Risk Of Biochemical Recurrence Research Articles

LBA02-01 BIOCHEMICAL RECURRENCE OF LOCALIZED PROSTATE CANCER ORIGINATING FROM THE TRANSITION VERSUS PERIPHERAL ZONE: A SYSTEMATIC REVIEW AND META-ANALYSIS

You have accessJournal of UrologyCME1 Apr 2023LBA02-01 BIOCHEMICAL RECURRENCE OF LOCALIZED PROSTATE CANCER ORIGINATING FROM THE TRANSITION VERSUS PERIPHERAL ZONE: A SYSTEMATIC REVIEW AND META-ANALYSIS Shijie Jin, Liyi Wu, and Weigang Yan Shijie JinShijie Jin More articles by this author , Liyi WuLiyi Wu More articles by this author , and Weigang YanWeigang Yan More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003361.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The influence of zonal origin of localized prostate cancer (PC) on biochemical recurrence (BCR) is still controversial. We performed a meta-analysis of published articles to compare BCR of localized PC originating from the transition versus peripheral zone. METHODS: Systematic research of Medline, Embase, Scopus, Web of Science, and the Cochrane Library was performed to identify all trials on BCR of localized PC originating from transition and peripheral zone. The incidences of BCR were pooled with a fixed or random effect model and reported as Risk Ratio (RR), and 95% Confidence Intervals (CI). Study heterogeneity was assessed using the I2 value. Substantial heterogeneity was defined as an I2 value >50%. Subgroup analysis was performed according to follow-up time, prostate-specific antigen (PSA) levels, Newcastle–Ottawa Scale (NOS) score, and whether a multivariate or univariate Cox regression model was used. RESULTS: A total of 16 cohorts with 19,365 patients were included. Overall, PC originating from transition zone was associated with a lower risk of BCR (RR, 0.79, 95%CI; 0.69-0.92, I2, 76.8%). This association was consistent in subgroup analyses of studies with median follow-up time ≥60 months (RR, 0.65; 95%CI, 0.48 to 0.88, I2 56.8%), median PSA <10ng/ml (RR, 0.68; 95%CI, 0.49 to 0.94, I2 84.4%), median PSA >10ng/ml (RR, 0.91; 95%CI, 0.88 to 0.94, I2 14.8%), NOS score ≥8 (RR, 0.70; 95%CI, 0.62 to 0.80, I2 32.4%), and studies using a multivariate regression model (RR, 0.57; 95%CI, 0.48 to 0.69, I2 23%). CONCLUSIONS: This meta-analysis showed a decreased incidence of BCR of localized PC originating from transition zone compared to peripheral zone, especially in studies using a multivariate regression model. Therefore, it was supported that PC originating from transition zone might be a different clinical entity with a significantly lower risk of BCR. Source of Funding: National High Level Hospital Clinical Research Funding of Peking Union Medical College Hospital [2022-PUMCH-A-063, 2022-PUMCH-B-009] © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1186 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Shijie Jin More articles by this author Liyi Wu More articles by this author Weigang Yan More articles by this author Expand All Advertisement PDF downloadLoading ...

MP40-14 ARE EAU RISK GROUPS RELIABLE IN THE STRATIFICATION OF MEN WITH BIOCHEMICAL RECURRENCE AFTER RADICAL PROSTATECTOMY AND RESTAGED WITH PSMA-PET?

MP40-14 ARE EAU RISK GROUPS RELIABLE IN THE STRATIFICATION OF MEN WITH BIOCHEMICAL RECURRENCE AFTER RADICAL PROSTATECTOMY AND RESTAGED WITH PSMA-PET?

Prognostic significance of PI-RADS 5 lesions in patients treated by radical prostatectomy.

To analyse the pathological features and survival of patients with a PI-RADS 5 lesion on pre-biopsy MRI. We extracted from a European multicentre prospectively gathered database the data of patients with a PI-RADS 5 lesion on pre-biopsy MRI, diagnosed using both systematic and targeted biopsies and subsequently treated by radical prostatectomy. The Kaplan-Meier model was used to assess the biochemical-free survival of the whole cohort and univariable and multivariable Cox models were set up to study factors associated with survival. Between 2013 and 2019, 539 consecutive patients with a PI-RADS 5 lesion on pre-biopsy MRI were treated by radical prostatectomy and included in the analysis. Follow-up data were available for 448 patients. Radical prostatectomy and lymph node dissection specimens showed non-organ confined disease in 297/539 (55%), (including 2 patients with a locally staged pT2 lesion and lymph node involvement (LNI)). With a median follow-up of 25months (12-39), the median biochemical recurrence-free survival was 54% at 2years (95% CI 45-61) and 28% at 5years (95% CI 18-39). Among the factors studied, MRI T stage [T3a vs T2 HR 3.57 (95%CI 1.78-7.16); T3b vs T2 HR 6.17 (95% CI 2.99-12.72)] and PSA density (HR 4.47 95% CI 1.55-12.89) were significantly associated with a higher risk of biochemical recurrence in multivariable analysis. Patients with a PI-RADS 5 lesion on pre-biopsy MRI have a high risk of early biochemical recurrence after radical prostatectomy. MRI T stage and PSA density can be used to improve patient selection and counselling.

Cribriform morphology is associated with higher risk of biochemical recurrence after radical prostatectomy in patients with Grade Group 5 prostate cancer.

Grade Group 5 (GG5) prostate cancer (PCa) is associated with a high risk of disease recurrence after radical prostatectomy (~75% at 5 years). However, this is a heterogeneous category that includes neoplasms with different combinations of Gleason pattern (GP) 4 and 5. Within GP4, large cribriform growth has been associated with adverse disease-specific outcomes in GG2-4 PCa. Less is known about the significance of cribriform morphology and the different histologic patterns of GP5 in GG5 PCa. In this study we evaluated the prognostic implications of cribriform morphology (either invasive or intraductal, henceforth "cribriform") and large solid growth or comedonecrosis (comedo/solid) in patients with GG5 PCa. One-hundred and thirty prostatectomies from a single institution were analysed. The presence of comedo/solid components was associated with a higher frequency of concurrent cribriform PCa (85.7% versus 45.9%, P <0.001), lymphovascular invasion (44.6% versus 27%, P=0.04), and biochemical recurrence (48.2% versus 28.4%, P=0.03). The presence of large cribriform growth was associated with a higher frequency of extraprostatic involvement (i.e. pT3a-b; 85.3% versus 68.7%, P=0.02), positive surgical margins (47.6% versus 29.2%, P=0.04) and biochemical recurrence (47.6% versus. 18.7%, P=0.001). Kaplan-Meier analysis demonstrated that GG5 PCa with cribriform or comedo/solid components had a higher probability of biochemical recurrence. Multivariable analysis showed that only cribriform components were an independent predictor of a higher risk of biochemical recurrence in this series. These findings highlight the importance of reporting the presence of cribriform components in GG5 PCa and suggest that cribriform morphology might help decide postsurgical management in these patients.

Convolutional Neural Network Quantification of Gleason Pattern 4 and Association With Biochemical Recurrence in Intermediate-Grade Prostate Tumors

Differential classification of prostate cancer grade group (GG) 2 and 3 tumors remains challenging, likely because of the subjective quantification of the percentage of Gleason pattern 4 (%GP4). Artificial intelligence assessment of %GP4 may improve its accuracy and reproducibility and provide information for prognosis prediction. To investigate this potential, a convolutional neural network (CNN) model was trained to objectively identify and quantify Gleason pattern (GP) 3 and 4 areas, estimate %GP4, and assess whether CNN-predicted %GP4 is associated with biochemical recurrence (BCR) risk in intermediate-risk GG 2 and 3 tumors. The study was conducted in a radical prostatectomy cohort (1999-2012) of African American men from the Henry Ford Health System (Detroit, Michigan). A CNN model that could discriminate 4 tissue types (stroma, benign glands, GP3 glands, and GP4 glands) was developed using histopathologic images containing GG 1 (n = 45) and 4 (n = 20) tumor foci. The CNN model was applied to GG 2 (n = 153) and 3 (n = 62) tumors for %GP4 estimation, and Cox proportional hazard modeling was used to assess the association of %GP4 and BCR, accounting for other clinicopathologic features including GG. The CNN model achieved an overall accuracy of 86% in distinguishing the 4 tissue types. Furthermore, CNN-predicted %GP4 was significantly higher in GG 3 than in GG 2 tumors (P = 7.2 × 10−11). %GP4 was associated with an increased risk of BCR (adjusted hazard ratio, 1.09 per 10% increase in %GP4; P = .010) in GG 2 and 3 tumors. Within GG 2 tumors specifically, %GP4 was more strongly associated with BCR (adjusted hazard ratio, 1.12; P = .006). Our findings demonstrate the feasibility of CNN-predicted %GP4 estimation, which is associated with BCR risk. This objective approach could be added to the standard pathologic assessment for patients with GG 2 and 3 tumors and act as a surrogate for specialist genitourinary pathologist evaluation when such consultation is not available.

A Liquid-Liquid Phase Separation-Related Index Associate with Biochemical Recurrence and Tumor Immune Environment of Prostate Cancer Patients.

To identify liquid-liquid phase separation (LLPS)-related molecular clusters, and to develop and validate a novel index based on LLPS for predicting the prognosis of prostate cancer (PCa) patients. We download the clinical and transcriptome data of PCa from TCGA and GEO database. The LLPS-related genes (LRGs) were extracted from PhaSepDB. Consensus clustering analysis was used to develop LLPS-related molecular subtypes for PCa. The LASSO cox regression analysis was performed to establish a novel LLPS-related index for predicting biochemical recurrence (BCR)-free survival (BCRFS). Preliminary experimental verification was performed. We initially identified a total of 102 differentially expressed LRGs for PCa. Three LLPS related molecular subtypes were identified. Moreover, we established a novel LLPS related signature for predicting BCRFS of PCa patients. Compared to low-risk patients in the training cohort, testing cohort and validating cohort, high-risk populations meant a higher risk of BCR and significantly poorer BCRFS. The area under receiver operating characteristic curve were 0.728, 0.762, and 0.741 at 1 year in the training cohort, testing cohort and validating cohort. Additionally, the subgroup analysis indicated that this index was especially suitable for PCa patients with age ≤ 65, T stage III-IV, N0 stage or in cluster 1. The FUS, which was the potential biomarker related to PCa liquid-liquid phase separation, was preliminarily identified and verified. This study successfully developed three LLPS-related molecular subtypes and identified a novel LLPS related molecular signature, which performed well in predicting BCRFS of PCa.

Pre-surgical 68Ga-PSMA-11 PET for biochemical recurrence risk assessment: Follow-up analysis of a multicenter prospective phase 3 imaging trial

Pre-surgical 68Ga-PSMA-11 PET for biochemical recurrence risk assessment: Follow-up analysis of a multicenter prospective phase 3 imaging trial

Identifying Patients in Whom the Follow-Up Scheme after Robot-Assisted Radical Prostatectomy Could Be Optimized in the First Year after Surgery: Reducing Healthcare Burden.

The currently advised follow-up scheme of PSA testing after robot-assisted radical prostatectomy (RARP) is strict and might pose a burden to our healthcare system. We aimed to optimize the 1-year follow-up scheme for patients who undergo RARP. All patients with histologically-proven prostate cancer (PCa) who underwent RARP between 2018 and August 2022 in the Prostate Cancer Network in the Netherlands were retrospectively evaluated. We excluded patients who underwent salvage RARP and patients who had <1 year of PSA follow-up. Postoperative PSA values were collected. Biochemical persistence (BCP) was defined as PSA level >0.10 ng/mL at 0-4 months after RARP, whereas biochemical recurrence (BCR) was defined as PSA level >0.2 ng/mL at any time point after RARP. We aimed to identify a group of patients who had a very low risk of BCR at different time points after surgery. Of all 1155 patients, BCP was observed in 151 (13%), of whom 79 (6.8%) had PSA ≥ 0.2 ng/mL. BCR further developed in 51 (4.7%) and 37 (3.4%) patients at 5-8 and 9-12 months after RARP, respectively. In 12 patients, BCR was found at 5-8 months after RARP in the absence of BCP. These patients represented 1.2% (12/1004) of the entire group. In other words, 98.8% (992/1004) of patients who had an unmeasurable PSA level at 0-4 months after RARP also had an unmeasurable PSA level 5-8 months after surgery. Limitations are the retrospective design and incomplete follow-up. Patients with an unmeasurable PSA level at 3-4 months after RARP may not need to be retested until 12 months of follow-up, as almost 100% of patients will not have the biochemically recurrent disease at 5-8 months of follow-up. This will reduce PSA testing substantially at the cost of hardly any missed patients with recurrent disease.

ERG Status at the Margin Is Associated With Biochemical Recurrence After Radical Prostatectomy With Positive Surgical Margins

Positive surgical margins at radical prostatectomy are associated with an increased risk of biochemical recurrence (BCR). However, there is considerable variability in outcomes, suggesting that molecular biomarkers—when assessed specifically at the margin tumor tissue—may be useful to stratify prognosis in this group. We used a case-cohort design for the outcome of BCR, selecting 215 patients from a cohort of 813 patients undergoing prostatectomy treated at the Johns Hopkins from 2008 to 2017 with positive margins and available clinical data. Tissue microarrays were created from the tumor adjacent to the positive margin and stained for PTEN, ERG, and Ki-67. Cases were scored dichotomously (PTEN and ERG) or by the Ki-67 staining index using previously validated protocols. The analysis used Cox proportional hazards models weighted for the case-cohort design. Overall, 20% (37/185) of evaluable cases had PTEN loss and 38% (71/185) had ERG expression, and the median Ki-67 expression was 0.42%. In multivariable analysis adjusting for the CAPRA-S score, adjuvant radiation, and grade group at the positive margin, ERG-positive tumors were associated with a higher risk of BCR compared to those that were ERGnegative (hazard ratio [HR], 2.4; 95% CI, 1.2-4.9; P = .012) regardless of PTEN status at the margin, and adding ERG to clinicopathologic variables increased the concordance index from 0.827 to 0.847. PTEN loss was associated with an increased risk of BCR on univariable analysis (HR, 3.19; 95% CI, 1.72-5.92; P = .0002), but this association did not remain after adjusting for clinicopathologic variables (HR, 1.06; 95% CI, 0.49-2.29; P = .890). Thus, in the setting of prostate tumors with positive surgical margins after prostatectomy, ERG-positive tumors with or without PTEN loss at the positive margin are associated with a significantly higher risk of BCR after adjusting for clinicopathologic variables. If validated, ERG status may be helpful in decision-making surrounding adjuvant therapy after prostatectomy.

A Personalized Clinical Dynamic Prediction Model to Characterize Prognosis for Patients With Localized Prostate Cancer: Analysis of the CHHiP Phase 3 Trial

The CHHiP trial assessed moderately hypofractionated radiotherapy in localised prostate cancer. We utilised longitudinal prostate-specific antigen (PSA) measurements collected over time to evaluate and characterise patient prognosis. We developed a clinical dynamic prediction joint model to predict the risk of biochemical or clinical recurrence. Modelling included repeated PSA values and adjusted for baseline prognostic risk factors of age, tumour characteristics and treatment received. We included 3,071 trial participants for model development using a mixed-effect submodel for the longitudinal PSAs, and a time-to-event hazard submodel for predicting recurrence of prostate cancer. We evaluated how baseline prognostic factor subgroups impacted on the nonlinear PSA levels over time and quantify the association of PSA on time-to-recurrence. We assessed bootstrapped optimism-adjusted predictive performance on calibration and discrimination. Additionally, we performed comparative dynamic predictions on patients with contrasting prognostic factors and investigated PSA thresholds over landmark times to correlate with prognosis. Patients that developed recurrence had generally higher baseline and overall PSA values during follow-up and had an exponentially rising PSA in the two-years before recurrence. Additionally, most baseline risk factors were significant in the mixed-effect- and relative risk submodels. PSA value- and rate-of-change was predictive of recurrence. Predictive performance of the model was good across different prediction times over an 8-year period, with an overall mean AUC of 0.70, mean Brier score of 0.10, and mean integrated calibration index of 0.048; these were further improved for predictions after 5 years of accrued longitudinal post-treatment PSA assessments. PSA thresholds less than 0.23ng/mL after 3 years were indicative of a minimal risk of recurrence by 8 years. We successfully developed a joint statistical model to predict prostate cancer recurrence, evaluating prognostic factors and longitudinal PSA. We showed dynamically updated PSA information can improve prognostication, which can be used to guide follow-up and treatment management options.

Prostate Cancer Morphologies: Cribriform Pattern and Intraductal Carcinoma Relations to Adverse Pathological and Clinical Outcomes—Systematic Review and Meta-Analysis

The present study aimed to assess the association between the cribriform pattern (CP)/intraductal carcinoma (IDC) and the adverse pathological and clinical outcomes in the radical prostatectomy (RP) cohort. A systematic search was performed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis statement (PRISMA). The protocol from this review was registered on the PROSPERO platform. We searched PubMed®, the Cochrane Library and EM-BASE® up to the 30th of April 2022. The outcomes of interest were the extraprostatic extension (EPE), seminal vesicle invasion (SVI), lymph node metastasis (LNS met), risk of biochemical recurrence (BCR), distant metastasis (MET) and disease-specific death (DSD). As a result, we identified 16 studies with 164 296 patients. A total of 13 studies containing 3254 RP patients were eligible for the meta-analysis. The CP/IDC was associated with adverse outcomes, including EPE (pooled OR = 2.55, 95%CI 1.23-5.26), SVI (pooled OR = 4.27, 95%CI 1.90-9.64), LNs met (pooled OR = 6.47, 95%CI 3.76-11.14), BCR (pooled OR = 5.09, 95%CI 2.23-11.62) and MET/DSD (pooled OR = 9.84, 95%CI 2.75-35.20, p < 0.001). In conclusion, the CP/IDC belong to highly malignant prostate cancer patterns which have a negative impact on both the pathological and clinical outcomes. The presence of the CP/IDC should be included in the surgical planning and postoperative treatment guidance.

Oncological outcomes with wide resection in robot-assisted radical prostatectomy as primary treatment for very high-risk prostate cancer.

357 Background: Patients with very high-risk prostate cancer (VHRPCa) have earlier biochemical recurrences (BCRs) and higher mortality rates. It remains unclear whether extended robot-assisted radical prostatectomy (eRARP) with intended wide resection can improve the outcomes of VHRPCa patients. We aimed to compare the oncological outcomes of eRARP versus standard RALP (sRARP) for primary treatment of VHRPCa. Methods: We retrospectively evaluated 168 patients classified by the National Comprehensive Cancer Network (NCCN) as very high-risk who were treated with RARP without neoadjuvant/adjuvant therapy between September 2011 and December 2020. eRARP was performed using the extra-fascial approach as reported by Gandaglia G et al. (Eur Urol. 71:249-256, 2017). We performed 1:1 propensity score matching to account for potential differences between eRARP and sRARP. Kaplan-Meier analysis and Cox regression models were used to test the effect of eRARP on the biochemical progression-free survival (bPFS). This observational study was approved by the Institutional Review Board. Results: There were 93 patients in the eRARP group and 75 in the sRARP group. The eRARP group had a worse clinical stage than the sRARP group ( p&lt; 0.001). Age, pretreatment prostate specific antigen (PSA), and pretreatment Gleason score were similar in the two groups. All patients in the eRARP group underwent pelvic lymph node dissection, compared with 89% in the sRARP group. The propensity-adjusted 3-year biochemical recurrence-free survival rates was 31.4% in the sRARP group and 67.4% in the eRARP group(p=0.001), respectively. The adjusted Cox regression analysis showed that the eRARP group had a significantly longer bPFS than the sRARP group (hazard ratio 0.415, p=0.0047). Conclusions: In patients with VHRPCa, eRARP was associated with a reduce risk of biochemical recurrence. These results suggest that eRARP may improve oncological outcomes in VHRPCa.

5-Year result of single-institute cohort study in single-fraction HDR monotherapy for localised prostate cancer.

362 Background: The aim if this single institute UK-based study was to look at 3-year and 5-year bRFS and toxicity profiles. Methods: It is a prospective data study with a total number of 174 patients who were treated with single-fraction HDR monotherapy between July 2014 and February 2017. Biochemical recurrence is defined using Phoenix criteria. Results: The median age was 67.5 years with the median presenting PSA of 8. Majority of patients were lower risk group with 55% for combined low and favourable intermediate risks. 81 patients had Gleason score 6(3+3) and 77 patients had GS 7(3+4). Total hormone duration was 8 months and median duration of hormone prior to HDR monotherapy was 4 months. Overall bRFS at 3 years was 96% and 5 years was 88%. 5-year bRFS as per risk stratification was 100% in low risk, 92% in favourable intermediate risk, 83% in unfavourable intermediate risk and 79% in high-risk groups. This study had better 5-year overall bRFS compared to published data in single fraction HDR monotherapy (88% vs 73.5%, p value 0.001) (Morton et al., 2020). Despite inferior 5-year overall bRFS in compared to 2-fractionated HDR monotherapy (88% vs 95%) (p value 0.001), no difference in 5-year bRFS noted in low and favourable intermediate risk groups (100% vs 100% and 92% vs 93% respectively) (Morton et al., 2020). Two-thirds (71%) of biochemically recurred patients found to have local recurrence disease. The median time of biochemical recurrence was 47 months. Higher risk groups had higher 5-year biochemical recurrence risk. Acute and late toxicity profiles were minimum with acute G2 GU toxicity (2%) and GI toxicity (1%); late G2 GU toxicity (2%) and GI toxicity (0%) with no G3, G4 GU or GI toxicities. Conclusions: This prospective study had shown better overall 5-year bRFS especially in low and favourable intermediate risk groups with minimal toxicities. Therefore, single-fraction HDR monotherapy could be considered for elderly or patients with significant co-morbidities who are more suitable for single treatment rather than 2 fractions in these risk groups. Further randomised multicentre studies in these risk groups are suggested.

European Association of Urology biochemical recurrence risk groups after radical prostatectomy: External validation and identification of independent risk factors for progression and death

BackgroundThe EAU proposed a progression and death risk classification in patients with biochemical recurrence after radical prostatectomy (PR). ObjectiveTo validate the EAU BCR-risk classification in our setting and to find factors related to progression and death. Material and methodsMulticenter, retrospective, observational study including 2140 patients underwent RP between 2011 and 2015. Patients with BCR were identified and stratified in low risk (PSA-DT >1yr and pGS <8) or high-risk (PSA-DT ≤1yr or pGS ≥8) grouping. PSA and metastatic free survival (PSA-PFS, MFS), cancer specific survival (CSS) and overall survival (OS) were calculated (Kaplan Meier curves and log-rank test). Independent risk factors were identified (Cox regression). Results427 patients experienced BCR (32.3% low-risk and 67.7% high-risk). Median PSA-PFS was 135,0 mo (95% CI 129,63-140,94) and 115,0 mo (95% CI 104,02-125,98) (p<0,001), for low and high-risk groups, respectively. There were also significant differences in MFS and OS. The EAU BCR risk grouping was independent factor for PSA-progression (HR 2.55, p 0.009). Time from PR to BCR, was an independent factor for metastasis onset (HR 0.43, 95% CI 0.18−0.99; p 0.044) and death (HR 0.17, 95% CI 0.26.0.96; 23 p 0.048). Differences in MFS (p 0.001) and CSS (p 0.004) were found for <12, ≥12–<36 and ≥36 months from PR to BCR. Others independent factors were early salvage radiotherapy and PSA at BCR. ConclusionsHigh-risk group is a prognostic factor for biochemical progression, but it has a limited accuracy on MP and death in our setting. The inclusion of other factors could increase its predictive power.

Predicting the risk of biochemical recurrence at five years in patients treated with radical prostatectomy for prostate cancer: The PIPEN categories

Predicting the risk of biochemical recurrence at five years in patients treated with radical prostatectomy for prostate cancer: The PIPEN categories

Risk stratification for early biochemical recurrence of prostate cancer in the era of multiparametric magnetic resonance imagining-targeted biopsy.

Multiparametric magnetic resonance imaging (MRI) and MRI-targeted biopsy are nowadays recommended in the prostate cancer (PCa) diagnostic pathway. Ploussard and Mazzone have integrated these tools into novel risk classification systems predicting the risk of early biochemical recurrence (eBCR) in PCa patients who underwent radical prostatectomy (RP). We aimed to assess available risk classification systems and to define the best-performing. Data on 1371 patients diagnosed by MRI-targeted biopsy and treated by RP between 2014 and 2022 at eight European tertiary referral centers were analyzed. Risk classifications systems included were the European Association of Urology (EAU) and National Comprehensive Cancer Network (NCCN) risk groups, the Cancer of the Prostate Risk Assessment (CAPRA) score, the International Staging Collaboration for Cancer of the Prostate (STAR-CAP) classification, the Ploussard and Mazzone models, and ISUP grade group. Kaplan-Meier analyses were used to compare eBCR among risk classification systems. Performance was assessed in terms of discrimination quantified using Harrell's c-index, calibration, and decision curve analysis(DCA). Overall, 152 (11%) patients had eBCR at a median follow-up of 31 months (interquartile range: 19-45). The 3-year eBCR-free survival rate was 91% (95% confidence interval [CI]: 89-93). For each risk classification system, a significant difference among survival probabilities was observed (log-rank test p < 0.05) except for NCCN classification (p = 0.06). The highest discrimination was obtained with the STAR-CAP classification (c-index 66%) compared to CAPRA score (63% vs. 66%, p = 0.2), ISUP grade group (62% vs. 66, p = 0.07), Ploussard (61% vs. 66%, p = 0.003) and Mazzone models (59% vs. 66%, p = 0.02), andEAU (57% vs. 66%, p < 0.001) and NCCN (57% vs. 66%, p < 0.001) risk groups. Risk classification systems demonstrated good calibration characteristics. At DCA, the CAPRA score showed the highest net benefit at a probability threshold of 9%-15%. The performance of risk classification systems using MRI and MRI-targeted information was less optimistic when tested in a contemporary set of patients. CAPRA score and STAR-CAP classification were the best-performing and should be preferred for treatment decision-making.

The percentage of positive biopsy cores in predicting biochemical recurrence and adverse pathology in prostate cancer patients after radical prostatectomy: a systematic review and meta-analysis

Background: Biochemical recurrence (BCR) occurs in more than one-third of prostate cancer (PCa) patients 10 years after radical prostatectomy. The percentage of positive biopsy cores (PPBC) obtained from prostate needle biopsy is suggested as one of the predictors of BCR. We aim to investigate the role of PPBC in predicting BCR and adverse pathology in PCa patients after RP. Methods: A systematic search was conducted based on PRISMA guidelines from Pubmed, Scopus, and Cochrane Library databases up to July 2022. We screened studies that met our inclusion criteria and NOS (Newcastle-Ottawa Scale) was utilized as the quality assessment tool. The primary outcome was BCR measured as Hazard Ratios (HRs). The secondary outcome was adverse pathology, including positive surgical margin (PSM), Extra-prostatic disease (EPD), and seminal vesicle invasion (SVI). Review Manager®5.4 was used as the statistical analysis tool. Results: A total of 5971 patients were included from eleven eligible studies with overall good quality scores. Eleven studies were included in the qualitative synthesis and five of them were analyzed in the meta-analysis. The pooled analysis demonstrated that higher PPBC has a 2.77 times risk of BCR (OR 2.77 (95% CI: 1.97, 3.9; p&lt;0.00001) after RP. Similarly, it has significant results in SVI (OR 2.61 (95% CI: 1.19, 5.73; p=0.02). However, there were insignificant results in terms of EPD (p=0.17) and PSM (p=0.33). Conclusion: This systematic review and meta-analysis (SRMA) indicate that a high PPBC is strongly correlated with a greater risk of BCR and SVI, but not EPD and PSM in patients following RP.

Salvage Radical Prostatectomy for Recurrent Prostate Cancer Following First-line Nonsurgical Treatment: Validation of the European Association of Urology Criteria in a Large, Multicenter, Contemporary Cohort

Salvage radical prostatectomy (sRP) is a potentially curative option for locally radiorecurrent prostate cancer (PCa) but is associated with significant morbidity. Therefore, the European Association of Urology (EAU) guidelines recommend restricting sRP to a favorable-prognosis group according to the EAU criteria, but these have been validated considering only biochemical recurrence (BCR). Our aim was to test these criteria in a large, multicenter, contemporary cohort. We retrospectively reviewed 1265 patients who underwent sRP at 14 referral centers (2000–2021), stratified by compliance with the EAU criteria. Our primary outcome was metastasis-free survival (MFS). We included 1030 men, of whom 221 (21.5%) fully met the EAU recommended criteria for sRP and 809 (78.5%) did not. The EAU-compliant group experienced more favorable pathological and functional outcomes (79% vs 63% wearing no pads at 1 yr; p < 0.001) and had significantly better MFS (90% vs 76% at 5 yr; p < 0.001), prostate-specific antigen–free survival (55% vs 38% at 5 yr; p < 0.001), and overall survival (89% vs 84% at 5 yr; p = 0.01). This was verified by Cox regression analysis for MFS (hazard ratio 1.84, 95% confidence interval 1.13–2.99; p = 0.01). We found that adherence to the EAU criteria is associated with a lower risk of BCR and, more importantly, of metastasis after surgery. Patient summaryWe looked at outcomes of surgical removal of the prostate for prostate cancer recurrence after radiotherapy or other nonsurgical treatments according to whether or not patients met the European Association of Urology (EAU) criteria for this surgery. We found that men who did not meet the criteria had a higher risk of metastasis and their benefit from surgery might be significantly less than for patients who do meet the EUA criteria.

Index grade group is superior to composite grade group for prediction of biochemical recurrence following radical prostatectomy

The pathological grade of prostate cancer is the strongest predictor of recurrence. It is unclear whether the better predictor is the composite of all carcinomas within the prostate, or the highest grade lesion (index). The purpose of this study was to determine whether composite or index grade group better predicts biochemical recurrence (BCR). We undertook a retrospective analysis from a prospective institutional cohort study of men who underwent radical prostatectomy for localised prostate cancer between 2009 and 2020, in which an index and composite grade group was reported. The index grade in this study was defined as the highest grade of any tumour, usually with the highest stage, regardless of volume. Multivariate analysis and Kaplan-Meier plots were utilised. A total of 2024 men underwent radical prostatectomy during the study period; we analysed 1605 with composite grade group 2 or 3 prostate cancer. Median preoperative prostate specific antigen (PSA) was 5.9 ng/L, mean follow up was 56.8 months, 54% were pT2, 76% had multifocal disease and 16% had discordant index and composite grades. Patients with discordant index grade group had a higher risk of BCR [hazard ratio (HR) 2.22, p<0.0001]. The prevalence of BCR in the discordant group was higher at 1, 3, 5 and 7 years (4.7% vs 8.9%, 8.3% vs 18.1%, 14.5% vs 28.8% and 22.5% vs 49.5%, respectively). In cases of discordance, a higher index grade group is associated with increased rates of BCR after radical prostatectomy. Index rather than composite grade group should be used to counsel men post-operatively regarding prognosis and follow-up.

WWOX Polymorphisms as Predictors of the Biochemical Recurrence of Localized Prostate Cancer after Radical Prostatectomy.

The downregulation of WW domain-containing oxidoreductase (WWOX), a tumor suppressor gene, is associated with the tumorigenesis and poor prognosis of various cancers. In this study, we investigated the associations between the polymorphisms of WWOX, clinicopathologic features of prostate cancer (PCa), and risk of postoperative biochemical recurrence (BCR). We evaluated the effects of five single-nucleotide polymorphisms (SNPs) of WWOX on the clinicopathologic features of 578 patients with PCa. The risk of postoperative BCR was 2.053-fold higher in patients carrying at least one "A" allele in WWOX rs12918952 than in those with homozygous G/G. Furthermore, patients with at least one polymorphic "T" allele in WWOX rs11545028 had an elevated (1.504-fold) risk of PCa with seminal vesicle invasion. In patients with postoperative BCR, the risks of an advanced Gleason grade and clinical metastasis were 3.317- and 5.259-fold higher in patients carrying at least one "G" allele in WWOX rs3764340 than in other patients. Our findings indicate the WWOX SNPs are significantly associated with highly aggressive pathologic features of PCa and an elevated risk of post-RP biochemical recurrence.