Consecutive Radical Prostatectomy Research Articles

Anti-Müllerian hormone: a novel biomarker for aggressive prostate cancer? Emerging evidence from a prospective study of radical prostatectomies.

Prostate cancer patients are a heterogeneous group as regards the aggressiveness of the disease. The relationship of steroid hormones with the aggressiveness of prostate cancer is unclear. It is known that the anti-Müllerian hormone (AMH) inhibits prostate cancer cell lines in vitro. The aim of this study is to investigate the relationship of AMH and steroid hormones with the aggressiveness of prostate cancer. This was a prospective study of consecutive radical prostatectomy patients. We measured the following hormones: total testosterone, sex hormone-binding globulin, albumin, luteinizing hormone, follicle-stimulating hormone, estradiol, dehydroepiandrosterone sulfate, androstenedione, and AMH. The minimum follow-up after radical prostatectomy was 5years. For the aggressiveness of prostate cancer, we considered the following three variables: post-operative Gleason score (GS) ≥ 8, TNM pΤ3 disease, and prostate-specific antigen (PSA) biochemical recurrence (BCR). In total, 91 patients were enrolled. The mean age and PSA were 64.8years and 9.3ng/dl, respectively. The median post-operative GS was 7. Low AMH blood levels were correlated with higher post-operative GS (p = 0.001), as well as with PSA BCR (p = 0.043). With pT3 disease, only albumin was (negatively) correlated (p = 0.008). ROC analysis showed that AMH is a good predictor of BCR (AUC 0.646, 95% CI 0.510-0.782, p = 0.043); a cutoff value of 3.06ng/dl had a positive prognostic value of 71.4% and a negative prognostic value of 63.3% for BCR. Cox regression analysis showed that AMH is a statistically significant and independent prognostic marker for BCR (p = 0.013). More precisely, for every 1ng/ml of AMH rise, the probability for PSA BCR decreases by 20.8% (HR = 0.792). Moreover, in Kaplan-Meier analysis, disease-free survival is more probable in patients with AMΗ ≥ 3.06ng/ml (p = 0.004). Low AMH blood levels were correlated with aggressive prostate cancer in this radical prostatectomy cohort of patients. Therefore, AMH could be a prognostic biomarker for the aggressiveness of the disease.

Neurovascular Structure-adjacent Frozen-section Examination (NeuroSAFE) increases Nerve-sparing Frequency and reduces Positive Surgical Margins in open and Robot-assisted Laparoscopic Radical Prostatectomy: Experience After 486 Consecutive Patients

Abstract Introduction/Objective: Introduction Intraoperative frozen-section analysis allows real-time histologic assessment of surgical margins (SMs) and identification of candidates for nerve-sparing (NS) procedures in radical prostatectomy (RP). Objective: To examine the efficacy of a systematic neurovascular structure-adjacent frozen-section examination (NeuroSAFE) during open and robotic assisted radical prostatectomy (RARP). Methods/Case Report From January 2019 to December 2020, 486 consecutive RPs were performed at the academic hospital Fuerth. Of these, 289 (59 %) were conducted with NeuroSAFE. Surgical procedure: NeuroSAFE included the whole laterorectal circumference of the prostate corresponding to the neurovascular bundle to determine the SM status. Outcome measurements and statistical analysis: The impact of NeuroSAFE on NS frequency and SM status was analyzed by chi-square test in matched cohorts. Data obtained from 289 RPs performed with NeuroSAFE were compaired to those from 197 RP without NeuroSAFE. Results (if a Case Study enter NA) In NeuroSAFE RPs, frequency of NS was significantly higher in lower pT stages (pT2 and pT3a: 78 % vs 68%, 58% vs 51%, p < 0.0001, p = 0.047, respectively), whereas in stage ≥ pT3b, there was no significant difference in NS rate (53% vs 34%; p = 0.14). PSM rates were significantly lower only in pT2 tumors (all stages: 35% vs 24%, p=0.06; pT2: 12% vs 15%; p=0.02; pT3a: 36% vs 35%; p=0.6 and ≥pT3b: 39% vs 52%, p=0.3) compared with the matched non-NeuroSAFE RPs. Positive SMs (PSMs) were leading to a secondary resection of the ipsilateral neurovascular tissue. Secondary wide resection resulted in conversion to a definitive negative SM (NSM) status in 85 % of the patients. Conclusion NeuroSAFE enables real-time histologic monitoring and oncologic safety of a NS procedure. Systematic NeuroSAFE significantly increases NS frequencies and reduces PSMs in stage pT2 tumors. Patients with a NeuroSAFE-detected PSM could be converted to a prognostically more favorable NSM status by secondary wide resection.

Clinicopathologic Significance of Anterior Prostate Cancer: Comparison With Posterior Prostate Cancer in the Era of Multiparametric Magnetic Resonance Imaging.

Anterior prostate cancer (APC) has been considered an indolent tumor, most commonly arising in the transition zone (TZ). More recently, detection of APC has been facilitated through multiparametric magnetic resonance imaging and improved biopsy techniques, enabling earlier detection. The pathologic features and clinical significance of pure APC in a large contemporary series of well-characterized tumors have, to date, not been elucidated. Cases with APC defined as cancer present anterior to the urethra only were identified from 1761 consecutive radical prostatectomy specimens accessioned between January 2015 and August 2016. The clinicopathologic features of these cases were compared with those of pure posterior prostate cancer (PPC) and the features of anterior peripheral zone (APZ) cancers were compared with those of TZ cancers. In addition, the tumor series from 2015 to 2016 was compared with a cohort of 1054 patients accessioned before the utilization of multiparametric magnetic resonance imaging in the routine workup of patients with prostate cancer. In the 2015-2016 series, there were 188 (10.7%) patients with APC compared with 5.4% in the series from the pre-multiparametric magnetic resonance imaging era. No difference was observed between APC and PPC with regards to patient age or mean serum prostate-specific antigen at presentation. Mean tumor volume and positive surgical margin (PSM) rates were significantly higher in APC. In contrast, PPC was more commonly high grade with more frequent extraprostatic extension (EPE). None of the cases of APC had infiltration of the seminal vesicle or lymph node involvement, in contrast to PPC, with almost 14% of cases in each category. The 3- and 5-year biochemical recurrence-free survival was significantly higher in APC when compared with PPC, although this was not retained on multivariable analysis which included tumor location. On division of APCs according to anatomic zone of origin, 45% were APZ cancer and 37% TZ cancer. On comparison of APZ and TZ cancers, there were no significant differences in mean age and serum prostate-specific antigen at presentation as well as tumor volume, Gleason score, and PSM rate. High-grade malignancy (Gleason score >3 + 4=7) was seen in 26% of TZ cancers which compared with 44% of APZ cancers and 56% of PPC cancers. The rate of EPE was significantly higher in APZ when compared with TZ cancer ( P< 0.0005); however, the biochemical recurrence rate was not significantly different between the groups. The prevalence of APC in radical prostatectomy specimens has increased in recent times, in association with earlier detection at a stage amenable to curative surgical treatment. APC, when compared with PPC, is less commonly high grade with less frequent EPE, despite the APC group having larger tumors and a higher PSM rate at presentation. However, not all anterior cancers are indolent. Anterior cancers are more commonly seen in the APZ than the TZ and APZ cancers appear more locally aggressive than TZ cancers.

Abstract 2270: Hyperlipidemia promotes aggressive variant prostate cancer via RNA-binding protein Quaking

Abstract Introduction: Hyperlipidemia has been associated with increased risk of advanced stage and high Gleason grade prostate cancer (PCa), yet the underlying mechanism is not completely understood. Quaking (QKI) is an RNA-binding protein (RBP) that regulate lipid metabolism. For PCa, QKI overexpression has been associated with increased chance of metastatic recurrence. Method: We performed RNA sequencing of prostate cancer tissues of hyperlipidemia (n = 12) and normolipidemia (n=32). Tissue samples were acquired by MRI-US fusion targeted biopsy. DESeq2 and GSEA was used to identify differently expressed genes and enriched genesets. A web-based RBP motif screening tool TRANSITE was utilized to identify active RBPs in hyperlipidemia-associated PCa. Results: PCa samples of hyperlipidemia patients exhibited poorer histology than normolipidemia PCA. RNA sequencing found that hyperlipidemia-associated PCa is enriched of Myc-regulated genes as well as interferon or innate immunity-associated genes. Interestingly, hyperlipidemia-associated PCa gene expression signature identified PCa samples devoid of common PCa genetic alterations - TMPRSS2-ERG fusion and PTEN deletion/mutation. RBP motif screening found QKI as one of the top enriched RBP in hyperlipidemia-associated PCa transcriptome. In a separate a consecutive radical prostatectomy series (n=190), we found that QKI-high (immunohistochemistry staining score 2-3) tumors had significantly higher serum cholesterol than QKI-low (score 0-1) tumors. Overexpression and knockdown experiments proved that QKI is responsible of rapid cell proliferation and interferon-related inflammatory gene expressions, In silico analysis predicted QKI overexpressing cancer cells are susceptive to stain-mediated ferroptosis-like cell death. Mechanistically, QKI regulates expression of acyl-CoA synthetase long-chain family member 4 (ACSL4), which dictates the sensitivity of QKI overexpressing cells to ferroptosis. Conclusion: Hyperlipidemia was associated with aggressive pathologic characteristics of PCa without TMPRSS2-ERG fusion or PTEN deletion/mutation, and high tissue expression of QKI, an RNA-binding protein. QKI overexpression in PCa increased sensitivity to ACSL4-mediated ferroptosis by statins. This explains the epidemiological associations between hyperlipidemia and PCa, and will guide molecular subtype-driven drug repurposing studies. Citation Format: Hyun Ho Han, Jin Sol Sung, Dong Wook Song, Cheol Keun Park, Nam Hoon Cho, Young Deuk Choi, Woo Jin Ko. Hyperlipidemia promotes aggressive variant prostate cancer via RNA-binding protein Quaking [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2270.

The pelvic anatomic index is an independent predictor for the difficulty of radical prostatectomy.

The aim of the study was to investigate whether a novel simple measurement of pelvic anatomy, the pelvic anatomical index (PAI), which is obtained from simple physical examination, was predictive for potential difficulty and adverse outcome in radical prostatectomy. Available data from 73 consecutive radical prostatectomy patients were analyzed. The distances between umbilicus and cranial edge of the symphysis pubis (USPD) and between root of the penis and umbilicus (PUD) were measured. PAI was obtained using the formula (PUD/USPD) × body mass index (BMI). Indicators of surgical difficulty assessed were operation time (OT), dorsal vein bleeding (DVB), total blood loss (TBL), and surgical margin (SM) status. Patients with below-median values of the OT, DVB, TBL, and had negative SM were grouped as favorable surgery (n = 18). Median OT, DVB, and TBL were 215 (IQR: 187.5-240) min, 380 (IQR: 200-500) cc, and 1000 (IQR: 700-1300) cc, respectively. Both PAI and BMI were significantly correlated with TBL, DVB, and OT (p < 0.05, for all). PAI and BMI significantly associated with favorable surgery (p = 0,006 and p = 0.048, respectively). However, only PAI was an independent predictor of favorable surgery in multivariable logistic regression analysis. A PAI 36kg/m2 was determined as the threshold value for favorable surgery with 83.3% sensitivity and 60% specificity. PAI significantly correlated with almost all surgical parameters and was a significant independent predictor of favorable surgery. PAI can enable the physician to select and discuss individualized treatment options for patients during preoperative planning.

PD61-02 PREOPERATIVE PSMA PET/CT AS A PREDICTOR OF BIOCHEMICAL PERSISTENCE AND EARLY BIOCHEMICAL RECURRENCE

You have accessJournal of UrologyProstate Cancer: Localized: Surgical Therapy V (PD61)1 Sep 2021PD61-02 PREOPERATIVE PSMA PET/CT AS A PREDICTOR OF BIOCHEMICAL PERSISTENCE AND EARLY BIOCHEMICAL RECURRENCE Diederik Baas, Melline Schilham, Joost de Baaij, Eric Vrijhof, Robert Hoekstra, Rick Hermsen, Diederik Somford, and Jean-Paul van Basten Diederik BaasDiederik Baas More articles by this author , Melline SchilhamMelline Schilham More articles by this author , Joost de BaaijJoost de Baaij More articles by this author , Eric VrijhofEric Vrijhof More articles by this author , Robert HoekstraRobert Hoekstra More articles by this author , Rick HermsenRick Hermsen More articles by this author , Diederik SomfordDiederik Somford More articles by this author , and Jean-Paul van BastenJean-Paul van Basten More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002098.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: This study aims to evaluate the predictive value of suspected lymph nodes (LN) metastases on prostate-specific-membrane-antigen (PSMA) PET/CT for biochemical persistence (BCP) and early biochemical recurrence (BCR) following radical prostatectomy (RP) with extended pelvic lymph node dissection (ePLND). METHODS: RP patients between September 1st, 2016 and October 1st, 2020 were evaluated. Men with intermediate or high-risk PCa with preoperative 68Ga/18F-PSMA PET/CT and subsequent ePLND were included. Performance of PSMA PET/CT was determined on a per patient level. BCP was defined as a serum PSA level ≥0.1 ng/mL between 6-20 weeks following RP. Early BCR was defined as detectable PSA >0.2 ng/mL ≤12 months of follow-up. Patients were grouped as PSMA- or PSMA+ depending on their LN status on PSMA PET/CT and subdivided according to histological LN status (pN) as determined by ePLND. RESULTS: From 1058 consecutive RP patients, 213 met the inclusion criteria. Median number of resected LN was 20 (IQR 15-26). PSMA PET/CT versus histological results of ePLND are presented in Table 1. Sensitivity, specificity, PPV, NPV and accuracy for preoperative detection of metastatic LNs were 29%, 83%, 33%, 80% and 71% respectively. BCP was observed in 26 of 211 patients (12%) and early BCR in 23 of 110 patients (21%). The incidence of BCP and BCR for patients subdivided according to their PSMA and pN status is illustrated in Figure 1. No correction was made for other risk factors. Patients with PSMA+/pN1 had a significantly increased risk of BCP and BCR compared with PSMA-/pN1 (p=0.004; p <0.001). CONCLUSIONS: ePLND should not be avoided in men with a pre-operative negative PSMA PET/CT, as 20% of patients do have histological N1 disease. Men with positive pre-operative PSMA PET/CT and confirmed pN1 disease have a significantly increased risk of BCP and early BCR compared to those with negative PSMA PET/CT. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1066-e1066 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Diederik Baas More articles by this author Melline Schilham More articles by this author Joost de Baaij More articles by this author Eric Vrijhof More articles by this author Robert Hoekstra More articles by this author Rick Hermsen More articles by this author Diederik Somford More articles by this author Jean-Paul van Basten More articles by this author Expand All Advertisement Loading ...

Percentage of Gleason pattern 4 and tumor volume predict adverse pathological stage and margin status at radical prostatectomy in grade Group 2 and grade Group 3 prostate cancers

Increasing percentages of Gleason pattern 4 (GP4%) in radical prostatectomy (RP) correlate with an increased likelihood of nonorgan-confined disease and earlier biochemical recurrence (BCR). However, there are no detailed RP studies assessing the impact of GP4% and corresponding tumor volume (TV) on extraprostatic extension (EPE), seminal vesicle (SV) invasion (SV+), and positive surgical margin (SM) status (SM+). In 1301 consecutive RPs, we analyzed each tumor nodule (TN) for TV, Grade Group (GG), presence of focal versus nonfocal EPE, SV+ , and SM+. Using GG1 (GP4% = 0) TNs as a reference, we recorded GP4% for all GG2 or GG3 TNs. We performed a multivariable analysis (MVA) using a mixed effects logistic regression that tested significant variables for risk of EPE, SV+, and SM+, as well as a multinomial logistic regression model that tested significant variables for risks of nonorgan-confined disease (pT2+, pT3a, and pT3b) versus organ-confined disease (pT2). We identified 3231 discrete TNs ranging from 1 to 7 (median: 2.5) per RP. These included GG1 (n = 2115), GG2 (n = 818), GG3 (n = 274), and GG4 (n = 24) TNs. Increasing GP4% weakly paralleled increasing TV (tau = 0.07, p < .001). In MVA, increasing GP4% and TV predicted a greater likelihood of EPE (odds ratio [OR]: 1.03 and 4.41), SV+ (OR: 1.03 and 3.83), and SM+ (1.01, p = .01 and 2.83), all p < .001. Our multinomial logistic regression model demonstrated an association between GP4% and the risk of EPE (i.e., pT3a and pT3b disease), as well as an association between TV and risk of upstaging (all p < .001). Both GP4% and TV are independent predictors of adverse pathological stage and margin status at RP. However, the risks for adverse outcomes associated with GP4% are marginal, while those for TV are strong. The prognostic significance of GP4% on BCR-free survival has not been studied controlling for TV and other adverse RP findings. Whether adverse pathological stage and margin status associated with larger TV could decrease BCR-free survival to a greater extent than increasing RP GP4% remains to be studied.

68Ga-Prostate-Specific Membrane Antigen Positron Emission Tomography-Computed Tomography-Based Primary Staging and Histological Correlation after Extended Pelvic Lymph Node Dissection in Intermediate-Risk Prostate Cancer

Objective: The objective of this study is to evaluate prostate-specific membrane antigen positron emission tomography-computed tomography (PSMA PET/CT)-based primary staging in exclusively D′Amico intermediate-risk prostate cancer (PCa) patients. Patients and Methods: We relied on the Braunschweig institutional database and retrospectively identified D′Amico intermediate-risk PCa patients who were administered to ⁶⁸Ga-PSMA PET/CT-based primary staging prior to consecutive radical prostatectomy and extended lymph node dissection. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for the detection of lymph node metastases were analyzed per-patient (n = 39), per-pelvic side (n = 78), and per-anatomic-region (external iliac artery and vein left/right vs. obturator fossa left/right vs. internal iliac artery left/right) (n = 203), respectively. Results: Sensitivity, specificity, PPV, and NPV per-patient were 20.0, 94.1, 33.3, and 88.9%, respectively. Sensitivity, specificity, PPV, and NPV per-pelvic-side were 16.7, 97.2, 33.3, and 93.3%, respectively. Sensitivity, specificity, PPV, and NPV per-anatomic-region were 16.7, 99.0, 33.3, and 97.5%, respectively. Conclusions: We recorded high rates of specificity and NPV for ⁶⁸Ga-PSMA PET/CT-based primary staging in D′Amico intermediate-risk PCa patients. Conversely, the sensitivity and PPV were lower than anticipated. Larger and favorably prospective trials are needed to verify our results and to unravel possible bias from such smaller studies.

How Much Reliable Is the Current Belief on Grade Group 1 Prostate Cancer?

Objective: To evaluate the clinicopathological characteristics of grade group 1 (GG1) prostate cancer in Korean populations. Methods: We retrospectively analyzed 492 consecutive radical prostatectomy specimens from our institution, which included those from 322 men with clinical GG1 and 170 with clinical GG2 tumors between years 2009 and 2018. The incidence of Gleason score (GS) upgrading, extraprostatic extension (EPE), and seminal vesicle invasion (SVI) were evaluated in patients with clinical GG1. In pathological GG1 cases, the distribution of adverse pathological features including EPE, lymphovascular invasion (LVI), perineural invasion (PNI), and biochemical recurrence (BCR) was analyzed. Results: Altogether, 78 (24.2%) out of 322 men in the clinical GG1 group demonstrated upgrading of GS, including 19 men with pathological Gleason score 4 + 3 = 7 and 6 with ≥ pathological Gleason score 4 + 4 = 8 cases. EPE was found in 37 (11.5%) and 22 (8.9%) men in clinical GG1 and pathological GG1 group, respectively. The incidence of LVI and PNI in the pathological GG1 cases was 2.8% (n = 7) and 28.6% (n = 71), respectively. BCR was observed in 4 men in pathological GG1 T2 (n = 226) and 2 men in GG1 T3 (n = 22) group. When we compared the pathological features between pathological GG1 T3 vs. GG2 T2, there was no statistical differences in the incidence of LVI and PNI between the two groups. Conclusions: Contrary to the current concept that GG1 is almost always clinically insignificant, it seems that GG1 still possess its respectable position as a group of cancer with aggressiveness. These findings should be kept in mind when deciding on treatment options for prostate cancer patients in the Asian populations.

Transition zone prostate cancer is associated with better clinical outcomes than peripheral zone cancer.

ObjectivesTo determine the biological significance of zonal origins in prostate cancer.Patients and methodsAltogether, 270 consecutive radical prostatectomy cases from 2009 to 2012 were adopted. Cases were divided into those having transition zone (TZ) cancer or peripheral zone (PZ) cancer. Cases with indeterminate tumor location and central zone cancers were excluded from the analyses. Prognosis and clinicopathological features were compared between the two tumor locations. Biochemical recurrence (BCR) and clinical progression (CP) were adopted as prognostic outcome measures. Immunohistochemical features of the v‐ets avian erythroblastosis virus E26 oncogene homolog (ERG)/serine peptidase inhibitor, Kazal‐type 1 (SPINK1) status, and loss of phosphatase and tensin homolog (PTEN‐loss), as well as conventional preoperative and postoperative characteristics, were analyzed.ResultsThis cohort comprised 93 cases of TZ cancer and 160 cases of PZ cancer. TZ cancer cases showed significantly higher BCR and CP‐free survival rate than PZ cancer cases. Notably, no TZ cancer cases developed CP during the 7.8 years of median follow‐up time. Tumor location was an independent predictive factor for BCR in the multivariate analysis. Additionally, TZ cancer cases showed a significantly lower prevalence of ERG‐overexpression and PTEN‐loss than PZ cancer cases (3.2% vs 20.1% and 2.2% vs 18.2%, respectively).ConclusionTZ cancer cases showed a better prognosis and different immunohistochemical features. Conservative treatment strategies could be considered for TZ cancer cases.

Inter-observer variability of cribriform architecture and percent Gleason pattern 4 in prostate cancer: relation to clinical outcome

The Grade group is an important parameter for clinical decision-making in prostate cancer. Recently, percent Gleason pattern 4 and presence of invasive cribriform and/or intraductal carcinoma (CR/IDC) have been recognized for their independent predictive value for prostate cancer outcome. There is sparse data on the inter-observer agreement for these pathologic features in practice. Our objectives were to investigate inter-observer variability of percent Gleason pattern and CR/IDC and to relate individual tumour scores to clinical outcome. Our cohort included 80 consecutive radical prostatectomies with a median follow-up 87.1 months (interquartile range 43.3–119.2), of which the slide with largest tumour volume was scored by six pathologists for Grade group (four tiers: 1, 2, 3 and 4/5), percent Gleason pattern 4 (four tiers: 0–25%, 26–50%, 51–75% and 76–100%) and presence of CR/IDC (two tiers: absent, present). The individual assignments were related to post-operative biochemical recurrence (20/80). Inter-observer agreement was substantial (Krippendorff’s α 0.626) for assessment of Grade group and moderate for CR/IDC (α 0.507) and percent Gleason pattern 4 (α 0.551). For each individual pathologist, biochemical recurrence rates incremented by Grade group and presence of CR/IDC, although such relation was less clear for percent Gleason pattern 4. In conclusion, inter-observer agreement for CR/IDC and percent Gleason pattern 4 is lower than for Grade groups, indicating awareness of these features needs further improvement. Grade group and CR/IDC, but not percent Gleason pattern 4 was related to biochemical recurrence for each pathologist, indicating overall validity of individual grade assignments despite inter-observer variability.

Variation in adjuvant and early salvage radiotherapy after robot-assisted radical prostatectomy for prostate cancer: a population-based cohort study

Purpose: The primary aim of the study was to assess the association between having a radiotherapy (RT) department on-site at the surgical centre and the performed postoperative treatment strategy for prostate cancer (PCa) patients. According to the current international guidelines, adjuvant radiotherapy (ART) or a regular prostate-specific antigen (PSA)-based follow-up with (early) salvage radiotherapy ((e)SRT) if needed is recommended in case of adverse pathological characteristics.Material and methods: Prospective data on consecutive robot-assisted radical prostatectomy (RARP) patients in Belgium from 2009 to 2016 were identified in the Belgian Robotic-Assisted-Laparoscopic-Prostatectomy (Be-RALP) database. Multivariable regression was used to evaluate patient- and facility-related factors associated with postoperative radiation treatment.Results: 2072 patients undergoing a RARP, suffering at least one of the following adverse pathological features, i.e., extracapsular extension (ECE), seminal vesicle invasion (SVI) or positive section margins (PSM), and with registered follow-up until 24 months were enrolled. After RARP, ART was applied to 9.1% and (e)SRT to 12.6% of the patients. Multivariable analysis demonstrated that patients were more likely to receive ART or (e)SRT if they were operated in a hospital with a RT department on-site (odds ratio, ART: 1.49 [1.07-2.07]; (e)SRT: 1.55 [1.16-2.06]). Furthermore, the presence of higher tumour category (T-category) and/or PSM on final pathology was associated with a higher chance of getting ART and (e)SRT (p < .01).Conclusion: Variations in ART and (e)SRT are not only driven by patient-related characteristics. In our nationwide cohort, the availability of a RT department on-site at the surgical centre was found to be an independent predictor for ART and (e)SRT, with a 1.5 times higher odds of receiving postoperative RT during the first 24 months after surgery.

Impact of Adherence to Multidisciplinary Recommendations for Adjuvant Treatment in Radical Prostatectomy Patients With High Risk of Recurrence

The purpose of this study was to investigate adherence to recommended adjuvant radiotherapy (aRT) in radical prostatectomy (RP) patients with adverse pathologic features and to analyse the outcome of patients who followed or denied this recommendation. We included 1140 consecutive RP patients (2006-2015) with non-organ confined (pT3) prostate cancer and either positive surgical margins (R1) and/or lymph node involvement (pN1) and non-detectable postoperative prostate-specific antigen who received multidisciplinary aRT recommendations. Patients were stratified into adherence versus non-adherence to recommendations. Additionally, subgroups within pathologic criteria (pT3R1N0, pT3R0N1, pT3R1N1) were analyzed. Kaplan-Meier, as well as multivariable Cox regression analyses were used to assess biochemical recurrence (BCR)-free survival, metastasis-free survival, cancer-specific survival, and overall survival. Overall, 508 (44.6%) patients were non-adherent. Of those, 273 (53.6%) did not receive any RT, and 235 (46.4%) received salvage RT. At 8 years, BCR-free survival was 57.7 versus 20.1%, metastasis-free survival was 76.5 versus 75.4%, cancer-specific survival was 91.7 versus 87.4%, and overall survival was 80.4 versus 75.8% in adherent versus non-adherent patients, respectively (P< .001). In multivariable Cox regression predicting BCR, metastatic progression, cancer-specific mortality, and overall mortality, non-adherence to aRT recommendation represented an independent predictor (hazard ratio [HR], 3.8; 95% confidence interval [CI], 3.1-4.5; HR, 1.6; 95% CI, 1.2-2.2; HR, 2.8; 95% CI, 1.5-5.3; and HR, 1.8; 95% CI, 1.2-2.8, respectively). Only about 55% of patients followed our multidisciplinary recommendations. Adherent patients were significantly less likely to experience BCR, metastatic progression, cancer-specific mortality, and overall mortality. Thus, patients with high risk of recurrence may be advised about the possibility of improved oncologic outcomes in case of adherence to aRT recommendations.

Minimum Magnetic Resonance Imaging-Ultrasound Fusion Targeted Biopsy Cores Needed for Prostate Cancer Detection: Multivariable Retrospective, Lesion Based Analyses of Patients Treated with Radical Prostatectomy.

We analyzed the number of multiparametric magnetic resonance imaging targeted biopsy cores per lesion needed to detect prostate cancer in patients treated with radical prostatectomy. Analyses focused on targeted biopsy of magnetic resonance imaging lesions suspicious for prostate cancer with a PI-RADS® (Prostate Imaging Reporting and Data System) score of 3 or greater and consecutive radical prostatectomy. Descriptive statistics included the frequency/proportion and IQR. Multivariable logistic regression analyses on the per lesion level were used to predict the number of targeted biopsies with prostate cancer. In the total cohort of 771 radical prostatectomy cases 437 (57%) and 334 (43%) were systematic transrectal ultrasound guided biopsy naïve or had 1 or more prior negative systematic transrectal ultrasound guided biopsies, respectively. A maximum PI-RADS score of 3, 4 and 5 was present in 67 (8.7%), 567 (74%) and 137 patients (18%), respectively. A total of 1,459 multiparametric magnetic resonance imaging lesions suspicious for prostate cancer were identified for analysis. Prostate cancer was detected based on an initial, second, third, or fourth or greater targeted biopsy in 79%, 92%, 98% and 100% of cases, respectively. The rate of prostate cancer detection on the first targeted biopsy core increased with higher PI-RADS scores of 3, 4 and 5 (67%, 79% and 87%, respectively). The number of prior negative systematic transrectal ultrasound guided biopsies and pathological tumor stage emerged as independent predictors on multivariate analysis, addressing the need for 2 or more targeted biopsy cores to detect clinically significant prostate cancer. Radical prostatectomy based analyses demonstrated that most cancers could be detected by 2 targeted biopsies only while in a minority of cases 3 or more targeted biopsies were necessary. Such findings might indicate that the targeted biopsy procedure and the related technology have improved, especially in patients with intermediate/high risk prostate cancer.

PT200 - Diagnostic and staging performance of mpMRI-US fusion prostate biopsy: Prospective analysis on consecutive radical prostatectomy specimens from a multicentre series

PT200 - Diagnostic and staging performance of mpMRI-US fusion prostate biopsy: Prospective analysis on consecutive radical prostatectomy specimens from a multicentre series

5hmC Level Predicts Biochemical Failure Following Radical Prostatectomy in Prostate Cancer Patients with ERG Negative Tumors.

This study aimed to validate whether 5-hydroxymethylcytosine (5hmC) level in combination with ERG expression is a predictive biomarker for biochemical failure (BF) in men undergoing radical prostatectomy (RP) for prostate cancer (PCa). The study included 592 PCa patients from two consecutive Danish RP cohorts. 5hmC level and ERG expression were analyzed using immunohistochemistry in RP specimens. 5hmC was scored as low or high and ERG was scored as negative or positive. Risk of BF was analyzed using stratified cumulative incidences and multiple cause-specific Cox regression using competing risk assessment. Median follow-up was 10 years (95% CI: 9.5–10.2). In total, 246 patients (41.6%) had low and 346 patients (58.4%) had high 5hmC level. No significant association was found between 5hmC level or ERG expression and time to BF (p = 0.2 and p = 1.0, respectively). However, for men with ERG negative tumors, high 5hmC level was associated with increased risk of BF following RP (p = 0.01). In multiple cause-specific Cox regression analyses of ERG negative patients, high 5hmC expression was associated with time to BF (HR: 1.8; 95% CI: 1.2–2.7; p = 0.003). In conclusion, high 5hmC level was correlated with time to BF in men with ERG negative PCa, which is in accordance with previous results.

Radical prostatectomy in T4 prostate cancer after inductive androgen deprivation: results of a single-institution series with long-term follow-up.

To determine the outcomes of complete surgical resection of T4 prostate cancer after inductive androgen-deprivation therapy (ADT), as inductive ADT and subsequent radical prostatectomy (RP) is not recommended by any guideline yet. A monocentric RP database was queried for patients initially diagnosed with T4 prostate cancer, considered primarily as inoperable because of a fixed mass defined by rectal examination in combination with high PSA level and/or large foci of biopsy confirmed undifferentiated prostate cancer. Treatment consisted of primary ADT until PSA nadir with consecutive RP. Patients underwent retropubic RP (RRP) or robot-assisted laparoscopic RP (RALP) after inductive ADT until achievement of the PSA nadir, which is in general reached after 6-7months. The intraoperative course and complications were analysed. Finally, Kaplan-Meier estimates were calculated for overall survival (OS) and prostate cancer-specific survival (PCSS). We retrospectively identified 116 patients treated between 2000 and 2014. At diagnosis, the median (range) PSA level was 37.6 (2.44-284) ng/mL. The preoperative median (range) PSA after inductive ADT was 0.73 (0.01-34) ng/mL. Thereafter, patients underwent RRP or, since 2006, RALP. The median (95% confidence interval) OS was 156 (118.9-193.1) months. The PCSS at 150months was 82%. Surgical therapy of primarily inoperable prostate cancer is feasible and safe after inductive ADT. The OS of this cohort seems comparable with results described for patients with primary operable high-risk prostate cancer.

Occurrence of pathologic stage T3 disease at radical prostatectomy with isup grade group 1 (Gleason 3+3=6) prostate cancer.

21 Background: Treatment of ISUP Grade Group 1 (Gleason 3+3 = 6) disease continues to evolve in the modern era. We examined our surgical database to investigate patterns of behavior in this pathologic subset. Methods: We reviewed the results of 1127 consecutive radical prostatectomies performed by our surgeons from 2012−2015 at various community and academic medical centers in Chicagoland. Specifically, we examined the ISUP Grade Group 1 (Gleason 3+3 = 6) patients in our database, 314 patients overall. Results: A review of our database revealed that of ISUP Grade Group 1 (Gleason 3+3 = 6) patients (n = 314), only 3.82% had pT3 disease (11 patients stage pT3a and 1 stage pT3b). The only patient of these 12 to have lymphovascular invasion (LVI) was the singular pT3b patient. Overall, ISUP Grade Group 1 (Gleason 3+3 = 6) pT3 disease represents only 1.06% of all prostatectomies in our database. Conclusions: In our large prostatectomy cohort, ISUP Grade Group 1 (Gleason 3+3 = 6) prostate cancer was rarely associated with extra−prostatic extension (pT3) or lymphovascular invasion (LVI), suggesting that it has very low metastatic potential. These findings give further support to the trend of increased utilization of active surveillance for low risk prostate cancer.

Incidence of Extraprostatic Extension at Radical Prostatectomy with Pure Gleason Score 3 + 3 = 6 (Grade Group 1) Cancer: Implications for Whether Gleason Score 6 Prostate Cancer Should be Renamed "Not Cancer" and for Selection Criteria for Active Surveillance

We assessed the risk of locally aggressive behavior in pure Gleason score 6 (Grade Group 1) prostate cancer using contemporary grading criteria. To our knowledge this has been studied in only 1 prior cohort. We evaluated consecutive radical prostatectomy specimens from an academic institution, including those from 3,291 men with Gleason score 6 and 4,202 with Gleason score 3 + 4 = 7 (Grade Group 2) disease between 2005 and 2016. For dichotomous variables the Pearson chi-square test was used. Of the 3,288 Gleason score 6 cancer cases 128 (3.9%) showed focal extraprostatic extension compared to 593 of the 4,202 (14.1%) with Gleason score 3 + 4 = 7 (p <0.0001). Of the 3,288 Gleason score 6 cancer cases 79 (2.4%) showed nonfocal extraprostatic extension compared to 639 of the 4,202 (15.2%) with Gleason score 3 + 4 = 7 (p <0.0001). The incidence of focal extraprostatic extension with Gleason score 3 + 4 = 7 with less than 5% Gleason pattern 4 was 129 of 1,147 cases (11.2%), which was between Gleason scores 6 and 3 + 4 = 7 with greater than 5% Gleason pattern 4. The incidence of nonfocal extraprostatic extension in Gleason score 3 + 4 = 7 with less than 5% Gleason pattern 4 was 96 of 1,147 cases (8.4%), which was between Gleason scores 6 and 3 + 4 = 7 with greater than 5% Gleason pattern 4. One of the 3,290 Gleason score 6 cases (0.03%) showed seminal vesicle invasion compared to 93 of the 4,202 (2.2%) of Gleason score 3 + 4 = 7 (p<0.0001). A limitation of our study was its retrospective design. It is not rare for pure Gleason score 6 prostate cancer to locally extend out of the prostate 3.9% focally and 2.4% nonfocally. In extremely rare cases Gleason score 6 can be associated with seminal vesicle invasion and yet not lymph node metastases. Our overall findings support the argument for continuing to use the term cancer for these tumors.

Short- and Long-term Functional Outcomes and Quality of Life after Radical Prostatectomy: Patient-reported Outcomes from a Tertiary High-volume Center

BackgroundResults from population-based studies and the Prostate Testing for Cancer and Treatment trial reported worse urinary continence (UC) and erectile function (EF) for radical prostatectomy (RP) patients compared with their radiation or active surveillance counterparts. ObjectiveTo investigate functional outcomes for patients undergoing RP in a high-volume center. Data, setting, and participantsA total of 8573 consecutive RP patients (2008–2012) were analyzed. InterventionRP. Outcome measurements and statistical analysisStandardized questionnaires assessing EF, UC, and quality of life (QoL), were completed at baseline and annually thereafter. UC was defined as use of 0 or 1 safety pad/d, whereas the regular use of 1 pad/d was considered incontinent. EF was defined as ≥3 points in the International Index of Erectile Function question two. QoL was assessed using the EORTC-QLQ-C30 Global Health/QoL item. Statistics relied on comparison of means and proportions. Results and limitationsEF and UC rates significantly decreased after RP. Overall, 12-mo, 24-mo, and 36-mo EF rates were 45%, 51%, and 53%, but reached up to 65.7% in preoperatively potent patients with bilateral nerve sparing. At 36 mo, 13% reported problems in their partnership. However, at the same time point, 77% were satisfied with their sexual intercourse. UC rates were 89.1%, 91.3%, and 89.0% at 12-mo, 24-mo, and 36-mo postoperatively. Mean EORTC-QLQ-C30 scores ranged from 74 to 79 and remained constant compared to baseline. ConclusionsAlthough varying definitions hinder direct comparisons to other studies, functional outcomes seemed favorable for patients undergoing RP in a high-volume center and most patients reported excellent QoL. Patient summaryResults of functional outcomes (urinary continence and potency) after radical prostatectomy are better in a high-volume center compared with those obtained from population-based data, and most patients report excellent quality of life after radical prostatectomy.