Radical Prostatectomy Findings Research Articles

A simple risk stratification model for prostate cancer using histopathologic findings of radical prostatectomy.

To develop a simple postoperative risk stratification based on histopathologic findings from radical prostatectomy specimens. This study included 3 cohorts of patients with a preoperative diagnosis of clinically localized prostate cancer: 1 derivation cohort (n=432) and 2 validation cohorts (n=506 and n=720). First, a postoperative risk stratification model was developed in the derivation cohort using the factors extraprostatic extension, surgical margin status, seminal vesicle invasion, and lymph node involvement. Each of the first 3 factors was assigned 0 or 1 point for negative or positive results, respectively, and the sum of the points, ranging from 0 to 3, was scored. pN1 was not scored but was analyzed separately. Validation cohorts were then used to evaluate the predictive accuracy of the model. Additionally, we compared the model with the Cancer of the Prostate Risk Assessment (CAPRA) score. Because the log-rank test showed no statistically significant differences between scores 1 vs 2 or score 3 vs pN1 in the derivation cohort, the following 3-level risk stratification was created: low risk (score 0), intermediate risk (score 1-2), and high risk (score 3 or pN1). There were statistically significant differences in recurrence-free survival between any of 2 groups of 3-level risk stratification. This model similarly worked in both validation cohorts. The C indexes for the model were higher than those for the CAPRA score. This simple postoperative risk stratification model, based on radical prostatectomy findings, has a prognostic impact that has been validated in a multicenter population.

Genetic ancestry and radical prostatectomy findings in Hispanic/Latino patients.

African ancestry is a known factor associated with the presentation and aggressiveness of prostate cancer (PC). Hispanic/Latino populations exhibit varying degrees of genetic admixture across Latin American countries, leading to diverse levels of African ancestry. However, it remains unclear whether genetic ancestry plays a role in the aggressiveness of PC in Hispanic/Latino patients. We explored the associations between genetic ancestry and the clinicopathological data in Hispanic/Latino PC patients from Colombia. We estimated the European, Indigenous and African genetic ancestry, of 230 Colombian patients with localized/regionally advanced PC through a validated panel for genotypification of 106 Ancestry Informative Markers. We examined the associations of the genetic ancestry components with the Gleason Grade Groups (GG) and the clinicopathological characteristics. No association was observed between the genetic ancestry with the biochemical recurrence or Gleason GG; however, in a two groups comparison, there were statistically significant differences between GG3 and GG4/GG5 for European ancestry, with a higher mean ancestry proportion in GG4/GG5. A lower risk of being diagnosed at an advanced age was observed for patients with high African ancestry than those with low African ancestry patients (OR: 0.96, CI: 0.92-0.99, p=0.03). Our findings revealed an increased risk of presentation of PC at an earlier age in patients with higher African ancestry compared to patients with lower African ancestry in our Hispanic/Latino patients.

Clinical significance of location of perineural cancer invasion detected on prostate needle core biopsy.

The clinical impact of site-specific perineural invasion (PNI) in prostate cancer remains poorly understood. We compared radical prostatectomy findings and oncologic outcomes in 434 patients with single-site PNI on systematic sextant biopsy. PNI was present in the right apex (n = 62; 14%), right mid (n = 70; 16%), right base (n = 89; 21%), left apex (n = 64; 15%), left mid (n = 58; 13%), and left base (n = 91; 21%). There were no significant differences in biopsy or prostatectomy findings, when comparing apex vs. mid vs. base PNI. Univariate analysis revealed that apex-localized PNI was associated with a significantly higher risk of progression, compared with base (P = 0.037) or mid/base (P = 0.024) PNI. Multivariable analysis showed that apex-localized PNI was an independent risk factor for progression (hazard ratio 2.049, P = 0.002). Among biopsies demonstrating PNI at one sextant site, apex-localized PNI is independently associated with poorer prognosis, though not worse histopathologic features on prostatectomy, compared with mid or base PNI.

Clinical impact of perineural invasion encircled completely vs. incompletely by prostate cancer on needle core biopsy

The clinical significance of the pattern or degree of perineural invasion (PNI) by prostate cancer remains largely unknown. We herein assessed radical prostatectomy findings and postoperative oncologic outcomes in 125 patients who had undergone systematic sextant prostate biopsy exhibiting only a single focus of PNI encircled completely (n = 57; 46 %) vs. incompletely (n = 68; 54 %) by cancer. Between these two cohorts, there were no significant differences in clinicopathological features on biopsy or prostatectomy, including tumor grade, stage, and length or volume, and surgical margin status, as well as the need for adjuvant therapy immediately after prostatectomy. Similarly, survival analysis demonstrated no significant difference in the risk of disease progression following prostatectomy in patients with encircled vs. non-encircled PNI on biopsy (P = 0.679). When the non-encircled cases were further divided into four groups [i.e. 1-25 % enclosed (n = 12; 18 %), 26–50 % enclosed (n = 18; 26 %), 51–75 % enclosed (n = 10; 15 %), 76–99 % enclosed (n = 28; 41 %)], the rates of progression-free survival were comparable among the five groups (P = 0.954). In prostate biopsy specimens exhibiting PNI at only one focus, the degree of nerve involvement thus appears to have little clinical impact. Accordingly, PNI detected on prostate biopsy may need to be similarly taken into consideration irrespective of the degree of nerve involvement.

Risk Stratification by Quantification of Perineural Cancer Invasion on Prostate Needle Core Biopsy: Should It Be Counted?

We assessed the prognostic significance of quantification of perineural invasion on prostate biopsy. We quantified actual perineural invasion foci in the entire prostate biopsy specimens from 724 patients and compared corresponding radical prostatectomy findings and long-term oncologic outcomes. No perineural invasion was detected in 524 (72.4%) prostate biopsies, whereas 1 (≥129; 17.8%), 2 (n=40; 5.5%), 3 (n=18; 2.5%), 4 (n=7; 1.0%), and 5-10 (n=6; 0.8%) perineural invasion foci were present in other cases. We confirmed a higher risk of recurrence after radical prostatectomy in patients with perineural invasion on prostate biopsy than in those with no perineural invasion (P < .001). Remarkably, recurrence-free survival was comparable between those with 0 vs 1 perineural invasion (P = .9) or 2 vs ≥3 perineural invasions (P = .3). Nonetheless, multifocal perineural invasion per prostate biopsy (vs single perineural invasion; P < .001) and >1 perineural invasion per 10-mm tumor (vs ≤1 perineural invasion; P = .008) were associated with worse outcomes. Interestingly, in a subgroup outcome analysis of single vs multifocal perineural invasions per prostate biopsy, there was a significant difference in patients showing perineural invasion involving only 1 of the sextant sites. In multivariable analysis, both multifocal perineural invasions/case (HR=5.48, P < .001) and >1 perineural invasion/10-mm tumor (HR=3.96, P < .001) showed significance for recurrence. Meanwhile, compared with CAPRA (Cancer of the Prostate Risk Assessment) score alone (0.687/0.685), Harrell's C index/AUC for predicting 5-year recurrence-free survival was gradually increased when 1 (0.722/0.740), 2 (0.747/0.773), or 3 (0.760/0.792) point(s) were additionally assigned to multifocal perineural invasion. Multifocal perineural invasion and >1 perineural invasion per 10-mm tumor on each prostate biopsy were thus found to be associated with poorer prognosis, as independent predictors, in men with prostate cancer undergoing radical prostatectomy.

Comedonecrosis within conventional prostatic adenocarcinoma vs. intraductal carcinoma of the prostate: their clinical significance is not comparable

It remains controversial if Gleason grade should be assigned to intraductal carcinoma of the prostate (IDC-P) and if the prognostic value of comedonecrosis associated with IDC-P is equivalent to that in conventional/invasive prostatic adenocarcinoma (CPA) as a Gleason grade 5 pattern. We herein assessed radical prostatectomy findings and postoperative outcomes in 287 patients with CPA exhibiting any Gleason pattern 5. Our cases were divided into 4 cohorts according to the absence or presence of necrosis within CPA and/or IDC-P: Cohort-1) no necrosis in CPA/IDC-P (n=179; 62.4%); Cohort-2) necrosis only in CPA (n=25; 8.7%); Cohort-3) necrosis only in IDC-P (n=62; 21.6%); and Cohort-4) necrosis in both CPA and IDC-P (n=21; 7.3%). Univariate analysis revealed patients with necrosis only in IDC-P (P<.001) or both CPA and IDC-P (P=.001) had a higher risk of progression than those with necrosis only in CPA, while the prognosis was comparable between the no necrosis group vs. the CPA only necrosis group (P=.680) or the IDC-P only necrosis group vs. the CPA/IDC-P necrosis group (P=.715). In a subgroup of patients exhibiting IDC-P (n=198), the presence of IDC-P necrosis was still associated with a significantly higher progression risk, compared with CPA necrosis only. In multivariable analysis, necrosis only in IDC-P (vs. necrosis only in CPA) showed significantly worse progression-free survival (HR=3.193, P=.003). IDC-P necrosis, as an independent predictor, was thus found to be associated with significantly worse oncologic outcomes, compared with necrosis only in CPA, and might therefore be better not to be simply considered as a grade 5 pattern.

Radical prostatectomy findings in patients with locally aggressive Grade group 5 prostatic adenocarcinoma and negative limited or extended pelvic lymph node dissection

Current management options for high-risk prostate cancer (PCa) patients include radical prostatectomy with lymph node dissection and other local or systemic therapeutic approaches. However, there is paucity of data in the pathology literature on the radical prostatectomy findings in patients with locally aggressive Grade group 5 PCa with negative limited or extended lymph node dissection. A search was made through our Urologic Pathology files and consults of the senior author for patients who had radical prostatectomy specimens with locally aggressive Grade group 5 PCa and limited or extended lymph node dissection from 2010 to 2022. Patients with lymph node metastasis were excluded. Clinicopathologic and follow up data were obtained. Forty-two patients were included in the study. Mean age was 64 years (range: 49–79 years). Forty-one (98 %) patients had PCa Gleason score 4 + 5 = 9 and 1 (2 %) patient had Gleason score 5 + 4 = 9. Extraprostatic extension and/or bladder neck invasion was present in 30 (71 %) patients and seminal vesicle invasion was present in 20 (48 %) patients, of which 10 (50 %) were bilateral. Extended lymph node dissection was performed in 18 patients with mean of 22 lymph nodes (range: 6–51 lymph nodes). Limited lymph node dissection was performed in 24 patients with mean of 7 lymph nodes (range: 2–25 lymph nodes). This study demonstrates that a subset of patients with very advanced/high grade PCa still benefit from radical prostatectomy/tumor debulking even in the setting of positive margins, and may not have lymph node metastasis.

The Clinical Significance of pT3a Lesions as Well as Unilateral Versus Bilateral Invasion Into the Seminal Vesicle in Men With pT3b Prostate Cancer: A Proposal for a New pT3b Subclassification.

Seminal vesicle invasion (SVI) as pT3b prostate cancer generally, but not uniformly, indicates poor prognosis. To determine the clinical impact of pT3a lesions (ie, extraprostatic extension other than seminal vesicle or bladder invasion [EPE], microscopic bladder neck invasion [mBNI]), as well as unilateral (Uni) versus bilateral (Bil) SVI in pT3b disease. We assessed radical prostatectomy findings and long-term oncologic outcomes in 248 consecutive patients with pT3b disease. Focal EPE, nonfocal EPE, mBNI, Uni-SVI, and Bil-SVI were identified in 13 (5.2%), 206 (83.1%), 48 (19.4%), 109 (44.0%), and 139 (56.0%) cases, respectively. Of possible combinations, we eventually divided our cases into 3 cohorts-Group 1: Uni/Bil-SVI and EPE-/mBNI- (n = 28; 11.3%); Group 2: Uni-SVI and EPE or mBNI (n = 103; 41.5%); and Group 3: Bil-SVI and EPE or mBNI (n = 70; 28.2%) or Uni/Bil-SVI and EPE+/mBNI+ (n = 47; 19.0%). Group 3 patients showed significant adverse histopathologic findings, compared with Group 1 or Group 2 patients. Kaplan-Meier analysis revealed that the prognosis was worse in the following order: Group 1, Group 2, and Group 3; and the differences in progression-free survival between any 2 groups were statistically significant. These significant differences were also seen in subgroups, such as those without or with adjuvant therapy before recurrence and those without lymph node metastasis. Additionally, Group 3 patients had a significantly higher risk of cancer-specific mortality than Group 2 patients. In multivariate analysis (Group 2 as a reference), Group 1 (hazard ratio [HR] = 0.169, P = .01) and Group 3 (HR = 1.620, P = .04) showed significance for progression. From these significant findings, we propose a novel pT3b subclassification, namely pT3b1 (Group 1), pT3b2 (Group 2), and pT3b3 (Group 3), which more accurately stratifies its prognosis.

Clinical Significance of Perineural Invasion by Prostate Cancer Detected on Needle Core Biopsy.

The clinical impact of the laterality of perineural invasion (PNI) by prostate cancer remains poorly understood. We herein compared radical prostatectomy (RP) findings and long-term oncologic outcomes in patients with prostate cancer with PNI in two prostate biopsy (PBx) sites. We retrospectively assessed 170 consecutive patients undergoing systematic sextant PBx where PNI had been detected in two of six PBx sites, followed by RP. PNI occurred unilaterally in 140 (82.4%) cases and bilaterally in 30 (17.6%) cases. Compared with unilateral PNI, bilateral PNI was significantly associated with a higher number of cancer-positive sites and longer total tumor length on PBx. However, there were no significant differences in RP findings, including tumor grade/stage and tumor volume, between unilateral and bilateral PNI cohorts. Kaplan-Meier analysis revealed that patients with bilateral PNI had a significantly higher risk of disease progression after RP than those with unilateral PNI (P = .038). In multivariate analysis, bilateral PNI (vs unilateral PNI) showed significance for progression (hazard ratio, 2.281; P = .023). In PBx specimens exhibiting PNI in two sextant sites, bilateral PNI was found to be associated with poorer prognosis as an independent predictor but not worse histopathologic features in RP specimens compared with unilateral PNI.

The Clinical Significance of Either Extraprostatic Extension or Microscopic Bladder Neck Invasion Alone Versus Both in Men With pT3a Prostate Cancer Undergoing Radical Prostatectomy: A Proposal for a New pT3a Subclassification.

The prognosis of prostate cancers exhibiting extraprostatic extension [other than bladder or seminal vesicle invasion (EPE)] and/or microscopic bladder neck invasion (mBNI) is variable, and further risk stratification is required. We herein assessed radical prostatectomy findings and long-term oncologic outcomes in consecutive 957 patients with pT3a disease. The patient cohort was divided into 4 groups, focal EPE (F-EPE) only (n=177; 18.5%), nonfocal/established (E-EPE) only (n=634; 66.2%), mBNI only (n=51; 5.3%). The rate of positive surgical margin and estimated volume of tumor were significantly higher in patients with both EPE and mBNI than in those with either. In addition, compared with F-EPE or mBNI only, E-EPE only was significantly associated with higher Grade Group, lymph node metastasis, and larger tumor volume. Kaplan-Meier analysis revealed a comparable prognosis after prostatectomy between those showing F-EPE only versus mBNI only ( P =0.986), and these 2 cohorts were combined for further analysis. Then, patients showing E-EPE only had a significantly higher or lower risk of progression compared with those showing F-EPE or mBNI only ( P <0.001) or both EPE and mBNI ( P <0.001), respectively. These significant differences in progression-free survival were also seen in subgroups, including those with or without undergoing adjuvant therapy before recurrence and those showing no lymph node metastasis. In multivariate analysis, F-EPE or mBNI only (hazard ratio=0.524, P =0.003) or both EPE and mBNI (hazard ratio=1.465, P =0.039) (vs. E-EPE only) showed significance for progression. Based on these findings, we propose a novel pT3a subclassification, pT3a1 (F-EPE or mBNI alone), pT3a2 (E-EPE alone), and pT3a3 (both EPE and mBNI).

Radical prostatectomy findings and oncologic outcomes in patients with prostate cancer detected on systematic sextant biopsy only, MRI-targeted biopsy only, or both.

Magnetic resonance imaging-targeted biopsy (T-Bx) has been shown to more accurately detect clinically significant prostate cancer. However, the clinical significance of cancer detection on T-Bx, followed by definitive treatment, needs to be further investigated. We herein investigated unique cohorts of patients with prostate cancer detected on systematic sextant biopsy (S-Bx) and/or T-Bx. We assessed consecutive patients who had undergone T-Bx with concurrent S-Bx (6 sites, ≥12 cores), followed by radical prostatectomy from 2015 to 2019. Within our Surgical Pathology database, we identified a total of 222 men who met the inclusion criteria for prostatic adenocarcinoma on either S-Bx or T-Bx, or both (B-Bx). Radical prostatectomy findings and oncologic outcomes were then compared among groups. Prostate cancer was detected on S-Bx only (n = 32; 14%), T-Bx only (n = 40; 18%), or B-Bx (n = 150; 68%). Compared to cases with cancer detected on S-Bx only, those on T-Bx only or B-Bx showed significantly higher tumor grade (highest Grade Group in each patient) on biopsy and significantly larger estimated tumor volume on prostatectomy. There were no significant differences in tumor volume on biopsy, tumor grade on prostatectomy (except S-Bx vs. B-Bx), pT or pN stage category, surgical margin status, or preoperative prostate-specific antigen level between cases where cancer was detected on S-Bx only vs. T-Bx only or B-Bx. There were also no significant differences in any of these clinicopathologic features between cancers detected on T-Bx only vs. B-Bx. Kaplan-Meier analysis revealed a significantly higher risk of biochemical recurrence after prostatectomy in patients whose cancer was detected on T-Bx only (P = 0.020) or B-Bx (P = 0.032) than in those on S-Bx only. No significant difference in recurrence-free survival between T-Bx only vs. B-Bx cases (P = 0.601) was seen. In multivariate analysis, cancer detection on T-Bx only (vs. S-Bx only) showed significance for recurrence (hazard ratio = 8.482, P = 0.045). Detection of prostate cancer on T-Bx, in addition to or instead of S-Bx, was found to be associated with larger tumor volume as well as worse prognosis. However, no significant clinicopathologic impact of simultaneous tumor detection on S-Bx was indicated in patients with prostate cancer present on T-Bx.

The Clinical Impact of Comedonecrosis Within Intraductal Carcinoma of the Prostate.

Intraductal carcinoma of the prostate (IDC-P) is considered a distinct form of aggressive prostate cancer where comedonecrosis, a grade 5 pattern, is occasionally present. Meanwhile, assigning a Gleason grade to IDC-P remains controversial. To assess the clinical significance of necrosis associated with IDC-P. We compared radical prostatectomy (RP) findings and oncologic outcomes in men with prostate cancer exhibiting IDC-P with (IDC-P+/N+) versus without (IDC-P+/N-) comedonecrosis. Of the 558 RPs examined, IDC-P was present in 213 cases (38.2%), including 167 (78.4%) with IDC-P+/N- and 46 (21.6%) with IDC-P+/N+. When comparing IDC-P+/N- versus IDC-P+/N+ cases, the presence of necrosis was significantly associated with higher tumor grade, higher incidence of pT3/pT3b or pN1 disease, and larger estimated tumor volume. Outcome analysis revealed a significantly higher risk of disease progression in IDC-P+/N+ patients than in IDC-P+/N- patients (P < .001). Significant differences in progression-free survival between IDC-P+/N- and IDC-P+/N+ patients were also seen in subgroups, such as those without (P = .01) or with (P = .03) adjuvant therapy immediately after RP, those with pN0 disease (P < .001), and, more interestingly, those exhibiting conventional Gleason pattern 5 component (P = .02). Multivariate analysis showed significance for IDC-P+/N+ when IDC-P (grade 4) and IDC-P+/N+ (grade 5) were (hazard ratio, 1.768; P = .049) or were not (hazard ratio, 2.000; P = .008) incorporated into the Gleason score. IDC-P+/N+ was found to be associated with worse histopathologic features on RP and poorer prognosis as an independent predictor. Pathologists may thus need to report the presence or absence of not only IDC-P but also comedonecrosis within IDC-P.

106 Cumulative Cancer Location Incidence and Cancer Progression in an Active Surveillance Cohort

OBJECTIVES/GOALS: Prostate cancer is the 2nd most common cancer among men. 1/3 of these men have a slow-growing disease that can be managed without intervention. Instead of treatment, they can enter an active surveillance program. The goal of this study is to examine if cumulative cancer location can predict one’s disease progression and be used as a clinical marker. METHODS/STUDY POPULATION: This is a retrospective cohort study consisting of men with Gleason Grade 1 prostate cancer enrolled in the Active Surveillance Program at Johns Hopkins. The cohort includes men who were enrolled in the program from 2007 to 2015 before prostate biopsies incorporated multiparametric MRI as of the prostate. We will assess if cumulative cancer location (CCLO), a sum of the total number of histological cancer-positive locations on diagnostic and confirmatory biopsy, can predict grade progression, adverse findings on radical prostatectomy findings, or protocol-based discontinuation. Kaplan Meier survival analyses and multivariable Cox regression will be used to determine if stratifying by CCLO can predict these outcomes. RESULTS/ANTICIPATED RESULTS: We included 1298 men in this study. The study will analyze variables that will be used in multivariable regression. Some variables of interest include age at diagnosis, PSA, PSA density, race/ethnicity, and number of positive cores. We expect that greater variability of tumor location, a higher CCLO score, will lead to more grade progression, protocol-based discontinuation, shorter time on active surveillance and adverse findings after radical prostatectomy. This hypothesis is based on a 2018 study that determined cancer location as a significant predictor of progression at the time of biopsy. Results will be discussed in full at the conference. DISCUSSION/SIGNIFICANCE: Finding a predictive marker of progression at the time of biopsy is clinically significant and can lead to adjusted patient observation and testing while on active surveillance. This will better stratify men on active surveillance, determine who would benefit from genetic testing, and better counsel patients as to how long they will be on surveillance.

The Clinical Significance of Perineural Invasion by Prostate Cancer on Needle Core Biopsy: Involvement of Single Versus Multiple Sextant Sites.

Perineural invasion (PNI) by prostate cancer has been associated with adverse pathology, including extraprostatic extension. However, the significance of PNI quantification on prostate biopsy (PBx) remains unclear. To compare radical prostatectomy (RP) findings and long-term outcomes in patients whose PBx had exhibited PNI. We assessed 497 consecutive patients undergoing sextant (6-site/≥12-core) PBx showing conventional adenocarcinoma followed by RP. PNI was found in 1 (n = 290)/2 (n = 132)/3 (n = 47)/4 (n = 19)/5 (n = 5)/6 (n = 4) of the sites/regions of PBx. Compared with a single PNI site, multiple PNIs were significantly associated with higher preoperative prostate-specific antigen, higher Grade Group (GG) on PBx or RP, higher pT or pN category, positive surgical margin, and larger estimated tumor volume. When compared in subgroups of patients based on PBx GG, significant differences in RP GG (GG1-3), pT (GG1-2/GG1-3/GG2/GG3), surgical margin status (GG1-3/GG3/GG5), or tumor volume (GG1-2/GG1-3/GG2/GG3) between 1 versus multiple PNIs were observed. Moreover, there were significant differences in prostate-specific antigen (PNI sites: 1-2 versus 3-6/1-3 versus 4-6/1-4 versus 5-6), RP GG (1-3 versus 4-6/1-4 versus 5-6), pT (1-2 versus 3-6/1-3 versus 4-6), pN (1-3 versus 4-6), or tumor volume (1-2 versus 3-6/1-4 versus 5-6). Outcome analysis revealed significantly higher risks of disease progression in the entire cohort or PBx GG1-2/GG1-3/GG2/GG3/GG5 cases showing 2 to 6 PNIs, compared with respective controls with 1-site PNI. In multivariate analysis, multisite PNI was an independent predictor for progression (hazard ratio = 1.556, P = .03). Multiple sites of PNI on PBx were associated with worse histopathologic features in RP specimens and poorer prognosis. PNI may thus need to be specified, if present, in every sextant site on PBx, especially those showing GG1-3 cancer.

The Clinical Impact of pT3a Lesions in Patients With pT3b Prostate Cancer Undergoing Radical Prostatectomy.

Seminal vesicle invasion (SVI) by prostate cancer (pT3b disease) has been considered as a key prognostic factor. To assess the clinical impact of T3a lesions (ie, extraprostatic extension other than bladder neck invasion [BNI] or SVI [EPE], microscopic bladder neck invasion [mBNI]) in pT3b disease. We compared radical prostatectomy findings and long-term oncologic outcomes in 248 patients with pT3b disease, with versus without EPE/mBNI. Extraprostatic extension/mBNI was found in 219 (88.3%)/48 (19.4%) cases, respectively. Extraprostatic extension was significantly associated with higher preoperative prostate-specific antigen (PSA) level, higher rates of positive surgical margin (pSM) and lymphovascular invasion (LVI), and larger tumor volume. Similarly, mBNI was significantly associated with higher PSA level, higher rates of Grade Group(s) 4-5 or 5, pSM, LVI, and pN1, and larger tumor volume. Significant differences in all of these clinicopathologic features (except lymph node metastasis) between EPE-/mBNI+ or EPE+/mBNI- and EPE+/mBNI+ cases were also observed. Outcome analysis revealed that patients with EPE (P < .001) or mBNI (P < .001) had a significantly higher risk of disease progression than respective controls. Notably, there were significant differences in progression-free survival between EPE-/mBNI+ or EPE+/mBNI- cases and EPE-/mBNI- (P = .001) or EPE+/mBNI+ (P < .001) cases. In multivariate analysis, EPE (hazard ratio [HR] = 6.53, P = .009) and mBNI (HR = 2.33, P = .003), as well as EPE-/mBNI+ or EPE+/mBNI- (HR = 11.7, P = .01) and EPE+/mBNI+ (HR = 25.9, P = .002) versus EPE-/mBNI-, showed significance for progression. From these significant findings, we propose a novel pT3b subclassification: pT3b1 (SVI alone without EPE or mBNI), pT3b2 (SVI with either EPE or mBNI), and pT3b3 (SVI with both EPE and mBNI).

The Clinical Impact of Unilateral Versus Bilateral Invasion Into the Seminal Vesicle in Patients With Prostate Cancer Undergoing Radical Prostatectomy.

Seminal vesicle involvement by prostate cancer has generally been considered as a key prognosticator. To assess the clinical significance of unilateral (Uni) versus bilateral (Bil) seminal vesicle invasion (SVI). We compared radical prostatectomy findings and long-term oncologic outcomes in 248 patients showing Uni-SVI (n = 139) versus Bil-SVI (n = 109). Tumor grade was significantly higher in Bil-SVI cases than in Uni-SVI cases. Additionally, Bil-SVI was significantly associated with a higher incidence of lymphovascular invasion, lymph node metastasis, or positive surgical margin, and larger estimated tumor volume. When the histopathologic features at SVI foci were compared, Grade Group (GG) 3-5/4-5/5 and cribriform morphology were significantly more often seen in Bil-SVI. Outcome analysis revealed that patients with Bil-SVI had a significantly higher risk of disease progression (P < .001) than patients with Uni-SVI. Significantly worse progression-free survival in patients with Bil-SVI was also observed in all subgroups examined, including those with no immediate adjuvant therapy (IAT) (n = 139; P = .01), IAT (n = 109; P = .001), pN0 disease (n = 153; P = .002), or pN1 disease (n = 93; P = .006). In multivariate analysis, Bil-SVI (versus Uni-SVI) showed significance for progression in the entire (hazard ratio [HR] = 1.83, P = .01), IAT (HR = 2.90, P = .006), and pN0 (HR = 2.05, P = .01) cohorts. Meanwhile, tumor grade at SVI (eg, GG4, GG5), as an independent predictor, was significantly associated with patient outcomes. Bil-SVI was found to be strongly associated with worse histopathologic features on radical prostatectomy and poorer prognosis. Pathologists may thus need to report Uni-SVI versus Bil-SVI, along with other histopathologic findings, such as Gleason score, at SVI in prostatectomy specimens.

PTEN and ERG expression in MRI-ultrasound guided fusion biopsy correlated with radical prostatectomy findings in men with prostate cancer.

Conventional systematic prostate biopsies (SBx) have multiple limitations, and magnetic resonance imaging (MRI)-ultrasound fusion targeting is increasingly applied (fusion biopsies [FBx]). In our previous studies, we have shown that loss of the tumor suppressor gene phosphatase and tensin homolog (PTEN) in radical prostatectomy (RP) specimens predicts poor disease-specific survival, andin active surveillance (AS), PTEN loss in SBx predicts an adverse AS outcome, although SBx PTEN status does not correlate well with the corresponding RP status. Here, we have hypothesized that PTEN and erythroblast transformation-specific related gene (ERG) status in FBx correlate better with RP than they would in SBx. A total of 106 men, who had undergone FBx and subsequent RP in a single center between June 2015 and May 2017 were included. Fifty-three of the men had concomitant or previous SBx's. All biopsy and RP specimens were collected, and tissue microarrays (TMA) were constructed from RP specimens. Immunohistochemical stainings for PTEN and ERG expression were conducted on biopsies and RP TMAs and results were compared by using Fisher's exact test. The immunohistochemical predictive power of FBx, determined by the concordance of biopsy PTEN and ERG status with RP, is superior to SBx (77.6% vs 66.7% in PTEN, 92.4% vs 66.6% in ERG). FBx was superior to SBx in correlation with RP Gleason Grade Groups and MRI prostate imaging reporting and data system scores. FBx grading correlates with RP histology and MRI findings and predicts the biomarker status in the RP specimens more accurately than SBx. A longer follow-up is needed to evaluate if this translates to better prediction of disease outcomes, especially in AS and radiation therapy where prostatectomy specimens are not available for prognostication.

Prostate Cancers Detected by Magnetic Resonance Imaging-Targeted Biopsies Have a Higher Percentage of Gleason Pattern 4 Component and Are Less Likely to Be Upgraded in Radical Prostatectomies.

In Gleason score (GS) 7 prostate cancers, the quantity of Gleason pattern 4 (GP 4) is an important prognostic factor and influences treatment decisions. Magnetic resonance imaging (MRI)-targeted biopsy has been increasingly used in clinical practice. To investigate whether MRI-targeted biopsy may detect GS 7 prostate cancer with greater GP 4 quantity, and whether it improves biopsy/radical prostatectomy GS concordance. A total of 243 patients with paired standard and MRI-targeted biopsies with cancer in either standard or targeted or both were studied, 65 of whom had subsequent radical prostatectomy. The biopsy findings, including GS and tumor volume, were correlated with the radical prostatectomy findings. More prostate cancers detected by MRI-targeted biopsy were GS 7 or higher. Mean GP 4 percentage in GS 7 cancers was 31.0% ± 29.3% by MRI-targeted biopsy versus 25.1% ± 29.5% by standard biopsy. A total of 122 of 218 (56.0%) and 96 of 217 (44.2%) prostate cancers diagnosed on targeted biopsy and standard biopsy, respectively, had a GP 4 of 10% or greater ( P = .01). Gleason upgrading was seen in 12 of 59 cases (20.3%) from MRI-targeted biopsy and in 24 of 57 cases (42.1%) from standard biopsy ( P = .01). Gleason upgrading correlated with the biopsy cancer volume inversely and GP 4 of 30% or less in standard biopsy. Such correlation was not found in MRI-targeted biopsy. Magnetic resonance imaging-targeted biopsy may detect more aggressive prostate cancers and reduce the risk of Gleason upgrading in radical prostatectomy. This study supports a potential role for MRI-targeted biopsy in the workup of prostate cancer and inclusion of percentage of GP 4 in prostate biopsy reports.

Abstract 4602: PTEN and ERG expression in MRI-ultrasound guided fusion biopsy correlated with radical prostatectomy findings in men with prostate cancer

Abstract Introduction &amp; Objectives We previously compared ERG and PTEN protein expression in systematic biopsies with radical prostatectomy (RP) findings. MRI-Ultrasound (MRI-US) guided biopsies are expected to more accurately reflect the biological changes in the RP specimens. Here, we studied the correlation of PTEN and ERG status in MRI-US fusion biopsies (FBx) and RP specimens, and assessed the predictive value of FBx on disease stage and grade at RP. Material &amp; Methods The study included patients who had undergone RP in Helsinki University Hospital between June 2015 and May 2017, and had preoperative FBx tissue available (n=110). Matched FBx specimens and tissue microarrays constructed from RP were immunostained with ERG and PTEN antibodies, and scored as either negative or positive. The RP TMA contained one to three clinically relevant cancer foci per patient. Results A high correlation of both PTEN and ERG status was observed between FBx and RP materials (Table 1). The correlation of PTEN status was particularly better compared with our previous findings in systematic 12-core biopsies (Lokman et al. 2017), where there was no significant concordance. High grade RP (grade group 4&amp;5) correlated with ERG negativity in FBx (p=0.021), whereas PTEN was lost in high stage RP (pT≥3) to a higher extent than in low stage RP (pT2, p= n.s). Higher FBx grade group was associated with stage increase in RP (p=0.014). Conclusions FBx is feasible method to assess ERG and PTEN status correctly in RP specimens. More validation studies, accompanied with MRI features, are warranted. Table 1A. Concordance of ERG IHC status in fusion biopsies (FBx) and radical prostatectomy (RP) specimens.RP ERG NegativeRP ERG PositiveP-valueFBx ERG Negative54 (90.0)6 (10.0)&amp;lt;0.001aFBx ERG Positive3 (7.1)39 (92.9)Table 1B. Concordance of PTEN IHC (Any PTEN Loss) status in FBx and RP specimens.RP Any PTEN LossRP PTEN IntactP-valueFBx Any PTEN Loss14 (73.7)5 (26.3)0.002aFBx PTEN Intact22 (32.4)46 (67.6)Table 1C. Concordance of PTEN IHC (Complete PTEN Loss) status in FBx and RP specimens.RP Complete PTEN LossRP PTEN IntactP-valueFBx Complete PTEN Loss6 (50.0)3 (50.0)&amp;lt;0.001aFBx PTEN Intact3 (4.0)72 (96.0)aFisher''s exact test. All p-values two-tailed. Citation Format: Andrew Erickson, Utku Lokman, Kanerva Lahdensuo, Sara Tornberg, Harri Visapää, Robin Bergroth, Henrikki Santti, Anssi Petas, Tuomas Mirtti, Antti Rannikko. PTEN and ERG expression in MRI-ultrasound guided fusion biopsy correlated with radical prostatectomy findings in men with prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4602.

Upgrading and upstaging at radical prostatectomy in the post–prostate-specific antigen screening era: an effect of delayed diagnosis or a shift in patient selection?

Prostate cancer management changed in recent times given the recommendation against prostate-specific antigen screening, adherence to active surveillance, and "cytoreductive" surgery. We hypothesized that radical prostatectomy (RP) findings changed as well. All consecutive RPs (n=1348) and first time prostate needle biopsies (n=1719) in a period of 9 years were reviewed. The cohort was separated into 3 groups: (1) from May 2006 to April 2009, (2) from May 2009 to April 2012, and (3) from May 2012 to April 2015. The number of RPs decreased 15% from 551 in group 1 to 476 in group 2 and decreased a further 35% to 311 in group 3. Pure Gleason 6 (grade group 1) decreased from 46% in group 1 to 24% in group 2 (P<.001) to 12% in group 3 (P<.001). Gleason score 4+3=7 (grade group 3) increased from 9.8% in group 1 to 13.4% in group 2 (P=.07) to 20.6% in group 3 (P=.01). Gleason score 8, 9, or 10 (grade groups 4 and 5) increased from 0.9% in group 1 to 8.4% in group 2 (P<.001) to 13.2% in group 3 (P=.04). Pathologic stage pT3 or above increased from 15.5% in group 1 to 29.2% in group 2 (P<.01) to 38.3% in group 3 (P=.01). In needle biopsies, there was no difference in number of cancer diagnoses, number of positive cores, or distribution of grades among 3 groups. More patients with low-risk disease are opting for active surveillance, and patients with high-risk disease are offered cytoreductive surgery. Lack of similar changes in needle biopsies suggests that a decrease in screening is not playing a role in the changes seen at RPs.