaluated the cost-effectiveness of a new RAT used in biopsy-naïve men aged 50+ with a PSA of 3-10 ng/mL using a time-dependent state-transition model. The model was informed by engaging patient partners and using linked administrative health data, supplemented with published literature. The incremental cost-effectiveness ratio and the probability of the RAT being cost-effective were calculated. Probabilistic analysis was used to assess parameter uncertainty. In the base case, a RAT based on an existing biomarker's characteristics was a dominant strategy associated with a cost savings of $44 and a quality-adjusted life years (QALY) gain of 0.00253 over 18 years of follow-up. At a cost-effectiveness threshold of $50,000/QALY, the probability that using a RAT is cost-effective relative to the SOC was 73%. Outcomes were sensitive to RAT costs and accuracy, especially the detection rate of high-grade PCa. Results were also impacted by PCa prevalence and assumptions about undetected PCa survival. Our findings showed that a more accurate RAT to guide biopsy can be cost-effective. Our proposed general model can be used to analyze the cost-effectiveness of any novel RAT.

Recent advances and future perspectives in the therapeutics of prostate cancer

Prostate cancer (PC) is one of the most common cancers in males and the fifth leading reason of death. Age, ethnicity, family history, and genetic defects are major factors that determine the aggressiveness and lethality of PC. The African population is at the highest risk of developing high-grade PC. It can be challenging to distinguish between low-risk and high-risk patients due to the slow progression of PC. Prostate-specific antigen (PSA) is a revolutionary discovery for the identification of PC. However, it has led to an increase in over diagnosis and over treatment of PC in the past few decades. Even if modifications are made to the standard PSA testing, the specificity has not been found to be significant. Our understanding of PC genetics and proteomics has improved due to advances in different fields. New serum, urine, and tissue biomarkers, such as PC antigen 3 (PCA3), have led to various new diagnostic tests, such as the prostate health index, 4K score, and PCA3. These tests significantly reduce the number of unnecessary and repeat biopsies performed. Chemotherapy, radiotherapy, and prostatectomy are standard treatment options. However, newer novel hormone therapy drugs with a better response have been identified. Androgen deprivation and hormonal therapy are evolving as new and better options for managing hormone-sensitive and castration-resistant PC. This review aimed to highlight and discuss epidemiology, various risk factors, and developments in PC diagnosis and treatment regimens.