Presence Of Extraprostatic Extension Research Articles

Pathological Assessment of Men with Grade Group 2 Prostate Cancer.

A variety of treatment options are now available for men with localized prostate cancer (PC); however, there is still debate in determining how and when to intervene for Grade Group (GG) 2 disease. Our study aims to formulate strategies to identify men at risk of upgrading and having adverse pathological outcomes. This retrospective study includes 243 patients with GG2 PC that were treated with radical prostatectomy between 2015 and 2021. Patients on active surveillance, previous history of prostate biopsy, hormonal and/or radiation therapy prior to surgery were excluded from this study. A retrospective analysis was conducted using clinicopathological data obtained from medical records. Prostate-specific antigen (PSA) and Prostate Imaging Reporting and Data System (PI-RADS) score were statistically significant variables for risk of upgrading. In men who had presence of composite poor outcomes, PSA, PI-RADS score, presence of extraprostatic extension and seminal vesical invasion on MRI, number of positive cores, percentage of high grade (pattern 4/5) on prostate biopsy and Gleason pattern 4 volume on biopsy were all statistically significant variables. Strategy 8 (PI-RADS 5 lesion or percentage high grade [Gleason pattern 4] on prostate biopsy grade >10% or >3 cores positive on prostate biopsy) had significant association to identifying the highest number of men with upgrading and composite poor outcomes. Our study supports the use of strategy 8 in treatment decision making of men with GG2 PC. Further validation of the use of this strategy is warranted.

Integrative multi-region molecular profiling of primary prostate cancer in men with synchronous lymph node metastasis

Localized prostate cancer is frequently composed of multiple spatially distinct tumors with significant inter- and intra-tumoral molecular heterogeneity. This genomic diversity gives rise to many competing clones that may drive the biological trajectory of the disease. Previous large-scale sequencing efforts have focused on the evolutionary process in metastatic prostate cancer, revealing a potential clonal progression to castration resistance. However, the clonal origin of synchronous lymph node (LN) metastases in primary disease is still unknown. Here, we perform multi-region, targeted next generation sequencing and construct phylogenetic trees in men with prostate cancer with synchronous LN metastasis to better define the pathologic and molecular features of primary disease most likely to spread to the LNs. Collectively, we demonstrate that a combination of histopathologic and molecular factors, including tumor grade, presence of extra-prostatic extension, cellular morphology, and oncogenic genomic alterations are associated with synchronous LN metastasis.

A Model for Predicting Clinically Significant Prostate Cancer Using Prostate MRI and Risk Factors

PurposeThe aim of this study was to develop and validate a predictive model for clinically significant prostate cancer (csPCa) using prostate MRI and patient risk factors. MethodsIn total, 960 men who underwent MRI from 2015 to 2019 and biopsy either 6 months before or 6 months after MRI were identified. Men diagnosed with csPCa were identified, and csPCa risk was modeled using known patient factors (age, race, and prostate-specific antigen [PSA] level) and prostate MRI findings (location, Prostate Imaging Reporting and Data System score, extraprostatic extension, dominant lesion size, and PSA density). csPCa was defined as Gleason score sum ≥ 7. Using a derivation cohort, a multivariable logistic regression model and a point-based scoring system were developed to predict csPCa. Discrimination and calibration were assessed in a separate independent validation cohort. ResultsAmong 960 MRI reports, 552 (57.5%) were from men diagnosed with csPCa. Using the derivation cohort (n = 632), variables that predicted csPCa were Prostate Imaging Reporting and Data System scores of 4 and 5, the presence of extraprostatic extension, and elevated PSA density. Evaluation using the validation cohort (n = 328) resulted in an area under the curve of 0.77, with adequate calibration (Hosmer-Lemeshow P = .58). At a risk threshold of >2 points, the model identified csPCa with sensitivity of 98.4% and negative predictive value of 78.6% but prevented only 4.3% potential biopsies (0-2 points; 14 of 328). At a higher threshold of >5 points, the model identified csPCa with sensitivity of 89.5% and negative predictive value of 70.1% and avoided 20.4% of biopsies (0-5 points; 67 of 328). ConclusionsThe point-based model reported here can potentially identify a vast majority of men at risk for csPCa, while avoiding biopsy in about 1 in 5 men with elevated PSA levels.

How Can We Identify Extraprostatic Extension (EPE) Before Surgery? The Use of a Preoperative Prostate MRI EPE Scoring System to Assess Postprostatectomy Locally Advanced Prostate Cancer.

Background: Distinguishing between organ-confined disease and extraprostatic extension (EPE) is crucial for the treatment of patients with prostate cancer. EPE is associated with an increased risk of biochemical recurrence, positive surgical margins, and metastatic disease. An MRI-based EPE scoring system was developed by Mehralivand in 2019; however, it has not been adopted in the Urology community. The purpose of this study is to evaluate the association of MRI-based EPE scoring with the pathologic EPE (pEPE) after radical prostatectomy. Methods: We conducted a retrospective review on a prospectively collected database of male patients who underwent a prostate MRI with EPE scoring by a trained genitourinary radiologist and subsequent robotic radical prostatectomy at our institution from September 2020 to December 2022. The associations between MRI EPE (mEPE) score and the presence of EPE on surgical pathology (pEPE) were examined using multivariable logistic regression. Results: A total of 194 patients met inclusion criteria with a median age of 63 years and prostate specific antigen (PSA) 7 ng/mL. Among those with mEPE score 3, 96% had pEPE. Those patients with an mEPE score ≥2 had an increased risk of pEPE compared with those with mEPE score 0 (odds ratio 3.79; 95% confidence interval 1.28-11.3) Furthermore, those with an mEPE score 3 were significantly more likely to have pEPE compared with those with mEPE score 0, 1 and 2 independently. Conclusion: MRI EPE is a straightforward tool that strongly correlates with the presence of pEPE. If validated prospectively, this scoring system could assist in counseling patients regarding nerve-sparing approach.

An updated model for predicting side-specific extraprostatic extension in the era of MRI-targeted biopsy.

Accurate prediction of extraprostatic extension (EPE) is pivotal for surgical planning. Herein, we aimed to provide an updated model for predicting EPE among patients diagnosed with MRI-targeted biopsy. We analyzed a multi-institutional dataset of men with clinically localized prostate cancer diagnosed by MRI-targeted biopsy and subsequently underwent prostatectomy. To develop a side-specific predictive model, we considered the prostatic lobes separately. A multivariable logistic regression analysis was fitted to predict side-specific EPE. The decision curve analysis was used to evaluate the net clinical benefit. Finally, a regression tree was employed to identify three risk categories to assist urologists in selecting candidates for nerve-sparing, incremental nerve sparing and non-nerve-sparing surgery. Overall, data from 3169 hemi-prostates were considered, after the exclusion of prostatic lobes with no biopsy-documented tumor. EPE was present on final pathology in 1,094 (34%) cases. Among these, MRI was able to predict EPE correctly in 568 (52%) cases. A model including PSA, maximum diameter of the index lesion, presence of EPE on MRI,highest ISUP gradein the ipsilateral hemi-prostate, and percentage of positive cores in the ipsilateral hemi-prostate achieved an AUC of 81% after internal validation. Overall, 566, 577, and 2,026 observations fell in the low-, intermediate- and high-risk groups for EPE, as identified by the regression tree. The EPE rate across the groups was: 5.1%, 14.9%, and 48% for the low-, intermediate- and high-risk group, respectively. In this study we present an update of the first side-specific MRI-based nomogram for the prediction of extraprostatic extension together with updated risk categories to help clinicians in deciding on the best approach to nerve-preservation.

Diagnostic Performance of PSMA-Based 18F-DCFPyL PET/CT in Prostate Cancer Patients After Definitive Treatment With PSA Level ≤0.2 ng/mL.

The aim of this study was to investigate the role of 18F-DCFPyL PET/CT in the evaluation of prostate cancer (PC) patients after definitive treatment and with low-level prostate-specific antigen (PSA) level of ≤0.2 ng/mL. This retrospective study was conducted in PC patients who received definitive treatments with PSA level of ≤0.2 ng/mL and underwent 18F-DCFPyL PET/CT within a 1-week interval of PSA examination, and without interval treatment change or history of other cancer. Patient and tumor characteristics at initial diagnosis, treatment regimens, and findings on 18F-DCFPyL PET/CT were collected. Patients with minimal 6-month (median, 11 months; range, 6-21 months) follow-up or definitive biopsy results of the suspected PET/CT findings were included. Imagine findings were reached with consensus among experienced board-certified nuclear medicine physicians. Comprehensive follow-up and/or biopsy results were used as definitive determination of presence or absence of disease. Comparisons between groups of positive and negative 18F-DCFPyL PET/CT were done by using descriptive statistics. A total of 96 18F-DCFPyL PET/CTs from 93 patients met the inclusion criteria. The median Gleason score (GS) of positive group is 8 (range, 6-10), whereas negative group is 7 (range, 6-10). The median age of positive group is 71 (range, 50-90), whereas negative group is 69 (range, 45-88). There were 49 positive (51%) and 47 negative 18F-DCFPyL PET/CTs (49%). Detection rates at PSA level of ≤0.1 and 0.2 ng/mL were 58.7% (27/46) and 44% (22/50), respectively. The scan-based sensitivity, specificity, positive predictive value, and negative predictive value are 100%, 95%, 96%, and 100% in group with PSA level of ≤0.1 ng/mL, and 100%, 97%, 95%, and 100% in group with PSA level of 0.2 ng/mL, respectively. Sites of involvement on positive 18F-DCFPyL PET/CTs were prostate bed, pelvic lymph nodes, bone, chest and supraclavicular lymph nodes, lung, and adrenal glands. The SUVmax value on positive lesions ranged from 1.9 to 141.4; the smallest positive lymph node was 0.4 cm. High GS of 8-10, known metastatic status (M1), presence of extraprostatic extension, presence of seminal vesicle invasion, and very high-risk PC are significantly associated with positive 18F-DCFPyL PET/CT results (P < 0.05). Of all analyzed treatment regimes, upfront surgery (radical prostatectomy with or without pelvic lymph node dissection) had strong correlation with negative PET/CT results (P < 0.001). If patients received ADT only, or ADT plus chemotherapy, the PET/CT results were most likely positive (P = 0.026). For other treatment regimes, there were no statistical differences between the groups (P > 0.05). In the presence of low PSA level in PC patients after definitive treatment, 18F-DCFPyL PET/CT is most beneficial in detection of disease in patients with GS of 8 or higher at the time of diagnosis, and the ones who have history of ADT only, or ADT plus chemotherapy. There is excellent negative prediction value of 18F-DCFPyL PET/CT. However, there is no cutoff PSA level for 18F-DCFPyL PET/CT indication and no correlation between PSA level and SUVmax of positive lesions on 18F-DCFPyL PET/CT.

Post-Prostatectomy Risk Stratification of Biochemical Recurrence Using Transfer Learning-Based Multi-Modal Artificial Intelligence

For patients undergoing radical prostatectomy for prostate cancer (PCa), accurate risk stratification is essential to guide post-prostatectomy therapeutic decision making. Recently, there has been success in the use of multi-modal artificial intelligence models for men after prostate biopsy to aid in risk stratification. Herein, we trained and tested a TRansfer learning-based multi-modal Artificial InteLligence model (TRAIL) for biochemical recurrence (BCR) risk stratification following radical prostatectomy. Patients contained within a prospective PCa registry at a single institution were utilized. Digital pathology slides from the diagnostic biopsies prior to radical prostatectomy for patients with clinically localized PCa were scanned at 20x resolution. Features were extracted for the TRAIL model from pathology slides via two transfer learning steps: (1) InceptionResNetv2 that first determines a heatmap of tumor areas, and (2) A ResNet18 that extracts representative features from the high tumor probability areas. Least Absolute Shrinkage and Selection Operator (LASSO) was used for feature selection from the pathology-extracted features. Finally, TRAIL combines the clinical and pathology-extracted features via a classification ensemble model based on weak tree learners to predict 2- and 5-year BCR defined as two consecutive serum PSA levels ≥0.2 ng/mL. TRAIL training was performed on 250 patients and was then locked and applied to the test set of 125 patients. Accuracy and the area under the curve (AUC) were calculated. Comparison to CAPRA-S and to clinical-only features were assessed. A total of 818 digital whole pathology biopsy slides from 375 patients treated with subsequent radical prostatectomy were included. Surgical margins were positive in 29% of the patients, and 41% had extra-prostatic extension. The median follow-up was 48 months (Range: 1-132 months). The rates of 2-and 5-year BCR were 11% and 18% respectively. A total of 19 digital pathology-driven features were included in TRAIL. Clinical factors included age, ISUPG, Gleason score, PSA, pathological T and N stages, surgical margin involvement, and the presence of extra-prostatic extension. On the testing set, TRAIL achieved a 2-year BCR AUC of 0.76 and accuracy of 0.87, and was superior to CAPRA-S (AUC = 0.57) and clinical-only features (AUC 0.50, accuracy 0.14). For 5-year BCR, TRAIL achieved an AUC of 0.69 and accuracy of 0.78, and performed better than CAPRA-S (AUC = 0.58), and clinical only features (AUC = 0.50, accuracy = 0.23). Through a combination of deep and ensemble learning, TRAIL incorporates clinical and histopathology features, enabling an improved BCR risk stratification post-prostatectomy when compared to the currently used clinicopathologic models. Future work with larger datasets with metastatic events is warranted to further optimize the model for clinical use.

Redefining 18F DCFPyl PSMA-PET detected local recurrence from radical prostatectomy histopathology.

18F-DCFPyL PET localises tumour recurrence in patients with biochemical recurrence post-radical prostatectomy. Correlations exist between disease recurrence and poor histopathological parameters such as the presence of extra prostatic extension (EPE) and positive surgical margins. We aim to assess topographic concordance between these histopathological features and the location of the PSMA PET local recurrences, qualitatively and quantitatively. Our cohort was selected from the 100 men who received a 18F-DCFPyL PET scan through IMPPORT trial, a prospective non-randomised study completed by GenesisCare Victoria. Eligibility included patients with a rising PSA (>0.2 ng/mL) post radical prostatectomy and PSMA PET detected local recurrence. Histopathological parameters collated included the location of tumour, EPE and positive margins. Criteria for the location and 'concordance' between histopathological features and local recurrences were predefined. 24 patients were eligible, median age was 71 years old, median PSA 0.37ng/ml and time between prostatectomy and PSMA PET was 2.6 years. 15 patients had recurrences within the vesicourethral anastomotic region and 9 within the lateral surgical margins. 100% concordance in the left to right plane between tumour location and local recurrence was found, with 79% of these lesions concordant three-dimensionally; across cranio-caudal, left-right and anterior-posterior planes. 10/16 (63%) patients' with EPE and 5/9 (55.5%) of patients' with positive margins had three-dimensional concordance between their pathology and their local recurrence. In quantitative assessment, 17 of the 24 patients, had local recurrences that correlated with the location of their original tumour in the cranio-caudal plane. Local recurrence is highly concordant with the position of the tumour within the prostate. Predicting the location of local recurrence using the location of the EPE and positive margins is less helpful. Further investigation into this field, could impact surgical technique and salvage radiotherapy clinical target volume.

PD21-02 ASSESSING THE GENERALIZABILITY OF RANDOMIZED EVIDENCE BY COMPARING RESULTS FROM A CLINICAL TRIAL AND ESTABLISHED QUALITY IMPROVEMENT COLLABORATIVE: RESULTS FROM G-MINOR AND MUSIC

You have accessJournal of UrologyCME1 Apr 2023PD21-02 ASSESSING THE GENERALIZABILITY OF RANDOMIZED EVIDENCE BY COMPARING RESULTS FROM A CLINICAL TRIAL AND ESTABLISHED QUALITY IMPROVEMENT COLLABORATIVE: RESULTS FROM G-MINOR AND MUSIC Udit Singhal, Ralph Jiang, Daniel E. Spratt, Matthew Schipper, Simpa S. Salami, Stephanie Daignault-Newton, Rodney Dunn, Thomas J. Maatman, Brian R. Lane, Frank N. Burks, Paul Rodriguez, Eduardo Kleer, Richard Sarle, Felix Y. Feng, Michael L. Cher, Robert T. Dess, and Todd M. Morgan Udit SinghalUdit Singhal More articles by this author , Ralph JiangRalph Jiang More articles by this author , Daniel E. SprattDaniel E. Spratt More articles by this author , Matthew SchipperMatthew Schipper More articles by this author , Simpa S. SalamiSimpa S. Salami More articles by this author , Stephanie Daignault-NewtonStephanie Daignault-Newton More articles by this author , Rodney DunnRodney Dunn More articles by this author , Thomas J. MaatmanThomas J. Maatman More articles by this author , Brian R. LaneBrian R. Lane More articles by this author , Frank N. BurksFrank N. Burks More articles by this author , Paul RodriguezPaul Rodriguez More articles by this author , Eduardo KleerEduardo Kleer More articles by this author , Richard SarleRichard Sarle More articles by this author , Felix Y. FengFelix Y. Feng More articles by this author , Michael L. CherMichael L. Cher More articles by this author , Robert T. DessRobert T. Dess More articles by this author , and Todd M. MorganTodd M. Morgan More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003287.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Although randomized controlled trials (RCTs) represent the gold standard for clinical research, results from RCTs are often substantially less dramatic when implemented in practice. Previous studies have evaluated the congruence of observational studies with RCTs and shown conflicting results. However, minimal to no data exist comparing RCT populations with their non-RCT contemporaries. We aimed to assess the generalizability of RCT evidence by comparing results from an RCT with those from a prospectively collected, geographically equivalent, quality improvement collaborative. METHODS: The G-MINOR RCT randomized 356 men with localized prostate cancer at high-risk of recurrence after prostatectomy to clinical risk stratification with or without Decipher testing to assess its utility in clinical decision-making. Enrollment of patients occurred across 12 practices within the Michigan Urological Surgery Improvement Collaborative (MUSIC). Matching between MUSIC and G-MINOR was performed using 3:1 nearest neighbor matching on propensity scores. Differences between the matched populations were assessed via Kaplan-Meier estimates and multivariable Cox regression, with a primary endpoint of failure-free survival (FFS), which was defined as any biochemical recurrence or receipt of salvage treatment. Secondary endpoints were adjuvant treatment-free survival and cumulative incidence of salvage treatment. RESULTS: After matching, a total of 1352 men were included in the analysis (338 G-MINOR, 1014 MUSIC), with no differences in age, race, comorbidity, PSA, grade group, clinical T-stage, margin status, presence of extra-prostatic extension, or Decipher risk between the groups. Despite matching, FFS was greater at 48 months follow-up in the G-MINOR group compared to MUSIC (20.1% vs 19.9%, p=0.041). Men in MUSIC received significantly more adjuvant therapy (20.1% vs 9.2%, p<0.0001), but salvage treatment rates were similar between the groups (G-MINOR 11.2% vs MUSIC 8.6%, p=0.62). CONCLUSIONS: Despite similar geographic, practice-level, and disease-related characteristics, men enrolled in a RCT were less likely to have failure after initial treatment compared to matched patients in the same communities not enrolled in the RCT. These results suggest possible unmeasured differences between these populations or unmeasured benefits of trial participation that may result in improved outcomes for RCT participants. Source of Funding: U.S. is supported by an AUA/UCF Research Scholar Award © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e590 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Udit Singhal More articles by this author Ralph Jiang More articles by this author Daniel E. Spratt More articles by this author Matthew Schipper More articles by this author Simpa S. Salami More articles by this author Stephanie Daignault-Newton More articles by this author Rodney Dunn More articles by this author Thomas J. Maatman More articles by this author Brian R. Lane More articles by this author Frank N. Burks More articles by this author Paul Rodriguez More articles by this author Eduardo Kleer More articles by this author Richard Sarle More articles by this author Felix Y. Feng More articles by this author Michael L. Cher More articles by this author Robert T. Dess More articles by this author Todd M. Morgan More articles by this author Expand All Advertisement PDF downloadLoading ...

The NeuroSAFE frozen section technique during radical prostatectomy - Implementation and optimization of technical aspects in a routine pathology workflow.

In prostate cancer patients, application of the NeuroSAFE frozen section technique during radical prostatectomy has been shown to increase the rate of nerve sparing surgery and to improve functional outcome for the patients. The aim of this study is to report on technical and organizational optimization opportunities of the procedure. All patients submitted to bilateral intraoperative frozen section from January 2018 until December 2020 (n=452) were retrospectively analyzed and parameters such as turnaround time, staff situation in the laboratory and histologic properties of the tumors were assessed. The median turnaround time per case was 40.3 (±10.5) min. In 2020 the average time needed from accessioning to diagnosis was 38.1min. Multivariate linear regression suggested that the number of technical assistants/cryotomes (46.1min vs. 39.13min; p<0.001), the place of microscopic examination (43.0min vs. 38.7min; p<0.001) and the presence of a positive margin (38.0 vs. 44.0min; p<0.001) were significant influential factors. The turnaround time was independent of the uropathological expertize of the consultant (39.84min vs. 40.7min; p=0.09), the tumor grade (42.3 vs 39.8min; p=0.493) and the presence of extraprostatic extension (44.0 vs 39.8min; p=0.099). The implementation of simple optimization measures in the workflow as well as structured training of all pathology staff involved in the examination leads to a significant increase in the efficiency of the examination while maintaining the same level of resources. The results could thus be a contribution to the broader application of the procedure.

Do not underestimate anterior prostate cancer.

With the introduction of magnetic resonance imaging in the diagnosis of prostate cancer and its use in targeted prostate biopsy, an increased incidence of anterior-predominant prostate cancer (APC) has been observed. We enrolled 200 patients who underwent radical prostatectomy at our department between 12/2017 and 04/2019. We evaluated tumour location in the individual segments of the prostate, index tumour location and volume, and compared the postoperative stage, Gleason score, grade group (GG), and the presence of extraprostatic extension (EPE) in APC and posterior prostate cancer (PPC). We assessed the rate of MRI scans prior to prostate surgery as well as the influence of family history and PSA on the presence of APC. We found a significantly higher rate of anterior tumours than previously reported (37%) and confirmed that these tumours are diagnosed with a significantly larger index tumour volume (P=0.003). We also showed that a mere 6.76% of APCs were low-risk tumours not requiring radical treatment. Furthermore, anterior tumours were found significantly more often (P=0.001) in patients who underwent preoperative MRI. No differences were observed between PSA values, family history, presence of EPE, or locally advanced disease in APC vs. PPC. The frequency of anterior tumours is higher than previously thought, and they include tumours requiring radical treatment. When these tumours are neglected, it may lead to patient undertreatment with impact on their life prognosis. Thus, we consider the use of MRI-targeted prostate biopsy to be a necessity both for ruling out APC in the case of repeatedly negative prostate biopsies and, in particular, before patient inclusion in active surveillance.

Postoperative Biochemical Failure in Patients With PI-RADS Category 4 or 5 Prostate Cancers: Risk Stratification According to Zonal Location of an Index Lesion

OBJECTIVE. The objective of our study was to assess postoperative biochemical failure in patients with prostate cancer according to zonal location of an index lesion classified as Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) category 4 or 5. MATERIALS AND METHODS. Consecutive patients (n = 232) with prostate cancer who had PI-RADSv2 category 4 or 5 lesions on MRI and who underwent radical prostatectomy were retrospectively evaluated. We investigated clinical (prostate-specific antigen density), MRI (PI-RADSv2 category of index lesion and zonal location, assessed as peripheral zone [PZ] or transition zone [TZ], of index lesion), and pathologic (tumor volume, tumor grade, and presence of extraprostatic extension) parameters. We analyzed Kaplan-Meier survival curves and the Cox proportional hazards model to assess 2-year biochemical failure-free survival and identify significant parameters associated with postoperative biochemical failure RESULTS. Biochemical failure occurred in 14.2% of patients (33/232). Two-year biochemical failure-free survival of patients with a PI-RADSv2 category 4 or 5 index lesion was 81.3%. For all patients, 2-year biochemical failure-free survival was different according to PI-RADSv2 category (category 4, 86.4%; category 5, 74.5%; p = 0.021) or zonal location (PZ, 75.3%; TZ, 96.8%; p = 0.003). Two-year biochemical failure-free survival in patients with category 4 lesions was similar in patients with PZ lesions (83.1%) and those with TZ lesions (100.0%) (p = 0.072), whereas it was different in patients with category 5 lesions (PZ, 62.0%; TZ, 95.0%; p = 0.002). In multivariate analysis, only zonal location of an index lesion on MRI was associated with biochemical failure (hazard ratio = 0.155; p = 0.012). CONCLUSION. Zonal location of an index lesion on MRI may be a useful imaging bio-marker to predict postoperative biochemical failure.

Extraprostatic extension in prostate cancer: primer for radiologists.

The presence of extraprostatic extension (EPE) on multiparametric MRI (mpMRI) is an important factor in determining the management of prostate cancer. EPE is an established risk factor for biochemical recurrence of prostate cancer after radical prostatectomy (RP) and patients with EPE may be considered for wider resection margins, non-nerve-sparing surgery, adjuvant radiation therapy (RT), or androgen deprivation therapy (ADT). Several statistical nomograms and scoring systems have been developed to predict pathological stage at time of RP but with varying accuracies. Using the current PI-RADS v2 mpMRI staging guidelines results in high specificity but lacks in sensitivity. These findings reveal the need for more standardization and further refinement of existing MRI protocols and prostate cancer prediction tools. Current studies have looked into indirect additional imaging criteria such as index tumor volume, length of capsular contact, and apparent diffusion coefficient. Measuring for these features can improve the robustness of mpMRI in staging prostate cancer, as they have been shown to be independent predictors of EPE. MRI/ultrasound fusion-guided targeted biopsy can detect EPE not found on standard biopsy. Collectively, these measurements and imaging techniques can augment the detection of EPE and subsequent risk stratification.

Nerve Sparing during Robot-Assisted Radical Prostatectomy Increases the Risk of Ipsilateral Positive Surgical Margins.

Available published studies evaluating the association between nerve sparing robot-assisted radical prostatectomy and risk of ipsilateral positive surgical margins were subject to selection bias. In this study we overcome these limitations by using multivariable regression analysis. Patients undergoing robot-assisted radical prostatectomy for prostate cancer at 4 institutions from 2013 to 2018 were included in the study. A multilevel logistic random intercept model, including covariates on patient level and side specific factors on prostate lobe level, was used to evaluate the association between nerve sparing and risk of ipsilateral positive margins. A total of 5,148 prostate lobes derived from 2,574 patients who underwent robot-assisted radical prostatectomy were analyzed. Multivariable analysis showed nerve sparing was an independent predictor for ipsilateral positive margins (OR 1.42, 95% CI 1.14-1.82). Other significant predictors for positive margins were prostate specific antigen density (OR 3.64, 95% CI 2.36-5.90) and side specific covariates including highest preoperative ISUP (International Society of Urological Pathology) biopsy grade (OR 1.58, 95% CI 1.13-2.53; OR 1.62, 95% CI 1.13-2.69; OR 2.11, 95% CI 1.39-3.59 and OR 4.43, 95% CI 3.17-10.12 for ISUP grade 2, 3, 4 and 5, respectively), presence of extraprostatic extension on magnetic resonance imaging (OR 1.42, 95% CI 1.03-1.91) and percentage of positive cores on systematic biopsy (OR 3.82, 95% CI 2.50-5.86). Nerve sparing was associated with an increased risk of ipsilateral positive surgical margins. The increased risk of positive margins should be considered when counseling patients who opt for nerve sparing robot-assisted radical prostatectomy.

Long noncoding RNA HOTTIP overexpression: A potential prognostic biomarker in prostate cancer

HOXA transcript at the distal tip (HOTTIP) is a long noncoding RNA (lncRNA), which is >200 nucleotides in length. HOTTIP expression has been demonstrated to play a crucial oncogenic role in cancer pathogenesis, and is said to be associated with poor human cancer prognosis. In prostate cancer, HOTTIP has been identified as an oncogene, but its clinicopathologic significance remains unclear. Array-based qRT-PCR was used to investigate lncRNA levels in 10 pairs of prostate cancer tissues and non-neoplastic parenchyma. Tissue microarray (TMA) was constructed using a total of 70 surgically resected prostatic adenocarcinoma tissues obtained from the Korea University Anam Hospital from 2009 to 2013. HOTTIP expression was determined by RNA in situ hybridization(ISH) and was correlated with clinicopathologic features. Increased HOTTIP expression was observed in all available prostate cancer tissue specimens compared with that in paired normal tissue. High HOTTIP expression was positively associated with bad clinicopathologic features, including higher pathologic T stage (p < 0.001), presence of extraprostatic extension (p < 0.001), seminal vesicle invasion (p < 0.001), perineural invasion (p < 0.001), and the tumor involvement of resection margin (p = 0.044). In particular, significantly increased HOTTIP expression was observed in specimens from patients in the high or very high-risk group, according to the 2018 National Comprehensive Cancer Network (NCCN) guidelines (p < 0.001). Also, patients with high HOTTIP expression showed poorer overall survival than those with low expression. In conclusion, we analytically validated the poor prognostic significance of HOTTIP overexpression and its association with bad clinicopathologic features, and present HOTTIP as a potential prognostic biomarker in prostate cancer.

Clinical and oncologic findings of extraprostatic extension on needle biopsy in de novo metastatic prostate cancer.

This study aimed to explore the clinical and oncologic findings in patients with de novo metastatic prostate cancer (mPCa) and extraprostatic extension (EPE) on biopsy. We retrospectively evaluated data on 630 patients with de novo mPCa between January 2009 and December 2017 in the West China Hospital (Chengdu, China), including evaluating the relationships between EPE and other variables and the association of EPE with survival outcomes by the Chi-square test, Kaplan–Meier curves, and the Cox proportional-hazards model. EPE was found in 70/630 patients, making a prevalence of 11.1%. The presence of EPE on biopsy was associated with higher Gleason scores and higher incidence of neuroendocrine differentiation (NED), intraductal carcinoma of the prostate (IDC-P), and perineural invasion (PNI). Compared with those without EPE, patients with EPE had shorter castration-resistant prostate cancer-free survival (CFS; median: 14.1 vs 17.1 months, P = 0.015) and overall survival (OS; median: 43.7 vs 68.3 months, P = 0.032). According to multivariate analysis, EPE was not an independent predictor for survival. Subgroup analyses demonstrated that patients with favorable characteristics, including negative NED or IDC-P status, Eastern Cooperative Oncology Group (ECOG) score <2, and prostate-specific antigen (PSA) <50 ng ml−1, had worse prognoses if EPE was detected. In patients with PSA <50 ng ml−1, EPE was a negative independent predictor for OS (hazard ratio [HR]: 4.239, 95% confidence interval [CI]: 1.218–14.756, P = 0.023). EPE was strongly associated with other aggressive clinicopathological features and poorer CFS and OS. These data suggest that EPE may be an indicator of poor prognosis, particularly in patients, otherwise considered likely to have favorable survival outcomes.

The effect of time from biopsy to radical prostatectomy on adverse pathologic outcomes.

ObjectiveTo assess the impact of time between prostate cancer diagnosis on biopsy and definitive intervention with radical prostatectomy (RP) in regard to adverse pathologic outcomes using a large multi-surgeon database.Materials and methodsWe retrospectively reviewed 2,728 patients who underwent RP between 2005 and 2014. Patients were stratified according to biopsy Grade Group (GG). Pathologic outcomes were evaluated for patients with <2 months between biopsy and surgery and then at monthly intervals of up to 6 months. Adverse pathological outcomes were defined as Gleason upgrading from biopsy, the presence of extraprostatic extension (EPE, pT3a) or seminal vesicle invasion (SVI, pT3b), positive surgical margins, and lymph node positivity. The chi-squared test was used for statistical analysis.ResultsIn total 2,310 patients met the inclusion criteria. Median time from biopsy to surgery was 83 days (range: 61–109 days). No difference was observed for patients in any risk category regarding the adverse pathologic outcomes, including GG upgrade from biopsy to prostatectomy, presence of EPE, SVI, positive surgical margins, and positive lymph node involvement, with delays of up to 6 months between biopsy and RP. Surgical margins were positive in 25% of cases with pT2 disease and 50.2% of cases with pT3 and greater disease. EPE and SVI were present in 24.5% and 7.5% of specimens, respectively.ConclusionSurgical delays of up to 6 months following prostate biopsy were not associated with an increased risk of GG upgrading, EPE, SVI, positive surgical margins, or lymph node involvement.

Pretreatment Multiparametric Magnetic Resonance Imaging Findings Are More Accurate Independent Predictors of Outcome Than Clinical Variables in Localized Prostate Cancer

To prospectively determine whether multiparametric magnetic resonance imaging (mpMRI)-based staging is a more accurate independent predictor of outcome than traditional clinical variables for patients undergoing brachytherapy and external beam radiation therapy. The primary endpoints were biochemical (nadir plus 2ng/mL) and metastatic failure. Descriptive, univariate, and multivariate competing risks analyses were performed. The cumulative incidence rates were estimated to describe the cumulative risk of the events of interest. The magnitude of the increased risk was estimated using univariate and multivariate subdistribution hazard ratios. A total of 185 patients had undergone prospective treatment (123 with high risk and 62 with intermediate risk). The median age was 71years (range 56-82). Of the patients, 20.5% had mpMRI-determined (mrT) stage mrT1-mrT2b, 37.3% had mrT2c, 31% had mrT3a, and 11.2% had mrT3b. The Gleason score was 6 in 22.2%, 7 in 49.5%, and 8 to 10 in 28.2%. The median baseline prostate-specific antigen was 11.7ng/mL (range 2.9-153). After a median follow-up period of 46months (range 16-70), 15 patients (8.1%) had developed biochemical failure and 9 (4.9%) had developed distant metastases. None of the traditional clinical variables (prostate-specific antigen, Gleason score, clinical stage) predicted for biochemical or metastatic failure. The multivariate competing risk analysis demonstrated that the 2 independent predictors of biochemical failure were the presence of extraprostatic extension (EPE; mrT3a; hazard ratio [HR] 4.80; P=.035) and presence of seminal vesicle invasion (SVI; mrT3b; HR 10.17; P=.003) on mpMRI. The only independent predictor of metastatic failure was the percentage of positive cores on prostate biopsy (HR 13.95; P=.014). After excluding patients with SVI, the only independent predictor of biochemical failure and metastatic failure was the presence of EPE (stage mrT3a) on mpMRI (HR 4.36; P=.042; and HR 5.76; P=.010, respectively). The pretreatment mpMRI findings might be more accurate independent predictors of the outcome than traditional clinical variables. In particular, the presence of EPE, SVI and a greater percentage of positive cores on biopsy predicted for a worse prognosis.

The NeuroSAFE PROOF study (An RCT to evaluate the use of frozen section technology to improve oncological and functional outcomes in robotic radical prostatectomy)

Background: Radical prostatectomy is an effective cure for organ confined prostate cancer. Men undergoing radical prostatectomy suffer side effects of incontinence (temporary) and impotence (permanent). Nerve sparing minimises these side effects. However, in the presence of extraprostatic extension, for which there is no reliable preoperative test, nerve sparing can cause positive surgical margin (PSM), necessitating adjuvant radiotherapy which compounds side effects. The NeuroSAFE method uses intraoperative frozen section to check that nerve sparing has not caused a PSM, allowing the nerve to be resected if there is a PSM.

Lesion size on prostate magnetic resonance imaging predicts adverse radical prostatectomy pathology

Objectives: To investigate the value of the maximal lesion diameter on preoperative multiparametric/bi-parametric magnetic resonance imaging for estimating the risk of adverse radical prostatectomy pathology.Patients and methods: Consecutive patients (n = 162) with prostate multiparametric or biparametric magnetic resonance images acquired before prostatectomy were retrospectively stratified into two groups: 65 patients with normal MRI (n = 18) or a suspicious lesion <15 mm in diameter (n = 47), and 97 patients with a lesion diameter ≥15 mm. The presence of extraprostatic extension, margin positivity, seminal vesicle invasion, and lymph node metastasis was examined in these groups using logistic regression analysis, including preoperative clinical parameters (prostate-specific antigen concentration, biopsy Gleason grade group, clinical T-stage, and D’Amico risk group).Results: The prevalence of extraprostatic extension, margin positivity, and seminal vesicle invasion was 53.1% (86/162), 22.8% (37/162), and 17.9% (29/162), respectively. Lymphadenectomy was performed in 64 men, of whom 14 had lymph node metastasis. Lesion diameter ≥15 mm strongly predicted extraprostatic extension (Odds ratio: 7.94, 95% confidence interval: 3.87−16.28, p < 0.001), margin positivity (Odds ratio: 7.86, 95% confidence interval 2.63−23.51, p < 0.001), and seminal vesicle invasion (Odds ratio: 7.57, 95% confidence interval 2.18−26.22, p = 0.001). Lesion diameter ≥15 mm was an independent risk factor for adverse prostatectomy pathology. Lesion diameter ≥20 mm, but not ≥15 mm, was a significant risk factor for lymph node metastasis.Conclusion: Magnetic resonance imaging lesion diameter ≥15 mm is an independent risk factor for extraprostatic extension, margin positivity and seminal vesicle invasion.