Initial Prostate-specific Antigen Research Articles

Is the Serum Prostate-Specific Antigen Level Affected by Urethral Catheterization in Patients with Acute Urinary Retention?

Background: The reason for elevated serum prostate-specific antigen (PSA) levels in patients undergoing urethral catheterization due to acute urinary retention (AUR) remains a significant and controversial issue. Objectives: To assess the serum PSA level in men with AUR and its changes after catheterization. Methods: This prospective quasi-experimental study (reviewer 1 - comment 7) was conducted on 43 patients who underwent transurethral catheterization following AUR caused by benign prostatic hyperplasia (BPH). Total PSA levels and free/total PSA ratios were measured before catheterization and one and three days after catheter insertion. Additionally, prostate volume and urine output after catheterization (UOAC) were recorded. Results: The mean age, prostate volume, and UOAC of the patients were 69.05 ± 9.45 years, 60.51 ± 26.35 g, and 844.04 ± 341.66 mL, respectively. The mean and median baseline total PSA levels were 12.59 ± 17.71 ng/mL and 6.30 ng/mL, respectively. These values changed to 13.73 ± 19.83 ng/mL (median = 4.80 ng/mL) and 11.57 ± 17.70 ng/mL (median = 4.40 ng/mL) after 1 and 3 days of catheterization, respectively. The changes in total PSA and free/total PSA levels during the study period were not statistically significant (P > 0.05). Moreover, the PSA levels showed no statistically significant difference before, 1 day, and 3 days after catheterization in groups with total PSA ≤ 4 and total PSA > 4 (P = 0.37; 0.22, respectively). Conclusions: Our results suggest an initial elevation in PSA levels in patients with AUR before urethral catheterization. Both PSA and free/total PSA ratios showed no statistically significant differences before and after urethral catheter insertion, and initial PSA levels did not affect their changes post-catheterization (reviewer 1 - comment 1).

Parathyroid hormone related-protein (PTHrP) in tissues with poor prognosis in prostate cancer patients.

Parathyroid hormone-related peptide (PTHrP) is known to have a pivotal role in the progression of various solid tumors, among which prostate cancer stands out. However, the extent of PTHrP expression and its clinical implications in prostate cancer patients remain shrouded in obscurity. The primary objective of this research endeavor was to shed light on the relevance of PTHrP in the context of prostate cancer patients and to uncover the potential underlying mechanisms. The expression of PTHrP, E-cadherin, and vimentin in tumor tissues of 88 prostate cancer patients was evaluated by immunohistochemical technique. Subsequently, the associations between PTHrP and clinicopathological parameters and prognosis of patients with prostate cancer were analyzed. Immunohistochemical analysis showed that the expression rates of PTHrP, E-cadherin, and vimentin in prostate cancer tissues were 95.5%, 88.6%, and 84.1%, respectively. Patients with a high level of PTHrP had a decreased expression of E-cadherin (P = .013) and an increased expression of vimentin (P = .010) compared with patients with a low level of PTHrP. Besides, the high expression of PTHrP was significantly correlated with a higher level of initial prostate-specific antigen (P = .026), positive lymph node metastasis (P = .010), osseous metastasis (P = .004), and Gleason score (P = .026). Moreover, patients with a high level of PTHrP had shorter progression-free survival (P = .002) than patients with a low level of PTHrP. The present study indicates that PTHrP is associated with risk factors of poor outcomes in prostate cancer, while epithelial-mesenchymal transition may be involved in this process.

Comment on: "Initial Postoperative Prostate Specific Antigen and PSA Velocity Are Important Indicators of Underlying Malignancy After Simple Prostatectomy" by Livingston et al.

N/A.

MAOB expression correlates with a favourable prognosis in prostate cancer, and its genetic variants are associated with the metastasis of the disease.

Monoamine oxidase B (MAOB), a neurotransmitter-degrading enzyme, was reported to reveal conflicting roles in various cancers. However, the functional role of MAOB and impacts of its genetic variants on prostate cancer (PCa) is unknown. Herein, we genotyped four loci of MAOB single-nucleotide polymorphisms (SNPs), including rs1799836 (A/G), rs3027452 (G/A), rs6651806 (A/C) and rs6324 (G/A) in 702 PCa Taiwanese patients. We discovered that PCa patients carrying the MAOB rs6324 A-allele exhibited an increased risk of having a high initial prostate-specific antigen (iPSA) level (>10 ng/mL). Additionally, patients with the rs3027452 A-allele had a higher risk of developing distal metastasis, particularly in the subpopulation with high iPSA levels. In a subpopulation without postoperative biochemical recurrence, patients carrying the rs1799836 G-allele had a higher risk of developing lymph node metastasis and recurrence compared to those carrying the A-allele. Furthermore, genotype screening in PCa cell lines revealed that cells carrying the rs1799836 G-allele expressed lower MAOB levels than those carrying the A-allele. Functionally, overexpression and knockdown of MAOB in PCa cells respectively suppressed and enhanced cell motility and proliferation. In clinical observations, correlations of lower MAOB expression levels with higher Gleason scores, advanced clinical T stages, tumour metastasis, and poorer prognosis in PCa patients were noted. Our findings suggest that MAOB may act as a suppressor of PCa progression, and the rs3027452 and rs1799836 genetic variants of MAOB are linked to PCa metastasis within the Taiwanese population.

The presence of intraductal carcinoma of prostate is a risk factor for poor pathologic response in men with high-risk prostate cancer receiving neoadjuvant therapy

ObjectiveTo explore the potential association between the presence of intraductal carcinoma of the prostate (IDC-P) on biopsy and pathologic response of primary tumor to neoadjuvant therapy in patients with high-risk prostate cancer. MethodsEighty-five patients with high-risk localized/locally advanced prostate cancer (CaP) who were given 6-month neoadjuvant therapies of androgen deprivation therapy plus docetaxel or abiraterone prior to radical prostatectomy in 2 prospective trials were included in this study. The presence of IDC-P in biopsy pathology was rereviewed by 2 experienced pathologists. Favorable pathologic response was defined as pathologic complete response or minimal residual disease <5 mm on whole-mount histopathology. Characteristics of clinical and biopsy pathology variables were included in univariate and multivariate logistic regression analyses to identify risk factors for the prediction of favorable pathologic response on final pathology. ResultsIDC-P was identified to be present on biopsy pathology of 35 patients (41.2%) while favorable pathologic responses were confirmed in 25 patients (29.4%). Initial prostate-specific antigen (PSA) (OR 3.592, 95% CI 1.176–10.971, P = 0.025) and the presence of IDC-P on biopsy pathology (OR 3.837, 95% CI 1.234–11.930, P = 0.020) were found to be significantly associated with favorable pathologic response in multivariate logistic regression analysis. ConclusionIDC-P on biopsy pathology was found to be an independent risk factor to predict a poor pathology response of primary CaP to neoadjuvant therapies.

Remission Depth in Metastatic Hormone-Sensitive Prostate Cancer Is Associated With Prognosis in Patients With Initial Prostate-Specific Antigen Values Above 100 Ng/ML.

Recently, new drugs have caused a paradigm shift in the treatment of metastatic hormone-sensitive prostate cancer (HSPC). Meanwhile, research has identified several prognostic factors of metastatic HSPC. The present study focused on remission depth in metastatic HSPC and evaluated its association with remission depth. We analyzed 427 patients diagnosed with metastatic HSPC with serum initial prostate-specific antigen (PSA) > 100 ng/ml. The nadir serum PSA value was used as a marker of remission depth for each duration to castration resistanceby using receiver operating characteristic (ROC) curves.Cox proportional hazards regression was used to assess for any correlation of progression-free survival (PFS) and overall survival (OS) with the nadir PSA level. The cut-off value for the nadir PSA level per time to castration resistance (TTCR) at three, five, seven, and nine years was calculated. The nadir PSA value alone was able to predict prognosis because of its high sensitivity, high specificity, and high AUC in ROC analysis. The nadir PSA level can be an independent prognostic marker not only for TTCR but also for OS on multivariate analysis. We identified the cut-off value for nadir PSA per TTCR period in patients with metastatic HSPC. The nadir PSA value alone can predict prognosis; this demonstrates utility in routine clinical practice due to its simplicity and accuracy.

Magnetic Resonance Imaging-guided Active Surveillance Without Annual Rebiopsy in Patients with Grade Group 1 or 2 Prostate Cancer: The Prospective PROMM-AS Study

BackgroundMultiparametric magnetic resonance imaging (mpMRI) may allow patients with prostate cancer (PC) on active surveillance (AS) to avoid repeat prostate biopsies during monitoring. ObjectiveTo assess the ability of mpMRI to reduce guideline-mandated biopsy and to predict grade group upgrading in patients with International Society of Urological Pathology grade group (GG) 1 or GG 2 PC using Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) scores. The hypothesis was that the AS disqualification rate (ASDQ) rate could be reduced to 15%. Design, setting and participantsPROMM-AS was a prospective study assessing 2-yr outcomes for an mpMRI-guided AS protocol. A 12 mo after AS inclusion on the basis of MRI/transrectal ultrasound fusion-guided biopsy (FBx), all patients underwent mpMRI. For patients with stable mpMRI (PRECISE 1–3), repeat biopsy was deferred and follow-up mpMRI was scheduled for 12 mo later. Patients with mpMRI progression (PRECISE 4–5) underwent FBx. At the end of the study, follow-up FBx was indicated for all patients. Outcome measurements and statistical analysisWe calculated the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for upgrading to GG 2 in the GG 1 group, and to GG 3 in the GG 2 group on MRI. We performed regression analyses that included clinical variables. Results and limitationsThe study included 101 patients with PC (60 GG 1 and 41 GG 2). Histopathological progression occurred in 31 patients, 18 in the GG 1 group and 13 in the GG 2 group. Thus, the aim of reducing the ASDQ rate to 15% was not achieved. The sensitivity, specificity, PPV, and NPV for PRECISE scoring of MRI were 94%, 64%, 81%, and 88% in the GG 1 group, and 92%, 50%, 92%, and 50%, respectively, in the GG 2 group. On regression analysis, initial prostate-specific antigen (p < 0.001) and higher PRECISE score (4–5; p = 0.005) were significant predictors of histological progression of GG 1 PC. Higher PRECISE score (p = 0.009), initial Prostate Imaging-Reporting and Data System score (p = 0.009), previous negative biopsy (p = 0.02), and percentage Gleason pattern 4 (p = 0.04) were significant predictors of histological progression of GG 2 PC. Limitations include extensive MRI reading experience, the small sample size, and limited follow-up. ConclusionsMRI-guided monitoring of patients on AS using PRECISE scores avoided unnecessary follow-up biopsies in 88% of patients with GG 1 PC and predicted upgrading during 2-yr follow-up in both GG 1 and GG 2 PC. Patient summaryWe investigated whether MRI (magnetic resonance imaging) scores can be used to guide whether patients with lower-risk prostate cancer who are on active surveillance (AS) need to undergo repeat biopsies. Follow-up biopsy was deferred for 1 year for patients with a stable score and performed for patients whose score progressed. After 24 months on AS, all men underwent MRI and biopsy. Among patients with grade group 1 cancer and a stable MRI score, 88% avoided biopsy. For patients with MRI score progression, AS termination was correctly recommended in 81% of grade group 1 and 92% of grade group 2 cases.

Prostate-Specific Antigen Response to Androgen Deprivation Therapy in the Neoadjuvant Setting for High-Risk Prostate Adenocarcinoma (PIRANHA): Pooled Analysis of Two Randomized Clinical Trials

A suboptimal prostate-specific antigen (PSA) response to neoadjuvant androgen deprivation therapy (ADT) among men who go on to receive definitive radiation therapy for prostate cancer might suggest the existence of castration-resistant disease or altered androgen receptor signaling. This in turn may portend worse long-term clinical outcomes, especially in men with high-risk disease. We set out to evaluate the prognostic impact of poor PSA response to neoadjuvant ADT in men with high-risk prostate cancer. This was a post hoc analysis of the multicenter TROG 03.04 RADAR and PCS IV randomized clinical trials. Inclusion criteria for this analysis were patients with high-risk prostate cancer (defined as Gleason score ≥8, initial PSA ≥20 ng/mL, or cT3a disease or higher) who received definitive radiation therapy, at least 18 months of ADT, and had a preradiation therapy PSA level drawn after at least 3 months of neoadjuvant ADT. Poor PSA response was defined as PSA >0.5 ng/mL. Cox regression and Fine-Gray models were used to test whether poor PSA response was associated with metastasis-free survival, biochemical recurrence, prostate-cancer specific mortality, and overall survival. Nine hundred thirty men met inclusion criteria for this analysis. Median follow-up was 130 months (interquartile range [IQR], 89-154 months). After a median of 3 months (IQR, 3-4.2 months) of neoadjuvant ADT, the median PSA was 0.60 ng/mL (IQR, 0.29-1.59). Overall, 535 men (57%) had a PSA >0.5 ng/mL. Poor PSA response was associated with significantly worse metastasis-free survival (hazard ratio [HR], 3.93; P=.02), worse biochemical recurrence (subdistribution HR, 2.39; P=.003), worse prostate-cancer specific mortality (subdistribution HR, 1.50; P=.005), and worse overall survival (HR, 4.51; P=.05). Patients with PSA >0.5 mg/mL after at least 3 months of neoadjuvant ADT had worse long-term clinical outcomes and should be considered for treatment intensification.

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.

Clinical Significance of Radical Prostatectomy in Clinical Lymph Node Metastasis in Prostate Cancer.

This study aimed to investigate the role of radical prostatectomy (RP) among clinical nodal metastasis prostate cancer and whether histological confirmation of lymph node metastasis through surgery can help with treatment. After excluding patients with distant metastatic prostate cancer or neoadjuvant androgen deprivation therapy, 42 patients with clinical nodal metastasis who underwent RP at our institution were included in the study. We classified them as having or not having pathological lymph node metastasis. Clinicopathologic data were analyzed in this retrospective chart review. Kaplan-Meier analysis was used to calculate the estimated castration-resistant prostate cancer (CRPC)-free survival, biochemical recurrence (BCR)-free survival, and cancer-specific survival (CSS). There is no significant difference in age, presence of diabetes mellitus, hypertension, BCR time, CRPC time, overall survival, salvage RT rate, and initial prostate-specific antigen level between the two groups. However, there is a significant difference in the pathology N1 group in terms of pathological T stage, pathologic Gleason score, BCR rate, CRPC rate, and CSS. A multivariate Cox proportional hazard regression analysis was used to identify predictors of CRPC-free survival. Patients with pathological lymph node metastasis had a shorter CRPC-free survival [hazard ratio (HR) 4.87; 95% confidence interval (CI) 1.25-19.00, p = 0.02]. Radical prostatectomy can confirm lymph node metastasis. Although pathologic diagnosis has no effect on time to BCR and CPRC, because it affects BCR rate, CRPC rate, and CSS, an accurate pathological diagnosis obtained through surgery is beneficial in the treatment of clinical lymph node metastasis prostate cancer.

Clinical utility of the prognostic nutritional index in patients with metastatic hormone-sensitive prostate cancer: A retrospective, multicenter, cohort study.

The prognostic nutritional index (PNI) based on the serum albumin level and the lymphocyte count has been investigated as a prognostic factor in patients with malignant tumors. However, it has been poorly studied in prostate cancer (PCa), and little is known about its clinical utility. Clinical data of 353 patients with de novo, metastatic, hormone-sensitive PCa (mHSPC) who received androgen deprivation therapy (ADT) were obtained from multiple institutions between 2000 and 2019. The impacts of the pretreatment PNI level on treatment response and survival, together with clinical parameters, were examined. The Mann-Whitney U test, Cox proportional hazards models, and Kaplan-Meier methods were used to evaluate significance. The median age and initial prostate-specific antigen level were 73 and 266.18 ng/mL, respectively. Patients with a low PNI had shorter progression-free survival (PFS), cancer-specific survival (CSS), and overall survival (OS) (p < 0.0001). On multivariate analysis, low PNI was an independent prognostic factor for OS (p = 0.0027, HR = 1.65), as well as advanced age (p = 0.049, HR = 1.38), the International Society of Urological Pathology (ISUP) grade group (GG) 5 (p = 0.0027, HR = 1.69), and elevated lactate dehydrogenase (LDH) (p < 0.0001, HR = 2.08). A propensity score-matching analysis showed that the PNI level remained a significant prognostic biomarker for PFS (p = 0.0263), CSS (p = 0.0006), and OS (p = 0.0015). Furthermore, a novel risk classification using PNI, LDH, and the ISUP GG was established to stratify patients' prognosis. An increase in the number of risk factors was significantly correlated with poor outcomes. A low pretreatment PNI might be an effective biomarker of poor treatment response and survival in patients with mHSPC undergoing ADT.

Predicting Positive Repeat Prostate Biopsy Outcomes: Comparison of Machine Learning Approaches to Identify Key Parameters and Optimal Algorithms.

Innovative strategies are necessary to enhance prostate cancer diagnosis whilst reducing unnecessary and invasive repeat biopsies. This study aimed to determine the significant parameters affecting repeat prostate biopsy outcomes and develop an optimal machine learning algorithm for predicting positive repeat prostate biopsy results. We analysed data from 174 men who underwent repeated prostate biopsies between January 2008 and December 2022. Systematic multiple-core, ultrasound-targeted prostate biopsies were performed, each two samples from prostatic transitional zone and peripheral zone were obtained bilaterally. Clinical characteristics were collected, including patients' age, initial prostate volume, prostate-specific antigen (PSA) level, free PSA (fPSA)/PSA ratio, biopsy core numbers, pathological result; The time interval between first and latest prostate biopsy; Latest PSA level, fPSA/PSA ratio, biopsy core numbers; And final pathological diagnosis. Six feature selection methods, namely, variable ranking, correlation matrix, random forest regression, recursive feature elimination, cross-validation and forward selection, were employed to identify key influencing factors for repeat biopsy outcomes. Subsequently, the performance of seven machine learning algorithms, namely, multivariable logistic regression (LR), K-nearest neighbour search (KNN), support vector classification (SVC), decision tree (DT), random forest classifier (RF), naïve Bayes classifier (NBC) and gradient booster tree (GB), was assessed based on accuracy, misclassification, recall, specificity, precision and receiver operating characteristic (ROC) area under the curve (AUC). About 70% of patients were used as the training dataset, meanwhile remaining 30% as validation dataset. 52 were ultimately diagnosed with prostate cancer following the final pathological examination. The remaining 122 patients were negative. Amongst six feature selection methods, the variable ranking emerged as the most effective method for identifying the essential factors influencing repeat biopsy results. Amongst the machine learning algorithms, SVC demonstrated superior accuracy (0.7365), low recall rate (0.2500) and low misclassification rate (0.2093) for both patients with cancer and healthy individuals. Meanwhile, the ROC curve of SVC showed a relatively high AUC (0.6871). We developed an SVC-based machine learning algorithm for predicting positive repeat prostate biopsy results. Our analysis revealed that initial and latest prostate volumes, initial and latest PSA levels, latest fPSA/PSA ratio and age are significant factors for this model.

Prevalence and Prognostic Implications of PSA Flares during Radium-223 Treatment among Men with Metastatic Castration Resistant Prostate Cancer.

Radium-223 (Ra233) prolongs the survival of men with symptomatic bone-predominant metastatic castration-resistant prostate cancer (mCRPC). However, prostate-specific antigen (PSA) response patterns are not closely associated with Ra223 therapy outcomes. Herein, we sought to analyze the impact of Ra223-induced PSA flares on patient outcome. Using a retrospective cohort study of Ra223 treatment in four Ontario/Canada cancer centres, we identified 134 patients grouped into sub-cohorts according to distinct PSA response patterns: (i) initial PSA flare followed by eventual PSA decline; (ii) PSA response (≥30% PSA decrease within 12 weeks of treatment); and (iii) PSA non-response. We analyzed patient characteristics and outcome measures, including overall survival (OS), using the Kaplan-Meier method and log-rank testing. PSA flares were observed in 27 (20.2%), PSA responses in 11 (8.2%), and PSA non-responses in 96 (71.6%) patients. Amongst PSA flare patients, 12 presented with post-flare PSA decreases below baseline and 15 with PSA decreases below the flare peak but above baseline. Although only six flare patients achieved ≥30% PSA decreases below baseline, the median OS of all flare patients (16.8 months, 95% CI 14.9-18.7) was comparable to that of PSA responders and non-responders (p = 0.349). In summary, around 20% of mCRPC patients experience Ra223-induced PSA flares, whose outcome is similar to that of men with or without PSA responses. Further studies are needed regarding suitable biochemical surrogate markers of response to Ra223.

Initial Postoperative Prostate Specific Antigen and Prostate Specific Antigen Velocity Are Important Indicators of Underlying Malignancy After Simple Prostatectomy.

Background: There is a paucity of guidelines for prostate-specific antigen (PSA) monitoring after simple prostatectomy (SP) despite these patients remaining at risk for prostate cancer (PCa). Our objective was to determine if PSA kinetics can be a potential indicator of PCa after SP. Methods: A retrospective review was performed of all simple prostatectomies at our institution from 2014 to 2022. All patients who met criteria were included in the study. Relevant clinical variables were collected preoperatively, including PSA value, prostate size, and voiding symptoms. Surgical and urinary function outcomes were analyzed. Results: A total of 92 patients were divided into two groups based on malignancy status. Sixty-eight patients did not have PCa, while 24 patients had known PCa before surgery (14) or were diagnosed as having incidental PCa from the pathological specimen (10). Patients with benign prostates had an initial postoperative PSA value of 0.76 ng/mL compared with 1.68 ng/mL for those with cancer (p < 0.01). PSA velocity for the first 24 months after surgery was 0.042 ± 1.61 ng/(mL·year) for the benign cohort compared with 1.29 ± 1.02 ng/(mL·year) for the malignant cohort (p = 0.01). Voiding improvements were noted by objective (postvoid residual and flow rate) and subjective (American Urological Association symptom score and quality of life score) measures in both groups. Conclusions: PSA interpretation and monitoring after SP have not been well established. Our study indicates that initial postoperative PSA value and PSA velocity are important indicators of underlying malignancy in patients after SP. Further efforts are needed to establish threshold values and formal guidelines.

The Association Between [68Ga]PSMA PET/CT Response and Biochemical Progression in Patients with High-Risk Prostate Cancer Receiving Neoadjuvant Therapy.

Our previous study found that the prostate-specific membrane antigen (PSMA) PET/CT response of primary prostate cancer (PCa) to neoadjuvant therapy can predict the pathologic response. This study was designed to investigate the association between [68Ga]PSMA PET/CT changes and biochemical progression-free survival (bPFS) in high-risk patients who underwent neoadjuvant therapy before radical prostatectomy (RP). Methods: Seventy-five patients with high-risk PCa in 2 phase II clinical trials who received neoadjuvant therapy before RP were included. The patients received androgen deprivation therapy plus docetaxel (n = 33) or androgen deprivation therapy plus abiraterone (n = 42) as neoadjuvant treatment. All patients had serial [68Ga]PSMA PET/CT scans before and after neoadjuvant therapy. Age, initial prostate-specific antigen level, nadir prostate-specific antigen level before RP, tumor grade at biopsy, treatment regimen, clinical T stage, PET imaging features, pathologic N stage, and pathologic response on final pathology were included for univariate and multivariate Cox regression analyses to identify independent predictors of bPFS. Results: With a median follow-up of 30 mo, 18 patients (24%) experienced biochemical progression. Multivariate Cox regression analyses revealed that only SUVmax derived from posttreatment [68Ga]PSMA PET/CT and pathologic response on final pathology were independent factors for the prediction of bPFS, with hazard ratios of 1.02 (95% CI, 1.00-1.04; P = 0.02) and 0.12 (95% CI, 0.02-0.98; P = 0.048), respectively. Kaplan-Meier analysis revealed that patients with a favorable [68Ga]PSMA PET/CT response (posttreatment SUVmax < 8.5) or a favorable pathologic response (pathologic complete response or minimal residual disease) had a significantly lower rate of 3-y biochemical progression. Conclusion: Our results indicated that [68Ga]PSMA PET/CT response was an independent risk factor for the prediction of bPFS in patients with high-risk PCa receiving neoadjuvant therapy and RP, suggesting [68Ga]PSMA PET/CT to be an ideal tool to monitor response to neoadjuvant therapy.

Higher Preoperative Maximum Standardised Uptake Values (SUVmax) Are Associated with Higher Biochemical Recurrence Rates after Robot-Assisted Radical Prostatectomy for [68Ga]Ga-PSMA-11 and [18F]DCFPyL Positron Emission Tomography/Computed Tomography.

This study aimed to investigate the association between the 68Ga- or 18F-radiolabeled prostate-specific membrane antigen (PSMA) tracer expression, represented by the maximum standardised uptake value (SUVmax) of the dominant intraprostatic lesion, and biochemical recurrence (BCR) in primary prostate cancer (PCa) patients prior to robot-assisted radical prostatectomy (RARP). This was a retrospective, multi-centre cohort study of 446 patients who underwent [68Ga]Ga-PSMA-11 (n = 238) or [18F]DCFPyL (n = 206) Positron Emission Tomography/Computed Tomography (PET/CT) imaging prior to RARP. SUVmax was measured in the dominant intraprostatic PCa lesions. [18F]DCFPyL patients were scanned 60 ([18F]DCFPyL-60; n = 106) or 120 ([18F]DCFPyL-120; n = 120) minutes post-injection of a radiotracer and were analysed separately. To normalise the data, SUVmax was log transformed for further analyses. During a median follow-up of 24 months, 141 (30.4%) patients experienced BCR. Log2SUVmax was a significant predictor for BCR (p < 0.001). In the multivariable analysis accounting for these preoperative variables: initial prostate-specific antigen (PSA), radiologic tumour stage (mT), the biopsy International Society of Urological Pathology grade group (bISUP) and the prostate imaging and reporting data system (PI-RADS), Log2SUVmax was found to be an independent predictor for BCR in [68Ga]Ga-PSMA-11 (HR 1.32, p = 0.04) and [18F]DCFPyL-120 PET/CT scans (HR 1.55, p = 0.04), but not in [18F]DCFPyL-60 ones (HR 0.92, p = 0.72). The PSMA expression of the dominant intraprostatic lesion proved to be an independent predictor for BCR in patients with primary PCa who underwent [68Ga]Ga-PSMA-11 or [18F]DCFPyL-120 PET/CT scans, but not in those who underwent [18F]DCFPyL-60 PET/CT scans.

Correlation between the Total Initial PSA , PSA Density, and Prostate Cancer Aggressiveness: A Retrospective Study In Two Urology Centers In Cameroon

Objectives: Our study aimed to determine the relationship between the initial total prostate-specific antigen (PSA), PSA density, and aggressiveness of prostate cancer (PCa) based on the new Gleason grade group in the two specialized urology centers in Cameroon. Method: A seven-year retrospective study was conducted from January 2012 to December 2019. The study concerned all men diagnosed with PCa graded using the novel Gleason grade group. Data were analyzed descriptively and analytically using Statistical Package for Social Sciences (SPSS) version 20.0. Bivariate analysis was done to identify independent associations. Results: A total of 253 files were reviewed; fulfilling the inclusion criteria. The mean age of our study population was 66.62±8.288 years with the most affected age being those aged between 59-69 years. The commonest finding on DRE was a hard-craggy prostate (46.0%). The mean initial total PSA was 98.78 ng/dL ± 300.17 ng/mL, while the mean PSA density was 1.73 ± 5.94ng/mL². Gleason grade group 2 was the commonest grade (30.6%). There was a positive correlation between initial total PSA and Gleason grade group (r = 0.314 (p-value 0.000)), and between PSA density and Gleason grade group (r = 0.919 (p-value 0.000)). Initial total PSA and the Gleason grade groups were independently associated with the radiological tumour stage (p-value 0.000 and p-value 0.03 respectively). Conclusion: There is a positive correlation between initial total PSA, PSA density, and novel Gleason grade group. We, therefore, recommend that more attention should be placed on PSA density in pre-biopsy decision making. This study enhances the stratification of therapeutic protocols for the management of PCa in Cameroon as well as across African Union member states.

Role of radiomic analysis of [18F]fluoromethylcholine PET/CT in predicting biochemical recurrence in a cohort of intermediate and high risk prostate cancer patients at initial staging.

To study the feasibility of radiomic analysis of baseline [18F]fluoromethylcholine positron emission tomography/computed tomography (PET/CT) for the prediction of biochemical recurrence (BCR) in a cohort of intermediate and high-risk prostate cancer (PCa) patients. Seventy-four patients were prospectively collected. We analyzed three prostate gland (PG) segmentations (i.e., PGwhole: whole PG; PG41%: prostate having standardized uptake value - SUV > 0.41*SUVmax; PG2.5: prostate having SUV > 2.5) together with three SUV discretization steps (i.e., 0.2, 0.4, and 0.6). For each segmentation/discretization step, we trained a logistic regression model to predict BCR using radiomic and/or clinical features. The median baseline prostate-specific antigen was 11ng/mL, the Gleason score was > 7 for 54% of patients, and the clinical stage was T1/T2 for 89% and T3 for 9% of patients. The baseline clinical model achieved an area under the receiver operating characteristic curve (AUC) of 0.73. Performances improved when clinical data were combined with radiomic features, in particular for PG2.5 and 0.4 discretization, for which the median test AUC was 0.78. Radiomics reinforces clinical parameters in predicting BCR in intermediate and high-risk PCa patients. These first data strongly encourage further investigations on the use of radiomic analysis to identify patients at risk of BCR. The application of AI combined with radiomic analysis of [18F]fluoromethylcholine PET/CT images has proven to be a promising tool to stratify patients with intermediate or high-risk PCa in order to predict biochemical recurrence and tailor the best treatment options. • Stratification of patients with intermediate and high-risk prostate cancer at risk of biochemical recurrence before initial treatment would help determine the optimal curative strategy. • Artificial intelligence combined with radiomic analysis of [18F]fluorocholine PET/CT images allows prediction of biochemical recurrence, especially when radiomic features are complemented with patients' clinical information (highest median AUC of 0.78). • Radiomics reinforces the information of conventional clinical parameters (i.e., Gleason score and initial prostate-specific antigen level) in predicting biochemical recurrence.

An Evaluation of Screening Pathways Using a Combination of Magnetic Resonance Imaging and Prostate-specific Antigen: Results from the IP1-PROSTAGRAM Study

BackgroundThe use of prostate-specific antigen (PSA) testing to screen for prostate cancer has been fraught with under- and overdiagnosis. Short, noncontrast magnetic resonance imaging (MRI) might detect more grade group ≥2 cancers with similar rates of biopsy. ObjectiveTo evaluate strategies that combined PSA and MRI to select men based in the community for a prostate biopsy. Design, setting, and participantsIP1-PROSTAGRAM was a prospective, population-based, paired cohort study of 408 men aged 50–69 yr conducted at seven UK primary care practice and two imaging centres (from October 10, 2018 to May 15, 2019). InterventionAll participants underwent screening with a PSA test, MRI (T2-weighted and diffusion), and transrectal ultrasound (b-mode and elastography). If any test was screen positive, a systematic 12-core biopsy was performed. Additional image-fusion targeted biopsies were taken if the MRI or ultrasound was positive. Outcome measurements and statistical analysisWe conducted an analysis, set out in the statistical plan a priori, comparing 13 different pathways including PSA-alone, MRI-alone, and a range of PSA thresholds and MRI scores. The performance of each pathway was evaluated focusing on the trade-offs between biopsy referral rates and detection of grade group ≥2 cancers. A targeted biopsy was performed only where the PROSTAGRAM MRI showed a lesion score of 3, 4, or 5. Results and limitationsThe standard PSA pathway (PSA ≥3 ng/ml + systematic biopsy) would lead to 10% of men being referred for a biopsy and a 1.0% detection rate of grade group ≥2 cancers. Pathways that relied on MRI alone set at a threshold score of 3 for a biopsy led to higher biopsy rates, but with benefit of high cancer detection rates. The pathway that combined an initial low PSA threshold (≥1.0 ng/ml) and MRI score ≥4 accurately identified a high rate of grade group ≥2 cancers (2.5%, 95% confidence interval 1.3–4.6) while recommending fewer patients for a biopsy (7.1%, 95% confidence interval 4.9–10.2). The results are pertinent to only one screening round, the impact of repeat screening rounds is not evaluated, and the required MRI capacity is currently lacking. ConclusionsOur results highlight the trade-off that exists between reducing excessive numbers of biopsies and maintaining grade group ≥2 cancer detection rates. A pathway that combines PSA ≥1 ng/ml and MRI score ≥4 maintains the detection of grade group ≥2 cancers while recommending fewer men for biopsies and would be the preferred strategy to evaluate in future studies at the first screening round. Patient summaryThe IP1-PROSTAGRAM study shows that PROSTAGRAM magnetic resonance imaging in men with a prostate-specific antigen level of ≥1.0 ng/ml could be a promising pathway to evaluate in future screening trials.

Development and External Validation of a Novel Nomogram to Predict the Probability of Pelvic Lymph-node Metastases in Prostate Cancer Patients Using Magnetic Resonance Imaging and Molecular Imaging with Prostate-specific Membrane Antigen Positron Emission Tomography

BackgroundPreoperative assessment of the probability of pelvic lymph-node metastatic disease (pN1) is required to identify patients with prostate cancer (PCa) who are candidates for extended pelvic lymph-node dissection (ePLND). ObjectiveTo develop a novel intuitive prognostic nomogram for predicting pathological lymph-node (pN) status in contemporary patients with primary diagnosed localized PCa, using preoperative clinical and histopathological parameters, magnetic resonance imaging (MRI), and prostate-specific membrane antigen (PSMA) positron emission tomography (PET). Design, setting, and participantsIn total, 700 eligible patients who underwent robot-assisted radical prostatectomy and ePLND were included in the model-building cohort. The external validation cohort consisted of 305 surgically treated patients. Logistic regression with backward elimination was used to select variables for the Amsterdam-Brisbane-Sydney nomogram. Outcome measurements and statistical analysisPerformance of the final model was evaluated using the area under the receiver operating characteristic curve (AUC), calibration plots, and decision-curve analyses. Models were subsequently validated in an external population. Results and limitationsThe Amsterdam-Brisbane-Sydney nomogram included initial prostate-specific antigen value, MRI T stage, highest biopsy grade group (GG), biopsy technique, percentage of systematic cores with clinically significant PCa (GG ≥2), and lymph-node status on PSMA-PET. The AUC for predicting pN status was 0.81 (95% confidence interval [CI] 0.78–0.85) for the final model. On external validation, the Amsterdam-Brisbane-Sydney nomogram showed superior discriminative ability to the Briganti-2017 and Memorial Sloan Kettering Cancer Center (MSKCC) nomograms (AUC 0.75 [95% CI 0.69–0.81] vs 0.67 [95% CI 0.61–0.74] and 0.65 [95% CI 0.58–0.72], respectively; p < 0.05), and similar discriminative ability to the Briganti-2019 nomogram (AUC 0.78 [95% CI 0.71–0.86] vs 0.80 [95% CI 0.73–0.86]; p = 0.76). The Amsterdam-Brisbane-Sydney nomogram showed excellent calibration on external validation, with an increased net benefit at a threshold probability of ≥4%. ConclusionsThe validated Amsterdam-Brisbane-Sydney nomogram performs superior to the Briganti-2017 and MSKCC nomograms, and similar to the Briganti-2019 nomogram. Furthermore, it is applicable in all patients with newly diagnosed unfavorable intermediate- and high-risk PCa. Patient summaryWe developed and validated the Amsterdam-Brisbane-Sydney nomogram for the prediction of prostate cancer spread to lymph nodes before surgery. This nomogram performs similar or superior to all presently available nomograms.