Pathological Gleason Score Research Articles

Prediction of early prostate cancer recurrence using a liquid biopsy approach.

386 Background: A critical clinical concern after radical prostatectomy for prostate cancer (PCa) is the timely identification of residual disease. Recurrent disease (biochemical recurrence: BCR) develops in approximately 30% of radical prostatectomies within 5 years of surgery. Currently, clinicopathological variables, including pathological tumor stage (pT-stage), Gleason score and PSA, or algorithmic combinatorial calculations (e.g., CAPRA-S) are used to predict BCR. Early and objective prediction of individuals at high risk of BCR would enable stratification of follow-up strategies and facilitate therapeutic therapy. To achieve these goals, we developed a liquid biopsy, the PROSTest, to identify PCa. This is a 27 multigene algorithmic signature with a high sensitivity and specificity (>90%) for PCa detection. We investigated if the PROSTest had utility as a predictive biomarker for BCR. Methods: Prospective recruitment of 60 PCa for radical prostatectomy with assessment of standard pathological, clinical and biomarker (PSA) data. D’Amico Risk scores and CAPRA-S were calculated. Blood was collected for PROSTest measurement pre-surgery. Target genes were amplified using qPCR and scored (0-100) using algorithmic analysis. Pre-surgical PROSTest scores were evaluated as predictors of BCR and compared with standard criteria as well as DR and CAPRA-S scores. Data was evaluated using Mann-Whitney U-test, multiple regression analyses, Kaplan-Meier survival analysis and Cox-proportional modeling. All data: median (range). Results: Consent was obtained in 48 (80%) patients. Median age (range) was 64 (50-82). Gleason was predominantly 7 (85%; 26: 7A, 15: 7B); TNM was primarily T2c (48%) and T3a (32%) with nodal disease evident in 8% and 0% cM1 disease. Resections were R0 (85%) and 7 R1. The median follow-up was 42 days (range: 14-782). Early BCR occurred in 8 (17%) patients. This included 3/7 (43%) of R1 and 5/41 (12%) R0 resections. PSMA imaging confirmed 3 LN recurrences and new visceral ( n=1) and bone ( n=1) disease. D’Amico Risk scores were mostly “high” (88% with risk score ≥50%) and were not associated with early BCR. CAPRA-S scores were higher in those who developed early BCR (5: 1-9) than in those who did not (2: 0-5). Pre-surgical PROSTest scores were elevated in all (median 59: 15-81). Multiple regression analysis identified only PROSTest score ≥60 and nodal status were associated with BCR. The median Recurrence Free Survival (mRFS) was 89 days compared to undefined in those with baseline PROSTest scores ≥60 (HR: 9.7; 95%CI: 2.16-43.7; p=0.003). No recurrences were identified in those with scores <60. Conclusions: Early biochemical recurrence (within 3 months of surgery) can be accurately predicted by elevated (≥60) pre-surgical PROSTest blood gene expression scores. This suggests the marker could be used as a stratification tool for neoadjuvant therapy, or to guide the frequency of monitoring during follow-up.

Novel nomogram to predict biochemical recurrence-free survival after radical prostatectomy.

Conditional survival represents the probability of subsequent survival given that patients have already survived a certain length of time. Several models predict biochemical recurrence (BCR) after radical prostatectomy. However, none of them include postoperative prostate-specific antigen (PSA). We aimed to analyze BCR-free survival evolution over time and develop a nomogram incorporating the postoperative PSA value to predict BCR-free survival. We included patients treated with robot-assisted radical prostatectomy (RARP) for prostate cancer between 2009 and 2021 and calculated conditional survival. Cox proportional hazard regression analysis was used to assess the predictive variables of BCR. We developed a nomogram predicting BCR-free survival three and five years after RARP. We used c-index and decision curve analyses to compare the nomogram with the Cancer of the Prostate Risk Assessment post-Surgical (CAPRA-S) score. We included 718 patients. The overall 3- and 5-year BCR-free survival rates were 85.1% and 75.7%, respectively. The 5-year BCR-free survival rates increased to 78.9%, 82.9%, 85.2%, and 84.7% for patients surviving 1, 2, 3, and 4years without BCR, respectively. We developed a nomogram including the pathological Gleason score and T stage, positive surgical margin, PSA ≥ 0.05ng/mL at one year, and lymph node involvement to predict BCR at 3 and 5years postoperatively. Our nomogram presented a higher c-index (0.89) than the CAPRA-S score (0.78; p = 0.001) and a positive net benefit at 3 and 5years postoperatively in the decision curve analyses. The 5-year conditional BCR-free survival increased with survival without BCR. The developed nomogram significantly improved the accuracy in predicting BCR-free survival after RARP.

Overexpression of Ubiquitin-Conjugating Enzyme E2C Is Associated with Worsened Prognosis in Prostate Cancer.

To evaluate the role of ubiquitin-conjugating enzyme E2C (UBE2C) in prostate cancer (PCa) progression and prognosis, the TCGA and our PCa tissue microarray cohort were included in the study. Weighted gene co-expression network analysis (WGCNA) and non-negative matrix factorization were used to cluster patients and to screen genes that play a vital role in PCa progression (hub gene). Immunohistochemistry staining was used to evaluate the protein level of UBE2C in prostatic tissues. Through WGCNA, we found a gene co-expression module (named the purple module) that is strongly associated with the Gleason score, pathologic T stage, and biochemical recurrent status. Genes in the purple module are enriched in cell cycle and P53 signaling and help us to cluster patients into two groups with distinctive biochemical recurrent survival rates and TP53 mutation statuses. Further analysis showed UBE2C served as a hub gene in the purple module. The expression of UBE2C in PCa was significantly higher than that in paracancerous tissues and was remarkably associated with pathologic grade, Gleason score, and prognosis in PCa patients. To conclude, UBE2C is a PCa-progress-related gene and a biomarker for PCa patients. Therapy targeting UBE2C may serve as a promising treatment of PCa in the future.

Effect of the COVID-19 Pandemic on Radical Prostatectomy: A Turkish Multicenter Study.

The present study examines the effects of the coronavirus disease 2019 pandemic on radical prostatectomy performed as part of localized prostate cancer treatment in Turkey. A retrospective analysis was made of the data of 176 patients from 8 centers in Turkey who underwent radical prostatectomy due to localized prostate cancer over the 2 years spanning March 1, 2019, to February 28, 2021. Within this timeframe, March 1, 2019, to February 28, 2020, was denoted the 1-year pre-coronavirus disease 2019 period, while March 1, 2020, to February 28, 2021, was denoted the 1-year coronavirus disease 2019 period. An analysis was made of whether there was a difference in the number of radical prostatectomies performed for prostate cancer, the time from biopsy to operation, and the biopsy and radical prostatectomy pathology between the 2 periods. It was found that the number of radical prostatectomies performed for localized prostate cancer during the coronavirus disease 2019 pandemic was statistically and highly significantly fewer than in the pre-coronavirus disease 2019 period (P <.001). The patients diagnosed with Gleason 3+3 (low risk) prostate cancer were statistically significantly fewer in number in the coronavirus disease 2019 period (P <.001). The pathological Gleason score was upgrading than the biopsy Gleason score in all patients who underwent in both periods (P <.001). When the periods were compared, the pathological involvement determined by lymph node dissection performed during radical prostatectomy was found to be decreased in the coronavirus disease 2019 period, although the difference was not statistically significant (P =.051). As with many diseases, the diagnosis and treatment of prostate cancer have been adversely affected by the coronavirus disease 2019 pandemic.

The oncological characteristics of non-prostate-specific membrane antigen (PSMA)-expressing primary prostate cancer on preoperative PSMA positron emission tomography/computed tomography.

The oncological characteristics of non-prostate-specific membrane antigen (PSMA)-expressing primary prostate cancer on preoperative PSMA positron emission tomography/computed tomography.

Establishment of a five-enzalutamide-resistance-related-gene-based classifier for recurrence-free survival predicting of prostate cancer.

To identify prostate cancer (PCa) patients with a high risk of recurrence is critical before delivering adjuvant treatment. We developed a classifier based on the Enzalutamide treatment resistance-related genes to assist the currently available staging system in predicting the recurrence-free survival (RFS) prognosis of PCa patients. We overlapped the DEGs from two datasets to obtain a more convincing Enzalutamide-resistance-related-gene (ERRG) cluster. The five-ERRG-based classifier obtained good predictive values in both the training and validation cohorts. The classifier precisely predicted RFS of patients in four cohorts, independent of patient age, pathological tumour stage, Gleason score and PSA levels. The classifier and the clinicopathological factors were combined to construct a nomogram, which had an increased predictive accuracy than that of each variable alone. Besides, we also compared the differences between high- and low-risk subgroups and found their differences were enriched in cancer progression-related pathways. The five-ERRG-based classifier is a practical and reliable predictor, which adds value to the existing staging system for predicting the RFS prognosis of PCa after radical prostatectomy, enabling physicians to make more informed treatment decisions concerning adjuvant therapy.

Clinicopathological significance of 114 cases with positive surgical margin in radical prostatectomy specimens

Objective: To analyze the clinicopathological features of positive surgical margins (PSM) after radical prostatectomy and to explore its associated factors. Method: A retrospective analysis was conducted on 274 patients who underwent radical prostatectomy in Beijing Hospital from June 2018 to June 2021. The margins of these specimens of radical prostatectomy were directly inked with black ink. According to the margin status (tumor present versus not), the patients were divided into PSM and negative surgical margin (NSM) groups. The clinicopathological characteristics were compared between two groups, including age, preoperative prostate specific antigen (PSA), number of tumors, tumor's location, postoperative pathological Gleason score, tumor burden and postoperative pathological staging. Results: Among the 274 cases, 114 showed PSM, and 160 showed NSM. PSM accounted for 41.6% of the cases. The mean age was 68.3 years, while the PSM group's mean age was 68.0 years, and that of the NSM group was 68.6 years, with no statistical significance between groups (P>0.05). The mean preoperative PSA was 15.8 μg/L in all patients, 21.5 μg/L in the PSM group and 11.3 μg/L in NSM group. PSA in the PSM group was statistically higher than that in the NSM group (P<0.001). The PSA level (10 μg/L, 10-20 μg/L, and >20 μg/L) was associated with the PSM rate (31.1%, 48.7%, and 69.4%). Regarding tumor numbers, 118 cases had a single focus, including 40 cases with PSM (33.9%). In the 156 cases of multiple foci, 74 cases had a PSM (47.4%). There were statistically more PSM cases in the cases with multi-focal disease (P<0.05). Tumors were seen in the transit zone of 44 cases, while 107 cases showed tumors in the peripheral zone, and 123 cases in the whole zone. The PSM rate was 27.3% (12/44), 40.2% (43/107), and 48.0% (59/123) by tumor location, respectively, but the difference among groups was not statistically significant (P>0.05). The postoperative Gleason scores were 3+3=6 in 51 cases, 3+4=7 in 98 cases, 4+3=7 in 81 cases, and ≥8 in 44 cases, with PSM rates of 19.6% (10/51), 38.8% (38/98), 45.7% (37/81) and 65.9% (29/44), respectively (P<0.001 for rate differences). The tumor burden was <30% in 157 cases, 30%-60% in 91 cases, and>60% in 26 cases, with PSM rate of 21.0% (33/157), 65.9% (60/91) and 80.8% (21/26), respectively (P<0.001 for rate differences). Moreover, there were 181 cases of pathological stage T2 (PSM rate, 29.3%) and 93 cases of pathological stage T3 (PSM rate, 65.6%), with statistical difference in PSM rates (P<0.001). The multivariable logistic regression analysis indicated that preoperative PSA >20 μg/L, postoperative Gleason score ≥8, high tumor burden and pathological stags were different between the PSM and NSM groups (P<0.05). Conclusions: The PSM of radical prostatectomy is closely related to the preoperative PSA level, the number of lesions, postoperative Gleason score, tumor burden and pathological stage. Preoperative PSA level >20 μg/L, postoperative Gleason score ≥8, high tumor burden and pathological stage are independent predictors for PSM.

Prognostic differences among Grade Group 4 subgroups in robotic-assisted radical prostatectomy.

ObjectivesTo investigate whether the International Society of Urological Pathology Grade Group 4 (GG 4) subgroups have different oncological outcomes in Japanese prostate cancer (PCa) patients undergoing robotic‐assisted radical prostatectomy (RARP).Patients and MethodsWe conducted a retrospective multicentre cohort study in PCa patients undergoing RARP at 10 institutions in Japan. Pre‐ and post‐operative variables were collected from enrolled patients. We evaluated biochemical recurrence and clinical and pathological variables in the different GG 4 subgroups.ResultsA total of 3195 patients were enrolled in the study. Among them, 298 patients with GG 4 tumours (pathological Gleason scores [GSs] of 3 + 5 [N = 37], 4 + 4 [N = 257] and 5 + 3 [N = 4]) based on RARP specimens were analysed. The median follow‐up period was 25.2 months. The 3‐year biochemical recurrence (BCR)‐free survival (BCRFS) rate in the overall population was 74.5%. The 3‐year BCRFS rates in the pathological GS 3 + 5, GS 4 + 4 and GS 5 + 3 subgroups were 93.8%, 71.9% and 50.0%, respectively (P = 0.01). In multivariate analysis, pathological GS based on RARP specimens, PSA levels at surgery, pathological T stage, pathological N stage and surgical margins were independent risk factors significantly associated with BCRFS. In particular, patients with pathological GSs 4 + 4 and 5 + 3 were at higher risk of BCR than patients with pathological GS 3 + 5 (hazard ratio 4.54, P = 0.03 and hazard ratio 11.2, P = 0.01, respectively). The study limitations include the lack of central pathological specimen evaluation.ConclusionsFor patients with localized PCa undergoing RARP, pathological GS 4 + 4 and GS 5 + 3 were significantly associated with worse BCRFS than pathological GS 3 + 5. Pathological GS 3 + 5 may be overrated in GG 4. This observation emphasizes that primary and secondary GS should be considered to accurately stratify the risk of BCR after RARP.

Short-term oncological and surgical outcomes of robot-assisted radical prostatectomy: A retrospective multicenter cohort study in Japan (the MSUG94 group).

We evaluated oncological outcomes of patients undergoing robot-assisted radical prostatectomy (RARP) for prostate cancer (PCa) and their perioperative complications in Japan. We investigated clinical and pathological covariates to predict biochemical recurrence (BCR) after RARP. A retrospective multicenter cohort study was conducted in RARP patients with PCa at 10 institutions in Japan. Pre- and postoperative covariates were collected from enrolled patients. The primary endpoint was defined as biochemical recurrence-free survival (BRFS). Additionally, the association between BCR and clinicopathological covariates was determined. We enrolled 2670 patients in this study. The median follow-up period was 26.0months. RARP-related perioperative complications were identified in 198 patients (7.4%), including 69 patients (2.6%) with grade 3/4 complications according to the Clavien-Dindo classification. The 2-year BRFS was 88.0%. Using the Kaplan-Meier method, initial prostate-specific antigen (PSA) level of ≤7.6ng/mL, biopsy and pathological Gleason score (GS) of ≤7, clinical and pathological T1/2, and low/intermediate risks according to the National Comprehensive Cancer Network risk classification, and negative surgical margin status had significant BRFS than their counterparts. In multivariate analysis, initial PSA, biopsy and pathological GS, clinical and pathological T stage, and surgical margin status significantly correlated with BCR after RARP. In this study, RARP achieved a lower incidence of perioperative complications than other studies.

3D laparoscopic prostatectomy: results of multicentre study

Introduction Three-dimensional laparoscopic prostatectomy (3D LRP) is a potentially cost-effective option for robot-assisted laparoscopic prostatectomy (RALP). Results for two-dimensional LRP and RALP are well documented; however, little has been published on the outcomes of 3D LRP. Our objective was to report the perioperative and short-term results of 3D LRP in a multicentre study. Materials and methods In total, 496 unselected men with prostate cancer underwent 3D LRP by three surgeons between December 2013 and December 2018. Median age was 64 (43–76) years. Median prostate-specific antigen (PSA) was 7.9 (0.7–148) ng/ml. Preoperative and perioperative data and complications according to the Clavien–Dindo classification were collected. PSA and continence results were reported at 3 and 12 months postoperatively. Data were analysed with IBM SPSS statistics (25). Results Pathological Gleason score was 6 in 29%, 7 in 55.4%, 8 in 9.1%, 9 in 5.2% and 10 in 1.2% of patients. Pathological tumour classification was T2c in 59.5%, T3a in 19.5% and T3b in 10.9% of cases. Positive surgical margins occurred in 27.2%. Lymphadenectomy was performed in 36.3%, with positive lymph nodes in 11.8%. Median operative time was 137 (78–334) min and median blood loss 200 (10–1100) ml. Clavien–Dindo IIIa and IIIb complications occurred in 6.9% and 1.6%, respectively. At 3 and 12 months postoperatively, 90.2% and 91.4% of patients, respectively, had PSA <0.2 ng/ml, while 77.1% and 87.7% of patients were completely dry or using a maximum of one pad daily. Conclusions 3D LRP shows promising results, comparable to similar studies published on RALP.

Effect of prostate and bony pelvic dimensions measured by preoperative magnetic resonance imaging on robot-assisted radical prostatectomy.

Bone pelvic dimensions and body habitus may have effects on robot-assisted radical prostatectomy (RARP). In this study, we examined the effects of body mass index, bone pelvis measurements and prostate measurements on console time (CT), decrease in postoperative hemogram level (DHL) and surgical margin(SM) in patients who underwent RARP for clinically localized prostate cancer in our institution. The data of transperitoneal RARP cases performed by a single surgeon between November 2016 and August 2020 were analyzed retrospectively. It was included in 125 patients who met the study criteria. Bone and soft tissue measurements were made on magnetic resonance imaging T2-weighted imaging in the mid-sagittal and transvers plane. In multivariate linear regression analyzes, only soft tissue width/transverse diameter of the prostate and CT were found to be correlated (p = 0.026). For the DHL, no pelvic dimension and body habitus had a significant association on multivariate linear regression analysis. In multivariate analyzes, a statistically significant difference was found only between pathological Gleason Score and SM (p = 0.008). Although we found statistically significant associations between prostate diameters and pelvic bone measurements and operative difficulties, we believe that further studies are needed to confirm these results. Such information can help identify patients with challenging anatomy and can be used in robotic surgery training to achieve optimal patient outcomes after RARP.

Value of transrectal contrast-enhanced ultrasound with clinical indicators in the prediction of bone metastasis in prostate cancer.

Transrectal contrast-enhanced ultrasound is an examination that can be used to diagnose and characterize prostate cancer by displaying tissue blood perfusion. To explore the value of transrectal contrast-enhanced ultrasound combined with clinical factors in predicting prostate cancer bone metastasis. We retrospectively analyzed transrectal contrast-enhanced ultrasound examination data, imaging examination data [single-photon emission computed tomography (SPECT)/computed tomography (CT), CT, magnetic resonance imaging (MRI), and/or bone scan], clinical laboratory data, and pathological Gleason score of 163 patients with prostate cancer. They were randomly divided into the modeling and validation data sets. A model for predicting prostate cancer bone metastasis was established by logistic regression in the modeling data set. The differentiation, consistency, and benefits of the model were verified using the validation data set. A nomogram of the prediction model for bone metastasis of prostate cancer was drawn. Among 163 patients with prostate cancer, 65 had bone metastasis. Total prostate-specific antigen, alkaline phosphatase, and the transrectal contrast-enhanced ultrasound parameter area under the curve were independently associated with prostate cancer bone metastasis, with OR values of 2.845, 2.839, and 1.004, respectively. The area under the receiver operating characteristic curve of the prostate cancer bone metastasis prediction model was 0.804. In the training set, using a cutoff of 0.659, sensitivity was 52.8%, and specificity was 95.7%. In the validation set, using a cutoff of 0.659, sensitivity was 58.6%, and specificity was 98.1%. The area under the curve of the validation set was 0.799. The Hosmer-Lemeshow goodness-of-fit test showed that the calibration ability of the validation set was not statistically different from the training set (P=0.136). The decision curve analysis showed that the model had high benefits. The nomogram that includes the transrectal contrast-enhanced ultrasound parameter area under the curve and the clinical parameters total prostate-specific antigen, and alkaline phosphatase can be used to personalize the risk of prostate cancer bone metastases.

Substantial Gleason reclassification in Black men with national comprehensive cancer network low-risk prostate cancer - A propensity score analysis.

Emerging evidence suggests that a subset of Black men with National Comprehensive Cancer Network (NCCN) low-risk prostate cancer (PCa) may harbor high volume and genomically aggressive disease. However, limited, and ambiguous research exist to evaluate the risk of extreme Gleason reclassification in Black men with low-risk PCa. This retrospective cohort study included 45,674 low-risk PCa patients who underwent prostatectomy and were not on active surveillance, from National Cancer Database (NCDB). A propensity score matched-pair design was employed, and the final cohort was limited to 1:1 matched 12,340 patients. Gleason score reclassification was used as primary endpoint. As such, any migration to pathologic Gleason score ≥7(3 + 4) was identified as overall, whereas migration to ≥7(4 + 3) was defined as extreme reclassification. A conditional Poisson regression model was used to estimate the risk of reclassification. Whereas spline model was used to estimate the impact of increasing time to treatment as a non-linear function on Gleason reclassification between race group. Upon matching there were no differences in the baseline characteristics between race groups. In a matched cohort, higher proportion of low-risk Black men (6.6%) reported extreme reclassification to pathologic Gleason score than White men (5.0%), p < 0.001. In a conditional Poisson regression model adjusted for time to treatment, the risk of overall (RR = 1.09, 95% CI, 1.05-1.13, p < 0.001) and extreme (RR = 1.30, 95% CI, 1.12-1.50, p = 0.004) reclassification was significantly higher in Black men as compared to their White counterpart. In spline model, the probability of Gleason reclassification in Black men was elevated with increasing time to treatment, especially after 180 days (53% vs. 43% between Black and White men). Risk of Gleason score reclassification is disparately elevated in Black men with low-risk PCa. Furthermore, time to treatment can non-linearly impact Gleason reclassification in Black men.

Nuclear expression of pSTAT3Tyr705 and pSTAT3Ser727 in the stromal compartment of localized hormone-naïve prostate cancer

BackgroundThe signal transducer and activator of transcription 3 (STAT3) is involved in the progression of different tumors including prostate cancer (PCa). The expression of STAT3 in benign and malignant epithelium has been described previously but it has not been described in the stromal compartment. The aim of the present study was to evaluate the nuclear expression and prognostic value of different forms of phosphorylated STAT3 in the stromal compartment of non-cancer and cancer areas of prostatic tissue. Material and methodsTissue microarray cores from radical prostatectomy of 225 patients with hormone-naïve localized PCa were immunostained for two phosphorylated forms of STAT3, pSTAT3Tyr705 and pSTAT3Ser727. The prognostic value of the expression levels was studied by Cox regression analysis and biochemical recurrence (BCR)-free survival illustrated by Kaplan-Meier curves. ResultsExpression of pSTAT3Tyr705 and pSTAT3Ser727 in the stromal compartment of cancer tissue was lower compared with non-cancer areas. In univariable and multivariable Cox regression analysis, expression levels of pSTAT3Tyr705 and STAT3Ser727 showed similar prognostic value as pathological T-stage, Gleason score and surgical margin status. Kaplan–Meier survival analysis showed that low nuclear expression levels of pSTAT3Tyr705 and pSTAT3Ser727 in stromal cells in cancer compartment and in non-cancer areas were related to BCR-free survival. ConclusionsNuclear expression of pSTAT3Tyr705 and pSTAT3Ser727 in the stromal cells mirrors previous findings in the epithelial component in that it displays prognostic value in men undergoing radical prostatectomy for localized hormone-naïve PCa.

Correlation Between iXip and Final Pathology in Patients Affected by Prostate Cancer Undergoing Radical Prostatectomy: A Multicenter Prospective Trial (PROXIMA—PROstate iXip Index Multicenter Analysis)

IntroductionThe Immune compleX Predictive Index (iXip) is a predictive tool for prostate cancer (PCa) diagnosis that integrates PSA, PSA-IgM, prostate volume, and patient age. The aim of the study was to assess the correlation between iXip and clinically significant PCa in patients who underwent radical prostatectomy.Material and MethodsA prospective multicenter study was conducted from February 2018 to August 2019 enrolling 235 patients. Stepwise-selected predictors were used to estimate multivariate regression models for each outcome, the reference model with only the set of predictors and the same model with the addition of iXip. The prediction accuracy of the two models was assessed calculating the partial area under the receiver operating characteristic curve.ResultsThe ROC curve analysis showed significant differences in terms of partial area under the curve between iXip and pathological Gleason Score ≥ 7 and between iXip and tumor volume ≥ 2.5 mm3. The scatter plot analysis showed a positive linear correlation between iXip and tumor volume (considered as a continuous variable). The subpopulations with pT3–4 disease and cT3 disease and with positive surgical margins showed a significant linear relationship between iXip and tumor volume.ConclusionWe found elements supporting a possible correlation between iXip and aggressive PCa in terms of Gleason Score ≥ 7 and tumor volume ≥ 2.5 mm3.

Long-Term Risk of Clinical Progression Utilizing Magnetic Resonance Imaging Findings of Locally Recurrent Prostate Cancer in Patients with Biochemical Recurrence following Radical Prostatectomy.

Our goal was to evaluate the long-term prognostic value of magnetic resonance imaging of the prostatectomy bed in patients with biochemical recurrence after radical prostatectomy for prostate cancer. Men with biochemical recurrence after radical prostatectomy who were studied by prostatectomy bed magnetic resonance imaging for suspected local recurrence were retrospectively evaluated. Locally recurrent tumors were noted and measured from imaging reports. Patients with nodal/bone lesions at the time of imaging were excluded. Kaplan-Meier and Cox regression analyses were used to assess systemic progression-free and prostate cancer-specific survival. A total of 896 men were enrolled and the imaging positive and negative groups for local recurrent tumor consisted of 441 and 455 men, respectively. On univariate analysis, preoperative prostate specific antigen (p=0.02), clinical tumor stage (p=0.006), pathological Gleason score from prostatectomy (p=0.02), subsequent salvage radiotherapy (p <0.001), biochemical recurrence to magnetic resonance imaging time interval (p <0.001), age at magnetic resonance imaging (p=0.047) and prostate specific antigen at magnetic resonance imaging (p <0.001) were significantly different between magnetic resonance imaging positive and negative groups. Patients with negative magnetic resonance imaging results had worse systemic progression-free survival rates (p=0.025) and better prostate cancer-specific survival (p=0.016) than those with recurrence. Larger lesion size significantly increased risk of prostate cancer death (hazard ratio: 1.07; p <0.001). On multivariable analysis, pathological Gleason scores ≥7 were independent prognostic factors of systemic progression (p <0.05). Prostatectomy bed magnetic resonance imaging provides long-term prognostic information for the evaluation of patients with biochemical recurrence after prostatectomy. Post-prostatectomy patients with recurrent lesions on imaging had longer progression-free survival but shorter prostate cancer-specific survival compared to those without lesions. Additionally, those with larger lesions were associated with poorer cancer-specific survival.

Establishment of Prospective Registry of Active Surveillance for Prostate Cancer: The Korean Urological Oncology Society Database.

To establish a prospective registry for the active surveillance (AS) of prostate cancer (PC) using the Korean Urological Oncology Society (KUOS) database and to present interim analysis. The KUOS registry of AS for PC (KUOS-AS-PC) was organized in May 2019 and comprises multiple institutions nationwide. The eligibility criteria were as follows: patients with (1) pathologically proven PC; (2) pre-biopsy prostate-specific antigen (PSA) ≤20 ng/mL; (3) International Society of Urological Pathology (ISUP) grade 1 or 2 (no cribriform pattern 4); (4) clinical T stage ≤T2c; (5) positive core ratio ≤50%; and (6) maximal cancer involvement in the core ≤50%. Detailed longitudinal clinical information, including multi-parametric magnetic resonance imaging and disease-specific outcomes, was recorded. From May 2019 to June 2021, 296 patients were enrolled, and 284 were analyzed. The mean±standard deviation (SD) age at enrollment was 68.7±8.2 years. The median follow-up period was 11.2 months (5.9-16.8 mo). Majority of patients had pre-biopsy PSA ≤10 ng/mL (91.2%), PSA density <0.2 ng/mL² (79.7%), ISUP grade group 1 (94.4%), single positive core (65.7%), maximal cancer involvement in the core ≤20% (78.1%), and clinical T stage of T1c or lower (72.9%). Fifty-two (18.3%) discontinued AS for various reasons. Interventions included radical prostatectomy (80.8%), transurethral prostatectomy (5.8%), primary androgen deprivation therapy (5.8%), radiation (5.8%), and focal therapy (1.9%). The mean±SD time to intervention was 8.9±5.2 months. The reasons for discontinuation included pathologic reclassification (59.6%), patient preference (25.0%), and radiologic reclassification (9.6%). Two (4.8%) patients with pathologic Gleason score upgraded to ISUP grade group 4, no biochemical recurrence. The KUOS established a successful prospective database of PC patients undergoing AS in Korea, named the KUOS-AS-PC registry.

A correlation of PI-RADS score and pathological grading outcome post radical prostatectomy: A retrospective review

Objective: To investigate the correlation between the PI-RADS score and the pathologic Gleason score in the final pathological grading and to detect risk factors associated with the outcomes. Materials and Methods: Data from January 2017 to September 2019 were reviewed. Inclusion criteria included patients who had undergone standard protocol prostate magnetic resonance imaging (MRI) in King Chulalongkorn Memorial Hospital and underwent radical prostatectomy during the period. Data collected were age, PI-RADS score, Gleason score (GS), prostate-specific antigen (PSA), prostate size, PSA density, lesion size, and extraprostatic extension (EPE) evident in MRI. Results: One hundred and eight patients were included. PI-RADS was significantly associated with GS (Chi-Square p = 0.039). The percentage of significant tumors found in PI-RADS 3, 4, 5 were 66%, 86% 90% respectively. Analysis of independent risk factors only found PI-RADS 5 to have a statistically significant association with GS ≥ 7 (OR6.67 (1.24-35.71) p = 0.03). The cut-off value of lesion size ≥ 15 vs &lt; 15 and PI-RADS 4 had a higher odds ratio than other parameters (OR 3.89 (0.82-18.41) p = 0.09, OR 3.29 (0.79-13.86) p = 0.11 respectively). Conclusion: The PI-RADS scoring system was found to be highly associated with Gleason’s grading score. No association was found between any significant risk factor and significant prostate cancer. Lesion size could be used to combine with the PI-RADS scoring system in the detection of significant tumors. A high percentage of significant tumors were found with a PI-RADS 3 score and it may be worth taking a biopsy in the case of a PI-RADS 3 lesion.

Predicting Cancer-Specific Survival Among Patients With Prostate Cancer After Radical Prostatectomy Based on the Competing Risk Model: Population-Based Study.

Introduction: We aimed to develop an easy-to-use individual survival prognostication tool based on competing risk analyses to predict the risk of 5-year cancer-specific death after radical prostatectomy for patients with prostate cancer (PCa).Methods: We obtained the data from the Surveillance, Epidemiology, and End Results (SEER) database (2004–2016). The main variables obtained included age at diagnosis, marital status, race, pathological extension, regional lymphonode status, prostate specific antigen level, pathological Gleason Score. In order to reveal the independent prognostic factors. The cumulative incidence function was used as the univariable competing risk analyses and The Fine and Gray's proportional subdistribution hazard approach was used as the multivariable competing risk analyses. With these factors, a nomogram and risk stratification based on the nomogram was established. Concordance index (C-index) and calibration curves were used for validation.Results: A total of 95,812 patients were included and divided into training cohort (n = 67,072) and validation cohort (n = 28,740). Seven independent prognostic factors including age, race, marital status, pathological extension, regional lymphonode status, PSA level, and pathological GS were used to construct the nomogram. In the training cohort, the C-index was 0.828 (%95CI, 0.812–0.844), and the C-index was 0.838 (%95CI, 0.813–0.863) in the validation cohort. The results of the cumulative incidence function showed that the discrimination of risk stratification based on nomogram is better than that of the risk stratification system based on D'Amico risk stratification.Conclusions: We successfully developed the first competing risk nomogram to predict the risk of cancer-specific death after surgery for patients with PCa. It has the potential to help clinicians improve post-operative management of patients.

ARRDC4 and UBXN1: Novel Target Genes Correlated with Prostate Cancer Gleason Score.

Simple SummaryProstate cancer (PCa) is the second most diagnosed malignancy in men. PCa is a heterogeneous disease, with the clinical presentation ranging from localized and indolent to a rapidly progressing lethal metastatic disease, therefore, we needed the predictor to diagnosis of aggressive PCa. The most important predictor of PCa outcomes has been demonstrated to be the histological Gleason score which was confirmed after prostate biopsy. In this study, we found that germline variants of ARRDC4 and UBXN1 could affect the prostate cancer Gleason score, which could be a potential marker to select aggressive PCa.To investigate potential markers of the prostate cancer (PCa) Gleason score (GS), genetic arrays in 841 PCa patients were conducted followed by functional validation in PCa cell lines. A total of 841 PCa patients who received radical prostatectomy (RP) from November 2003 to July 2019 were enrolled. HumanExome BeadChip 12v1-1 (Illumina, Inc.; San Diego, CA, USA) exomic arrays were performed on RP tissue samples. Unconditional logistic regression was used to calculate odds ratios to generate estimates of the relative risk of pathologic GS (≥8); SNPs with the highest association were selected and validated using PCa cell lines (PC3, LNCaP, 22Rv1 and DU145). Following transfection with target-gene siRNA, assays for cell viability, wound healing, and transwell invasion were performed. Mean age of enrolled subjects was 66.34 years and median PSA was 8.43 ng/mL. After RP, 122 patients (14.5%) had pathological Gleason scores ≥8. The results from genotyping with 242,186 SNPs by exomic array revealed that 4 SNPs (rs200944490, rs117555780, rs34625170, and rs61754877) were significantly associated with high pathological GS (≥8) within cut-off level to p < 10−5. The most highly associated rs200944490 in ARRDC4 (p = 1.39 × 10−6) and rs117555780 in UBXN1 (p = 2.92 × 10−5) were selected for further validation. The knockdown of UBXN1 and ARRDC4 led to significantly reduced cell proliferation and suppressed migration and invasiveness in PCa cell lines. Epithelial mesenchymal transition (EMT) markers were significantly down-regulated in si-ARRDC4 and si-UBXN1-transfected cells. The expression levels of PI3K-phosphorylation and Akt phosphorylation and NF-κB were also suppressed following knockdown of UBXN1 and ARRDC4. The rs200944490 (ARRDC4) and rs117555780 (UBXN1) were identified as candidate markers predictive of PCa Gleason score which is strongly associated with cancer aggressiveness. Additional validation in future studies is warranted.